(Jurg Hodler) Diseases of The CH - Desconocido PDF

IDKD and Satellite
Diseases
of the Chest
SYLLABUS and Heart
Courses 2015-2018
Diagnostic Imaging and

Interventional Techniques
Editors
J. Hodler
R.A. Kubik-Huch
G.K. von Schulthess
Ch.L. Zollikofer
123
Diseases of the Chest and Heart 2015-2018
Diagnostic Imaging and Interventional Techniques
J. Hodler R.A. Kubik-Huch G.K. von Schulthess
Ch.L. Zollikofer (Eds)
DISEASES OF THE
CHEST AND HEART
2015-2018
DIAGNOSTIC IMAGING AND INTERVENTIONAL
TECHNIQUES
47th International Diagnostic Course

in Davos (IDKD)
Davos, March 22-27, 2015
including the
Nuclear Medicine Satellite Course Diamond
Davos, March 21-22, 2015
Pediatric Radiology Satellite Course Kangaroo

Davos, March 21, 2015
Breast Imaging Satellite Course Pearl

Davos, March 21, 2015
and additional IDKD Courses 2015-2018
presented by the Foundation for the

Advancement of Education in Medical Radiology, Zurich
IV S.M. Ascher
Editors
J. HODLER R.A. KUBIK-HUCH

Radiology Radiology
University Hospital Kantonsspital
Zurich, Switzerland Baden, Switzerland
G.K. VON SCHULTHESS CH.L. ZOLLIKOFER

Nuclear Medicine Kilchberg/Zurich, Switzerland
University Hospital
Zurich, Switzerland
DOI 10.1007/978-88-470-5752-4
ISBN 978-88-470-5751-7 ISBN 978-88-470-5752-4 (eBook)
Springer Milan Dordrecht Heidelberg London New York
Library of Congress Control Number: 2015931953
Springer-Verlag Italia 2015
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V
IDKD 2015-2018
Preface
The International Diagnostic Course in Davos (IDKD) is a unique learning

experience for imaging specialists. The course is useful for experienced radiologists,
imaging specialists in training and clinicians wishing to be updated on the current
state of the art and the latest developments in the fields of imaging and image-
guided interventions.
This organ based and disease oriented course deals with imaging of the chest
and heart, and includes pediatric imaging. In addition, there will be satellite
courses covering pediatric radiology and nuclear medicine related to the chest and
heart in more depth. In addition a breast imaging satellite course is offered.
During the last few years there have been considerable advances in this field
driven by clinical as well as technological developments. These will be highlight-
ed in the workshops given by internationally known experts in their field. The pre-
sentations encompass all the relevant imaging modalities including CT, MRI,
PET, and conventional radiology.
This Syllabus contains condensed versions of the topics presented in the work-
shops. As a result, this book offers a comprehensive review of the state-of-the-art
in imaging and intervention of chest and cardiac diseases as well as the breast.
This Syllabus was initially designed to provide the relevant information for the
course participants in order to allow them to fully concentrate on the lectures and
participate in the discussions without the need of taking notes. However, the
Syllabus has developed into a convenient update for radiologists, radiology resi-
dents, nuclear physicians and clinicians interested in lung and heart diseases.
Additional information on IDKD courses can be found on the IDKD website:

www.idkd.org
J. Hodler
R.A. Kubik-Huch
G.K. von Schulthess
Ch.L. Zollikofer
IDKD 2015-2018
Table of Contents
Workshops
Update in the Diagnosis and Staging of Lung Cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
Jos Vilar, Jeremy J. Erasmus
Computed Tomography Diagnosis and Management of Focal Lung Disease . . . . . . . . . 17

Ioannis Vlahos, Gerald F. Abbott
Approach to Imaging of Mediastinal Conditions in the Adult . . . . . . . . . . . . . . . . . . . . . . . 23

Sanjeev Bhalla, Jos Caceres
Current Approaches to Chronic and Acute Airway Diseases . . . . . . . . . . . . . . . . . . . . . . . . . . 29

Philippe A. Grenier, Jeffrey P. Kanne
Investigating a Child with a Cough: A Pragmatic Approach . . . . . . . . . . . . . . . . . . . . . . . 37

Maria do Rosario Matos, George A. Taylor, Catherine M. Owens
Thoracic Manifestations of Pediatric Systemic Diseases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 46

Edward Y. Lee, Alan S. Brody
Modern Diagnosis in the Evaluation of Pulmonary Vascular Disease . . . . . . . . . . . . . . . . 57

Alexander A. Bankier, Christoph Engelke
Imaging of Pulmonary Infections . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 63

Philip Goodman, Helmut Prosch, Christian J. Herold
Imaging of Thoracic Trauma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 71

Loren Ketai, Caroline Chiles
Missed Lung Lesions: Side by Side Comparison of Chest Radiography with MDCT . . . 80
Nigel Howarth, Denis Tack
Plain Film and HRCT Diagnosis of Interstitial Lung Disease . . . . . . . . . . . . . . . . . . . . . . . . . 88

Sujal R. Desai, Jeffrey R. Galvin
A Systematic Approach to Chest Radiographic Diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . 94

Melissa L. Rosado-de-Christenson, Jeffrey S. Klein
Diseases of the Chest Wall, Pleura, and Diaphragm . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 101

Aine Kelly, Nicola Sverzellati
Pulmonary Manifestations of Systemic Diseases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 110

Cornelia Schaefer-Prokop, Brett M. Elicker
CT Evaluation of Chest Pain: Acute Coronary Syndrome and Acute Aortic Syndrome 119
Dominik Fleischmann, Udo Hoffmann
VIII Table of Contents
Incidental Findings on Thoracic and Cardiac CT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 129

Lynn S. Broderick, Shawn D. Teague
Cardiac Magnetic Resonance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 134

Didier Revel, David A. Bluemke
An Integrative Approach to the Imaging of Ischemic Heart Disease . . . . . . . . . . . . . . . . . 143

Albert de Roos, Danilo Neglia
Acute Aortic Syndrome: State-of-the-Art Diagnostic Imaging . . . . . . . . . . . . . . . . . . . . . . . 149

Thomas Grist, Geoffrey D. Rubin
Interventional Techniques in the Thorax of Adults . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 157

Dierk Vorwerk
Nonvascular Interventional Radiology of the Thorax . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 165

Albert A. Nemcek, Jr.
Dose-Lowering Strategies in Computed Tomography Imaging of the Lung

and Heart . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 168
Andr Euler, Zsolt Szucs-Farkas, John R. Mayo, Sebastian T. Schindera
Nuclear Medicine Satellite Course Diamond

FDG-PET Imaging for Advanced Radiotherapy Treatment of Non-Small-Cell
Lung Cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 177
Matthias Guckenberger, Leonie Rudofsky, Nicolaus Andratschke
Staging, Restaging and Response Evaluation of Non-Small-Cell Lung Cancer . . . . . . . 183

Lars Husmann, Paul Stolzmann
How To Approach Incidental Findings on Computed Tomography Images of the

Lungs Obtained in Hybrid Imaging . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 189
Jeffrey P. Kanne
Integrated Cardiac Imaging . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 198

Philipp A. Kaufmann, Tobias A. Fuchs
FDG PET/CT in the Imaging of Mediastinal Masses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 202

Pek-Lan Khong
Integrated Cardiovascular PET/MR: Lessons Learned . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 209

Christoph Rischpler, Stephan G. Nekolla, Markus Schwaiger
Pediatric Radiology Satellite Course Kangaroo

Pediatric Chest Tumors Including Lymphoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 219
Alexander Oshmyansky, Thierry A.G.M. Huisman
Pediatric Cardiovascular Diseases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 226

Edward Y. Lee
Table of Contents IX
The Radiology of Diffuse Interstitial Pulmonary Disease in Children: Pearls,

Pitfalls and Newly Recognised Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 235
Catherine M. Owens
Neonatal Medical and Surgical Lung Diseases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 240

George A. Taylor
Breast Imaging Satellite Course Pearl

Scintimammography . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 247
Einat Even-Sapir
Breast MRI BI-RADS: Second Edition Highlights . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 250

Elizabeth A. Morris
Recent Developments in Breast Ultrasound with a Special Focus on Shear-Wave

Elastography . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 255
Claudia Kurtz
Magnetic Resonance Imaging of Breast Implants and the Reconstructed Breast . . . 264
Isabelle Thomassin-Naggara, Michael Atlan, Jocelyne Chopier, Emile Darai
IDKD 2015-2018
List of Contributors
Abbott G.F., 17 Kaufmann P.A., 198

Andratschke N., 177 Kelly A., 101
Atlan M., 264 Ketai L., 71
Bankier A.A., 57 Khong P.L., 202
Bhalla S., 23 Klein J.S., 94
Bluemke D.A., 134 Kurtz C., 255
Broderick L.S., 129 Lee E.Y., 46, 226
Brody A.S., 46 Mayo J.R., 168
Caceres J., 23 Morris E.A., 250
Chiles C., 71 Neglia D., 143
Chopier J., 264 Nekolla S.G., 209
Darai E., 264 Nemcek A.A., Jr., 165
de Roos A., 143 Oshmyansky A., 219
Desai S.R., 88 Owens C.M., 37, 235
do Rosario Matos M., 37 Prosch H., 63
Elicker B.M., 110 Revel D., 134
Engelke C., 57 Rischpler C., 209
Erasmus J.J., 3 Rosado-de-Christenson M.L., 94
Euler A., 168 Rubin G.D., 149
Even-Sapir E., 247 Rudofsky L., 177
Fleischmann D., 119 Schaefer-Prokop C., 110
Fuchs T.A., 198 Schindera S.T., 168
Galvin J.R., 88 Schwaiger M., 209
Goodman P., 63 Stolzmann P., 183
Grenier P.A., 29 Sverzellati S., 101
Grist T., 149 Szucs-Farkas Z., 168
Guckenberger M., 177 Tack D., 80
Herold C.J., 63 Taylor G.A., 37, 240
Hoffmann U., 119 Teague S.D., 129
Howarth N., 80 Thomassin-Naggara I., 264
Huisman T.A.G.M., 219 Vilar J., 3
Husmann L., 183 Vlahos I., 17
Kanne J.P., 29, 189 Vorwerk D., 157
WORKSHOPS
IDKD 2015-2018
Update in the Diagnosis and Staging of Lung Cancer

Jos Vilar1, Jeremy J. Erasmus2
1 Hospital Universitario Dr. Peset, Valencia, Spain
2 Department of Radiology, MD Anderson Cancer Center, Houston, TX, USA
Introduction Clinical Manifestations of NSCLC
Primary lung cancer is the leading cause of cancer mortal- Most patients are in their fifth and sixth decades of life
ity in the world and its incidence is expected to rise in the and approximately three quarters of patients are sympto-
next several decades, especially in more recently industri- matic at presentation [1]. Many patients present with
alized countries such as China. This high mortality is nonspecific systemic manifestations of malignancy, in-
largely explained by the fact that patients with lung cancer cluding anorexia, weight loss, or fatigue. Symptoms also
often present with advanced stage disease. Imaging is im- depend on the local effects of the primary mass, the pres-
portant in the early detection and clinical staging of lung ence of regional or distant metastases, and the coexis-
cancer. Indeed, both the therapeutic options and the man- tence of paraneoplastic syndromes. While solitary pe-
agement of patients with lung cancer are to a considerable ripherally located tumors tend to be asymptomatic, cen-
degree dependent upon disease stage at presentation. De- tral endobronchial tumors can manifest as fever, dyspnea,
tailed knowlegde and the appropriate use of imaging in the hemoptysis, and cough. Symptoms that can occur as a re-
staging evaluation of patients with non-small cell lung can- sult of local growth and the invasion of adjacent nerves,
cer (NSCLC) are required to avoid unnecessary procedures, vessels, and mediastinal structures include chest pain, vo-
excess radiation, and redundant information. This is facil- cal cord paralysis and hoarseness, facial and upper trun-
itated by the use of guidelines as well as the participation cal edema, headaches, neck vein distention, enlarged col-
of multidisciplinary teams in which radiologists, patholo- lateral chest wall vessels (superior vena cava obstruc-
gists, pulmonologists, surgeons, and medical and radiation tion), and dysphagia (esophageal involvement). Clinical
oncologists discuss and reach a consensus on individual- signs and symptoms can also be caused by tumor excre-
ized imaging and treatment. The main objective of this tion of a bioactive substance, or hormone, or as a result
chapter is to review the basic concepts related to the de- of immune-mediated neural tissue destruction caused by
tection, staging, and follow-up of patients with NSCLC. antibody- or cell-mediated immune responses. These
paraneoplastic syndromes occur in 1020% of lung can-
cer patients. Antidiuretic and adrenocorticotropin hor-
Detection of Lung Cancer mones are the more frequently excreted hormones and
can result in hyponatremia and serum hypo-osmolarity
Preclinical Detection and in Cushings syndrome (central obesity, hypertension,
glucose intolerance, plethora, hirsutism), respectively [1].
The most common finding in an asymptomatic patient
with NSCLC is the solitary pulmonary nodule (SPN), de-
fined as a single intraparenchymal lesion 3 cm in di- Role of Imaging in Detecting Lung Cancer
ameter that is not associated with atelectasis or lym-
phadenopathy. When the lesion is 3 cm, it is defined as Imaging has an important role in screening for a lung ma-
a mass. SPNs are detected incidentally on chest radio- lignancy because diagnosis at an early stage, before clin-
graphs or computed tomography (CT) but can also be de- ical presentation, is associated with an improved progno-
tected by screening programs for lung cancer. The chance sis. Lung cancer screening is typically performed with
of a pulmonary nodule being a cancer is directly related low-dose CT (LDCT), as screening with chest radiogra-
to the prevalence of the disease (pretest probability) and phy has been shown to have limited benefit. Randomized
thus is much higher in high-risk groups such as heavy control trials have been or are being conducted to exam-
cigarette smokers. ine the role of screening in lung cancer management. The
Diseases of the Chest and Heart 2015-2018,

DOI: 10.1007/978-88-470-5752-4_1 Springer-Verlag Italia 2015 3
4 J.Vilar, J.J. Erasmus
National Lung Screening Trial (NLST), a randomized nodules growth can manifest not only as an increase in
study comparing the effectiveness of LDCT vs. chest ra- size but also as an increase in attenuation and/or the de-
diography in more than 50,000 participants, reported sig- velopment or increase in size of a solid component. These
nificant reductions in lung cancer (20%) and all-cause imaging features of growth are suspicious for an in-
mortality (6.7%) [2]. Accordingly, LDCT is currently ad- creased risk of malignancy [7]. The measurement of ser-
vocated as a screening tool for lung cancer. However, op- ial volumes, rather than diameters, together with the com-
timal screening strategies have not been determined. puter-calculated volume doubling time of small nodules
Thus, it is uncertain whether younger patients and/or has been suggested as an accurate and potentially useful
smokers with fewer pack-years of smoking history than method to assess growth [8, 9]. In an analysis of the
stated in the eligibility criteria used for individuals ex- growth rates of stage I lung cancers determined with se-
amined in the NLST (55- to 74-year-old patients with at rial volumetric CT measurements, the median time to a
least 30 pack-years of smoking history and still active volume doubling was 207 days (50% of the tumors dou-
smokers, or former smokers who stopped smoking with- bled in volume at 8 weeks and 75% at 14 weeks) [9]. Re-
in the previous 15 years) will also benefit from screen- cently, nodule mass, defined as the combination of nod-
ing. It is hoped that contentious issues, including over di- ule volume and density, was proposed as a more accurate
agnosis bias, whether detection of pre-clinical disease af- determination of the growth of partly solid nodules [10].
fects survival, and the cost-effectiveness of screening By multiplying nodule volume and density, mass mea-
programs, will be resolved in the coming years [3-5]. surements, which are subject to less variability than vol-
The detection of lung cancer can be incidental, by ume or diameter measurements, may allow earlier detec-
screening, or when the lesion has caused symptoms. Low- tion of the growth of partly solid nodules.
dose CT is more sensitive than chest radiographs for de-
tecting early lung cancer. Morphology
Lung cancers typically have irregular or spiculated mar-
Characterization of a Pulmonary Nodule gins, although this finding can occasionally be seen with
benign nodules as well (Fig. 1). A smooth margin, a fea-
Previous chest radiographs or CT images, if available, ture typical of benign nodules, cannot be used to exclude
may suffice in characterizing a nodule as benign, i.e., if lung cancer because malignant nodules may also have this
there is stability in size for 2 years. However, nodules, appearance. The presence of fat (attenuation 40 to 120
especially subsolid (pure ground glass or partly solid) Hounsfield units, HU) in a pulmonary nodule or mass in-
nodules, can remain stable for 2 years due to their very dicates benignity, usually a hamartoma or, less frequently,
slow growth rates and ultimately prove to be indolent lipoid aspiration pneumonia (Fig. 2). Characteristic pat-
adenocarcinomas. The absence of prior studies or the terns of benign calcification, whether central (involving
presence of signs of radiologic change are indications for 10% of the cross-sectional area of the nodule), diffuse,
CT evaluation to better characterize an SPN. Size, growth or laminated, are usually indicative of prior granuloma-
and morphology are the main parameters of an SPN that tous disease. Popcorn-type calcification is typically due to
should be analyzed with CT. Positron emission tomogra- the chondroid tissue in pulmonary hamartomas but can be
phy (PET) can provide useful information about the
metabolic behavior of the nodule.
Growth
Growth can be estimated by evaluating prior imaging
studies. Lung cancers typically double in volume (a 26%
increase in diameter) between 30 and 400 days (average,
240 days). Very rapid duplication times are generally in-
consistent with malignancy. Rather, volume doubling
times 2030 days are suggestive of an infectious or in-
flammatory etiology but they can also occur with lym-
phoma or rapidly growing metastases. Lung cancers can
have long volume doubling times. In a CT screening
study analyzing the growth rates of small lung cancers,
the volume doubling time ranged from 52 to 1733 days
(mean, 452 days) and approximately 20% of these ma-
lignancies had a volumetric doubling time 2 years [6].
Fig. 1. Poorly differentiated adenocarcinoma. Computed tomogra-
These nodular opacities were typically well-differentiat- phy (CT) shows a nodule with a spiculated margin in the right
ed adenocarcinomas. In contrast to the growth of solid upper lobe. Note that spiculation is typical for primary lung ma-
nodules assessed only on the basis of size, in subsolid lignancy. At resection pleural invasion was present
Update in the Diagnosis and Staging of Lung Cancer 5
soft-tissue component on CT [14, 15]. The frequencies of

lobulation, spiculation, and pseudocavitation (small focal
lucencies) are also significantly higher in malignant part-
ly solid nodules.
Significant changes in the pathologic classification of
lung adenocarcinoma were proposed in 2011 [16].The new
adenocarcinoma classification now includes the terms ade-
nocarcinoma in situ (AIS), a preinvasive lesion, minimally
invasive adenocarcinoma (MIA), and invasive adenocarci-
noma [16]. AIS was formerly classified as a bronchio-
loalveolar cell carcinoma and is a small (3 cm), localized
adenocarcinoma that has no stromal, vascular, or pleural in-
vasion and demonstrates lepidic growth [16]. MIA is a soli-
tary adenocarcinoma (3 cm) with 5-mm invasion in any
one focus and a predominantly lepidic pattern of growth
[16]. MIA is excluded if the tumor invades the lymphatics,
blood vessels, or pleura or contains necrosis. Invasive ade-
nocarcinomas are composed of a complex heterogeneous
mixture of histologic subtypes and are classified according
Fig. 2. Hamartoma in a 76-year-old woman. CT shows a 2-cm cen-
trally located nodule in the right upper lobe containing focal low
to the most predominant one (lepidic, acinar, papillary, mi-
attenuation (50 HU), consistent with a hamartoma cropapillary, or mostly solid patterns) [16]. For mucinous
malignancies, the term invasive mucinous adenocarcinoma
has replaced mucinous bronchioloalveolar cell carcinoma.
seen in carcinoid tumors. The presence of calcium does These tumors differ from mucinous AIS and MIA by a size
not exclude the diagnosis of cancer and has been reported 3 cm and/or showing invasion 0.5 cm and/or multiple
to occur in up to 14% of lung cancers histologically. Gen- nodules, or the lack of a circumscribed border with miliary
erally, this calcification is amorphous or, if focal, is not spread into adjacent lung parenchyma. Invasive mucinous
central in location or it forms only a small portion of the adenocarcinomas typically manifest as solid nodules or con-
nodule. The widespread use of thin-collimation CT im- solidative opacities.
ages has increased the detection of nodules with low at-
tenuation [11-13]. These subsolid nodules (pure ground Positron Emission Tomography (PET) Findings
glass nodules and partly solid) have a higher incidence of
malignancy than solid nodules (Fig. 3). According to one The conventional radiologic assessment of an SPN is
study, 63% of partly solid nodules are malignant as op- complemented by the use of PET and the radiopharma-
posed to 18% for ground glass opacities and 7% for solid ceutical 18F-2-deoxy-D-glucose (FDG), a D-glucose ana-
nodules [11]. Importantly, with these nodules the likeli- log labeled with fluorine-18. The reported sensitivity and
hood of malignancy varies according to the size of the specificity of PET for malignant pulmonary lesions are
97% and 78%, respectively. The spatial resolution of PET
scanners is in the range of 6 mm; therefore, smaller le-
sions should not be evaluated with PET. When FDG up-
take by a solid nodule 1 cm in diameter is low, the like-
lihood of malignancy is generally considered to be low.
However, in a study of 360 patients with lung nodules
evaluated by FDG-PET, 43 patients had solid nodules
with a standardized uptake value (SUV) 2.5, 16 of
which were malignant [17]. False-negative results for ma-
lignancy include slow-growing cancers, especially ade-
nocarcinomas with subsolid morphology and carcinoid
tumors (Fig. 4). Nomori et al. reported that nine of ten
well-differentiated adenocarcinomas manifesting as
ground glass nodular opacities were falsely negative on
FDG-PET [18]. The sensitivity (10%) and specificity
(20%) for ground glass opacities in that study were sig-
nificantly lower than for solid nodules (90% and 71%, re-
spectively). False-positive results are most commonly
Fig. 3. Invasive adenocarcinoma in a 79-year-old man. CT shows a
partly solid nodule in the left upper lobe with an 8-mm solid com- caused by infections and inflammatory processes, includ-
ponent (arrowheads). Note that the presence of a 5-mm soft-tis- ing Wegeners granulomatosis, sarcoidosis, organizing
sue component on CT makes the likelihood of malignancy high pneumonia, amyloid, and rheumatoid nodules.
a b
Fig. 4 a, b. Adenocarcinoma in situ in an 89-year-old man. CT shows a 3-cm pure ground glass nodu-
lar opacity in the right upper lobe. b Whole-body positron emission tomography (PET) maximum
intensity projection image shows low-grade 18F-2-deoxy-D-glucose (FDG) uptake in the nodule
(arrow). Note that adenocarcinomas manifesting as ground glass nodular opacities are frequently
falsely negative on FDG-PET
Pulmonary nodules can be characterized according to Low-Risk Populations (Little or No History of Smoking, and No
their growth, morphology, and metabolic activity. Stan- Other Risk Factors)
dard imaging protocols based on the pretest probability
(risk) should be used to rule out malignancy. 1. Nodules 4 mm have a very small likelihood of ma-
lignancy such that re-assessment is not necessary.
2. Nodules 4-mm but 6-mm should be re-assessed us-
Guidelines for the Evaluation of an Incidentally ing CT at 12 months; if stable, no further evaluation is re-
Detected Pulmonary Nodule quired. The exception is the non-solid or partially solid
nodule, for which re-assessment may need to be contin-
The Fleischner Society guidelines for the evaluation of ued to exclude the risk of an indolent adenocarcinoma.
an incidentally discovered solid nodule in an adult pa- 3. Nodules 6 mm but 8 mm should be re-assessed us-
tient integrate lesion morphology, growth rate, patient ing CT at 612 months and, if stable, again at 1824
age, and smoking history (see below). In addition, to months.
complement the recommendations for incidentally de- 4. Nodules 8 mm should either be re-assessed using CT
tected solid nodules, the Society recently published rec- at 3, 9, and 24 months, to determine their size stabili-
ommendations specifically aimed at the management of ty, or further evaluated with contrast-enhanced CT, CT-
ground glass and partly solid nodules (see below) [19, PET, biopsy, or resection.
20]. Importantly, for both, risk factors such as smoking
history, family history of lung cancer, or exposure to car- High-Risk Populations (History of Smoking, or Other Exposure
cinogenic agents are not considered in the current guide- or Risk Factor)
lines due to a lack of sufficient data. Other issues to be
aware of are that a slight temporary decrease in size can 1. Nodules 4 mm should be re-assessed at 12 months;
be seen with adenocarcinomas manifesting as ground if stable, no further evaluation is required. The excep-
glass or partly solid nodules, due to fibrosis or atelecta- tion is the non-solid or partially solid nodule, for
sis, and enlargement and/or increasing attenuation with which re-assessment may need to be continued to ex-
or without the new appearance of a solid component dur- clude the risk of an indolent adenocarcinoma.
ing follow up should be managed with a high degree of 2. Nodules 4 mm but 6 mm should be re-assessed us-
suspicion [20]. ing CT at 612 months and, if stable, again at 1824
months.
3. Nodules 6 mm but 8 mm should be re-assessed us-
ing CT at 36 months and, if stable, again at 912
Recommendations for the Management of Incidentally months and 24 months.
Detected Solid Nodules 4. Nodules 8 mm should either be re-assessed using CT
at 3, 9, and 24 months to assess stability or a contrast-
The Fleischner Society guidelines [19] are summarized enhanced CT, CT-PET, biopsy, or resection should be
in the following. performed.
Recommendations for the Management of Incidentally ing (MRI) and/or PET/CT. A contrast-enhanced CT of the
Detected Solitary Ground Glass and Part Solid Nodules chest is recommended for the evaluation of all patients
with known or suspected primary lung cancer [21]. CT ac-
The Fleischner Society guidelines [20] are summarized curately assesses most characteristics of the primary tu-
in the following. mor (T descriptor), including size and location, but loco-
1. Solitary pure ground glass nodules 5 mm require no regional invasion can be difficult to determine. CT is also
CT follow-up. useful in detecting nodal metastasis and determining the
2. Nodules 5 mm should be initially followed-up at 3 absence or presence of intra- and extrathoracic metastatic
months using CT to confirm persistence, followed by disease, including contralateral lung nodule(s), pleural
annual surveillance CT for a minimum of 3 years. and pericardial nodule(s) and effusions, bone metastases,
3. Solitary, partly solid nodules should be initially fol- and adrenal nodules/masses. CT of the chest alone is suf-
lowed-up at 3 months using CT to confirm persistence. ficient for the staging of patients with pure ground glass
If persistent, with a solid component 5 mm, yearly sur- nodules and an otherwise normal study, and for patients
veillance CT should be performed for a minimum of 3 with peripheral stage IA disease [21]. Otherwise, further
years. If persistent with a solid component 5 mm, then imaging with FDG-PET is recommended for patients eli-
biopsy or surgical resection is recommended. PET/CT gible for curative treatment. FDG-PET/CT has an in-
should be considered for partly solid nodules 10 mm. creasing role in staging, particularly for detecting nodal
(N descriptor) and distant (M descriptor) metastasis.
When PET is unavailable or cannot be performed, a con-
trast-enhanced CT of the abdomen is recommended [21].
Recommendations for the Management of Incidentally
Detected Multiple Ground Glass and Part Solid T Descriptor
Nodules
The T descriptor defines the size, location, and extent of
1. Pure ground glass nodules 5 mm should be fol- the primary tumor and is based on differences in survival
lowed-up using CT at 2 and 4 years. (Fig. 5). However, although a T4 descriptor generally pre-
2. Pure ground glass nodules 5 mm without a dominant cludes resection, tumors with cardiac, tracheal, and ver-
lesion(s) should be initially followed-up using CT at 3 tebral-body invasion are designated in the 7th edition
months to confirm persistence, after which annual sur- staging system as being potentially resectable in the ab-
veillance CT for a minimum of 3 years should be per- sence of N2 and or N3 disease.
formed. The following parameters must be analyzed regarding T
3. A dominant nodule(s) with a partly solid or solid com- descriptor determination: (1) size, (2) location, (3) ex-
ponent should be initially followed-up at 3 months us- tension.
ing CT to confirm persistence. If persistent, biopsy or 1. Tumor size is a determinant of the T descriptor and es-
surgical resection is recommended, especially for le- sential to define surgical and radiotherapy strategies as
sions with a solid component 5 mm. well as to evaluate the response to treatment. In the 7th
edition of the TNM classification, size is a significant
parameter related to survival. T1 is subclassified as T1a
Staging of Lung Cancer (2 cm) or T1b (2 cm to 3 cm); T2 is subclassified
as T2a (3 cm to 5 cm or T2 by other factor and 5
Staging, a standardized anatomic description of disease cm) or T2b (5 cm to 7 cm); tumors 7 cm are clas-
extent, is determined both clinically and pathologically sified as T3. Size is usually measured on CT or MRI.
and guides appropriate treatment. In general, the clinical On CT, lung window settings should be used, as medi-
stage underestimates the extent of disease compared with astinal windowing may underestimate the size.
the pathologic stage. Radiologic imaging is an essential 2. Tumor location is important in that it provides infor-
component of clinical staging and allows the assessment mation to surgeons and radiation oncologists that can
of disease manifestations that are important for surgical, affect therapeutic management. For instance, centrally
oncological, and radiation therapy planning, including located tumors close to the spinal cord impose radia-
size of the primary tumor, its location and relationship to tion dose-volume constraints, and determining tumor
normal anatomic structures in the thorax, and the presence margins is important as they can affect radiotherapy
of nodal and or metastatic disease. The 7th edition of the delivery. This is especially important with the increas-
tumor node metastasis (TNM) staging system allows a ing use of conformal radiation therapy, in which mul-
standardized definition of stage and, consequently, indi- tiple radiation beams are used to generate dose distri-
cates the most appropriate treatment. While useful in as- butions that conform tightly to target volumes. The re-
certaining advanced disease, chest radiography is limited lation of the tumor to a fissure must be reported, as it
in accurately determining TNM descriptors in patients may imply a change in surgical technique (pneu-
with potentially resectable disease, which typically re- monectomy instead of lobectomy) when there is evi-
quires imaging with CT and/or magnetic resonance imag- dence that the lesion crosses the fissure (Fig. 6). The
Fig. 5. Descriptions of malignant lung

tumors, nodes, and metastases for classifi-
cation purposes. Reprinted with permis-
sion courtesy of the International Associa-
tion for the Study of Lung Cancer. Copy-
right 2009 IASLC
proximity to a main pulmonary artery can also involve pulmonary artery involvement may require a pneu-
a change in surgical approach. monectomy rather than a lobectomy in order to obtain
3. Tumor extension can be divided into local and distant. clear surgical margins. Additionally, involvement of the
Local extension is included in the T descriptor, whereas origin of the lobar bronchus or main bronchus may re-
distant metastases relate to the M descriptor. In the quire a sleeve resection or pneumonectomy. Thoracic
TNM staging system, additional pulmonary nodules in wall invasion does not preclude surgery but must be re-
the same lobe are classified as T3, nodule/s in other ip- ported to the surgeon to ensure appropriate surgical re-
silateral lobes are T4 and nodule/s in the contralateral section, typically en bloc resection of the chest wall.
lung are M1a.The determination of the degree of pleur-
al, chest-wall, and mediastinal invasion, as well as central Role of Imaging in T Descriptor Determination
airways, pulmonary veins, and artery involvement is im-
portant not only to radiation oncologists but also to sur- CT and MRI are useful in determining gross chest wall
geons evaluating the tumor for resectability. For instance, or mediastinal invasion (Fig. 7). However, limited loco-
Fig. 6. Poorly differentiated adenocarcinoma in a 60-year-old man.

CT shows a lobular mass in the right lower lobe with extension Fig. 8. Superior sulcus tumor in a 66-year-old man presenting with
through the major fissure (arrowheads). The patient was treated numbness of the upper arm extending to the elbow. Sagittal T1-
definitively with concurrent chemoradiation weighted magnetic resonance image shows a mass (M) in the left
upper lobe. The mass extends above the first rib and involves the
C7 and C8 nerve roots of the brachial plexus (arrowheads). There
regional invasion is difficult to differentiate from abut- is also extension of the mass into the soft tissues of the thorax pos-
ment. MRI can be used to assess myocardial invasion and teriorly into the T1/2 and T2/3 intevertebral foramina. The mass en-
to evaluate superior sulcus tumors for involvement of the cases the subclavian artery (*). Note that involvement of the
brachial plexus, regional vasculature, and adjacent spine brachial plexus roots superior to the T1 nerve root is an absolute
contraindication to surgical resection. C clavicle, R1 first rib, R2
and vertebra (Fig. 8). This is important since involvement second rib
of the brachial plexus roots or trunks superior to the T1
nerve root, invasion of the trachea or esophagus, and
50% invasion of a vertebral body are absolute con- CT and MRI play fundamental roles in T descriptor de-
traindications to surgical resection [22, 23]. termination. PET/CT is an additional tool in specific sit-
uations.
Tumor size, location, and extension are the fundamental
T descriptors. The radiologist must have a thorough knowl- N Descriptor
edge of the anatomic implications of the T descriptors in
relation to surgery, radiotherapy, and chemotherapy. The N descriptor, which specifies the presence and loca-
tion of nodal metastatic disease, has a significant effect
on management (Fig. 5). N descriptors are designated ac-
cording to lymph node maps in which the nodal stations
are numbered based on relationships to anatomic struc-
tures [24, 25]. For the 7th TNM edition, a standardized
nodal map with seven node zones, created by unifying the
Mountain/Dressler-ATS (MD-ATS) node map and the
Japanese Naruke map, is used. The International Associ-
ation for the Study of Lung Cancer (IASLC) nodal map
designates the oncologic midline of the superior medi-
astinum to correspond with the left lateral border of the
trachea, such that all nodes anterior to the trachea are
grouped with right paratracheal nodes (Fig. 9). Surgical
resection and the potential use of adjuvant therapy de-
pend on the N descriptor, such that its accurate determi-
nation is important. Ipsilateral peribronchial, or hilar
Fig. 7. Non-small-cell lung cancer in a 50-year-old man with chest- (N1) nodes are usually resectable while mediastinal
wall pain. CT shows a large cavitary mass in the right upper lobe
with invasion of the chest wall (arrowheads). Note that chest wall in- nodes have a major influence on resectability. Specifical-
vasion does not preclude surgery but usually changes the resection ly, ipsilateral mediastinal (including subcarinal) nodal
from a lobectomy to an en bloc resection of the lobe and chest wall metastasis (N2) can be resectable (usually after induction
Fig. 9. Positions and descriptions of malig-

nant nodes. Reprinted with courtesy per-
mission of the International Association
for the Study of Lung Cancer. Copyright
2009 IASLC and 2008 Aletta Ann Frazier
chemotherapy), while contralateral mediastinal and but their accuracy in detecting metastases to hilar and
scalene or supraclavicular disease (N3) is not. To poten- mediastinal nodes is not optimal because enlarged
tially improve patient management, data are currently be- nodes can be hyperplastic and small nodes can contain
ing collected based on grouping nodal stations together in metastases. A meta-analysis of CT accuracy for nodal
six zones within the current N1 and N2 patient subsets staging in 3438 patients showed a sensitivity of 57%, a
for further evaluation [26]. specificity of 82%, a positive predictive value of 56%,
and a negative predictive value of 83% [27]. MRI has a
Role of Imaging in N Descriptor Determination reported sensitivity of 90.1%, a specificity of 93.1%,
and an accuracy of 92.2% on a per patient basis in de-
In the imaging evaluation of nodal metastasis, size is the tecting nodal metastasis [28, 29]. FDG-PET and FDG-
only diagnostic criterion, with nodes 10 mm in their PET/CT have improved the sensitivity and specificity
short-axis diameter considered abnormal. Chest radio- for detecting mediastinal nodal metastasis compared
graphs are neither sensitive nor specific in evaluating with CT alone (Fig. 10). A meta-analysis showed an
nodal metastases. CT and MRI are better in this regard overall sensitivity of 83% and specificity of 92% for
a b
c d
Fig. 10 a-d. Nodal metastasis in a 78-year-old man with non-small-cell lung cancer.
a, b CT shows a large mass in the left lower lobe, enlarged subcarinal/azygo-esophageal
(short-axis diameter 1 cm) nodes, and left and right lower paratracheal lymph nodes
(* in b). c Whole-body PET maximum intensity projection image shows increased FDG
uptake within the mass (M) and in the subcarinal/azygo-esophageal nodes (* in c) and
paratracheal nodes (arrows in c). d FDG-PET/CT shows increased FDG uptake in the
paratracheal nodes bilaterally. Mediastinoscopy confirmed nodal metastasis. Because
N3 (contralateral mediastinal) nodal metastasis is nonresectable, the patient was treated
palliatively
FDG-PET in detecting mediastinal nodal metastases when there are no distant metastasis (M0), or to redirect
compared with 59% and 78% on CT [30]. de Langen et nodal sampling by identifying an otherwise undetected
al. showed that nodal sampling may not be necessary for site of metastasis.
nodes measuring 1015-mm on CT, as long as they are
negative on FDG-PET. However, mediastinal lymph The location of nodal metastasis is of major impor-
nodes 16 mm, even if negative on FDG-PET, have a tance in determining management. Ipsilateral hilar (N1)
21% post-test probability of metastatic involvement, ne- nodes are resectable, ipsilateral mediastinal or subcari-
cessitating preoperative pathologic staging [31]. Current nal adenopathy (N2) may be resectable (usually after in-
recommendations for FDG-PET imaging are that it duction chemotherapy); contralateral mediastinal
should be performed in patients with no CT findings of adenopathy and scalene or supraclavicular adenopathy
nodal metastatic disease to corroborate CT findings (N3) are unresectable.
M Descriptor
Patients with NSCLC commonly have metastases to the
lung, adrenals, liver, brain, bones, and extrathoracic
lymph nodes at presentation. The M1 descriptor describes
these metastases and is divided into two subsets based on
outcome data showing a modest but significant survival
difference [32]. M1a includes nodule(s) in the contralat-
eral lung, pleural effusion and nodule(s), and pericardial
nodule(s) while M1b designates extrathoracic metastasis
(Fig. 5) [32, 33].
Role of Imaging in M Descriptor Determination

Detecting metastases is important to determine whether
the patient will be a candidate for surgical resection or
will receive palliative radiation and chemotherapy. CT is
useful in determining the absence or presence of intratho-
racic metastatic disease, including contralateral lung nod- Fig. 11. Malignant pleural effusion in a 62-year-old man with non-
small-cell lung cancer: Contrast computed tomography shows a
ule(s), pleural and pericardial nodule(s), and effusions. Al- large effusion and focal pleura thickening (arrows) due to meta-
though a nodule in the contralateral lung is potentially a stases
metastasis (M1a), most (approximately 75%) additional
pulmonary nodules on CT imaging in patients with po-
tentially operable clinical stages I to IIIA lung cancer are finding of low attenuation is useful to characterize an ade-
benign [34, 35]. Furthermore, an additional nodule can be noma, up to 30% of adenomas do not contain sufficient
a synchronous second primary lung cancer (incidence ap- lipid to demonstrate low attenuation on CT imaging [41].
proximately 1.52% of patients per year) [34]. Addition- In these cases, delayed contrast-enhanced CT or MRI, us-
ally, pleural thickening and nodularity on CT suggest ing chemical shift analysis and dynamic gadolinium en-
metastatic pleural disease (M1a) but these abnormalities hancement, has been shown to be of use in identifying
may not be present in association with a malignant ef- lipid-poor adenomas [42-45]. FDG-PET/CT is also useful
fusion and can occur with benign effusions in detecting an adrenal metastasis and in distinguishing
(Fig. 11). Whole-body MRI is being used for the detection benign from malignant adrenal masses detected on CT
of M1b disease. A study in 203 patients with NSCLC who [46]. A meta-analysis of 21 studies (1391 lesions), in
underwent whole-body MRI with diffusion-weighted which 5 specifically focused on patients with lung cancer,
imaging (DWI) reported a sensitivity of 68%, a specifici- reported a combined sensitivity of 94% and a specificity
ty of 92%, and an accuracy of 88% in detecting distant of 82% of FDG-PET in detecting adrenal metastasis in pa-
(M1b) metastatic disease. Accordingly, with an accuracy tients with lung cancer [46]. FDG-PET/CT is now often
equivalent to that of FDG-PET/CT, MRI with DWI may used as the definitive imaging modality rather than MRI
offer an alternative imaging option for the assessment of to evaluate an indeterminate adrenal mass, particularly
M1b in patients with NSCLC [36]. However, FDG-PET when the adrenal mass is small (Fig. 13). Central nervous
and FDG-PET/CT are more commonly used in detecting system metastases are common at presentation. Their de-
M1b disease as a means to improve the accuracy of CT tection rate in patients with CT and/or MRI and a nega-
staging [21]. Nonetheless, the appropriate role of FDG- tive clinical examination is low (010%) [47]. However,
PET/CT in the staging of patients with early-stage imaging of the brain may be indicated for the exclusion of
NSCLC is debated because occult distant metastases brain metastases in patients with clinically resectable, lo-
(M1b) are rarely detected (5%) [37]. The incidence of cally advanced NSCLC with non-squamous histology.
occult metastatic disease discovered with FDG-PET in- Furthermore, patients with clinical stage III or IV NSCLC
creases with higher T and N descriptors [38]. In more ad- should have routine imaging of the brain with MRI even
vanced NSCLC, FDG-PET was shown to detect extratho- if the clinical evaluation is negative for brain metastases
racic metastatic disease in up to 24% of patients poten- [47]. FDG-PET/CT is more sensitive for osseous metasta-
tially eligible for curative resection [38, 39]. Generally, tic disease than bone scintigraphy with 99mtechnetium
CT is the primary modality used to diagnose and charac- (Tc)-methylene diphosphonate (MDP). A meta-analysis
terize intra-abdominal lesions, and a confident diagnosis reported an overall sensitivity and specificity of 92% and
of benignity or malignancy is frequently possible. For in- 98%, respectively, for osseous metastases on PET/CT,
stance, CT and MRI are useful in the evaluation of adren- compared with a sensitivity of 86% and a specificity of
al masses and a confident diagnosis of benignity can be 88% for 99mTc MDP bone scintigraphy. FDG PET/CT
made if an adrenal mass has an attenuation value 10 HU has to a large extent replaced the use of 99mTc MDP in
on non-contrast-enhanced CT (Fig. 12) [40]. Although the patients with NSCLC (Fig. 14) [48-50].
Fig. 12 a, b. Squamous cell carcinoma in a 61-year-old woman. a, b CT shows a 1.5-cm nodule in the left lower lobe (arrow in a) and a
large, low-attenuation (10 HU) left adrenal mass (* in b). Note that an attenuation value of 10 HU on non-contrast-enhanced CT is
diagnostic of a benign etiology and no further evaluation is required
a b
Fig. 13 a-c. Adrenal metastases in a 78-year-old man with non-

small-cell lung cancer. a Chest radiograph shows a large mass in
the right upper lobe. b CT shows a left adrenal mass (*). c FDG-
PET/CT shows increased uptake by the adrenal metastasis (*)
a b
Fig. 14 a-c. Bone metastases in an 80-year-old man with non-small-

cell lung cancer. a CT shows a mass in the left lower lobe.
b Whole-body PET maximum intensity projection image shows in-
creased FDG uptake within the mass (*) and focal increased
uptake in the pelvis (arrow). c FDG-PET/CT reveals increased
FDG uptake in the sacrum due to a metastasis. Note that FDG
PET/CT is more accurate than CT in detecting occult metastasis.
C cardiac uptake of FDG (physiologic)
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MR imaging vs. coregistered FDG-PET/CT: quantitative and 47. Kozower BD, Meyers BF, Reed CE (2008) Does positron emis-
qualitative assessment of N-stage in non-small-cell lung can- sion tomography prevent nontherapeutic pulmonary resections
cer patients. J Magn Reson Imaging 26:1071-1080. for clinical stage IA lung cancer? Ann Thorac Surg 85:1166-
30. Birim O, Kappetein AP, Stijnen T, Bogers AJ (2005) Meta- 1169; discussion 1169-1170.
analysis of positron emission tomographic and computed to- 48. Min JW, Um SW, Yim JJ et al (2009) The role of whole-body
FDG PET/CT, Tc 99m MDP bone scintigraphy, and serum al- phy for diagnosis of bone metastases in patients with lung can-
kaline phosphatase in detecting bone metastasis in patients with cer. Eur J Radiol 81:1007-1015.
newly diagnosed lung cancer. J Korean Med Sci 24:275-280. 50. Liu N, Ma L, Zhou W et al (2010) Bone metastasis in patients
49. Qu X, Huang X, Yan W et al (2012) A meta-analysis of with non-small cell lung cancer: the diagnostic role of F-18
(1)(8)FDG-PET-CT, (1)(8)FDG-PET, MRI and bone scintigra- FDG PET/CT. Eur J Radiol 74:231-235.
IDKD 2015-2018
Computed Tomography Diagnosis and Management of Focal Lung Disease

Ioannis Vlahos1, Gerald F. Abbott2
1 Department of Radiology, St. Georges Hospital and NHS Trust, St Georges Medical School, University of London, UK
2 Thoracic Imaging FND-202, Massachusetts General Hospital, Boston, MA, USA
Introduction an erroneously low measurement due to partial volume

average effects of the adjacent low-density lung
Focal pulmonary opacities can be broadly categorized as parenchyma. Previously, pixel-mapping was used to iden-
nodules, masses, or focal parenchymal airspace disease, tify voxels with HU 0 on thicker sections as it com-
but their diagnosis is often challenging. Computed to- pensated for the partial volume average effects of more
mography (CT), supplemented by thin section or high- solid parts of the nodule. Today, in the era of isotropic da-
resolution CT imaging, is better than chest radiography in ta CT acquisition, this method is no longer advocated.
the determination of the characteristics of these lesions. There is no absolute HU measurement that confirms cal-
Nodules are spherical well-defined opacities measur- cification, although measurements 200 are usually re-
ing 3 cm in diameter. In practice, ill-defined or irregu- lated to pixels occupied by calcific material. Visual com-
lar nodules are also included in the category of nodules, parison to other thoracic osseous structures is considered
although more appropriately these should be considered sufficient for determining the calcific nature of lesions.
as nodular opacities. The improved ability of CT to cate- Central, lamellated, or popcorn-type calcification is di-
gorize nodules and masses is based on morphometric agnostic of a benign lesion. The presence of central or
evaluation of their density and contour. However, CT lamellated calcification is usually indicative of granulo-
densitometry is usually only a part of the evaluation of matous disease (Fig. 1). The presence of fat or popcorn
these abnormalities, as specific CT techniques to deter-
mine enhancement (nodule enhancement studies, dual- a b
energy CT), follow-up imaging to verify evolution,
positron emission tomography (PET)/CT to assess phys-
iological activity and, ultimately, fine-needle aspiration
or biopsy are also likely to play a role.
Features of Benign Solid Nodules

c d
The principle application of CT in the evaluation of a
solitary pulmonary nodule is in determining whether it
has specific benign density characteristics, such as in-
tralesional calcification or fat. The identification of either
one is aided by the use of thin-section contiguous images
(13 mm) through nodules of interest. These imaging
techniques are preferably performed with a targeted re- e f
construction of the nodule itself (field of view: 1012
cm). Although bulk fat may be evident by visual inspec-
tion alone, on CT fat will have an intensity of less than
30 to 40 Hounsfield units (HU) and often as low as
150 HU. Measurements should be performed using a
suitably sized region of interest that encompasses an area
that is still within the nodule on the slice above and the Fig. 1 a-f. Types of calcification. Benign: a central, b central mul-
slice below the measured slice. This reduces the risk of tifocal, c uniform, d lamellar. Indeterminate: e eccentric, f stippled

18 I. Vlahos, G.F. Abbott
Fig. 2. Pulmonary hamartoma. Intralesional fat and popcorn calci-

fication are seen
calcification is diagnostic of a pulmonary hamartoma

(Fig. 2). It is important to determine the central location
of a calcification on coronal or sagittal images, as the ec- Fig. 3. CT bronchus sign in an adenocarcinoma of the lung
centric nature of calcification is often only noted in these
planes. Eccentric calcification is most often benign, re-
lated to granulomatous disease; however, eccentric calci-
fication occasionally reflects a small granuloma that has infectious diseases, including mycobacterial disease.
become engulfed within an enlarging adjacent neoplasm. Cavitation is a feature that can be seen in neoplastic as
Dystrophic or stippled calcifications are well-recognized well as benign infectious diseases (including bacterial,
to occur within carcinoid lesions, non-small cell carcino- mycobacterial, and fungal diseases) and inflammatory
ma, and small cell-carcinoma; hence, they are not a help- diseases (e.g., vasculitides, Langerhans cell histiocyto-
ful discriminator between benign and malignant nodules. sis). The appearance of thicker-walled cavities on chest
Other morphological features that are associated with radiographs has historically been described as a feature
benign lesions include a polygonal, elongated (length: favoring neoplasia [1]; however, this earlier radiographic
width ratio 2), elliptical, linear, or plaque-like shape, interpretation has not been corroborated by CT evalua-
particularly when related to the fissures or pleural sur- tion of the wall thickness of nodules or masses [2].
faces. Indeed, not all such lesions are by definition strict-
ly nodules, as some are best characterized as scars. Ellip-
toid nodules in the upper lobes are occasionally due to CT Studies of Nodule Enhancement
benign intrapulmonary lymph nodes. These findings are
reported with variable incidence by pathologists and with Evaluation of the physiology of a solid lung nodule may
variable incidence and confidence by radiologists. The be of assistance in determining whether the lesion is be-
confident accurate diagnosis of benign intrapulmonary nign or malignant. Nodule enhancement studies consist
lymph nodes requires an upper lobe location of an elon- of a non-contrast acquisition through the lesion at 120
gated nodule aligning lengthwise along typical lymphat- kVp followed by repeated post-contrast acquisitions at 1,
ic locations, such as the fissures or bronchi of the central 2, 3, 4, and 5 min. Adapted protocols that evaluate initial
axial interstitium. nodule enhancement to extract perfusion metrics have al-
so been developed. A multicenter study by Swensen et al.
demonstrated that nodules that enhance 15 HU are
Features of Malignant Solid Nodule highly likely to be benign [3]. Nodules that enhance more
than 15 HU may be benign or malignant. Important
Specific features of malignancy are common in larger caveats to this study are that the region of interest for
nodules but relatively uncommon in nodules smaller than evaluating nodule density before and after contrast
1 cm. Spiculation, microlobulation, pleural tags, satellite should cover at least 70% of the lesions surface area and
nodules, and the presence of a bronchus leading directly that heterogeneous or cavitary lesions cannot be evaluat-
into a nodule (CT bronchus sign) (Fig. 3) are associ- ed by nodule enhancement studies. Moreover, false-neg-
ated with a high probability of neoplastic disease, al- ative results are frequently obtained in mucin-rich lesions
though occasionally they are also seen in inflammatory or such as mucinous adenocarcinomas. The clinical value of
Computed Tomography Diagnosis and Management of Focal Lung Disease 19
Table 1. Fleischner guidelines for incidentally detected solid nodules
Nodule size Low risk High risk

4 mm No follow-up 12 months follow-up
No changeStop
46 mm 12 months follow-up 612 months then
No changeStop 1824 months follow-up
No changeStop
68 mm 612 months then 1824 3-6, 912 months, then 24
months follow-up months follow-up
No changeStop No changeStop
8 mm 3, 9, 24 months follow-up, or CT/PET, or biopsy
formed the management of these nodules [7]. It should be

noted that the guidelines apply to the management of in-
cidentally detected solid nodules in patients over the age
Fig. 4. Dual-energy CT demonstrating peripheral enhancement of a
pulmonary metastasis of 35 who are not immune-suppressed. The guidelines
vary according to whether patients are smokers (high
risk) or non-smokers (low risk) but significantly elimi-
this imaging approach is in its very high negative predic- nate the need for follow-up of small nodules in low-risk
tive value (96%). However, in clinical practice only a patients and greatly reduce the frequency of follow-up in
small fraction of benign lesions exhibit low level en- other patients (Table 1). In addition, these guidelines do
hancement; thus, even after this imaging approach the not apply to subsolid nodules, nor to patients with sus-
vast majority remain indeterminate. Therefore, PET/CT pected neoplastic disease. In the former, a more infre-
is gaining increasing favor as an alternative physiological quent follow-up may be appropriate (see below); in the
assay of nodule activity, as it is more likely to alter the latter, a more aggressive follow-up schedule or correla-
pre-test probability of malignancy or benignity. tion with biopsy or PET may be indicated.
The introduction of dual-energy CT, either by dual-
source or rapid kVp switching, has permitted the accurate
determination of contrast enhancement without the need Role of Computer-Assisted Diagnosis for Solid Nodules
for pre-contrast images [4]. This may be helpful in as-
sessing the extent and pattern of lesion enhancement, per- Computer-aided detection (CAD) improves the detection
haps as a surrogate marker of enhancement before and af- of pulmonary nodules, although its sensitivity varies de-
ter treatment (Fig. 4). Yet, it is unclear whether this tech- pending on the characteristics of the lesion, including its
nological evolution can be used to distinguish benign size, density, and location. Sensitivity also depends on
from malignant disease. Certainly, the implementation of technical parameters, such as the thickness of the evalu-
nodule enhancement is problematic in that in the original ated CT images. Moreover, there are vendor-specific is-
studies imaging was performed at 120 kVp. As such, ap- sues related to CT algorithm optimization with the goal
propriate thresholds for enhancement evaluation at kVp of obtaining high detection rates with an acceptable rate
values ranging from 80 to 140 kVp have not been deter- of false-positive detections. Most CAD systems also con-
mined. tain computer-aided diagnosis (CADx) features for the
evaluation of pulmonary nodules. CADx systems may in-
corporate algorithms that can perform two- or three-di-
Indeterminate Solid Nodules mensional analysis of the density of focal lung opacities
as well as morphometry to determine the likelihood of
Unfortunately, the majority of nodules are indeterminate malignancy, often expressed as a percentage probability
on CT imaging, as they do not demonstrate features that of malignancy. But while this complex method of analy-
can be definitively considered as benign or malignant. In sis performs better than human readers across multiple
the Mayo screening series of more than 1,500 patients, cases, it is difficult to reliably apply percentage probabil-
over 3,300 indeterminate non-calcified nodules were ities to individual cases [8].
identified, the vast majority of which were small (4 One of the most useful features of CADx is the abili-
mm) and benign [5]. Even in established smokers, the ty to segment individual nodules, which permits a three-
risk of malignancy in nodules of this size is 1% [6]. The dimensional evaluation of the lesions size and shape and
management of indeterminate nodules was previously a can be coupled with follow-up examinations to determine
matter of debate. However, recent evidence-based guide- volumetric growth. This approach is based on the obser-
lines from the Fleischner Society have greatly trans- vation that the doubling time of benign lesions is far
a b
Fig. 5 a, b. Adenocarcinoma of the lung. Computer aided 3-D volumetric evaluation demonstrating asymmetric growth over an 11-month
period. a Initial evaluation, b follow-up evaluation
longer than that of malignant lesions [9]. Volumetric eval-

uation of growth is also more reliable than reader-gener-
ated uni- or bidimensional size measurements [10].
Moreover, volumetric evaluation may be more sensitive
to the detection of asymmetric growth, a feature that is
limited to malignant lesions (Fig. 5). A commonly ap-
plied threshold for the volume doubling time of a solid
lesion is 400 days, although several authors have advo-
cated a threshold of 500 days [11-13]. This extended
threshold is perhaps more prudent when the veracity of
volumetric nodule evaluation is assessed. The accuracy
and reproducibility of lung nodule segmentation have
been confirmed in artificial and porcine models. Howev-
er, the reproducibility of in vivo human nodule measure-
ments can vary by up to 15%. This was demonstrated by
evaluating the same nodule in different phases of inspira-
tion or by using CT data based on different slice thick-
nesses or obtained with different software packages
[13, 14]. Less significant changes may occur as a result
of different reconstruction algorithms or radiation-dose Fig. 6. Multifocal subsolid lesions. Mixed ground glass/solid-density
variation. The presence or absence of intravenous con- lesions in a patient with multifocal adenocarcinoma
trast appears to play a largely inconsequential role.
Nonetheless, by ensuring that a similar technique is em-
ployed on initial and follow-up examinations, lung nod- jointly by the International Association for the Study of
ule volumetry shows great promise and may further re- Lung Cancer, the American Thoracic Society, and the Eu-
duce the need for follow-up examinations. ropean Respiratory Society [16]. This new classification
was based on observations regarding heterogeneities in
sub-solid neoplastic lesions that influenced their progres-
Subsolid Nodules sion and clinical impact. For example, Aoki et al. [17] ob-
served that AAH and lower-grade lesions of what was
Subsolid nodules include lesions that are pure ground previously termed bronchioloalveolar cell carcinoma
glass in density as well as lesions that are partly solid and (BAC, Noguchi subtype A, B, C) were associated with le-
partly ground glass. Lesions with these characteristics, sions that were nearly exclusively ground glass in nature.
and especially those of the latter type, are associated with Conversely, higher-grade lesions (Noguchi D, E, F) were
higher rates of malignancy than solid lesions (Fig. 6) associated with lesions that became progressively more
[15]. Malignant sub-solid nodules lie along a spectrum of reticular, demonstrated tractional bronchiolectasis, and,
disease that extends from the suspected malignant pre- eventually, increasing solid components [17, 18].
cursor lesion of atypical adenomatous hyperplasia The current 2011 classification replaces the heteroge-
(AAH) to invasive adenocarcinoma. In 2011, a reclassifi- neous lesion termed BAC with several different designa-
cation of pulmonary adenocarcinoma was introduced tions. Pre-invasive lesions, AAH, and adenocarcinoma in
Computed Tomography Diagnosis and Management of Focal Lung Disease 21
situ (AIS), are typically pure ground glass lesions 5 Table 2. Fleischner guidelines for subsolid nodules
mm and 3 cm, respectively, in size. Minimally invasive
Characteristics Imaging/Management
adenocarcinoma (MIA) is typically a partly solid lesion
with an invasive component measuring 5 mm. Larger Solitary pure ground No follow-up
subsolid lesions with more extensive solid invasive tumor glass nodule, 5 mm
are now termed lepidic predominant adenocarcinoma Multiple pure ground 2- and 4-year follow-up
(LPA). Invasive multifocal mucinous adenocarcinoma re- glass nodule, 5 mm
places the entity of multicentric BAC. Solitary pure ground 3 months (then at 1, 2, and 3 years)
Lesions that are exclusively ground glass or have min- glass nodule, 5 mm
imal solid components were observed to progress with a Multiple pure ground 3 months (then at 1, 2, 3 years)
very slow growth rate. In one study, a comparison of glass nodule, one 5 mm
mean volume doubling times in lung cancer patients with Solitary part solid 3 months (then biopsy/resect)
solid, partly solid, or pure ground glass neoplastic lesions 5 mm solid (1, 2, 3 years?)
demonstrated a stepwise increase in the CT-calculated
Multiple part solid 3 months (then biopsy/resect)
volume-doubling times (853 vs. 457 vs. 158 days) [19]. Treat dominant lesion(s)
Therefore, for a subsolid lesion suspected to reflect a
neoplasm in the adenocarcinoma spectrum, the demon-
stration of a 2-year stability may not be enough to ensure
its benign nature. In these cases, an initial follow-up ex- imaging strategies for single and multiple ground glass
amination at 3 months may be performed to determine lesions and indicate potential clinical diagnostic and
whether the lesion has persisted and is inflammatory. Fol- management pathways (Table 2), including more aggres-
low-up may then be performed at longer intervals (12 sive surgical management when a lesion exceeds 1 cm
years). In these irregular, ill-defined lesions, it can be dif- overall or when there is a significant increase in its solid
ficult to measure incremental size; thus, evaluation component. Conversely, according to the recent guide-
should include comparison of comparable contiguous lines, pure ground glass lesions less than 5 mm in size do
thin-section images and a determination of whether the not require follow-up as these almost always reflect be-
ground glass or solid component geographically extends nign entities or atypical adenomatous hyperplasia. The
around more vessels or airways. In this setting, CAD may management of patients with multiple lesions of varying
be of assistance. Although the technology is evolving to density is more complex, especially as radiologically it is
evaluate ground glass lesions, it remains less reliable than not always possible to determine the extent of neoplasia
in solid lesions. It is also important to note that the nat- in multiple ground glass opacities. Current treatment
ural evolution of these lesions also includes transient re- strategies may include resection of the initial lesions fol-
duction in size that may occur when there is histological lowed by localized resection of progressive or recurrent
alveolar collapse. lesions, although there are no standardized long-term da-
The definitive determination that a subsolid lesion is ta to support this approach.
malignant can be problematic. A progressive increment in
the overall size or in the size of the solid component
strongly favors malignancy. PET/CT imaging in these Focal Parenchymal Airspace Disease
cases may be non-contributory because these lesions of-
ten have low SUVmax activity. Additionally, the evalua- A multitude of etiologies underlie the development of fo-
tion of predominantly ground glass lesions by CT-guided cal air-space opacities. The majority of these will be mul-
fine-needle aspiration or biopsy should be considered tifocal and infective in nature. A distinction of pre-
with great caution, as the results are vulnerable to signif- disposing etiologies is impossible unless there are
icant sampling-error effects and likely to vary signifi- uncommon specific features, e.g., the ground-glass halo
cantly from the ultimate excision specimen. The extent of typical of invasive aspergillosis. The differential diagno-
invasive adenocarcinoma in particular can be significant- sis may be narrowed by referring to a combination of ra-
ly underestimated by percutaneous needle sampling, even diological features, chronicity, progression, response to
if directed to the more solid components. treatment, and the immune status of the patient.
There is no consensus on the optimal management of The presence of cavitation in airspace disease can be
patients with single subsolid lesions. Patients with lesions helpful, although the differential can again be broad, in-
characterized by a higher ground glass percentage com- corporating staphylococcal or gram-negative bacterial in-
position are less likely to have nodal disease and have a fections, mycobacterial disease, or fungal infection.
better prognosis than patients with nodules having a Rounded pneumonia is more common in children but it
greater solid component, in which invasive adenocarci- also occurs in adults, usually due to S. pneumoniae in-
noma likely predominates [20, 21]. Expanding on the infection. Appearances are mass-like, without air-bron-
terim guideline published in 2009, the Fleischner Soci- chograms resulting from disease propagation through the
etys definitive guidelines, published in 2013, have collateral air-drift mechanisms of the pores of Kohn and
helped to homogenize practice [22, 23]. They address the canals of Lambert. Focal consolidative opacity that is
chronic may be characterized by minor volume loss and 10. Jennings SG, Winer-Muram HT, Tarver RD, Farber MO (2004)
tractional bronchiectasis; these features are more com- Lung tumor growth: assessment with CTcomparison of di-
ameter and cross-sectional area with volume measurements.
mon in patients with chronic eosinophilic lung disease or Radiology 231:866-871.
organizing pneumonia. While organizing pneumonia may 11. Jennings SG, Winer-Muram HT, Tann M et al (2006) Distrib-
also present with a reverse halo appearance, central ution of stage I lung cancer growth rates determined with ser-
ground glass opacities with peripheral consolidation, this ial volumetric CT measurements. Radiology 241:554-563.
appearance is not specific for the disease. Progressive fo- 12. Revel MP, Merlin A, Peyrard S et al (2006) Software volumet-
ric evaluation of doubling times for differentiating benign ver-
cal airspace disease may reflect neoplastic disease, in- sus malignant pulmonary nodules. AJR Am J Roentgenol
cluding bronchoalveolar cell carcinoma, lymphoma, or, 187:135-142.
occasionally, mucinous metastases from gastrointestinal 13. Honda O, Kawai M, Gyobu, T et al (2009) Reproducibility of
primary tumors. Calcification may be present in myco- temporal volume change in CT of lung cancer: comparison of
bacterial disease and in some cases of amyloidosis. computer software and manual assessment. Br J Radiol
82:742-747.
14. Bolte H, Riedel C, Muller-Hulsbeck S et al (2007) Precision of
computer-aided volumetry of artificial small solid pulmonary
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949. ripheral lung adenocarcinomas: CT findings correlated with
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73-80. 18. Noguchi M, Morikawa A, Kawasaki M et al (1995) Small ade-
4. Chae EJ, Song JW, Seo JB et al (2008) Clinical utility of dual- nocarcinoma of the lung. Histologic characteristics and prog-
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5. Swensen SJ, Jett JR, Hartman TE et al (2005) CT screening for small lung cancers detected on mass CT screening. Br J Radi-
lung cancer: five-year prospective experience. Radiology ol 73:1252-1259.
235:259-265. 20. Kodama K, Higashiyama M, Yokouchi H et al (2001) Prog-
6. Piyavisetpat N, Aquino SL, Hahn PF et al (2005) Small inci- nostic value of ground-glass opacity found in small lung ade-
dental pulmonary nodules: how useful is short-term interval nocarcinoma on high-resolution CT scanning. Lung Cancer
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scans: a statement from the Fleischner Society. Radiology small lung adenocarcinoma. Ann Thorac Surg 68:2069-2073.
237:395-400. 22. Godoy MC, Naidich DP (2009) Subsolid pulmonary nodules
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IDKD 2015-2018
Approach to Imaging of Mediastinal Conditions in the Adult

Sanjeev Bhalla1, Jos Caceres2
1 Mallinckrodt Institute of Radiology, Washington University, St. Louis, MO, USA
2 Centro Medico Teknon, Barcelona, Spain
Introduction Anterior Mediastinum

The mediastinum is an anatomic space defined by the Most anterior mediastinal masses are thymic in origin.
thoracic inlet superiorly and the diaphragm inferiorly. Even lymphomas and germ cell tumors tend to arise in
It extends from the sternum to the vertebral bodies. cells within the thymus. A useful differential diagnosis
Yet, despite its landmarks, there are no structures that should be based on patient age, as germ cell tumors are
completely separate the mediastinum from the neck almost unheard of in individuals older than 45 years.
above or the retroperitoneum below. Thus, imaging of Most anterior mediastinal massed tend to be lymphomas,
the mediastinum and generating a relevant different di- germ cell tumors, or thymomas. Many texts will include
agnosis rest on the principles of localization and char- thyroid goiter in the list of anterior mediastinal lesions.
acterization. However, we have found that most goiters tend to extend
Once a process or mass can be localized to the medi- into the middle mediastinum.
astinum, it should be further localized within the medi- Observing fluid-attenuation or intensity can be very
astinum. Many of us use an approach first championed helpful in approaching anterior mediastinal masses. Pure
by Ben Felson. Using a lateral radiograph or sagittal cystic lesions are benign (usually thymic or pericardial
computed tomography (CT) or magnetic resonance cysts). As the amount of soft tissue within the lesion in-
(MR) image, a line is drawn from the anterior tracheal creases, one should consider the increased likelihood of
wall to the posterior inferior vena cava. This line sepa- a malignancy. Both lymphoma and cystic thymoma may
rates the anterior mediastinum from the middle medi- have small areas of fluid, but these are far outweighed by
astinum. A second line is drawn 1 cm posterior to the the soft tissue elements. Germ cell tumors also follow
anterior margin of the vertebral body. This line sepa- this rule. The classic teaching is that the germ cell tumor
rates the middle from the posterior mediastinum. No have an attenuation like that of fat. Many teratomas do
anatomic structures actually divide the mediastinal contain some fat elements, but almost all are cystic. As
compartments but this approach can be useful in creat- with the other lesions, if the soft tissue elements domi-
ing concise, meaningful differential diagnoses. Keep in nate, then a malignant germ cell tumor should be favored,
mind that certain processes may involve more than one such as seminoma. Interestingly, malignant germ cell tu-
compartment and that a large mass may be hard to lo- mors are quite rare in female patients.
calize. Visualization of fat intensity or attenuation can also be
After localization, cross-sectional imaging (either CT very helpful (Fig. 1). In the anterior mediastinum, most
or MR) should be performed for lesion characterization. fatty masses are benign. As described above, an anterior
Knowing whether a lesion has a significant vascular, flu- mediastinal mass with fat and fluid suggests a teratoma
id, or fat component can be very helpful in suggesting a (benign germ cell tumor). If the mass is purely fat, it may
more specific diagnosis. Positron emission tomography be the very rare thymolipoma, but more likely it will be
(PET-CT) is used mainly to evaluate lymph node metas- a fat pad or anterior hernia (Morgagni hernia). In our
tases in lung cancer, but it can also be used in the evalu- practices, patients with infarction of a pericardial fat pad
ation of solid mediastinal masses. or fat within the Morgagni hernia may present with chest
This approach to localization and characterization will pain. In the era of the frequent use of CT in the evalua-
provide the interpreting radiologist with a solid foundation of potential pulmonary embolism or dissection, these
tion in mediastinal imaging. areas of fat necrosis can simulate a neoplasm. Awareness
of this potential pitfall will allow the patients to be treat-
ed appropriately.

24 S. Bhalla, J. Caceres
a b
Fig. 1 a, b. Teratoma. Posteroanterior chest X-ray shows a left ante-

rior mediastinal mass (a). Axial CT demonstrates a large soft-
tissue mass with a fat component (b, arrow)
a b
Fig. 2 a, b. Thymoma. Peripheral calcification is visible in the chest

radiograph (a, arrows), confirmed with CT (b, arrows)
The incidence of calcification in thymomas varies Middle Mediastinum

from 10% to 40%. Circular peripheral calcification may
occur in solid thymomas, simulating a cyst (Fig. 2). Ter- Most middle mediastinal masses represent lym-
atomas contain calcium in about 35% of cases. Untreat- phadenopathy, foregut duplication cysts, vascular lesion,
ed lymphomas do not calcify and about 5% of them show or esophageal processes. They usually present with right
calcifications after radiation therapy. paratracheal widening on a frontal chest radiograph or,
Vascular or hyperenhancing lesions may present within occasionally, the doughnut sign on a lateral examination.
the anterior mediastinum. Occasionally, coronary or bypass As with anterior mediastinal conditions, an assessment of
aneurysms can simulate an anterior mediastinal mass. The attenuation or intensity can be helpful.
key is to think about this potential, especially when a pa- If the mass is fluid in character, the middle mediasti-
tient with median sternotomy wires presents for imaging. nal mass most likely represents a foregut duplication cyst
Approach to Imaging of Mediastinal Conditions in the Adult 25
a b
Fig. 3 a, b. Asymptomatic bronchogenic cyst. The cyst was discovered on the chest radiograph (a, arrow) and confirmed with CT (b, arrow).
Note the high attenuation, similar to that of the soft tissue
a b
Fig. 4 a, b. Large endothoracic goiter. There is with marked tracheal displacement in the chest radiograph (a). Axial CT shows marked
contrast enhancement of the thyroid tissue (b, arrow)
(either bronchogenic or esophageal). These cysts occa- Unlike the anterior mediastinum, fat in a middle me-
sionally are higher in attenuation as a result of infection diastinal lesion cannot be considered benign. Although
or hemorrhage (Fig. 3) and may even contain a fluid- esophageal or tracheal lipomas and esophageal fibrovas-
calcium level from the milk of calcium. The risk of malig- cular polyps contain fat, so may mediastinal liposarco-
nancy in these conditions tends to be low. As with ante- mas. These rare lesions may insinuate through the medi-
rior mediastinal lesions, the ratio of soft tissue to fluid astinum and often have a predilection for the middle me-
needs to be considered. A foregut duplication cyst should diastinum.
have no soft tissue, enhancing element. If soft tissue is Hypervascular lesions in the middle mediastinum are
encountered, one must consider a potentially more sig- most often hypervascular lymph nodes and intrathoracic
nificant process, usually low-attenuating lymphadenopa- extension of a goiter (Fig. 4). These hypervascular nodes
thy. Such low-attenuating lymph nodes may be encoun- (defined as higher in attenuation than skeletal muscle)
tered in lung cancer, mucinous neoplasms, and mycobac- may be seen with melanoma, plasmacytoma, Castlemans
terial disease. disease, Kaposi sarcoma, sarcomas, and thyroid and renal
a b
Fig. 5 a, b. Ganglioneuroma. The lesion, visible as a mass in the right apex (a), was confirmed with enhanced CT (b, arrow). Note the low
CT density, which may create confusion with a cystic mass
cell cancers. When the high attenuating structure is tubu- metastases are often considered, one cannot forget about
lar, a vessel must be considered. Aortic arch anomalies diskitis/osteomyelitis. This latter condition can present as
and azygos vein enlargement often present as a middle insidious back pain and can easily be overlooked.
mediastinal mass on radiography. As with the other compartments, attenuation or inten-
Most mediastinal lymphadenopathy will present in the sity can be helpful. On CT, a potential pitfall is that
middle mediastinum. Occasionally, these nodes will be myelin-rich neurogenic lesions may look cystic (Fig. 5).
calcified. These calcified nodes are usually indicative of For this reason, with posterior mediastinal lesions we of-
an old granulomatous process, such as healed tuberculo- ten rely on MR imaging. True posterior mediastinal cys-
sis or histoplasmosis or sarcoidosis, but care must be tak- tic lesions are rare. Although neuroenteric cysts exist,
en to remember that certain tumors also tend to present they are often associated with vertebral anomalies and
with calcified mediastinal lymph nodes, including ovari- rarely encountered de novo in adults. Instead, a cystic le-
an serous adenocarcinomas, mucinous colon neoplasms, sion in the posterior mediastinum is much more likely to
and osteosarcomas. represent a lateral meningocele or post-traumatic nerve
Another potential for a perceived middle mediastinal root avulsion.
mass on radiography will be a dilated esophagus. Al- Fatty lesions are unusual in the posterior mediastinum
though a distal mass may also result in esophageal di- but when encountered may invoke extramedullary
latation, it is usually only achalasia that results in hematopoiesis. While rare, in patients with anemia, ex-
esophageal widening that can be seen on a chest radio- tramedullary hematopoiesis may develop in the posterior
graph. mediastinum. The etiology of this condition remains un-
known. Some authors have postulated that it develops
from extruded marrow while others have suggested that
Posterior Mediastinum it develops from totipotent cells in the paravertebral
space. When the patient is anemic, extramedullary
A vast majority of posterior mediastinal masses will be hematopoiesis will present with bilateral masses that en-
neurogenic in origin. In adults, these tend to be benign hance similar to spleen without a connecting bridge. As
nerve sheath tumors, usually schwannomas and neurofi- the patient returns to normal hematocrit, the yellow mar-
bromas. In children and younger adults, they tend to be row will take over. The net effect is bilateral posterior me-
sympathetic ganglion in origin, such as ganglioneuro- diastinal fatty masses. In the elderly, Bochdalek hernias
blastoma, neuroblastoma, or ganglioneuroma. The key in should be included in the differential diagnosis (Fig. 6).
separating the two groups is to assess the overall shape, Hypervascular lesions in the posterior mediastinum
comparing the z-axis to the xy-axis. Nerve sheath tumors are less helpful than with the other compartments. Most
tend to be spherical (equal in all 3 axes), while the gan- often these are related to an aneurysmal aorta or enlarged
glion lesions are longer in the z-axis and are more cylin- collateral vessels as with aortic coarctation. As described
drical. Osseous lesions represent the second most com- above, extramedullary hematopoiesis may be seen with
mon group of posterior mediastinal disease. Although bilateral hypervascular paravertebral masses.
Approach to Imaging of Mediastinal Conditions in the Adult 27
a b
Fig. 6 a, b. Bochdalek hernia. Lateral chest radiograph shows a large

posterior mediastinal mass (a). Sagittal CT demonstrates abdominal
fat herniating through a posterior diaphragmatic defect (b, arrow)
Table 1. Mediastinal masses based on location and characteristics
Mediastinal compartment Most common Fluid Fat Hypervascular

Anterior Thymoma Thymic cyst Teratoma Heart
Lymphoma Pericardial cyst Thymolipoma Coronary arteries
Germ cell tumor Lymphoma Fat pad Ascending aorta
Morgagni hernia
Middle Lymphadenopathy Duplication cyst Lipoma Arch anomaly

Duplication cyst Lymphadenopathy Liposarcoma Azygos vein
Vascular anomaly Fibrovascular polyp Lymph nodes
Hiatal hernia Goiter
Posterior Neurogenic Neuroenteric cyst Extramedullary Aorta or collaterals

Osseous metastases Lateral meningocoele hematopoiesis
Diskitis Traumatic Bochdalek hernia
More than 1 Infection Lymphangioma Liposarcoma Hemangioma

Hematoma Lipomatosis
Lung cancer
Conditions That Disregard the Compartment Model Of course, lung cancer may present with metastases to
any compartment and, unfortunately, tends to metastasize
Certain conditions tend to disregard the compartment to more than one region.
model of the mediastinum. Even with these lesions, un-
derstanding the attenuation or intensity can be helpful.
These include infection and hematoma, which will result Conclusion
in fat stranding and soft tissue attenuation throughout the
mediastinum, often in more than one compartment. The mediastinum represents a space that may be impact-
Lymphangiomas and hemangiomas also tend to disre- ed by a large number of lesions. Having an approach
gard the compartment model. The former tend to be flu- based on location and characterization will allow the ra-
id in their attenuation and insinuate throughout, while the diologist the ability to create a useful, targeted differen-
latter will be higher in attenuation. tial diagnosis (Table 1).
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IDKD 2015-2018
Current Approaches to Chronic and Acute Airway Diseases

Philippe A. Grenier1, Jeffrey P. Kanne2
1 University Pierre & Marie Curie, Hospital Piti-Salpetrire, Paris, France
2 University Of Wisconsin School Of Medicine and Public Health, Madison, WI, USA
Introduction Table 4. Diffuse tracheobronchial wall thickening

Infectious tracheobronchitis (TB, aspergillosis)
Volumetric multidetector computed tomography (MD- Relapsing polychondritisa
CT) using thin collimation during a single breath hold Tracheobronchial amyloidosis
Tracheobronchopathia osteochrondroplastica
has become the ideal imaging technique for assessing air- Tracheobronchitis associated with ulcerative colitis
way diseases. Volumetric high-resolution data sets pro-
a Calcific deposits
vide precise morphologic evaluation of both proximal
and distal airways.
The different CT patterns of airways diseases and their Table 5. Tracheobronchial dehiscence, fistulas, and diverticula
main causes are reported in Tables 15. The different dis-
Tracheal or bronchial rupture
eases affecting the airways that are presented in this chap- Bronchial dehiscence occurring after lung transplantation
ter include neoplastic and non-neoplastic tracheobronchial Tracheal diverticula (tracheocele)
diseases, bronchiectasis and small airway diseases, asth- Accessory cardiac bronchus
ma, and chronic obstructive pulmonary disease (COPD). Multiple tracheobronchial diverticula (COPD)
Nodobronchial and nodobronchoesophageal fistulas
Tracheoesophageal fistulas
Table 1. Luminal filling defect Bronchopleural fistulas
Benign tracheobronchial neoplasm

Malignant primary tracheobronchial neoplasm
Metastasis
Mucus secretions CT Acquisition and Post-processing Techniques [1,2]
Foreign body
Broncholithiasis
MDCT acquisition is performed through the entirety of
the lungs at full suspended inspiration, using thin colli-
Table 2. Multinodular appearance of the inner surface of the airway mation (0.61.5 mm) without the administration of con-
Granulomatosis with polyangiitis
trast material. Axial images are reconstructed with thin
Tracheobronchial metastases (hematogeneous spread) slice thickness (0.81.5 mm) and overlap (50% is ideal).
Respiratory papillomatosis Complementary MDCT acquisition at full continuous
Adenoid cystic carcinoma (multicentric) forced expiration using a reduced technique (120 Kv;
Tracheobronchial amyloidosis 2040 mA) is often recommended and is particularly use-
Tracheobronchopathia osteochondroplastica
ful for assessing tracheobronchial collapsibility and expi-
ratory air trapping.
Table 3. Focal tracheobronchial narrowing
The images are best interpreted on a PACS worksta-
tion. Evaluation of the overlapped thin-section axial im-
Post-traumatic strictures ages in cine-mode allows the bronchial divisions to be
Post-infectious stenoses (e.g. tuberculosis)
Tracheobronchial neoplasms (primary and secondary easily followed, from the carina to the smallest peripher-
malignant) al bronchi visible on CT. Real-time manipulation of the
Granulomatosis with polyangiitis data set allows the radiologist to select the optimal plane
Sarcoidosis to better depict the distribution and extent of airway ab-
Inflammatory bowel disease normalities. Furthermore, multiplanar reformations using
Extrinsic compression
minimum and maximum intensity projections can be

30 P.A. Grenier, J.P. Kanne
helpful to display airway abnormalities. Minimum inten- Marked homogeneous early contrast enhancement of an
sity projections can highlight airway dilation, diverticu- endobronchial nodule reflects the high vascularity of this
la, and fistulas, as well as the extent of expiratory air tumor.
trapping and emphysema. Maximum intensity projec- Mucoepidermoid carcinoma is a rare tumor that origi-
tions accentuate foci of mucoid impaction and small cen- nates from the minor salivary glands lining the tracheo-
trilobular nodules and tree-in-bud opacities. bronchial tree. It occurs in young patients (40 years-
Volume-rendering techniques (CT bronchography) old) and mainly involves the segmental bronchi, resulting
consist of segmentation of the lumen-wall interface of in airway obstruction. The typical CT appearance is a
the airways. This technique has proven to be of particu- smooth, ovoid, or lobulated endobronchial mass with oc-
lar interest in diagnosing mild changes in airway caliber casional punctuate calcifications and variable contrast
and understanding complex tracheobronchial abnormal- enhancement.
ities. Virtual bronchoscopy provides an internal render- Lymphoma of the trachea is rare and is usually related
ing of the tracheobronchial inner surface. It is used to to mucosa-associated lymphoid tissue. The CT appear-
detect mucosal nodularity indicative of granulomatous ance is non-specific.
or tumoral lesions in proximal airways.
Secondary Tracheobronchial Malignancy
Tracheobronchial Tumors Direct invasion of the central airways by neoplasms of
the thyroid, esophagus, lung, and larynx is much more
MDCT plays a key role in depicting tumors of the tra- common than hematogeneous metastases. CT demon-
cheobronchial tree [3-5] and in assessing their extent strates the primary neoplasm and its extension by conti-
within the lumen, airway wall, and surrounding struc- guity within the main airways (endoluminal mass, de-
tures before treatment planning. Airway lesions 5 mm struction of cartilage, and tracheo-bronchial-esophageal
are usually detected on CT because of the natural con- fistula).
trast between luminal air and soft-tissue attenuation of Many cancers have the potential to metastasize to the
the lesions. trachea and bronchi. Endotracheal or endobronchial
metastases appear as endotracheal nodules or an eccen-
Primary Malignant Tumors tric thickening of the airway wall or as soft-tissue atten-
uation with contrast enhancement.
Compared to laryngeal or bronchial cancers, primary ma-
lignant tumors are rare in the trachea. The most frequent Benign Tracheobronchial Neoplasms
histological types are squamous cell carcinoma and ade-
noid cystic carcinoma, accounting for nearly 80% of all Benign tracheal neoplasms are rare, accounting for 2%
tracheal neoplasms. of lung neoplasms. On CT, they present as endoluminal
Adenoid cystic carcinoma (sialadenoid tumor) is a masses confined within the tracheobronchial lumen with-
low-grade malignancy that is not associated with ciga- out evidence of involvement of surrounding structures.
rette smoking. It occurs in patients in their forties with- Benign neoplasms are typically sharply marginated,
out any sex predilection. In the central airways, adenoid round, and 2 cm in diameter. Because they originate in
cystic carcinoma has a propensity to infiltrate the wall of the mucosa or submucosa, the overlying epithelium is
the airways, with submucosal extension manifesting as a usually intact, resulting in a smooth appearance of the tu-
sessile, polypoid, annular, or diffuse infiltration. The in- mor surface in the airway lumen.
ner surface is smooth and regular. Extraluminal growth, Histology includes mainly hamartomas, lipomas,
visible on CT scan, is a common feature. leiomyomas, fibromas, chondromas, and schwannomas.
Squamous cell carcinoma is the most common prima- Endobronchial harmartomas account for 30% of
ry malignancy of the trachea and primarily occurs in old- intrathoracic hamartomas. The presence of fat with or
er men with a history of cigarette smoking. On CT, the without calcification is diagnostic.
tumor appears as a polypoid intraluminal mass or as an Respiratory papillomatosis (laryngotracheobronchial
eccentric irregular wall thickening with an irregular sur- papillomatosis) is a neoplastic disease caused by human
face. The tumor has a tendency to spread to adjacent me- papillomavirus infection transmitted from mother to
diastinal lymph nodes and to directly invade the medi- child at birth or acquired from orogenital contact. Pa-
astinum. pillomas arise in the larynx and involve the trachea and
Carcinoid tumor is a low-grade malignant neuroen- proximal bronchi in up to 50% of cases. Involvement of
docrine neoplasm representing 12% of primary lung tu- the lungs is rare, occurring in 1% of patients, and
mors. It appears on CT scan as a well-circumscribed manifests on imaging studies as multiple lung nodules
polypoid mass that protrudes into the airway lumen, usu- and cavitary and cystic lesions in the parenchyma. Ma-
ally located in a main or lobar bronchus. Segmental or lignant transformation into squamous cell carcinoma is
lobar atelectasis and obstructive pneumonitis, as well as a rare but serious complication of respiratory papillo-
foci of calcification, are present in 30% of cases. matosis.
Current Approaches to Chronic and Acute Airway Diseases 31
Non-neoplastic Tracheobronchial Disorders [3, 6, 7] become thickened and calcified. Cartilaginous erosions
and ulcerations also may be seen. Stenosis may be pre-
Post-traumatic Stenoses sent in any main, lobar, or segmental bronchus. Develop-
ing nodular or polypoid lesions can protrude into the air-
Post-traumatic strictures of the trachea are usually the way lumen.
result of ischemic injury from a cuffed endotracheal or
tracheostomy tube or extrinsic neck trauma. These in- Relapsing Polychondritis
juries initially heal by the formation of granulation tis-
sue, with subsequent scarring characterized by dense Relapsing polychondritis is a rare systemic autoimmune
mucosal and submucosal fibrosis associated with distor- disease that affects cartilage at various sites, including
tion of cartilage plates. The two principal sites of steno- the ears, nose, joints, and tracheobronchial tree. Histo-
sis following intubation or tracheostomy tube are at the logically, the acute inflammatory infiltrate in both carti-
stoma or at the level of the endotracheal or tracheosto- lage and perichondrial tissue induces progressive disso-
my tube balloon. CT with multiplanar reformations lution and fragmentation of the cartilage followed by fi-
clearly depicts the severity and length of the stricture. brosis. Symmetric subglottic stenosis is the most frequent
Post-intubation stenosis extends for several centimeters manifestation in the chest. As the disease progresses, the
and typically involves the trachea above the level of the distal trachea and bronchi may be involved. CT scans
thoracic inlet. Post-tracheostomy stenosis typically be- show a smooth thickening of the airway wall associated
gins 1.01.5 cm distal to the inferior margin of the tra- with diffuse narrowing. In the early stages of the disease,
cheostomy stoma and extends over 1.52.5 cm. These the posterior wall of the trachea is spared but in advanced
strictures typically have an hourglass configuration with disease, circumferential wall thickening can occur. Tra-
a thickened tracheal wall. Less commonly, tracheal or cheobronchomalacia can develop as a result of weaken-
bronchial stenosis may present as a thin membrane or ing of cartilage, resulting in considerable luminal col-
granulation tissue protruding into the airway lumen. In lapse on expiration. Gross destruction of the cartilagi-
select cases, the degree of stenosis may also be assessed nous rings with fibrosis may cause stenosis.
by virtual bronchoscopy.
Amyloidosis
Infections
Amyloid deposition in the trachea and bronchi may occur
A number of infections, both acute but more often in association with systemic amyloidosis or as an isolat-
chronic, may affect the trachea and proximal bronchi, reed process. The deposits can present as single, multifocal,
sulting in both focal and diffuse airway disease. Subse- or diffuse submucosal plaques or masses. The overlying
quent fibrosis can lead to localized airway narrowing. mucosa is usually intact. Dystrophic calcification or os-
The most common causes of infectious tracheobronchitis sification is frequently present. CT scans show focal or,
are acute bacterial tracheitis in immunocompromised pa- more commonly, diffuse thickening of the airway wall
tients, tuberculosis, rhinoscleroma (Klebsiella rhinoscle- and narrowing of the lumen. Calcification may be pre-
romatis), and necrotizing invasive aspergillosis. CT clear- sent. Narrowing of the proximal bronchi can lead to dis-
ly demonstrates the extent of irregular and circumferen- tal atelectasis, bronchiectasis, or both, with or without
tial tracheobronchial narrowing. In some patients an ac- obstructive pneumonia.
companying mediastinitis is evident, manifesting as infil-
tration of mediastinal fat. With active infection, the nar- Tracheobronchopathia Osteochondroplastica
rowed trachea and frequently one or more main bronchi
have an irregularly thickened wall. In the fibrotic or This rare disorder is characterized by the presence of
healed phase, the airway is narrowed but the wall is multiple cartilaginous nodules and bony submucosal
smooth and of normal thickness. Occasionally, because nodules on the luminal surface of the trachea and proxi-
of the presence of chronic fibrous or granulomatous hili- mal airways. Tracheobronchopathia osteochondroplastica
tis/mediastinitis, tuberculosis of the trachea and/or prox- involves males more frequently than females, and most
imal bronchi may mimic airway malignancy on CT. patients are older than 50 years. Histologically, the nod-
ules contain heterotopic bone, cartilage, and calcified
Granulomatosis with Polyangiitis (Wegener Granulomatosis) acellular protein matrix. The overlying bronchial mucosa
is normal, and, because it contains no cartilage, the pos-
Involvement of the large airways is a common manifes- terior wall of the trachea is spared. On CT, tracheal car-
tation of granulomatosis with polyangiitis. Inflammatory tilages are thickened and show irregular calcifications.
lesions may be present with or without subglottic or The nodules may protrude from the anterior and lateral
bronchial stenosis, ulcerations, and pseudotumors. Radio- walls into the lumen; they usually show foci of calcifica-
logic manifestations include thickening of the subglottic tion. The majority of patients are asymptomatic, with on-
and proximal trachea, with a smooth symmetric or asym- ly a small number developing obstructive signs and
metric narrowing over variable length. Tracheal rings can symptoms.
Saber-sheath Trachea ameter of the trachea becomes significantly larger than

the sagittal one, producing a lunate configuration to the
Saber-sheath trachea is characterized by narrowing of the trachea.
transverse diameter and an increase in the sagittal diam-
eter of the intrathoracic trachea. It is almost always asso- Broncholithiasis
ciated with COPD. The pathogenesis is unclear but is
likely related to the altered mechanics resulting from the This rare condition is characterized by erosion into or dis-
intrathoracic pressure changes associated with COPD. On tortion of a bronchus from an adjacent calcified lymph
radiographs and CT, the internal transverse diameter of node. The underlying abnormality is usually granuloma-
the trachea is decreased to half or less than the corre- tous lymphadenitis caused by Mycobacterium tuberculo-
sponding sagittal diameter. The narrowing usually affects sis or fungi such as Histoplasma capsulatum. A few cas-
the whole intrathoracic trachea, with an abrupt return to es associated with silicosis have been reported. Calcified
normal caliber at the thoracic inlet. The trachea most of- material in the bronchial lumen or bronchial distortion re-
ten shows a smooth inner margin but occasionally has a sults in airway obstruction, leading to collapse, obstruc-
nodular contour. Calcification of the tracheal cartilage is tive pneumonitis, mucoid impaction, or bronchiectasis.
common. Symptoms include cough, hemoptysis, and recurrent
episodes of fever and purulent sputum production. Occa-
Tracheobronchomegaly (Mounier-Kuhn Syndrome) sionally, patients will expectorate calcific fragments
(lithoptysis). Broncholithiasis is recognized on CT by the
Tracheobronchomegaly is characterized by the abnor- presence of a calcified endobronchial or peribronchial
mal dilation of the trachea and main bronchi and a re- lymph node, associated with bronchopulmonary compli-
current lower respiratory tract infection. The etiology is cations related to obstruction in the absence of an associ-
not fully understood, but many patients have congeni- ated soft-tissue mass.
tally atrophic smooth muscle and elastin fibers.
Mounier-Kuhn syndrome is often associated with tra-
cheal diverticulosis and bronchiectasis. The diagnosis is Tracheobronchial Fistula and Dehiscence [2, 3]
based on radiologic findings. The immediately subglot-
tic trachea typically has a normal diameter, but the tra- Multidetector MDCT with thin collimation is the most
cheal diameter expands toward the carina, often involv- accurate technique to identify peripheral bronchopleural
ing the central bronchi. Prolapse of the atrophic mucosa fistulas, which are most commonly caused by necrotizing
between cartilage rings gives the trachea a characteris- pneumonia or trauma. Nodobronchial and nodobron-
tically corrugated appearance. The corrugations may be- choesophageal fistulas are characterized by the presence
come exaggerated to form sacculations or diverticula. of gas in cavitated hilar or mediastinal lymph nodes ad-
On CT, a tracheal diameter of 3 cm (measured 2 cm jacent to the airways and are usually the result of tuber-
above the aortic arch) and a diameter for the right and culosis. Occasionally, congenital tracheal diverticula and
left bronchi of 2.4 cm and 2.3 cm, respectively, are di- tracheobronchoesophageal fistulas, especially the H-
agnosing criteria. Additional findings include tracheal type, may not present until adulthood.
scalloping or diverticula (especially along the posterior Malignant neoplasms, particularly esophageal, are the
membranous tracheal wall). most common cause of tracheoeosophageal fistula in
adults. Infection and trauma are the most frequent non-
Tracheobronchomalacia malignant causes.
MDCT has a high degree of sensitivity and specifici-
Tracheobronchomalacia [8, 9] is characterized by weak- ty for depicting bronchial dehiscence occurring after lung
ened tracheal cartilages and occurs in association with a transplantation. Bronchial dehiscence is seen as a
number of disorders, including tracheobronchomegaly, bronchial wall defect at the anastomosis, associated with
COPD, diffuse tracheal inflammation such as relapsing extraluminal gas collections.
polychondritis, as well as following trauma. The cardiac bronchus is an uncommon airway anom-
Dynamic expiratory multislice CT may offer a feasi- aly characterized by a supernumerary bronchus arising
ble alternative to bronchoscopy in patients with suspect- from the inferomedial aspect of the mid bronchus inter-
ed tracheobronchomalacia. It may show complete col- medius. The cardiac bronchus typically is a blind-ending
lapse or collapse of 80% of the airway lumen. In- pouch but occasionally supplies a very small number of
volvement of the central tracheobronchial tree may be pulmonary lobules. Most cardiac bronchi are clinically
diffuse or focal. On expiration, the airway may have an silent and thus are incidentally detected on chest CT.
oval or crescent shape. The crescent form is due to bow- However, they may serve as a reservoir for retained se-
ing of the posterior membranous trachea. The increased cretions, leading to chronic inflammation and hypervas-
compliance reflects the loss of integrity of the walls cularity and thus to recurrent episodes of infection or he-
structural components and is particularly associated moptysis. Importantly, a cardiac bronchus should not be
with damaged or destroyed cartilages. The coronal di- mistaken for a bronchial fistula or tear.
Bronchiectasis Table 6. Specific causes of disseminated bronchiectasis

Acute, chronic, or recurrent infections
Bronchiectasis [3, 10-12] is a chronic condition charac- Genetic abnormalities
terized by local, irreversible dilation of bronchi, usually Cystic fibrosis
associated with inflammation. Despite the decreased Dyskinetic (immotile) cilia syndrome
prevalence of bronchiectasis in developed countries, it re- Young syndrome
Williams-Campbell syndrome
mains an important cause of hemoptysis and chronic spu- Mounier-Kuhn syndrome (tracheobronchomegaly)
tum production. Among the many causes of bronchiecta- Immunodeficiency syndromes
sis, there are three main underlying mechanisms: Yellow nail syndrome
bronchial obstruction, bronchial wall damage, and -1-antitrypsin deficiency
parenchymal fibrosis. With the first two mechanisms, the Noninfectious inflammatory diseases
Allergic bronchopulmonary aspergillosis
combination of mucus plugging and bacterial coloniza- Asthma
tion lead to a vicious cycle of progressive airway-wall Systemic diseases (rheumatoid arthritis, Sjgren syndrome,
damage, as a result of cytokine and enzyme release by in- systemic lupus erythematosus, inflammatory bowel disease)
flammatory cells in addition to toxin secretion by bacte- Post-transplantation bronchiolitis obliterans
ria. With parenchymal fibrosis, dilation of bronchi,
termed traction bronchiectasis, occurs by the maturation an obstructive involvement of the small airways (con-
and retraction of fibrous tissue formed in the parenchy- strictive). The extent and severity of bronchiectasis and
ma adjacent to an airway. bronchial wall thickening correlate with airflow obstruc-
tion. In patients with bronchiectasis, bronchial wall thick-
Pathology ening and the extent of decreased lung attenuation are the
strongest determinants of airflow obstruction. Bronchial
Pathologically, bronchiectasis is classified into three sub- wall thickening on baseline CT correlates with function-
types, reflecting the increasing severity of the disease: al deterioration over time.
(1) cylindrical, characterized by relatively uniform airway MDCT with thin collimation is the optimal imaging test
dilation; (2) varicose, characterized by non-uniform and to assess the presence and extent of bronchiectasis. Several
somewhat serpentine dilation; and (3) cystic. As studies have shown that multiplanar reformations increase
bronchiectasis progresses, the lung parenchyma distal to the detection rate of bronchiectasis, readers confidence as
the affected airway shows increasing collapse. to the distribution of bronchiectasis, and agreement
among observers as to the diagnosis of bronchiectasis.
CT Findings The reliability of CT for distinguishing among the
causes of bronchiectasis is somewhat controversial. An
The CT findings of bronchial dilation include lack of ta- underlying cause for bronchiectasis is found in fewer than
pering of the bronchial lumina (the cardinal sign of half of the patients, and CT features alone do not usual-
bronchiectasis), an internal diameter of the bronchi ly allow a confident distinction between idiopathic
greater than that of the adjacent pulmonary artery bronchiectasis versus known causes of bronchiectasis.
(signet ring sign), bronchi visible within 1 cm of the The various specific causes of disseminated bronchiecta-
costal pleura or abutting the mediastinal pleura, and mu- sis are listed in Table 6.
cus-filled dilated bronchi. With varicose bronchiectasis,
the bronchial lumen assumes a beaded configuration.
Cystic bronchiectasis appears as a string of cysts caused Small Airway Diseases
by irregular dilated bronchi along their lengths, or a clus-
ter of cysts, caused by multiple dilated bronchi lying ad- Although normal bronchioles are below the resolution of
jacent to each other. Clusters of cysts are most common- thin-section CT, they can become detectable when in-
ly seen in an atelectatic lobe. Fluid levels, caused by re- flammation of the airway wall and an accompanying exu-
tained secretions, may be present in the dependent por- date develop. Some bronchiolar changes are too small to
tion of the dilated bronchi. Accumulation of secretions be visible directly but result in indirect signs on CT. Bron-
within bronchiectatic airways is typically recognizable as chiolar obstruction can manifest as mosaic attenuation on
lobulated V- or Y-shaped structures (finger in glove CT, with decreased attenuation and abnormally smaller
sign). CT may show a completely collapsed lobe con- vessels as a result of reflex vasoconstriction. Expiratory
taining bronchiectatic airways. Subtle degrees of volume CT confirms the presence of air trapping. Four different
loss may present in lobes in relatively early disease. CT patterns can express small airway pathology [3, 4, 13].
Associated CT findings of bronchiolitis are present in
about 70% of patients with bronchiectasis. These abnor- Small Centrilobular Nodular and Branching Linear Opacities
malities are very common in patients with severe (tree-in-bud)
bronchiectasis and can even precede the development of
bronchiectasis. The obstructive defect on pulmonary test- Tree-in-bud opacities are defined as small centrilobular
ing in patients with bronchiectasis is the consequence of nodular and branching linear opacities, usually V- or Y-
shaped, reflecting abnormally dilated bronchioles with Table 7. Causes of and association with obliterative (constrictive)
thickened walls and mucus or exudate filling the lumens. bronchiolitis
Associated peribronchiolar inflammation is often present, Post-infection
contributing to the CT appearance. Tree-in-bud opacities Childhood viral infection (adenovirus, respiratory syncytial
are characteristic of acute or chronic infectious bronchi- virus, influenza, parainfluenza)
Adulthood and childhood (Mycoplasma pneumoniae, Pneu-
olitis. They also occur in diffuse panbronchiolitis and as- mocystis jirovecii in AIDS patients, endobronchial spread of
piration. tuberculosis, bacterial bronchiolar infection)
Post-inhalation (toxic fumes and gases)
Diffuse aspiration bronchiolitis (chronic occult aspiration in the
Poorly Defined Centrilobular Nodules elderly, patients with dysphagia)
Connective tissue disorders (rheumatoid arthritis, Sjgren syn-
Poorly defined centrilobular nodules reflect the presence drome)
of peribronchiolar inflammation in the absence of airway Allograft recipients (bone-marrow transplant, heart-lung, or
filling. When the distribution of nodules is diffuse and lung transplant)
homogeneous, the pattern is suggestive of bronchiolar or Drugs (penicillamine, lomustine)
vascular diseases. Bronchiolar diseases associated with Ulcerative colitis
Other conditions
poorly defined centrilobular nodules include respiratory Bronchiectasis
bronchiolitis, bronchiolitis associated with hypersensitiv- Cystic fibrosis
ity pneumonitis, and follicular bronchiolitis. Hypersensitivity pneumonitis
Diffuse idiopathic pulmonary neuroendocrine cell hyperpla-
sia (DIPNECH)
Decreased Lung Attenuation and Mosaic Perfusion Excessive Sauropus androgynus (katuk, sweet leaf, or star
gooseberry) ingestion
Areas of decreased lung attenuation associated with de- Idiopathic
creased vessel caliber on CT reflect bronchiolar obstruc-
tion and associated reflex vasoconstriction. In acute bron-
chiolar obstruction, decreased perfusion represents a phys-
iologic reflex of hypoxic vasoconstriction whereas irre- minal bronchioles, has a variety of causes and, rarely, is
versible vascular remodeling occurs with chronic bronchi- idiopathic (Table 7). Bronchial wall thickening and
olar obstruction. Areas of decreased lung attenuation re- bronchiectasis, both central and peripheral, are also com-
lated to hypoperfusion can be patchy or widespread. They monly present.
are poorly defined or sharply demarcated, or have a geo- Mosaic attenuation may also be seen in patients with
graphical outline, but in all cases represent a collection of chronic thromboembolic disease; however, in this condi-
affected pulmonary lobules. Redistribution of blood flow tion, frank dilation of the proximal pulmonary arteries
to the normally ventilated areas causes localized increased within the hyperattenuated areas and extensive areas of
attenuation. The patchwork of abnormal areas of low at- hypoattenuation and hypoperfusion are almost always
tenuation and normal lung or less diseased areas results in present.
mosaic attenuation on CT, also termed mosaic perfusion.
Expiratory CT accentuates the pattern of mosaic attenua- Expiratory Air Trapping
tion where areas of air trapping remain low in attenuation
whereas normal lung increases in attenuation. Usually, the Lobular areas of air trapping may be readily apparent on
regional heterogeneity of lung attenuation is apparent on expiratory CT but are occult on inspiratory CT. Foci of
full inspiration on thin-section CT. However, with more lobular air trapping are usually well demarcated, reflecting
extensive air trapping, the lack of regional homogeneity of the geometry of individual or joined lobules. Lobular ar-
lung attenuation can be challenging to detect on inspirato- eas of air trapping may be present on expiratory CT scans
ry scans; as a result, mosaic attenuation becomes visible of normal individuals, especially in the medial and poste-
only on expiratory scans. In patients with particularly se- rior basal segments and apical portions of the superior seg-
vere and widespread involvement of the small airways, the ments of the lower lobes. However, when lobular air trap-
patchy distribution of hypoattenuation and a mosaic pat- ping occurs in the non-dependent portions of the lung or
tern is lost. Inspiratory scans show an apparent uniformi- the overall extent is equal to or greater than one segment,
ty of decreased attenuation in the lungs, and scans ob- the air trapping should be considered as abnormal. Expi-
tained at end expiration may appear normal. In these pa- ratory air trapping occurs in smokers and in patients with
tients, the most striking features are the paucity of pul- asthma, constrictive bronchiolitis, and bronchiolitis asso-
monary vessels and the lack of a change in the cross-sec- ciated with hypersensitivity pneumonitis and sarcoidosis.
tional area of lung between inspiration and expiration.
Mosaic attenuation is seen in patients who have con-
strictive bronchiolitis, bronchiolitis associated with hy- Asthma
persensitivity pneumonitis, asthma, and COPD.
Constrictive bronchiolitis, characterized by submucos- Asthma [3, 14-16] is a chronic inflammatory condition
al circumferential fibrosis along the central axis of ter- resulting from airway hyper-responsiveness to several
stimuli. It is characterized by episodes of wheezing, centrilobular nodules primarily in the upper lobes reflect
coughing, and dyspnea due to airflow obstruction that re- inflammatory changes in and around the bronchioles (res-
solves spontaneously or following treatment with bron- piratory bronchiolitis), which can be reversible after smok-
chodilators. Over time, airway remodeling (fibrosis, ing cessation and steroids. Mosaic attenuation and expira-
smooth muscle hypertrophy and hyperplasia, and neovas- tory air trapping reflect obstructive bronchiolitis and re-
cularity) leads to persistent airflow obstruction. modeling of the small airways.
The main clinical indication for imaging patients with Large airway disease is also commonly present in
asthma is to identify diseases that can mimic asthma clin- COPD patients [19, 20]. Saber-sheath trachea occurs
ically, particularly hypersensitive pneumonitis, constric- specifically in COPD, particularly males. Bronchial wall
tive bronchiolitis, and tracheal or carinal obstruction by thickening and irregularities, although nonspecific, are
neoplastic or non-neoplastic tracheal disorders. CT scans frequently present. A quantitative assessment of bronchial
of patients with asthma can be normal or show bronchial wall thickening on CT scans can provide an estimate of
abnormalities. Mucoid impaction and linear bands, re- airway remodeling in the absence of extensive emphyse-
flecting subsegmental or segmental atelectasis, are re- ma. Bronchial wall thickness is one of the strongest de-
versible on follow-up. Bronchial wall thickening is com- terminants of FEV1 in patients with COPD. Moderate
monly present and correlates with clinical severity and tubular bronchiectasis can occur, particularly in the lower
the duration of asthma and the degree of airflow obstruc- lobes, following injury to cartilage. Bronchiectasis is of-
tion. It also correlates with pathologic measures of re- ten associated with more severe COPD exacerbations,
modeling from bronchial biopsies. Bronchiectasis may lower airway bacterial colonization, and increased sputum
also be present; its extent is associated with an increased inflammatory markers [21, 22]. However, the presence of
severity of asthma. bilateral varicose and cystic bronchiectasis in patients
In patients with persistent moderate asthma, mosaic at- with panlobular emphysema should raise the diagnosis of
tenuation reflects remodeling in the small airways. The -1-antitrypsin deficiency. Cartilage deficiency in COPD
extent of expiratory air trapping does not change after in- may also induce abnormal collapse of the airway lumen at
halation of salbutamol. By contrast, in patients with mild expiration, contributing to airflow limitation. Tracheoma-
or moderate uncontrolled asthma, therapy with inhaled lacia can also develop.
corticosteroids reduces the degree of air trapping on CT,
suggesting that CT can be used as a surrogate marker for
assessing disease control. References
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the airways: technique and normal results. Radiol Clin North
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2. Grenier PA, Beigelman-Aubry C, Fetita C et al (2002) New
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tion. The two types of lesions can coexist in the same pa- 7. Grenier PA, Beigelman-Aubry C, Brillet PY (2009) Nonneo-
tient, and small airway disease may precede the appear- plastic tracheal and bronchial stenoses. Radiol Clin North Am
47:243-260.
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CT scans showing different morphologic appearances. For Am 47:261-269.
example, one patient with extensive emphysema on CT 9. Ridge CA, ODonnell CR, Lee EY et al (2011) Tracheobron-
can have the same degree of airflow obstruction as anoth- chomalacia: current concepts and controversies. J Thorac
Imaging 26:278-289.
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sis and management. Clin Chest Med 32:535-546.
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ical trials and, ultimately, for a more personalized treat- ease (SAD). Radiol Clin North Am 47:307-316.
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normalities of the small and large airways. Poorly defined Totowa, NJ, USA.
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16. Aysola RS, Hoffman EA, Gierada D et al (2008) Airway re- 20. Sverzellati N, Ingegnoli A, Calabr E et al (2010) Bronchial
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IDKD 2015-2018
Investigating a Child with a Cough: A Pragmatic Approach

Maria do Rosario Matos1, George A. Taylor2, Catherine M. Owens3
1 Radiology Department of Hospital Dona Estefnia, Centro Hospitalar de Lisboa Central, Lisbon, Portugal
2 Harvard Medical School and Boston Childrens Hospital, Boston, MA, USA
3 Great Ormond Street Hospital for Children, London, UK
Introduction ception, which may overestimate or misinterpret impor-

tant situations of cough, like foreign-body aspiration.
Cough in children has a wide range of causes, is fre-
quently misdiagnosed and consequently inappropriately
treated [1]. Definitions
A vast bibliography describing the assessment and
management of cough is available, and guidelines have Cough is defined as a forced expulsive maneuver against
recently been proposed [1, 2]. This review discusses the a closed glottis and is associated with a characteristic
role of imaging in the assessment of cough, in the inves- sound [1].
tigation of a specific diagnosis. We emphasize important Acute cough is defined as a recent onset of cough last-
clues related to the patients clinical condition that should ing 3 weeks; chronic cough is one that lasts 8 weeks
be considered when selecting the most appropriate exam- [1, 7].
ination, as part of an organized investigation plan. Prolonged acute cough resolves over a 3- to 8-week
The pattern of respiratory illness in children is differ- period. An example is Pertussis cough, which may need
ent from that in adults. The airways in children are less an additional period of time to elapse before further in-
mature, as are the respiratory muscles, chest wall struc- vestigations are performed.
ture, sleep-related features, and respiratory reflexes. Recurrent cough refers to repeated (2/year) cough
Viruses associated with common cold in adults can cause episodes not related to head colds, each lasting 714
serious respiratory illnesses, such as bronchiolitis and days [8, 9]. It can be difficult to distinguish from persis-
croup, in previously well young children [3]. Also, the tent chronic cough. Most simple infective causes of
common big three causes of chronic cough in adults cough resolve in 3-4 weeks. Children with chronic cough
(cough variant asthma, postnasal drip and gastro- may require further investigations.
esophageal reflux) [4] do not necessarily apply to the pe- Based on the suggested etiology, cough can be catego-
diatric age. Other considerations for the etiology of cough rized as normal or expected cough, specific cough,
include inhalation of a foreign body, airway lesions, envi- and non-specific cough (Fig. 1). Normal children cough
ronmental toxicants, respiratory infections, and otogenic 11 times a day on average, although some children expe-
causes [2, 5] (Table 1). Tumors are common in adults but rience more than 30 episodes a day, as shown in recent
are extremely rare in children, although this possibility studies [10, 11]. Frequency and severity increase during
must not be forgotten in a child with a specific chronic upper respiratory tract infection, which occurs in more
cough [6]. Medical history is often limited to parental per- frequently in the pediatric age group than in adults [1, 2].
Table 1. Influence of age on the causes of cough

Infancy Early childhood Late childhood
Gastroesophageal reflux Post-viral airway hyper-responsiveness Asthma
Infection Asthma Post-nasal drip
Congenital malformation Passive smoking Smoking
Congenital heart disease Gastroesophageal reflux Pulmonary tuberculosis
Passive smoking Foreign body Bronchiectasis
Environmental pollution Bronchiectasis Psychogenic cough
Asthma

38 M. do Rosario Matos, G.A. Taylor, C.M. Owens
Non-Specific
isolated
Normal persistent
or cough
expected
cough
Specific
cough
Fig. 1. Venn diagram of different types of cough
When there are symptoms and signs that point to a cer-

tain diagnosis, thus demanding further investigation,
cough is defined as specific.
Non-specific cough describes cases in which cough
usually dry is the only symptom (isolated cough) and
the child is otherwise well. Most cases are thought to be
post-viral and related to increased cough receptor sensi- Fig. 2. Chest X-ray showing nodular consolidation behind the heart
tivity [12, 13] and less likely to asthma or gastro-
esophageal reflux [1].
Chronic Cough
Acute Cough There may be an overlap between recurrent and chronic
cough, which is why for investigation purposes these cat-
Acute cough is most commonly caused by viral respira- egories, along with prolonged acute cough, are not sepa-
tory tract infections [14], which may or may not be asso- rated. Most children with chronic cough have recurrent
ciated with acute bronchitis. Other causes include sea- viral bronchitis or post viral syndromes (subacute cough).
sonal allergic rhinitis, hay fever, an inhaled foreign body, Causes of chronic cough may be classified in two
and the first presentation of a chronic disorder. groups [15]: (1) chronic isolated (no wheezing) non-spe-
According to British Thoracic Society guidelines cific cough in an otherwise healthy child and (2) a chron-
[1], if acute cough is due to an uncomplicated upper ic cough in which the child has a serious underlying lung
respiratory tract infection (absence of fever, tachypnea, condition (Table 2).
and chest signs), no further investigation is needed. If
an inhaled foreign body is suspected as the cause, then Evaluation
an urgent rigid bronchoscopy should be performed. A
chest radiograph is considered when lower respiratory Specific cough requiring further investigation is suggest-
signs are present (Fig. 2), when there are hemoptysis, ed by specific pointers identified in the history and clin-
or the suggestion of a chronic respiratory disorder or ical examination of the patient. Historical information in-
when a cough is relentlessly progressive beyond 23 cludes time of onset, quality of cough, triggering and al-
weeks. leviating factors, and presence of hemoptysis (Table 3).
Table 2. Influence of pre-existing disease on the causes of cough

Chronic cough in an otherwise healthy child Chronic cough with a significant underlying cause
Recurrent viral bronchitis Cystic fibrosis
Post-infectious cough Immune deficiencies
Pertussis-like illness Primary ciliary dyskinesia
Cough variant asthma Protracted bacterial bronchitis
Allergic rhinitis, post-nasal drip and sinusitis Recurrent pulmonary aspiration
Psychogenic cough Tracheoesophageal fistula, gastroesophageal reflux, hiatal hernia
Habit (tic like) Retained inhaled foreign body
Bizarre honking cough Tuberculosis
Gastroesophageal reflux Anatomical disorder (airway or lung)
Interstitial lung disease
Investigating a Child with a Cough: A Pragmatic Approach 39
Table 3. Influence of the time of onset on the causes of cough ble of performing the maneuvers (generally those over
Time of onset Neonatal, infancy and childhood the age of 5 years) [1, 2].
Nature Dry or productive In children with a specific cough, further investiga-
Quality Brassy, croupy, honking, paroxysmal, tions may be warranted (Figs. 3, 4), except when asthma
staccato is the main cause [1, 2]. The next sections discuss the var-
Timing Persistent, intermittent, nocturnal, on ious etiologies of chronic cough.
awaking
Triggering factors Cold air, exercise, feeding, seasonal,
starts with a head cold
Alleviating factors Bronchodilators, antibiotics
Chronic Sinusitis
Associated symptoms Wheezing, shortness of breath
Sinusitis is a very common condition in children.
Chronic sinusitis (lasting 3 months) involves symp-
Clinical examination pointers include digital clubbing toms that include nasal obstruction, nasal discharge,
and asymmetrical auscultatory signs. halitosis, and headache [16]. Although some authors re-
Two situations are commonly indicative of significant port a high incidence of incidental sinus opacification
disease. The first is neonatal onset of the cough, suggest- in children [17], those data may be biased by different
ing: (a) a congenital defect leading to feeding problems interpretations of mucosal thickening and by the true
and pulmonary aspiration, (b) cystic fibrosis, (c) primary health condition of the population included in such
ciliary dyskinesia, (d) an anatomical airways abnormali- studies [18]. Tatli et al. [18] found a 52% prevalence of
ty, for example a cyst compressing the airway or tracheo- moderate to severe opacification of the paranasal sinus
malacia, or (e) a chronic viral pneumonia (e.g., cy- on computed tomography (CT) in children with chron-
tomegalovirus or Chlamydia) acquired in utero or during ic cough, with 90% involvement of the maxillary si-
the perinatal period [1, 2]. nuses.
The second situation is persistent productive (moist or Radiographs are used as a screening method for patho-
wet) cough, which requires investigation for the presence logical conditions involving the sinuses but CT remains
of bronchiectasis or any specific suppurative lung condi- the imaging modality of choice for the evaluation of
tion [1, 2]. acute and chronic sinus inflammatory processes [19]. The
association between adenoidal hypertrophy and rhino-
Investigation sinusitis with upper airway inflammation is increasingly
recognized, with one study [20] stating that magnetic
A chest radiograph is indicated for most children with resonance imaging (MRI) can document changes in ade-
chronic cough, unless there is also a minor identified dis- noid size associated with the resolution of rhinosinusitis
order, such as asthma or allergic rhinitis (Table 4). (Fig. 5). Further studies are necessary to define the role
Spirometry should be always attempted in children capa- of MRI in adenoidal hypertrophy.
Table 4. Imaging in a child with cough

Indication for chest X-ray Features Likely common diagnose
Uncertainty about the diagnosis Fever and rapid breathing Pneumonia
of pneumonia Chest signs
Persisting high fever
Unusual course in bronchiolitis
Cough and fever persisting beyond 45 days
Possibility of an inhaled Choking episode may not have been witnessed Inhaled foreign body
foreign body Sudden onset X-ray may be normal
Asymmetrical wheeze Needs bronchoscopy
Hyperinflation
Suggestion of a chronic Failure to thrive See Fig. 3
respiratory disorder Finger clubbing
Overinflation
Chest deformity
Unusual clinical course Relentlessly progressive beyond 23 weeks Pneumonia
Recurrent fever Enlarging intrathoracic lesion
Tuberculosis
Inhaled foreign body
Lobar collapse
Hemoptysis Acute pneumonia
Chronic lung disorder (e.g., cystic fibrosis)
Inhaled foreign body
Tuberculosis
Pulmonary hemosiderosis
Tumor
Specific cough pointers present or Consider early consultation with pediatric

abnormal CXR or spirometry (if >3-6 years old) pulmonologist for assessment
Reversible airway
obstruction?
Asthma Yes No
If cough does
not settle consider:
Assessment of risk factors for
Bronchietasis Aspiration Chronic Interstitial Airway Other less common Cardiac

or recurrent or less common lung abnormality pulmonary
pneumonia - Primary or infections disease -Tracheo- conditions - Pulmonary hypertension
- Cystic fibrosis secondary - TB - Rheumatic bronchomalacia - Primary and - cardiac edema
- Ciliary dyskinesia - Neurologically - Non-tuberculous - Cytotoxic - Other infra- secondary
- Previous severe abnormal mycobacteria drugs luminal lesions tumors
pneumonia - Altered swallow - Mycoses - Radiation e.g. tumors Pediatric
- Immunodeficiency - Weak cough - Parasites etc. - Extrinsic cardiologist
- Structural airway reflex compressive
lesions - Neuromuscular lesions
- Congenital lung disease
disease - Laryngeal
- Missed foreign abnormalities
body - Tonsil adenoid Mantoux Autoimmune Bronchoscopy Echo
- TEF, H1 fistula hypertrophy bronchoscopy markers & lavage cardiac
- TEF, H1 fistula & lavage HRCT chest CT chest catheter
- Severe GERD HRCT chest Lung biopsy MRI chest
Sweat test Barium swallow

Bronchoscopy Bronchoscopy & lavage
Cilia biopsy Video fluoroscopy
Immune workup pH monitor
HRCT chest Lung milk
Barium swallow Scan/salivagram
Fig. 3. Flow chart illustrating the specific pathways for the investigation of children with specific cough, an abnormal chest X-ray, or ab-
normal spirometry. TEF, tracheoesophageal fistula; GERD, gastroesophageal reflux disease; HRCT, high-resolution computed tomography,
MRI, magnetic resonance imaging
Tracheoesophageal fistula (TEF) or laryngeal clefts

Chronic cough cause cough due to aspiration, especially during meals.
Following surgery for TEF or esophageal atresia, children
CLINICAL usually have tracheomalacia and cough.
POINTERS A seal-like barking cough occurs in children with any
cause of airway compression or stenosis. In the study of
Gormley et al. [21], 75% of children with tracheomalacia
secondary to congenital vascular anomalies had persis-
CHEST X RAY Specific
cough FURTHER tent chronic cough at presentation. However, those au-
INVESTIGATION thors did not take into account asymptomatic children.
Mediastinal masses, such as bronchogenic cysts, need al-
so to be considered in children presenting with the relat-
SPIROMETRY IMAGING ed symptoms (Fig. 6).
The barium esophagogram is the main imaging
modality for identifying TEF. However, some infants
Fig. 4. Pathway for the investigation of chronic cough with associated medical problems and on life support
systems are poor candidates, in which case CT is an ac-
curate diagnostic alternative [22]. The diagnostic utili-
Congenital Airway Disorders ty of the new generations of multislice CT scans, per-
formed appropriately with air insufflation into the tra-
Anatomical abnormalities of the airways may be the cause chea or esophagus during image acquisition, permits
of chronic cough. Tracheobroncomalacia often causes a the rapid, safe, and accurate diagnosis of H-type TEF
brassy, barking, or seal-like cough, with a neonatal onset. [23].
a b c
Fig. 5 a-c. Coronal (a), sagittal (b), and axial (c) T2-weighted spin echo magnetic resonance images illustrate paranasal sinus mucosal
thickening and adenoidal hypertrophy in a child with chronic cough related to rhinosinusitis
a b
Fig 6. a, b. Chest X-ray

(a) and axial contrast-
enhanced computed to-
mography (CT) (b) in a
child with cough due to
a mediastinal broncho-
genic cyst adjacent to
the descending aorta
a b c
Fig. 7 a-c. Chest X-ray and axial contrast enhanced CT scan with volume rendered tomo-
graphy (VRT) in a child with cough and stridor related to a pulmonary artery sling. a Chest
X-ray shows splaying of the trachea (arrows), with an obtuse carinal angle. b Axial CT
shows the narrow trachea (open arrow) with the abnormal LPA passing behind the trachea,
in a sling like fashion. c The VRT image shows long segment tracheal stenosis with a ru-
dimentary R apical tracheal bud (open arrow), with an obtuse carinal angle and narrowing
of the origins of the R and L main bronchi (stovepipe trachea) (white arrow)
Barium swallow and echocardiography can demon- opment of high-speed, high-resolution CT scanning, gen-
strate the presence of a vascular ring. Bronchoscopy in eral anesthesia is usually unnecessary. According to Turn-
this context has to be defined prospectively [15]. Both er et al. [25], the first examination should be a barium
CT and MRI are noninvasive imaging modalities that swallow, followed by a high-resolution chest CT scan in
may help in the planning of surgery [24]. With the devel- the study of vascular rings (Fig. 7).
a b
Fig. 8 a, b. An expiratory chest X-ray (a) and virtual bronchoscopy (b) show gross over-inflation, due to air trapping in a child with obstructive
overinflation and ball valve effect in the right main bronchus due to an inhaled foreign body. This imaging approach increases the diagnostic
accuracy for inhaled FB, whose findings include atelectasis, areas of unilateral or bilateral hyperinflation, or nonspecific opacification
Foreign-Body Aspiration resulting from bronchiectasis are chronic cough and spu-
tum production, although some patients may have a non-
Cough may be an important symptom in acute foreign- productive cough [32].
material inhalation. Foreign-body aspiration (FBA) is Patients without an obvious cause of bronchiectasis
much more frequent in boys than in girls and is more should be diagnostically evaluated for an underlying
common in those under 4 years of age [15]. Although the disorder because the results may lead to treatment that
presentation is usually acute [26], the problem may go can potentially slow or halt progression of the disease
unrecognized for prolonged periods of time if the diag- [32]. Cystic fibrosis (CF) occurs in 1 per 2,0003,000
nosis is missed initially [27]. In that case, the natural his- live births and is probably the most common identifi-
tory may include hemoptysis, cough producing casts in able cause of bronchiectasis in the United States and
the airways, associated wheezing, and associated recur- Europe [32]. CF-related cough may have a neonatal on-
rent pneumonia and infiltrates [1]. set and can be productive or paroxysmal. It may be as-
An expiratory chest X-ray increases the diagnostic ac- sociated with hemoptysis, ill health, recurrent pneumo-
curacy in patients with FBA [7]. Findings include atelec- nia, or pulmonary infiltrates [1]. Non-CF causes of
tasis, areas of unilateral or bilateral hyperinflation, or bronchiectasis include post-infectious disease, primary
nonspecific opacification [28] (Fig. 8). However, a nor- ciliary dyskinesia, immunodeficiency states, retained
mal chest X-ray does not exclude the possibility of FBA. airway foreign body, connective tissue disorders, chron-
If the history is unclear and there are no localized physi- ic aspiration and allergic bronchopulmonary aspergillo-
cal or X-ray findings, flexible bronchoscopy should be sis [33].
performed to locate the inhaled object and rigid bron- In patients with clinically suspected bronchiectasis
choscopy to remove it [7, 29]. without a characteristic chest radiograph, a CT scan can
Virtual bronchoscopy associated with MCDT is a non- confirm the diagnosis. Criteria include an increased
invasive modality for the identification of endobronchial le- bronchial/adjacent pulmonary artery ratio, non-tapering
sions. Helical CT scanning with virtual bronchoscopy may bronchial walls, bronchi visualized at lung periphery,
be performed in selected cases of suspected FBA. When the thickened bronchial walls, mucous plugging and focal
chest radiograph is normal and the clinical diagnosis sug- air-trapping related to small airway disease [33, 34]. CT
gests an aspirated foreign body, helical CT and virtual bron- is also of great value in cases of superadded infection,
choscopy can be considered as a means to avoid rigid bron- such as allergic bronchopulmonary aspergillosis and non-
choscopy if the clinical suspicion is low [30, 31]. tuberculous mycobacterial infection [33] (Fig. 9).
Because CF may be diagnosed early in life due to non-
pulmonary findings (e.g., meconium ileus, malabsorp-
Bronchiectasis tion, and failure to thrive due to pancreatic insufficiency),
CT is used for the diagnosis of its complications rather
Bronchiectasis is defined as abnormal dilatation of thick- than the primary diagnosis. However, in non-CF causes
walled airways. Regardless of the etiology, symptoms of bronchiectasis, CT plays a role in the primary diagno-
a b
Fig. 9 a, b. CT is of value in pa-

tients with cystic fibrosis
with superadded infection,
such as allergic bronchopul-
monary aspergillosis (a) and
non-tuberculous mycobacte-
rial infection (b)
a b c
Fig. 10 a-c. Axial (a) and (b) sagittal CT scans and (c) virtual bronchoscopy show an endobronchial mass in the right main bronchus of a
child with cough and hemoptysis related to endobronchial Mycobacterium tuberculosis infection.
sis and detection of complications (if chest X-ray is in- chogenic spread, miliary nodules, and segmental or lobar
sufficient) as well as prior to lung surgery [33]. consolidation, which may evolve to caseating necrosis.
CT also defines the extent of disease and its complica-
tions [36] (Fig. 10).
Tuberculosis
Chronic or less common infections that may lead to Considerations on Pediatric CT Radiation Burden
chronic cough are tuberculosis (TB) and non-tuberculous
mycobacteria, fungal, and parasitic infections. TB should The utility of CT scans in the pediatric age needs to be
be considered in any child with a persistent productive balanced with radiation effects. Children are considerably
cough, particularly if there are systemic features such as more sensitive to radiation than adults and have a longer
fever, weight loss, or general malaise. Specific pointers life expectancy, resulting in a higher lifetime cancer mor-
towards this diagnosis in cough investigation are hemo- tality risk [37].
ptysis, associated with severe ill health, recurrent pneu- CT settings in the diagnosis of chest disease can be re-
monia, or pulmonary infiltrates [1]. Since most TB induced significantly while maintaining diagnostic image
fections are transmitted by inhalation, primary lesions oc- quality. Jogeesvaran and Owens [33] reported that the
cur in the lungs in over 95% of infected children [34]. dose for a volumetric CT scan is between three and five
Although chest radiography remains the first-line times higher than for a non-contiguous high-resolution
imaging technique in the evaluation of pulmonary TB in CT. Moreover, there is a strong argument that chronic dif-
children, in selected cases CT can provide important in- fuse diseases of the lung parenchyma are adequately im-
formation in the diagnosis and management of the dis- aged with non contiguous CT. The authors recommended
ease. CT typically shows low-attenuation lymph nodes a volumetric scan at the initial diagnostic stage of chron-
with rim enhancement and, eventually, calcification. ic lung disease to exclude co-existent or unsuspected tra-
These findings in HIV-positive patients are considered cheobronchial and vascular anomalies. For children sus-
sufficient to warrant instituting empirical anti-TB thera- pected of having diffuse interstitial lung diseases at diag-
py [35]. Parenchymal lesions include nodules of bron- nosis and at follow-up of either airways or diffuse infil-
trative lung disease, a limited, non-contiguous, conven- 10. Munyard P, Bush A (1996) How much coughing is normal?
tional high-resolution CT should be the preferred exam. Arch Dis Child 74:531-534.
11. Shann F (1996) How often do children cough? Lancet
348:699-700.
12. Chang AB, Phelan PD, Sawyer SM et al (1997) Airway hyper-
Conclusion responsiveness and cough-receptor sensitivity in children with
recurrent cough. Am J Respir Crit Care Med 155:1935-1939.
In the management of illness in children, adult-based da- 13. Chang AB, Phelan PD, Sawyer SM et al (1997) Cough sensi-
tivity in children with asthma, recurrent cough, and cystic fi-
ta should not be extrapolated: children are different from brosis. Arch Dis Child 77:331-334.
adults. 14. Boujaoude ZC, Prat MR (2010) Clinical approach to acute
Most children with cough due to a simple upper respi- cough. Lung 188(Suppl 1):4146.
ratory tract infection will not need further investigations. 15. Jongste JC, Shields MD (2003) Cough 2: Chronic cough in
Chest radiograph should be considered in the presence children. Thorax 58:998-1003.
16. Triulzi F, Zirpoli S (2007) Imaging techniques in the diagno-
of: lower respiratory tract signs, relentlessly progressive sis and management of rhinosinusitis in children. Pediatr Al-
cough, hemoptysis, or features of an undiagnosed chron- lergy Immunol 18:46-49.
ic respiratory disorder. 17. Glasier CM, Ascher DP, Williams KD (1986) Incidental
Children with chronic cough require careful and sys- paranasal sinus abnormalities on CT of children. Am J Neuro-
tematic evaluation for the presence of specific diagnostic radiol 7:861-864.
18. Tatli M, Sanb I, Karaoglanogluc M (2001). Paranasal sinus
indicators and should undergo, as a minimum, a chest ra- computed tomographic findings of children with chronic
diograph and spirometry. cough. Int Journ Pediatr Otorhinolaryngol 60:213-217.
In children with specific cough, further investigations 19. Mafee MF, Tran BH, Chapa AR (2006) Imaging of rhinosi-
may be warranted, except when asthma is the etiologic nusitis and its complications: plain film, CT, and MRI. Clin
Rev Allergy Immunol 30:165-186.
factor. 20. Georgalas C, Thomas K, Owens C et al (2005) Medical treat-
Children with chronic productive purulent cough ment for rhinosinusitis associated with adenoidal hypertrophy
should always be investigated, to document the presence in children: an evaluation of clinical response and changes on
or absence of bronchiectasis and to identify underlying magnetic resonance imaging. Ann Otol Rhinol Laryngol
and treatable causes such as CF and immune deficiency. 114:638-644.
21. Gormley PK, Colreavy MP, Patil N et al (1999) Congenital
Chronic cough starting in the neonatal period usually vascular anomalies and persistent respiratory symptoms in
indicates significant disease, especially if it starts in the children. Int J Pediatr Otorhinolaryngol 51:23-31.
first few days or weeks of life. 22. Johnson JF, Sueoka BL, Mulligan ME, Lugo EJ (1985) Tra-
There are advantages of CT in children but the tech- cheoesophageal fistula: diagnosis with CT. Pediatric Radiolo-
niques and guidelines regarding the use of the different gy 15:134-135.
23. Ou P, Seror E, Layouss W et al (2007) Definitive diagnosis and
modalities in the pediatric population must be kept in surgical planning of H-type tracheoesophageal fistula in a crit-
mind, and the potential risks balanced accordingly. ically ill neonate: First experience using air distension of the
esophagus during high-resolution computed tomography ac-
quisition. Thorac Cardiovasc Surg 133:1116-1117.
24. Chun K, Colombani PM, Dudgeon DL et al (1992) Diagnosis
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IDKD 2015-2018
Thoracic Manifestations of Pediatric Systemic Diseases

Edward Y. Lee1, Alan S. Brody2
1 Department of Radiology, Boston Childrens Hospital and Harvard Medical School, Boston, MA, USA
2 Department of Radiology and Pediatrics, Cincinnati Childrens Hospital and the University of Cincinnati College of Medicine, Cincinnati,
OH, USA
Introduction nile dermatomyositis, and systemic lupus erythematosus

(SLE) [1]. Of these collagen vascular diseases, JIA most
There are a wide variety of systemic diseases that have a commonly affects children whereas SLE is more often
component of thoracic manifestations in pediatric pa- seen in adults than in children. In JIA particularly, find-
tients. Although the imaging findings of these systemic ings on chest computed tomography (CT) are more com-
diseases may be varied and non-specific, an understand- mon than clinically significant disease.
ing of their characteristic manifestations in the chest may In general, collagen vascular diseases affect the lung
allow the radiologist to suggest a diagnosis in often com- less frequently in children than in adults. However, pedi-
plex cases. Systemic diseases that have either a primary atric patients with this diverse group of collagen vascular
or a secondary component of thoracic manifestations in diseases may have various lung abnormalities, including
pediatric patients include collagen vascular diseases, im- nonspecific interstitial pneumonitis (NSIP), pulmonary
munodeficiencies, lysosomal storage disease, systemic lymphoid hyperplasia, organizing pneumonia, hemor-
granulomatous disorders, vasculitis, and miscellaneous rhage, bronchiolitis, and bronchiectasis [2]. Ultimately
conditions such as cystic fibrosis, sickle cell disease, pulmonary fibrosis and subsequent pulmonary hyperten-
Langerhans cell histiocytosis, and tuberous sclerosis. It is sion, which can be a complication of pulmonary involve-
important to recognize that systemic diseases may have ment by collagen vascular diseases, may develop (Fig. 1).
secondary effects that affect the chest. Abnormal host de- On imaging studies such as chest radiograph and CT,
fenses result in increased infectious complications. Ab- these abnormalities can be suggestive of pulmonary nod-
normal esophageal motility may result in aspiration. Flu- ules, diffuse ground glass opacities, and diffuse alveolar
id overload due to treatment may result in pulmonary parenchymal opacities. Pleural effusion and pericardial
edema. In many cases, these nonspecific findings are effusion are also frequently present in pediatric patients
more common than the changes that are characteristic of with underlying collagen vascular diseases [1, 3, 4].
a specific disease. The overarching goal of this chapter is
to review the typical clinical presentation as well as the
characteristic thoracic and extrathoracic imaging mani-
festations of important systemic diseases in the pediatric
population.
Spectrum of Thoracic Manifestations of Pediatric

Systemic Diseases
Collagen Vascular Diseases

The collagen vascular diseases are a subgroup of autoim-
mune connective tissue disorders, all of which have un-
derlying inflammation or fragility of the connective tis-
sues. The four most commonly encountered collagen vas-
cular diseases in the pediatric population are juvenile Fig. 1. A 13-year-old girl with juvenile idiopathic arthritis. Axial
idiopathic arthritis (JIA, previously referred to as juvenile lung window computer tomography (CT) shows bronchiectasis in
rheumatoid arthritis), juvenile systemic sclerosis, juve- the posterior lower lobes. Right pleural effusion is also seen

Thoracic Manifestations of Pediatric Systemic Diseases 47
Predominantly Antibody Deficiencies

The predominantly antibody deficiencies are character-
ized by a decreased ability to produce immunoglobulins
from B-cells. The predominantly antibody deficiencies
predispose affected patients to recurrent respiratory tract
infection with encapsulated bacteria such as Streptococ-
cus and Haemophilus influenzae. Recurrent infections
from these organisms can lead to permanent lung damage
such as irreversible bronchiectasis. The four most com-
monly encountered predominantly antibody deficiencies
are IgA deficiency, X-linked agammaglobulinemia, com-
mon variable immunodeficiency disorder (CVID), and
hyper-IgM syndrome.
Fig. 2. A 15-year-old girl with a known diagnosis of systemic lupus In children with IgA deficiency, which is the most
erythematosus who presented with shortness of breath, desatura- common primary immunodeficiency syndrome, pyogenic
tion, and decreased hematocrit. Axial lung window CT shows multi-
focal airspace opacifications compatible with pulmonary hemor-
sinopulmonary infections are the most frequent finding
rhage. A subsequently performed bronchoalveolar lavage con- [7]. X-linked agammaglobulinemia most often results
firmed the diagnosis from a mutation in the X-linked gene encoding Bruton
tyrosine kinase (Fig. 3). Following recurrent pulmonary
infections from Streptococcus, H. influenzae, and My-
Some specific lung abnormalities are associated with coplasma, bronchiectasis in the lower lobes is often seen.
a specific collagen vascular disease. For example, lipoid Diminutive adenoid tissue on the lateral airway radio-
pneumonia, caused by deposition of cholesterol granulo- graph can be helpful clue for diagnosing X-linked
mas in the interstitium and alveoli, is associated with agammaglobulinemia in affected children. CVID is de-
JIA, which may be related to an underlying macrophage scribed as variable because of the different clinical
activation syndrome that is often present in JIA [5]. courses of different patients, rather than to changing
Alveolar hemorrhage, which is more common in children manifestations over time in a single patient. CVID is
than in adults, may present in pediatric patients with SLE caused by the failed terminal differentiation of B-cells to
and decreased hematocrit level (Fig. 2). The early and ac- plasma cells, resulting in hypogammaglobulinemia. Ap-
curate diagnosis of alveolar hemorrhage in SLE patients proximately 75% of affected patients develop a lung dis-
is essential because it can be potentially treated success- ease characterized by bronchiectasis, bronchial wall
fully with steroids and cytotoxic agents. Furthermore, thickening, and endobronchial mucus plugging closely
shrinking lung syndrome, which describes a progres- resembling cystic fibrosis [8] (Fig. 4). Splenomegaly is
sive decrease in lung volumes and is sometimes seen in seen in approximately 25% of patients with CVID [7]. Af-
patients with SLE, can be detected on imaging studies fected patients also have an increased risk for developing
when there is a progressive elevation of the diaphragm
despite attempted full inspiration [6]. Although the un-
derlying etiology of shrinking lung syndrome is not
known, a combination of pleural restriction due to recur-
rent pleural inflammation and pulmonary fibrosis, and
weakness of the diaphragm and chest wall musculature
may be responsible.
Immunodeficiencies
Defects in one or more of the essential components of the
immune system can result in an increased risk of devel-
oping thoracic abnormalities in pediatric patients [3].
When assessing the chest of children with an immuno-
deficiency, the radiologists role includes: (1) detecting
characteristic imaging features of a specific immuno-
deficiency, (2) evaluating infections, and (3) detecting
malignancies that can occur as a complication of certain
immunodeficiencies. Because of the large number of im-
munodeficiencies, only the disorders that are the most Fig. 3. A 3-year-old boy with X-linked agammaglobulinemia. En-
common or have the most characteristic thoracic mani- hanced coronal reformatted CT shows multi-focal pneumonia from
festations are discussed in the following. Streptococcus infection
48 E.Y. Lee, A.S. Brody
infections from the same pathogens that afflict those with

antibody deficiencies. In addition, opportunistic infec-
tions from Mycobacteria, viruses, Pneumocystis, and oth-
er fungi can occur [11]. The two most common combined
T-cell and B-cell immunodeficiencies are severe com-
bined immunodeficiency (SCID) and combined immuno-
deficiency (CID).
In patients with SCID, the most severe form of the pri-
mary immunodeficiencies, recurrent, persistent, or op-
portunistic respiratory infections along with thrush, der-
matitis, chronic diarrhea, or failure to thrive begin in ear-
ly infancy. Without hematopoietic stem cell transplanta-
tion, gene therapy or enzyme replacement therapy, the
disease is almost always fatal in the first two years of life
Fig. 4. A 16-year-old boy with common variable immunodeficien- [12]. In patients with CID, particularly with signal trans-
cy disorder. Axial lung window CT shows bronchial wall thicken-
ing and bronchiectasis closely resembling cystic fibrosis ducer and activator of transcription 5B (STAT5b) defi-
ciency, the chronic lung disease in the form of lympho-
cytic interstitial pneumonitis can result in death from res-
piratory failure [13].
autoimmune cytopenia, lymphoproliferative disease,
lymphoma, and gastric cancer. In addition, patients with Well-Defined Syndromes Associated with Immunodeficiency
CVID may develop granulomatous lymphocytic-intersti-
tial lung disease (GLILD). On imaging studies, GLILD is The five most common well-defined syndromes associ-
characterized by a non-caseating granulomatous and lym- ated with immunodeficiency in the pediatric population
phoproliferative histologic pattern often seen as pul- are: (1) DiGeorge syndrome, (2) Wiscott-Aldrich syn-
monary nodules, consolidation, and ground-glass or drome, (3) hyper-IgE syndrome, (4) dyskeratosis con-
reticular opacities [9] (Fig. 5). Children affected with genita, and (5) ataxia-telangiectasia.
hyper-IgM syndrome may present with recurrent respira- DiGeorge syndrome, also known as a velocardiofacial
tory and gastrointestinal tract infections by encapsulated syndrome, is characterized by developmental malforma-
bacteria, viruses, fungi, and parasites [10]. An increased tion of the third and fourth pharyngeal pouches. This
risk of developing Pneumocystis jirovecii pneumonia leads to distinctive facial features (hypertelorism, saddle
(PCP) and hepatocellular carcinoma has been also re- nose, short philtrum, low-set ears, cleft palate),
ported in patients with hyper-IgM syndrome. conotruncal malformations (including tetralogy of Fal-
lot, interrupted aortic arch, or truncus arteriosus), thymic
Combined T-cell and B-cell Immunodeficiencies hypoplasia, and parathyroid hypoplasia [14]. Typical tho-
racic imaging findings that may be present in pediatric
Pediatric patients with combined T-cell and B-cell im- patients with DiGeorge syndrome are a narrowed medi-
munodeficiencies are at increased risk of developing astinum related to a small thymus, an abnormal cardiac
silhouette related to a conotruncal malformation, and re-
current pulmonary infections. Large-airway abnormality,
such as tracheobronchomalacia, and osseous anomalies
involving the ribs or vertebrae may be also present. In
Wiscott-Aldrich syndrome, pulmonary infections with
encapsulated Streptococcus pneumoniae and Pneumo-
cystis are often seen [15]. In patients with hyper-IgE
syndrome, recurrent pneumonia, lymphadenopathy,
post-infectious pneumatoceles, and bronchiectasis are
typically features on imaging studies. In addition, some
patients have osseous findings, including osteoporosis,
fractures, and scoliosis [16]. Children with dyskeratosis
congenita, which is a progressive multisystemic disor-
der, characteristically present with rapidly progressing
pulmonary fibrosis after hematopoietic stem cell trans-
plantation [17] (Fig. 6). Ataxia-telangiectasia is due to
Fig. 5. A 17-year old girl with common variable immunodeficiency
underlying autosomal recessive mutations in the ATM
disorder. Axial lung window CT shows nodules as well as ground- gene, which encodes a DNA damage response protein.
glass and subtle reticular opacities in both lungs, compatible with Affected pediatric patients are highly susceptible to DNA
granulomatous lymphocytic-interstitial lung disease (GLILD) damage from ionizing radiation and the subsequent
Fig. 6. A 15-year-old girl with dyskeratosis congenital status post

hematopoietic stem cell transplantation. Axial lung window CT
shows fibrotic lung changes in the peripheral portion of the lungs
Fig. 8. A 14-year-old girl with chronic granulomatous disease. En-
hanced axial CT shows a large lung abscess (arrow) from S. aureus
infection. Also note the esophageal thickening due to chronic in-
development of cancer, including lymphoma, leukemia, fective esophagitis
and leiomyosarcoma. Thus, in these patients, every effort
should be made to limit imaging using ionizing radia-
tion. Characteristic thoracic imaging findings include a scess formation from catalase-positive S. aureus, fungi,
small thymus, recurrent pneumonia (from S. aureus, H. or atypical mycobacteria (Fig. 8). Although CGD can af-
influenzae, and S. pneumoniae), bronchiectasis, and lym- fect any organs, the lungs are the most common location
phadenopathy [18] (Fig. 7). In addition, a chronic inter- of infection [19]. Depending on the infectious organism
stitial lung disease unique to ataxia-telangiectasia (AT- and disease chronicity, nodules, ground-glass opacities,
ILD) may occur. On imaging studies it is characterized consolidation, septal thickening, and cysts can be seen in
by pulmonary fibrosis presenting as interstitial and the early phase. Later, recurrent and long-standing lung
pleural thickening. infections can lead to permanent damage, such as pul-
monary fibrosis, honey-combing, and pulmonary hyper-
Congenital Defects of Phagocyte Number and/or Function tension. Extrapulmonary thoracic manifestations include
suppurative lymphadenopathy, pleuritis, empyema, and
The most commonly encountered immunodeficiency rib or vertebral osteomyelitis.
syndrome related to congenital defects of phagocytes in
children is chronic granulomatous disease (CGD). Af- Acquired Immunodeficiency
fected children typically present with granuloma and ab-
The two most commonly encountered acquired immuno-
deficiencies in the pediatric population are human im-
munodeficiency syndrome (HIV) and neutropenia due to
chemotherapy for cancer or allogeneic hematopoietic
stem cell transplantation. The lungs are the organ most
commonly affected by infections in children with ac-
quired immunodeficiency.
Many bacterial and viral infections have diverse non-
specific radiographic appearances in children with HIV.
Pulmonary infection with PCP has more characteristic
imaging findings; these include bilateral diffuse or
patchy ground-glass or reticulonodular opacities with
perihilar to peripheral progression [20]. In addition, pul-
monary cysts, which can rupture and result in pneumo-
thorax or pneumomediastinum, may also present on imag-
ing studies in children with HIV. Lymphocytic interstitial
Fig. 7. An 11-year-old girl with ataxia-telangiectasis who under- pneumonitis (LIP) is a form of pulmonary lymphoid hy-
went MRI of the lungs due to increased susceptibility to DNA
damage from ionizing radiation associated with CT. Axial MRI
perplasia classically present in HIV-infected children old-
shows multiple nodular and airspace opacities from histoplasmosis er than 2 years of age. The imaging appearance of LIP in-
infection. The patient also later developed lymphoma (not shown) cludes nodules in a subpleural, septal centrilobular, or
Fig. 9. An 18-year-old girl with lymphocytic interstitial pneumoni-

tis. Axial lung window CT shows numerous small nodules and
ground-glass opacities in both lungs
peribronchial distribution, and ground-glass opacities

with or without lymphadenopathy [21] (Fig. 9). Other in-
trathoracic processes, such as thymic cysts and non-
Hodgkin lymphoma, may occur in children with HIV in-
Fig. 11. A 10-year-old girl with aspergillus infection. Axial lung
fections. window CT shows a circumferential area of lucency (air-crescent
In patients with acquired neutropenia, the characteristic sign) within a nodular opacity (arrow) due to an underlying fun-
imaging findings of the halo sign and the air-crescent gal ball
sign can help radiologists make an early and accurate di-
agnosis. The halo sign consists of a ground-glass halo of
alveolar hemorrhage around a nodular or consolidative fo- ciency, particularly following allogeneic hematopoietic
cus of infarcting lung from fungal vascular invasion and stem-cell transplantation, are susceptible not only to op-
thrombosis; it strongly suggests invasive fungal disease portunistic pulmonary infections, but also to noninfectious
(Fig. 10). An air-crescent sign presents as a crescent- pulmonary disorders including pulmonary edema, alveolar
shaped or circumferential area of radiolucency within a hemorrhage, drug reaction, bronchiolitis obliterans, graft-
parenchymal consolidation or nodular opacity, and strong- versus-host disease, and lymphoproliferative disease.
ly suggests an underlying fungal ball (Fig. 11). It impor-
tant to recognize that children with acquired immunodefi- Lysosomal Storage Diseases
Lysosomal storage diseases (LSDs) result from the ab-
sence or dysfunction of a lysosomal enzyme, with subse-
quent accumulation of the lipid, glycol-protein, or mu-
copolysaccharide substrate. The three most commonly
encountered LSDs in the pediatric population are Gauch-
er disease, Niemann-Pick disease, and mucopolysaccha-
ridosis.
Gaucher disease, the most common LSD, is due to a
congenital defect involving -glucocerebrosidase. It re-
sults in the accumulation of glucocerebroside-laden
macrophages in various organ systems, particularly the
liver (hepatomegaly), spleen (splenomegaly and splenic
infarcts), and bone marrow (osteonecrosis, endosteal
scalloping, and Erlenmyer-flask deformities). Lung in-
volvement is rare (~2%) but, when present, small nod-
ules, ground-glass opacities, and septal thickening can be
seen [22]. Niemann-Pick disease is due to the deficiency
Fig. 10. A 14-year-old boy with leukemia. Axial lung window CT
of sphingomyelinase, which results in the accumulation
shows a round nodular opacity (arrow) surrounded by ground-glass of foamy macrophages. Lung involvement as seen on
opacity (halo sign) from invasive aspergillus infection imaging studies is characterized by diffuse interstitial
Fig. 12. A 5-year-old girl with Niemann-Pick disease. Axial lung

window CT shows diffuse septal thickening in both lungs
thickening due to lipid-laden macrophages infiltrating

the pulmonary interstitium [23] (Fig. 12). A crazy- Fig. 13. A 16-year-old girl with Crohns disease who presented with
paving appearance, which refers to the appearance of progressively worsening shortness of breath. Axial lung window
ground-glass opacities with superimposed interlobular CT shows bronchiectatic areas associated with ground glass and
septal thickening and intralobular reticular thickening, consolidative opacities
can be seen on the CT scans of patients affected with the
type C2 form. The mucopolysaccharidoses (MPS) result ground-glass opacities and consolidation are often seen
from the accumulation of glycosaminoglycans in multi- [1, 25]. In patients with stage 4 disease, pulmonary fi-
organ systems. Affected children typically present with brosis characterized by underlying architectural distor-
upper- and lower-airway obstruction, restrictive pul- tion, septal thickening, traction bronchiectasis, and hon-
monary disease, and respiratory tract infections. Large- eycombing are the predominant findings [1, 3, 25]. Al-
airway involvement in MPS reflects excessive gly- though much less frequent than intestinal manifesta-
cosaminoglycan deposition in the airway walls, which tions, abnormalities involving the lung parenchyma
may result in tracheobronchomalacia, airway-wall defor- (eosinophilic pneumonia, organizing pneumonia, gran-
mity, and airway luminal narrowing. Underlying con- ulomatous pneumonitis, interstitial pneumonitis), the
comitant skeletal dysplasia limiting chest wall motion small airways (bronchiolitis obliterans), and the large
and hepatosplenomegaly limiting diaphragmatic motion central airways (chronic bronchitis and bronchiectasis)
can cause extrinsic restrictive lung disease in affected may be seen in pediatric patients with Crohns disease
children [24]. [26] (Fig. 13).
Systemic Granulomatous Disorders Vasculitis

Two important systemic granulomatous disorders in pe- Vasculitis is an inflammatory disease of the blood vessel
diatric patients are sarcoidosis and Crohns disease [1, walls. According to the size of the vessel affected, vas-
3, 25]. Sarcoidosis is characterized by the presence of culitis can be classified as: 1) large-vessel disease, e.g.,
multiple small and well-circumscribed granulomas Takayasus arteritis, temporal arteritis, and polymyalgia
without necrosis that are typically located along lym- rheumatic; 2) medium-size vessel disease, e.g., Kawasa-
phatic pathways [25]. It is a systemic disease process of ki disease, polyarthritis nodosa, Buergers disease, and
unknown etiology with multisystem involvement. Pul- cutaneous vasculitis; and 3) small-vessel disease, e.g.,
monary involvement of sarcoidosis is traditionally clas- granulomatosis with polyangiitis, Henoch-Schonlein pur-
sified into four different stages of disease progression: pura, Behcets syndrome, and Churg-Strauss syndrome
(1) isolated lymphadenopathy, (2) lymphadenopathy [1, 3]. Among them, granulomatosis with polyangiitis,
with pulmonary disease, 3) isolated pulmonary disease, formerly known as Wegener granulomatosis, is the most
and 4) pulmonary fibrosis [1, 25]. The imaging findings common pediatric necrotizing systemic vasculitis with
of sarcoidosis mainly depend on the state of disease pro- thoracic manifestations and is thus the only one discussed
gression. In patients with stages 13 pulmonary sar- in this review [1, 3].
coidosis, small peribronchial nodules (3 mm) and in- Granulomatosis with polyangiitis is a rare systemic
terstitial thickening intermixed with the areas of disorder that primarily affects the upper and lower respi-
Fig. 14. A 14-year-old boy with granulomatosis with polyangiitis Fig. 16. A 13-year-old boy with granulomatosis with polyangiitis
(Wagner granulomatosis). Axial lung window CT shows pul- who presented with neck pain and shortness of breath. Frontal 3D
monary nodules (arrows) volume-rendered image of the large airway shows a marked nar-
rowing (arrows) of the subglottic airway
ratory tract and the kidney. Typical thoracic manifesta- Miscellaneous Disorders
tions include multiple pulmonary nodules usually rang-
ing in size from 2 mm to several centimeters in diameter Cystic Fibrosis
[1, 3] (Fig. 14). Associated cavitation is seen in larger
pulmonary nodules (2 cm). Consolidation due to un- Cystic fibrosis (CF), the most common cause of pul-
derlying pulmonary hemorrhage and/or ischemic necro- monary insufficiency in childhood, is caused by a muta-
sis may also be present (Fig. 15). In addition, there may tion in the gene encoding the cystic fibrosis transmem-
be large-airway involvement, such as tracheobronchial brance regulator (CFTR) [1, 3]. CF typically affects chil-
wall thickening, tracheobronchial stenosis, or bronchiec- dren of European heritage, with an estimated incidence of
tasis [3] (Fig. 16). 1:2,500 live births. Affected individuals commonly pre-
sent with failure to thrive, meconium ileus syndrome,
malabsorption syndrome, or chronic respiratory infec-
tion. The diagnosis is currently most often made during
newborn screening. An abnormal sweat test or genetic
test can provide a definite diagnosis.
In children with early stage of CF, the thoracic mani-
festations include mild to moderate air trapping (hyper-
inflation) due to an underlying obstruction of the small
airways by abnormally viscid mucus and/or bronchial
wall thickening. Upper lobe predominant bronchiectasis,
peribronchial wall thickening, centrilobular nodular and
tree-in-bud opacities, and mucus plugging with air-trap-
ping are usually present in children with later or ad-
vanced CF [1, 3] (Fig. 17a). Because of the chronic and
recurrent superimposed lung infection, concomitant reac-
tive hilar and mediastinal lymphadenopathy as well as en-
larged bronchial arteries are also often present (Fig. 17b).
Although many patients with CF are evaluated by chest
radiograph, it is not sensitive enough to detect the early
Fig. 15. A 15-year-old girl with granulomatosis with polyangiitis
who presented with dyspnea and a decreased hematocrit. Axial
or subtle lung changes. Currently, high-resolution CT is
lung window CT shows multifocal airspace consolidations in both the most sensitive diagnostic imaging modality for as-
lungs, compatible with pulmonary hemorrhage sessing the morphologic changes of CF lung disease.
a b
Fig. 17 a, b. A 15-year-old girl with cystic fibrosis. a Coronal lung window CT shows extensive upper-lobe-predominant bronchiectatic
changes consistent with lung changes due to cystic fibrosis. b Coronal soft-tissue window CT shows extensive mucus plugging and en-
larged bronchial arteries from chronic infection
A previously published study showed that CT is more hemoglobin can result in anemia and bone marrow in-
sensitive than chest radiographs for detecting CF-related farction. Eventually, sickle cell disease leads to various
lung abnormalities, and that the CT score correlates well acute and chronic complications in multi-organ systems.
with the forced vital capacity (FVC), one-second forced Two main chest complications of sickle cell disease are
expiratory volume (FEV1) ratio on a pulmonary function acute chest syndrome (ACS) and pneumonia [1, 3]. The
test [27]. A major consideration in the imaging of CF pa- former refers to the clinical situation in which patients
tients is the higher risk posed by ionizing radiation expo- with sickle cell disease develop a new opacity on chest
sure. Therefore, in CF patients, MRI with advanced tech- radiographs accompanied by chest pain, fever, and respi-
niques including fast imaging sequences, high-resolution ratory syndrome [29] (Fig. 18). Possible underlying etio-
sequences, and hyperpolarized gas is being actively in- logies for ACS include infection, pulmonary infarction,
vestigated for evaluating CF lung disease [28]. In addi- and fat embolism from vaso-occlusive crises involving
tion to pulmonary disease, pancreatic disease is another the bone marrow. A lack of interval resolution of the pul-
primary abnormality in CF patients. monary opacities on the follow-up study should raise the
Although lung infections are treated with antibiotics, possibility of a superimposed infectious process such as
lung transplantation may be required for survival in pe- pneumonia. The two most common cardiovascular imag-
diatric patients with advanced CF. A broad range of ther- ing findings in pediatric patients with sickle cell disease
apies, including mucolytics and inhaled antibiotics, have are cardiomegaly and pulmonary vascular plethora relat-
improved both the life expectancy and the quality of life ed to chronic anemia. Abnormal osseous changes due to
in CF patients. New medications targeting the specific underlying bone infarction are also frequently present. In
defect in CFTR have recently become available, and the spine, recurrent bone infarction causes indentation of
gene therapy continues to be investigated as a potential the upper and lower vertebral endplates (H-shaped verte-
treatment. bral bodies). Humeral head sclerosis or fragmentation re-
lated to bone infarction can be observed on chest radio-
Sickle Cell Disease graphs. Hand-foot syndrome, which is characterized by a
painful swelling of the hands and feet, may occur in
Sickle cell disease is due to an abnormality in the oxygen- young infants and children. Pediatric patients with hand-
carrying hemoglobin molecule of red blood cells, such foot syndrome may also have soft-tissue swelling and pe-
that the cells have a propensity for to assume an abnor- riosteal new bone formation (Fig. 19). In addition, the
mal, sickle-like shape. Overproduction of abnormal spleen, the function of which is to clear red blood cells,
is almost always infarcted before the end of childhood in

affected patients. The functional asplenia can lead to an
increased susceptibility to infections caused by bacteria
with polysaccharide capsules.
Langerhans Cell Histiocytosis

Langerhans cell histiocytosis (LCH) is characterized by a
clonal proliferation and the subsequent infiltration of tis-
sues by Langerhans cells originating from the bone marrow
[3]. In the past, LCH was classified into eosinophilic gran-
uloma, Letterer-Siwe disease, and Hand-Schuller-Christian
disease. The current classification divides affected patients
into two groups: single-organ system involvement and
multisystem involvement. The latter is more frequently
seen in pediatric patients younger than 2 years old. Pul-
monary involvement by LCH can be seen in pediatric pa-
tients with either single-organ system (primary pulmonary
LCH) or multisystem disease. A recent study of 420 pedi-
atric patients with multisystem LCH reported that pul-
monary involvement was present at diagnosis in 24% of af-
Fig. 18. A 17-year-old boy with sickle cell disease who presented fected patients [30]. Pediatric patients with pulmonary
with chest pain, fever, and respiratory distress. Frontal chest radio- LCH typically present with nonspecific symptoms such as
graph shows new airspace opacities in the right lung and car- cough, dyspnea, tachypnea, and chest pain.
diomegaly, compatible with acute chest syndrome
Pulmonary manifestations of LCH can be categorized
into two stages: early and advanced [1, 3]. Randomly dis-
tributed reticular nodular opacities with or without cysts
are usually seen in patients with early-stage pulmonary
involvement by LCH. Cysts in affected patients can
sometimes rupture and result in spontaneous pneumo-
thorax (Fig. 20). In patients with advanced or long-stand-
ing disease, both pulmonary fibrosis characterized by ar-
eas of architectural distortion and cysts are present. LCH
involvement of other organ systems includes thymus (cal-
cification, cyst formation, and enlargement), liver (he-
patomegaly), and spleen (splenomegaly). Recognition of
the characteristic pulmonary manifestation of LCH in
conjunction with other organ system involvement can be
helpful in reaching an early diagnosis.
Fig. 19. An 8-month-old boy with sickle cell disease who presented
with pain and swelling involving the right foot. Frontal radiograph
of the right foot shows lytic bony changes associated with sclerot-
ic new bone formation involving the first and second metatarsals.
Soft-tissue swelling overlying the first metatarsal is also seen. The Fig. 20. A 17-year-old girl with Langerhans cell histiocytosis in-
constellation of imaging findings is compatible with hand-foot volving the lungs. Axial lung window CT shows randomly distrib-
syndrome in a sickle cell disease patient uted reticulonodular opacities and cysts in both lungs
Tuberous Sclerosis a
Tuberous sclerosis (TS) is a multisystem genetic disease

that results from a mutation of either of two genes, TSC1
and TSC2, which code for hamartin and tuberin, respec-
tively. These two proteins act as tumor growth suppressors
regulating cell proliferation and differentiation. Affected
patients typically present with the classic clinical triad of
mental retardation, seizures, and adenoma sebaceum.
Two characteristic pulmonary manifestations of TS are
lymphangioleiomyomatosis (LAM) and multifocal mi-
cronodular pneumocyte hyperplasia (MMPH) [1, 3].
Dyspnea or acute respiratory distress related to sponta-
neous pneumothorax is the usual clinical presentation in
a TS patient with lung involvement from LAM. On imag-
ing studies, multiple small cysts with thin or impercepti-
ble walls that are evenly distributed throughout the lungs
are seen in affected children with early-stage LAM (Fig.
21). These cysts are located within adjacent normal lung
parenchyma and usually do not coalesce. Concomitant
spontaneous pneumothorax or chylous effusions may al-
so present. Patients with late-stage LAM with extensive
cystic lung involvement eventually require lung trans- b
plantation for survival. In TS patients with MMPH, mul-
tiple, well-defined pulmonary nodules that may resemble
metastases can be seen on imaging studies. These repre-
sent proliferations of enlarged type II pneumocytes that
form ill-defined papillae and fill the alveolar spaces. Be-
cause the imaging findings of these pulmonary nodules
are non-specific, lung biopsy with pathological evalua-
tion may be required for a definitive diagnosis.
In addition to lung abnormalities, pediatric patients
with TS often present with characteristic findings indicat-
ing the involvement of other organ systems, such as giant
cell astrocytoma, cortical tubers, sub-ependymal nodu-
les of the brain (Fig. 22a), rhabdomyomas of the heart
(Fig. 22b), and angiomyolipomas of the kidneys and liver
(Fig. 22c). Recognition of the characteristic pulmonary
manifestation of TS in conjunction with other organ system c
involvement can be helpful in reaching an early diagnosis.
Fig. 22 a-c. A 5-day old boy with tuberous sclerosis. a Axial T1

FLAIR MRI shows cortical tubers. b Axial T2 MRI demonstrates
Fig. 21. A 15-year-old girl with tuberous sclerosis and lymphangio- a large cardiac rhabdomyoma (asterisk). c Longitudinal renal ul-
leiomyomatosis. Axial lung window CT shows multiple small thin- trasound shows echogenic renal lesion (arrow) consistent with re-
walled cysts distributed relatively evenly in both lungs nal angiomyolipoma
Conclusion 14. Demczuk S, Aurias A (1995) DiGeorge syndrome and related

syndromes associated with 22q11.2 deletions. A review. Ann
Genet 38:59-76.
With clear knowledge of the characteristic thoracic imag- 15. Notarangelo LD, Miao CH, Ochs HD (2008) Wiskott-Aldrich
ing features of systemic diseases, the radiologist may be syndrome. Curr Opin Hematol 15:30-36.
the first to suggest a particular diagnosis, which in turn 16. Chandesris MO, Melki I, Natividad A et al (2012) Autosomal
can lead to early and optimal pediatric patient care. dominant STAT3 deficiency and hyper-IgE syndrome: molec-
ular, cellular, and clinical features from a French National Sur-
vey. Medicine 91:e1-e19.
17. Giri N, Rees L, Faro A et al (2011) Lung transplantation for
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IDKD 2015-2018
Modern Diagnosis in the Evaluation of Pulmonary Vascular Disease

Alexander A. Bankier1, Christoph Engelke2
1 Department of Radiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
2 Department of Radiology, University of Goettingen, Goettingen, Germany
Introduction resolution, not only to detect subtle morphologic abnor-

malities but also to adequately visualize the thoracic ves-
Conventional chest radiography, computed tomography sels on CT angiography (CTA) and to differentiate be-
(CT), and, with restrictions, magnetic resonance imaging tween normal and abnormal vascular dimensions. How-
(MRI) are the three most commonly used imaging modal- ever, high spatial resolution is optimally employed when
ities for evaluating patients with suspected pulmonary short overall examination times and high temporal reso-
vascular disease. Very recently, the clinical usefulness of lution (i.e., short acquisition times of the individual axial
fluorodeoxyglucose positron emission tomography (FDG- image planes) are available simultaneously. This enables
PET) and FDG-PET/CT in the diagnosis of large-vessel the analysis of high-resolution images with a minimum of
vasculitis also has been recognized. However, in daily motion artifacts. The development of multidetector-row
general clinical routine, most patients with suspected pul- CT (MDCT) has allowed radiologists to image the entire
monary vascular disease will be evaluated by CT. More- thorax with increasing spatial resolution in shorter time
over, the utility of CT has been improved by technical de- intervals. Consequently, more patients are able to main-
velopments such as dual-source and dual-energy scanners, tain a breath-hold throughout the entire period of data ac-
which simultaneously generate morphological and func- quisition, which results in a substantial decrease in the
tional information from a sole dataset. In patients with number and frequency of respiratory motion artifacts.
pulmonary vascular diseases, this approach is of major in- Furthermore, shorter CT rotation times have enabled
terest for three main reasons: (1) Pulmonary vascular dis- shorter acquisition times and thus contributed to the sub-
orders require a thorough morphological evaluation, not stantial reduction in artifacts caused by cardiac motion.
only of the vascular tree per se, but also of the surround- In the past, cardiac motion artifacts not only reduced the
ing lung parenchyma; (2) given that we have reached an quality of images obtained close to the heart but also
upper limit in terms of morphologic image resolution, but caused pulsation artifacts at the anatomical level of the
can simultaneously obtain functional information, CT ide- systemic and pulmonary vessels, thus mimicking en-
ally combines high-end morphologic imaging with perfu- dovascular abnormalities such as thrombi and neoplastic
sion and ventilation imaging; and (3) it is becoming in- lesions. To image patients with the highest temporal res-
creasingly important to determine the cardiac conse- olution and shortest examination time possible requires
quences or causes of pulmonary vascular diseases, which the shortest rotation time and the highest pitch, defined
requires all of the advantages that CT can provide. For as the table feed per rotation divided by the nominal
these reasons, and because of the general importance of beam width at the isocenter of the scanner. For example,
CT, it is the focus of this chapter. Other imaging modali- on a 64-slice MDCT using a single X-ray source, rotation
ties are not ignored; rather, they are discussed in case- times range from 0.30 and 0.40 s, resulting in a temporal
based presentations and in their distinct clinical contexts. resolution per image not better than half the rotation time,
and with pitch values usually not exceeding 1.5 [1]. The
introduction of dual-source 64-slice MDCT has improved
Optimized Evaluation of Pulmonary Vessels on Chest the technical requirements for CT. When both available
CT Examinations tubes are operated at the same kilovoltage, the temporal
resolution of each image is 1/4 of the rotation time, each
Temporal Resolution of Pulmonary CT Angiograms of the two detectors contributing 90 of data in parallel-
ray geometry to each image plane [2]. Moreover, the sec-
Given the anatomical complexity of the lungs, a crucial ond measurement system of dual-source CT (DSCT) al-
prerequisite for optimal chest imaging is a high spatial lows for a higher pitch mode than available with a single-

58 A.A. Bankier, C. Engelke
a b c
Fig. 1 a-c. Acute pulmonary embolism. Transverse contrast-enhanced CT section (a) allows the diagnosis of a large intraluminal clot (arrow).
Multiplanar reconstructions in the sagittal (b) and coronal (c) planes show the true sagittal and coronal extent of the clot (arrows)
source CT, but without image distortion inside the field to improve the visualization of small pulmonary arteries
of view of the second detector. Tacelli et al. showed that at 80 kV(p) [9].
this scanning mode yields CTA examinations of excellent
quality for thoracic applications in routine clinical prac-
tice, including in patients in pulmonary vascular diseases Perfusion Imaging with Dual-Energy CT
such as acute pulmonary embolism (PE) (Fig. 1) [3].
Lung perfusion with dual-energy CT does not reflect
Improved Morphological Evaluation of the Peripheral blood flow analysis per se, as it provides a measurement
Pulmonary Vasculature at only one time point; rather, it yields an iodine map of
the lung microcirculation at a particular time point. Nu-
With the introduction of MDCT, CTA is now recognized merous parameters are known to influence the distribu-
as the reference standard for diagnosing acute PE [4]. A tion of iodine within pulmonary capillaries; some are
main advantage of MDCT over single-slice CT is the technique-related whereas others are due to the anatomi-
ability to scan the entire volume of the thorax with sub- cal and/or physiological circumstances under which the
millimetric collimation in a very short period of time, data were acquired. Dual-energy CTA is performed using
most often under the duration of a single breath-hold. a scanning protocol similar to the one used in clinical
This is particularly useful when evaluating dyspneic pa- practice. The acquisitions proceed from the top to the bot-
tients. These technological advances have improved both tom of the chest, with an injection protocol similar to that
evaluations of the peripheral pulmonary arteries and the of standard CTA obtained with a single energy on a 64-
accuracy of CT in the workup of acute PE. Simultane- slice scanner. Two categories of images can be recon-
ously, MDCT allows radiologists to scan patients at a structed: Diagnostic scans correspond to contiguous
low kilovoltage, with reductions in the dose of contrast 1-mm-thick transverse CT scans generated from the raw
material and the overall radiation dose. This is of partic- spiral projection data of tube A and tube B (60% from the
ular importance in young female patients who may be acquisition by tube A; 40% from the acquisition by tube
exposed to substantial levels of radiation to breast tissue. B). Lung perfusion scans (i.e., images of the perfused
In the context of acute PE, the latter concern is clinical- blood volume of the lung parenchyma) are generated af-
ly relevant given the lower prevalence of acute PE, which ter determination of the iodine content of every voxel of
has dropped from 33% on angiographic studies to 20% the lung parenchyma on the separate 80- and 140-kVp
on CT/MDCT scans. To date, several studies have inves- images. The images can be rendered in gray-scale or color-
tigated the clinical benefits of low-kilovoltage tech- coded. All images can be displayed as transverse scans,
niques, i.e., 80100 kV(p) vs. 120140 kV(p), the para- complemented as needed by corona land sagittal refor-
meters at which CTA is typically performed. However, mats. Even though a dual-energy acquisition does not
for obvious ethical reasons, these studies were based on correspond to true perfusion imaging, several applica-
the comparative analysis of different populations tions of this pulmonary micro-CTA technique have been
scanned with single-source CT [5-8]. The limitations of investigated [10].
these comparisons include the lack of systematic ad-
justment for individual patient morphology, cardiac he- Acute Pulmonary Embolism
modynamics, and potential underlying respiratory dis-
ease. With the introduction of DSCT, the two tubes can Dual-energy CT can detect endoluminal clots on aver-
be set at different kilovoltages. In addition to the op- aged images obtained with tubes A and B as reliably as
portunity to evaluate lung perfusion, there are benefits can single-source CTA [11]. In a preliminary study, the
for standard CTA as this scanning mode has been shown detectability of perfusion defects beyond obstructive
Modern Diagnosis in the Evaluation of Pulmonary Vascular Disease 59
clots was validated. Perfusion defects in the adjacent Obstructive Airways Diseases
lung parenchyma have the typical perfusion-territorial
triangular shape well known from pulmonary angio- Abnormalities of pulmonary perfusion are a feature of
graphic, scintigraphic, and MRI perfusion studies. Dual- numerous smoking-related respiratory diseases. Peinado
energy CTA can help predict perfusion defects without et al. showed that endothelial dysfunction of the pul-
directly identifying peripheral endoluminal clots that monary arteries is present even in patients with mild
may be located in subsegmental or more distal pul- chronic obstructive pulmonary disease (COPD) [13]. In
monary arterial branches. It can also help differentiate these patients, as well as in smokers with normal lung
lung infarction from less specific peripheral lung con- function, some arteries show a thickened intima, sug-
solidation. gesting that tobacco consumption plays an important role
in the pathogenesis of pulmonary vascular pathologies in
Chronic Pulmonary Embolism COPD. Several structural changes in the early stages of
COPD have been described in experimental and animal
Dual-energy CTA can depict perfusion defects distal to models, including proliferation of smooth-muscle fibers
chronic clots (Fig. 2). Three vascular characteristics of within peribronchiolar arterioles and collagen and elastin
chronic PE may manifest on dual-energy CT imaging. deposition in the thickened intima of vessels [14, 15]. In
First, chronic PE causes a mosaic pattern of lung attenu- preliminary studies, Hoffman et al. [16] showed an in-
ation, characterized by areas of ground-glass attenuation, creased heterogeneity of the local mean transit times of
with enlarged vascular segments intermingled with areas contrast material within the pulmonary microvasculature
of normal lung attenuation and smaller vascular seg- of smokers with normal pulmonary function tests. In
ments. When present, these findings are suggestive of their dual-source, dual-energy CTA study of pulmonary
blood flow redistribution, but they are not consistently lobar perfusion in COPD patients, Pansini et al. [17]
seen on conventional CT in patients with chronic PE. In found that nonsmokers had no alterations in lung struc-
these patients, dual-energy CT can detect ground-glass ture and observed a uniform distribution of iodine con-
attenuation of vascular origin based on the high iodine tent within the upper and lower lobes and between the
content within the areas of ground-glass attenuation, thus right and left lungs. Perfusion scans showed significantly
enabling their distinction from ground-glass attenuation lower iodine content within the lung microcirculation of
secondary to bronchial or alveolar diseases [12]. Second, the upper lobes in emphysematous patients than in smok-
chronic PE can cause calcifications within partially or ers without emphysema and a significantly lower perfu-
completely occlusive chronic clots as well as within pulsion in the upper than in the lower lung zones, consistent
monary artery walls, when chronic PE is complicated by with the destruction of the lung parenchyma. These struc-
longstanding or severe pulmonary hypertension. The cal- tural abnormalities have important implications given the
cifications are detectable using virtual non-contrast epidemiologic and socioeconomic burden of COPD.
imaging, accessible by dual-energy CT imaging. Third,
the images generated at 80 kV can improve visualization Restrictive Airways Diseases
of the systemic collateral supply characteristic of chron-
ic PE and originating from bronchial and non-bronchial The substantial importance of pulmonary hypertension
systemic arteries. on the clinical course and prognosis of patients with
a b c
Fig. 2 a-c. Chronic thromboembolic disease. Transverse CT section (a) shows a web in the pulmonary artery of the right lower lobe (arrow),
which is confirmed (arrow) by a coronal multiplanar reconstruction (b). Lung window (c) shows a dilated main pulmonary artery (black
arrows), dilated peripheral pulmonary artery (white arrow), and parenchymal areas of hypoperfusion (open arrows)
fibrotic lung disease has been extensively recognized. hold duration [21], (2) a two-phase protocol to scan both
However, the mere measurement of pulmonary artery di- the entire thorax and cardiac cavities with the highest
ameters might not be a reliable parameter in the assess- spatial resolution [22], and (3) a dedicated cardiac MD-
ment of disease severity, due to the potentially confound- CT protocol to assess right ventricular function and myo-
ing role of parenchymal traction on central and peripher- cardial mass [23]. In a comparison of ECG-gated 16-slice
al pulmonary vessels. Moreover, because of the age of the MDCT with equilibrium radionuclide ventriculography,
population in which these diseases usually occur, age- these studies confirmed both the feasibility of the former
related changes have to be taken into account in morpho- in a population of hemodynamically stable patients and
metric-based clinical decision-making and disease classi- the accuracy of the CT-estimated right ventricular ejec-
fication. Overall, and despite promising initial scientific tion fraction. The introduction of 64-slice scanners also
evidence, the roles of MDCT and DSCT in assessing pa- offered further improvement in the integration of mor-
tients with fibrotic lung diseases still need to be deter- phology and cardiac function. Salem et al. reported that
mined. The many ongoing pharmacological trials, notably right and left ventricular function was assessable in 93%
in patients with usual interstitial pneumonits, may proof their study patients with various respiratory disorders;
vide an ample study ground in this field. in the remaining patients, an imprecise segmentation of
the right and left ventricular cavities was the limiting fac-
tor for precise calculation of end-systolic and end-dias-
Are There Indications for ECG-Gated CTA Examinations tolic ventricular volumes [24]. The positive results were
When Exploring Pulmonary Vascular Diseases? achievable with dose length-product (DLP) values lower
than those recommended for standard non-ECG-gated
Pulmonary Hypertension examinations. This was possible because of the concur-
rent use of two-dose modulation systems, in particular,
Although a pulmonary trunk diameter 33.2 mm has the adjustment of the milliampere setting for patient size
95% sensitivity for the diagnosis of pulmonary hyperten- and anatomical shape and an ECG-controlled tube cur-
sion (PHT), the specificity of this measurement is only rent.
58%, which is insufficient for the accurate diagnosis of Overall, there is increased evidence and awareness in
PHT, notably in patients with mild disease [18]. More- the radiological community that new scanner technology
over, no correlation has been found between the degree has opened up new opportunities for imaging the car-
of PHT and pulmonary trunk diameter. Electrocardio- diopulmonary system [25, 26]. The techniques have also
graph (ECG)-gated MDCT acquisitions of the entire tho- received increased attention in the field of translational
rax enable the evaluation of novel functional parameters research [27].
in addition to the standard morphology. In patients with
PHT, right pulmonary artery distensibility was recently
shown to be an accurate predictor of PHT on ECG-gated Imaging of Pulmonary Vasculitis
64-slice MDCT scans of the chest [19]. In that study, its
diagnostic value was superior to that of the single mea- Systemic primary vasculitides are idiopathic diseases that
surement of pulmonary trunk diameter. cause an inflammatory injury to the vessel walls. Pul-
monary involvement is frequent, and chest-CT often in
Right Ventricular Function combination with PET/CT is the reference imaging tech-
nique in its assessment. Pulmonary vasculitis occurs in a
Fast rotation speed and dedicated cardiac reconstruction wide variety of systemic and pulmonary vascular disor-
algorithms designed to extend the conventional multislice ders. Most vasculitic entities affecting the lung induce
acquisition data scheme have opened up new opportuni- overlapping disease patterns such as pneumonitis with or
ties for cardiac and thoracic imaging applications. The without capillaritis, diffuse alveolar damage, and acute
first method for ECG-gated examinations of the entire pulmonary hemorrhage, or inflammatory obstruction of
thorax was introduced by Flohr et al., using 4-slice MD- the central pulmonary arteries down to the small vessels,
CT technology [20]. This approach provided greater with chronic secondary pulmonary hypertension with or
anatomical coverage than achieved with standard ECG- without interstitial lung disease. Therefore the clinical
gated spiral scanning. When used with reconstruction ap- symptoms per se or the CT-morphology alone are often
proaches for cardiac applications, precise morphologic nonspecific.
data at the level of the larger mediastinal vessels can be Owing to their complimentary value in the imaging of
obtained. Despite this improvement, major progress in central and peripheral vascular territories and their sec-
fast-scanning multislice CT technology came with the in- ondary parenchymal or interstitial abnormalities, CTA,
troduction of 16-slice MDCT, which allowed the integra- high-resolution CT, and fusion imaging play key roles in
tion of cardiac functional information. Three approaches the noninvasive workup of patients with suspected pul-
were proposed: (1) investigating cardiac global function monary vasculitis. They can indicate the need for further
during a whole-chest multislice CT acquisition with a clinical tests, imaging, or invasive diagnostics and direct
16-1.5-mm collimation to ensure an acceptable breath- medical treatment during follow-up.
Modern Diagnosis in the Evaluation of Pulmonary Vascular Disease 61
The Role of CT in the Differential Diagnosis of Pulmonary monary embolism: improvement of vascular enhancement
Vasculitis with low kilovoltage settings. Radiology 241:899-907.
8. Heyer CM, Mohr PS, Lemburg SP et al (2007) Image quality
and radiation exposure at pulmonary CT angiography with
In large-vessel vasculitis, CT is the method of choice, of- 100- or 120-kVp protocol: prospective randomized study. Ra-
ten in combination with PET, to discriminate macrospcop- diology 245:577-583.
ic vascular abnormalities presenting key pathological fea- 9. Gorgos AB, Remy-Jardin M, Duhamel A et al (2009) Evalua-
tures, such as pulmonary arterial wall thickening with late tion of peripheral pulmonary arteries at 80 kV and at 140 kV:
enhancement, steno-occlusive or thrombo-obliterating dis- dual-energy computed tomography assessment in 51 patients.J
Comput Assist Tomogr 33:981-986.
ease with resulting oligemia, infarction in the dependent 10. Remy-Jardin M, Faivre JB, Pontana F et al (2010) Thoracic ap-
lung, or arterial aneurysms, as a facultative cause of mas- plications of dual energy. Radiol Clin North Amer 48:193-205.
sive pulmonary hemorrhage. CT is the modality of choice 11. Pontana F, Faivre JB, Remy-Jardin M et al (2008) Lung perfu-
to demonstrate the effects of peripheral small-vessel pulsion with dual-energy multidetector-row CT (MDCT): Feasi-
monary vasculitis on the central pulmonary arteries, such bilityfor the evaluation of acute pulmonary embolism in 117
consecutive patients. Acad Radiol 15:1494-1504.
as secondary chronic pulmonary hypertension due to re- 12. Pontana F, Remy-Jardin M, Duhamel A et al (2010) Lung per-
duction of the total cross-sectional area with arteriolar re- fusion with dual energy multidetector-row CT: can it help rec-
modeling or narrowing of the capillary bed in capillaritis. ognize ground glass opacities of vascular origin? Acad Radiol
Because CT-determined pathologies of the lung 17:587-594.
parenchyma, vessels, and airways are highly variable, di- 13. Peinado VI, Barber JA, Ramirez J et al (1988) Endothelial
dysfunction in pulmonary arteries of patients with mild COPD.
agnosis is a challenging interdisciplinary task. Clinical Am J Physiol 274:L908-L913.
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15. Santos S, Peinado VI, Ramirez J et al (2002) Characterization
features. CT-pathologic correlates of the peribronchovas- of pulmonary vascular remodelling in smokers and patients
cular axial interstitium, pulmonary hemorrhage, types of with mild COPD. Eur Respir J 19:632-638.
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pathologies such as organizing pneumonia, should be con- functional assessment of the lung via multidetector-row com-
sidered with reference to the revised 2012 International puted tomography. Proc Am Thorac Soc 3:519-534.
17. Pansini V, Remy-Jardin M, Faivre JB et al (2009) Assessment
Chapel Hill Consensus Conference on Pulmonary Vas- of lobar pulmonary perfusion in COPD patients: preliminary
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19:2834-2843.
Acknowledgment. We thank Prof. Martine Remy-Jardin, 18. Edwards PD, Bull RK, Coulden R (1998) CT measurement of
main pulmonary artery diameter. Br J Radiol 71:1018-1020.
Lille, France, for her previous work in this field, which 19. Revel MP, Faivre JB, Remy-Jardin M et al (2009) Pulmonary
served as an inspiration and blueprint for this contribu- hypertension: ECG-gated 64-section CT angiographic evalua-
tion. tion of new functional parameters as diagnostic criteria. Radio-
logy 250:558-566.
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IDKD 2015-2018
Imaging of Pulmonary Infections

Philip Goodman1, Helmut Prosch2, Christian J. Herold2
1 Duke University Medical Center, Durham, NC, USA
2 Department of Radiology, Vienna General Hospital, Medical University of Vienna, Vienna, Austria
Introduction room. Most CAP patients are children (1535 of 1,000

children per year) and the elderly (3040 per 1,000 per-
Pulmonary infection is one of the most frequent caus- sons per year). The mode of transmission in CAP is usu-
es of morbidity and mortality throughout the world. ally person-to-person, via water or mucus droplets laden
Many infections occur in individuals with concomitant with viruses or bacteria. The most frequent pathogens
intrapulmonary or extrathoracic diseases; however, are gram-positive bacteria, such as Streptococcus pneu-
they commonly develop in otherwise healthy people. In moniae (Pneumococcus) and Staphylococcus aureus,
the non-immunocompromised population, pneumonia and gram-negative bacteria, such as Haemophilus in-
is the most prevalent community-acquired infection fluenzae and atypical bacteria, including Mycoplasma
and the second most common nosocomial infectious pneumoniae, Chlamydia pneumoniae, and Legionella
disorder. In immunocompromised patients, in children, pneumophila. Viral forms commonly include those
and in the elderly, pneumonia, as well as other pul- caused by respiratory viruses, such as influenza viruses,
monary infections, may develop into a life-threatening human metapneumovirus, respiratory syncytial virus
condition. (RSV), rhinovirus, parainfluenza viruses, adenoviruses,
In this chapter, the most important principles regard- and corona viruses. According to the literature, the spec-
ing the epidemiology, pathogenesis, classification, and trum of organisms varies according to patient-related,
clinical and radiographic diagnoses of pneumonias are temporal, geographic, and diagnostic factors.
reviewed. Our aim is to formulate an integrated approach In CAP, the patients health and socioeconomic status
to the diagnosis of pneumonia that combines clinical and may provide clues as to the spectrum of causative or-
radiologic information. As such, we focus on: (1) com- ganisms. Healthy people are most likely to contract my-
munity-acquired pneumonia (CAP); (2) nosocomial coplasma pneumonia or a mild form of pneumococcal
pneumonia (NP); and (3) pneumonia in immunocompro- pneumonia. Debilitated patients, alcoholics, and the
mised patients including those infected with the human chronically ill more often present with severe pneumo-
immunodeficiency virus (HIV). The differentiation be- coccal pneumonia or infections caused by H. influenzae,
tween CAP, NP, and other forms of pneumonia is of para- S. aureus, or gram-negative bacilli. L. pneumophila and
mount importance because of the potentially different eti- Chlamydia infections are more common in patients with
ologies, clinical features, diagnostic approaches, radio- some form of mild immunologic compromise. Patients
logic patterns, and therapeutic strategies. Although the with poor oral hygiene and occasional loss of con-
spectrum of causative organisms differs between these sciousness (epilepsy, alcoholism) may suffer from
disorders, there is considerable overlap with regard to anaerobic pulmonary infections. In these patients, My-
their radiologic features. cobacterium tuberculosis infections are more prevalent
than in healthy individuals without risk factors. Recur-
rent pneumonia in outpatients usually indicates an un-
Community-Acquired Pneumonia derlying problem, such as congenital or acquired im-
munologic disorder; airway abnormalities, such as
Pathogenesis chronic bronchitis, bronchiectasis, and bronchogenic
carcinoma; cardiac conditions (congestive heart fail-
Pneumonias acquired in the community are the form of ure); or systemic diseases, such as diabetes, chronic al-
pneumonia most often seen in the offices of general coholism, and intravenous drug abuse. Up to 10% of
practitioners, private radiologists, and, in a hospital set- CAPs are aspiration pneumonias caused by the aspira-
ting, in the outpatient department or the emergency tion of colonized oropharyngeal or gastric contents. The

64 P. Goodman, H. Prosch, C.J. Herold
most frequently isolated pathogens in aspiration pneu- group prospectively compared the clinical and radiologic
monia are gram-negative bacteria. Aspiration pneumo- features of CAP caused by L. pneumophila to those of pa-
nia must be differentiated from aspiration pneumonitis, tients with pneumococcal infections AUHA (Ahuja and
which is a chemical pneumonitis that results from the Kanne, 2014). The authors concluded that Legionella in-
aspiration of noncolonized gastric contents (Mendel- fection may clinically as well as radiologically resemble
sons syndrome). a typical bacterial pneumonia.
The definition of CAP has been challenged over the The chest radiogram is the first-line tool in evaluating
last few years, as it also includes pneumonia in patients patients with suspected CAP. Computed tomography
from nursing homes, rehabilitation hospitals, and outpa- (CT) is reserved for assessing complications or for guid-
tient-based surgical centers who routinely receive inva- ing further diagnostic procedures. It is definitely indicat-
sive medical treatment. The bacteriology and outcome of ed in investigating patients with recurrent or persistent
these patients are more similar to those of NPs. There- pulmonary opacifications.
fore, it has been proposed that pneumonia in outpatients
hospitalized for more than 2 days over the previous 3 Nosocomial Pneumonia
months or who reside in nursing homes or extended-care
facilities should be categorized as health-care-associated By definition, NPs develop in a hospital environment.
pneumonia (HCAP). The incidence of NP ranges from 0.5 to 5 cases per 100
admissions, but in the subgroup of ventilated patients in
Clinical Diagnosis an intensive care setting it may reach 741%. Mortality
rates reported for NPs range from 20% in multihospital
Patients suffering from CAP usually present with fever, studies to 50% in single referral centers and universi-
cough, dyspnea, sputum production, and pleuritic chest ty hospitals.
pain, as well as laboratory signs, such as leukocytosis. Mortality is related to the causative agent. The prog-
Because the clinical symptoms are nonspecific, most nosis associated with aerobic gram-negative pneumonias
people who have fever and cough do not have pneumo- is considerably worse than that associated with gram-
nia; in fact, about 30% of patients, and especially the positive or viral agents.
elderly, are afebrile at presentation. Imaging is one of
the most important tools in the diagnosis of CAP. The Pathogenesis
radiographic identification of a new pulmonary infil-
trate is, in the appropriate clinical setting, indicative of NP develops from bacterial colonization of the orophar-
pneumonia. Conversely, a patient who has fever and ynx followed by the aspiration of oropharyngeal secre-
cough but does not have radiologic proof of pneumonia tions and gastrointestinal contents into the lungs. The
cannot be considered to have pneumonia. In CAP, the majority of NPs are caused by gram-negative bacilli, in-
causative organism is frequently not identified because cluding Pseudomonas aeruginosa, Klebsiella spp., En-
noninvasive tests such as sputum cultures correctly terobacteriaceae spp., Escherichia coli, Serratia marce-
identify the offending organism in only 50% of cases, scens, and Proteus, and to a lesser extent by gram-posi-
and invasive procedures are rarely used in patients with tive cocci, atypical bacteria such as L. pneumophila, and
pneumonia. viruses such as RSV. Microbial contamination of insert-
ed tubes, lines, and catheters is an important source of
Radiographic Diagnosis infection. Less commonly, NP is the result of bacteremia
originating from right-sided endocarditis or septic pelvic
In patients with CAP, the primary role of the radiologist thrombophlebitis. Risk factors are either patient-related
is to detect or to exclude pneumonia. A second task is to (underlying illness, previous surgery, prolonged hospital
aid the clinician in determining the etiologic diagnosis. care) or iatrogenic (intravascular catheters, tracheal
Categorization of the causative organism is sometimes tubes, indwelling catheters, respirator equipment).
possible by integrating clinical and laboratory informa- Sources of infections are hospital personnel and patients
tion with radiographic pattern recognition (see the section with active infections. The inappropriate use of broad-
Radiographic Patterns). A specific etiologic diagnosis, spectrum and prophylactic antibiotics is an additional
however, is difficult to establish, given the increasing and important factor leading to an increased susceptibil-
spectrum of causative organisms and their overlapping ity to NPs.
radiographic features. In a prospective study of 359
adults with CAP, Fang and coauthors compared the radio- Clinical Diagnosis
graphic, clinical, and laboratory features of patients with
bacterial pneumonia (caused by H. influenzae, S. pneu- Compared with CAP, it may be difficult for the clini-
moniae, S. aureus, and aerobic gram-negative bacilli) and cian to diagnose pneumonia in a hospitalized patient.
those with atypical pneumonia (caused by M. pneumoniae The classical findings for pneumonia, such as new
and Chlamydia spp.). The authors found no features that fever, new pulmonary opacification on chest radio-
could reliably differentiate these two groups. Another graphs, cough, sputum production, and elevated
Imaging of Pulmonary Infections 65
leukocyte count may not be present in the hospitalized disease (bronchopneumonia) and bilateral diffuse dis-
patient with NP. Moreover, even if these symptoms are ease.
present, they may not necessarily be caused by pneu- Most commonly, consolidation, confined to a segment
monia. Microbiologic evaluation of the patient with or a lobe of one or both lungs, is caused by typical and
suspected NP (sputum, bronchoalveolar lavage) may or atypical bacteria, whereas bronchopneumonia common-
may not be helpful because of the difficulties in differ- ly relates to Staphylococcus aureus, Haemophilus, My-
entiating contamination from true infection. In addi- coplasma, and tuberculous infection. Diffuse bilateral
tion, pulmonary disease in a hospital environment may lung disease, frequently developing over time, can in
be caused by more than one agent. Therefore, identify- most cases be attributed to viruses and fungi such as
ing a pulmonary infection, the various methods used to Pneumocystis jirovecii. Nodular disease may be attrib-
obtain a specimen, and the value of isolating potential uted to septic emboli (small nodules), larger nodules can
pathogens are matters of constant discussion in the be caused by Nocardia and fungal disorders in immuno-
clinical diagnosis of NP. compromised hosts.
Again, these patterns are nonspecific, they overlap,
Radiographic Diagnosis may be mimicked by non-infectious lung disease and
masked by pre- or coexisting lung conditions. Patterns
Because of the potential difficulties in the clinical diag- can be identified both on chest radiography and CT but
nosis of pneumonia in the hospitalized patient, the radio- CT may help to identify complex or coexisting patterns
logist has an important role in detecting and classifying and aid the novice in establishing a diagnosis.
suspected cases. However, the radiographic diagnosis of
a pulmonary opacity in suspected NP is not as straight-
forward as it is in patients with CAP. The radiographic Opportunistic Infections
diagnosis of a pneumonia may be hampered by preexist-
ing disorders or concomitant lung disease, such as fi- Infectious agents that cause opportunistic pneumonia in
brosing alveolitis, lupus pneumonitis, hemorrhage or humans include representatives from the classifications
contusion, acquired respiratory distress syndrome bacteria, virus, fungus, protozoa, and parasite. In the fol-
(ARDS), tumor, atelectasis, and embolic infarcts. These lowing, we review some of these pathogens and their ap-
disorders may obscure or alter the otherwise characteris- pearance on chest film and CT. Usually, the chest radio-
tic radiographic appearance of a pulmonary opacifica- graph will reveal the abnormality but, occasionally, the
tion and thus render the etiologic approach using pattern increased sensitivity of CT is necessary and even rec-
recognition difficult. ommended to see the pneumonia. Whereas the findings
The difficulties in diagnosing NP can be readily on chest imaging may not be totally pathognomonic of
demonstrated by two examples. Winer-Muram et al. as- the underlying etiology of infection, they may still be
sessed the diagnostic accuracy of bedside chest radio- highly suggestive and will certainly lead to a reasonable
graphy for pneumonia in ARDS patients. The overall di- differential diagnosis.
agnostic accuracy in these patients was only 42% be-
cause of false-negative and false-positive results origi- Human Immunodeficiency Syndrome
nating from diffuse parenchymal areas of increased
opacity that obscured the radiographic features of pneu- Since the first description of HIV/acquired immune de-
monia. Wunderink et al. compared premortem chest ra- ficiency syndrome (AIDS), pneumocystis pneumonia
diographic findings with pulmonary autopsy studies in caused by Pneumocystis jirovecii (PJP) has been one of
ventilated patients with NP. No radiographic sign had a its most common complications. (Previously it was
diagnostic efficiency greater than 68%. The only radio- thought that Pneumocystis carinii was the cause of
graphic sign that correlated with pneumonia, correctly these infections, but this is not the case. The abbrevia-
predicting 60% of the cases, was the presence of an air tion PCP is still used in some circles to refer to pneu-
bronchogram. mocystis pneumonia.) In recent years the incidence of
CT is used more often when an NP is suspected than PJP as a presenting abnormality in patients with AIDS
in patients with CAP, as it can detect early morphologic has decreased. Nevertheless it still accounts for a con-
signs of infection (for example, ground-glass densities). siderable amount of diseases in patients not on highly
CT can also identify a pulmonary opacification in areas active antiretroviral therapy (HAART) or prophylactic
of preexistent disease, detect complications, and guide therapy and should be considered as a diagnosis when
invasive diagnostic procedures, such as bronchoscopy or characteristic radiographic findings are noted. Patients
percutaneous biopsy. with PJP typically present with increasing shortness of
breath; the disease may run a gradual or fulminant
Radiographic Patterns course. Chest films classically reveal a bilateral fine to
medium reticulonodular pattern, generally bilateral but
In general terms, imaging patterns can be grouped into occasionally focal or unilateral. If the patient remains
airspace consolidation (lobar pneumonia), bronchiolar untreated, the radiograph progressively becomes more
opaque and bilateral homogeneous opacities may ulti- and/or superior segment lower-lobe heterogeneous
mately be seen. While upper lobe involvement is more opacities with or without cavitation; on CT scans, imag-
frequent, any lobe may be involved. On CT imaging ing may also demonstrate centrilobular nodules and/or
PJP presents as ground-glass opacification in the areas tree-in-bud opacities. In patients with low CD-4 cell
of involvement, typically perihilar in distribution. The counts and primary infection, homogeneous lobar opac-
chest film occasionally may worsen within a few days ities with adenopathy similar to immune competent
of intravenous trimethoprim-sulfamethoxazole treat- hosts may be seen on chest films, but increased
ment secondary to overhydration and the production of adenopathy may also be present. With post-primary dis-
pulmonary edema, but this can be treated quite effec- ease, the organism disseminates more widely, creating a
tively with diuretics. diffuse, coarse, nodular pattern on chest film similar to
Otherwise, with treatment, the radiographic course is the pattern seen with fungal infections. Cavitation does
one of steady improvement, with complete resolution not develop, as the bodys immune response is weak,
usually occurring by day 11. Pneumatoceles , as seen on such that well-formed granulomas and necrosis are un-
chest films, develops in 10% of patients; the inci- usual. In patients with improving cell-mediated immu-
dence is probably higher in patients evaluated by CT nity secondary to HAART, more typical findings of
scanning. These air-filled cysts are frequently multiple, cavitation might be seen. If the organism is sensitive to
located in the upper lobes, measure 15 cm in diameter, the appropriate therapy, then some resolution of the ab-
and will resolve within 2 months. However, in 35% of normal findings should be observed on chest film with-
patients, pneumatoceles may lead to pneumothorax, in 1 week.
which can be extremely difficult to treat. Overall, pneu- Ordinary bacterial infections now occur with in-
mothorax develops in 5% of patients with PJP and creased frequency and among some patients with HIV
AIDS. In about 10% of patients with PJP, the chest film are the most common type of infection. This increasing
may be normal. In some of these patients with normal percentage of bacterial infections may reflect the larg-
radiographs, a CT scan will show the typical geograph- er number of pulmonary infections in populations in
ic, ground-glass opacities associated with pneumocystis whom antiretroviral and prophylactic therapy is avail-
pneumonia. Lymphadenopathy and pleural effusions are able. Common organisms are S. pneumoniae, H. in-
not part of the PJP picture. fluenzae, S. aureus, and P. aeruginosa. In the immuno-
Cytomegalovirus (CMV) may mimic the appearance compromised, pneumonias caused by these bacteria
of PJP on chest film, with diffuse bilateral fine to medi- usually appear as they do in normal hosts, i.e., as ho-
um reticulonodular opacities. On CT, centrilobular nod- mogeneous, peripheral, lobar opacities. Parapneumonic
ules and ground-glass opacities are reported. In some effusions may be present. S. aureus, and P. aeruginosa
patients with CMV, the presence of discreet nodules, pneumonias may present with cavitations. These should
sometimes several centimeters in size, may help distin- begin to resolve within days of instituting antibacterial
guish between these two entities. Lymphocytic intersti- therapy, with complete resolution of abnormalities usu-
tial pneumonia may also mimic PJP with fine reticular ally occurring in about 2 weeks. Other bacterial etiolo-
opacities on chest radiographs, ground-glass opacities gies, such as Rhodococcus equi and Nocardia aster-
on CT scans, and air-filled cysts seen on both forms of oides, are less common and may present as nodules or
imaging. masses with or without cavitation.
Disseminated fungal infections, such as histoplasmo- With the use of antiretroviral therapy, noninfectious
sis and coccidiomycosis, generally produce bilateral, fair- etiologies of disease have become more prevalent, such
ly symmetric, coarse, nodular opacities on chest radio- as pulmonary hypertension and chronic obstructive pul-
graphs. monary disease (COPD), including emphysema and
The nodules and occasionally reticular opacities are chronic bronchitis. Also, the immune reconstitution in-
larger than those seen with PJP, which may aid in distin- flammatory syndrome (IRIS), occurring in up to 30% of
guishing between the two processes. Discreet larger nod- patients after the initiation of antiretroviral treatment,
ule(s) or disseminated disease may be seen with other may cause confusing clinical and radiological findings.
fungal infections such as aspergillosis and cryptococco- With improving immune status, patients are able to
sis. With angio-invasive fungal infections cavitation may mount a greater inflammatory response to existing or-
occur secondary to ischemia, regardless of the CD-4 lym- ganisms, resulting in worsening clinical disease and in-
phocyte count. creasing lung parenchymal abnormalities and lym-
The imaging appearance of tuberculosis (TB) de- phadenopathy. This usually develops in individuals with
pends on the patients immune status. In patients with low CD-4 counts and high viral loads, typically about
relatively normal CD-4 lymphocyte cell counts, TB will one month after starting therapy (but as early as within
look much like it does in the general population. That days and as late as after several months). It is more com-
is, with primary infection, patients will present with a monly seen in patients with partially treated tuberculo-
homogeneous lobar opacity and ipsilateral hilar and/or sis or non-tuberculous mycobacterial infection. Worsen-
mediastinal adenopathy. With post-primary infection, ing of other infections and the development of sar-
chest films will show apical and posterior upper-lobe coidosis have also been attributed to HAART and IRIS.
Two infection-related neoplasms, non-Hodgkins lateral involvement. On chest film, varicella pneumonia
lymphoma (NHL) and Kaposis sarcoma, may also be usually produces bilateral symmetric acinar opacities
seen in patients with AIDS and could cause confusion (poorly marginated nodules 710 mm in diameter) that
in generating a differential diagnosis. NHL will pro- may coalesce as the disease worsens. CT shows similar-
duce well-defined, discete, nodules on chest films. The sized nodules and distribution as well as ground-glass
nodules range in size from about 1 cm to several cen- opacities.
timeters. Solitary or multiple nodules may be noted. Among the fungal organisms seen with some regular-
Lymphadenopathy and pleural effusions are also ob- ity in this group of immunocompromised patients are
served. The nodules have a tendency to grow extreme- PJP, Cryptococcus, and Aspergillus. Other emerging
ly rapidly. agents include Pseudallescheria/Scedosporium species,
Whereas the nodules with NHL are very well defined, Fusarium spp., and Mucorales spp. The appearance of
those associated with Kaposis sarcoma are not. This dis- PJP is similar to that described for patients with
ease produces poorly marginated nodules that tend to co- HIV/AIDS. A recent report suggested that PJP in pa-
alesce and occur in the perihilar lung and lower lobes. tients with HIV/AIDS as opposed to non-HIV/AIDS pa-
On CT, the distribution is along bronchovascular path- tients might have a higher incidence of pneumatoceles,
ways. but less extensive ground-glass opacities (Hardak et al.,
(Other diseases seen in HIV/AIDS patients which oc- 2010).
cur along the bronchovascular bundles include lym- Cryptococcus has numerous types of presentation on
phocitic interstitial pneumonia (LIP), Castleman disease, chest film. Perhaps most common is the appearance of
and sarcoidosis). In almost all cases of Kaposis sarcoma well-defined nodules, usually solitary but sometimes
involving the lungs, cutaneous lesions are also common, multiple. If the nodules become masses, the margins may
as is pleural fluid. become indistinct. The nodules may cavitate. Cryptococ-
cus may also manifest as a lobar pneumonia or diffuse
Other Conditions of the Immune-Compromised heterogeneous reticulonodular opacities.
Aspergillus fumigatus is responsible for many lung
Increasing numbers of transplant procedures, both sol- infections. Up to 10% of pneumonias following allo-
id organ and hematopoietic stem cell, have led to new geneic transplantation are due to Aspergillus. The pat-
populations of immunosuppressed individuals. The un- tern of abnormality seen on chest film depends on the
derlying diseases (e.g. leukemia) or the widespread use patients immune status. In the setting of immunosup-
of induced immunosuppression for treatment purposes pression (neutropenia), the typical appearance is that of
may result in neutropenia or other causes of immune invasive aspergillosis. In this form, the chest film ini-
dysfunction. Steroids are also being used with in- tially demonstrates a poorly marginated area or areas of
creased frequency for a number of medical conditions. homogeneous opacity that may resemble ordinary bac-
Thus, infectious and non-infectious complications in terial pneumonia in appearance and distribution but is
the setting of transplantation or steroid use have be- occasionally rounder and farther from the subpleural
come a major problem. Prophylactic drug treatment for lung than common community infections. In some cas-
pneumocystis, CMV, and occasional fungi may reduce es, the disease is peripheral and wedge-shaped sec-
the number of infections in some, but not all of these ondary to infarction caused by the angio-invasive ob-
patients. struction of pulmonary vessels. In time, the lesions be-
Bacterial pneumonias caused by a variety of organ- come more discreet and rounder, thus resembling lung
isms (e.g., Pseudomonas, Nocardia, Legionella) have a masses.
typical appearance of peripheral homogeneous opacifi- As patients are treated and immune status improves,
cation with or without air-bronchograms. More than one there may be cavitation within the masses with the for-
lobe might be involved. In the case of Legionella the mation of an air crescent. Wall thickness of the cavity is
opacification may simulate a mass. generally moderate. The air crescent is created by the
The appearances on chest film and CT scans of CMV contained necrotic debris within the cavity. On CT, ini-
will be similar to that seen in patients with HIV infec- tially, the areas of homogeneous opacity may have air
tion, as described above. Other viral pathogens are also bronchograms, and commonly, additional regions of in-
seen in this setting, including RSV, parainfluenza virus, volvement are identified. A ground glass opacity that
adenovirus, and influenza virus in lung transplant pa- surrounds (frequently incompletely) a more opaque cen-
tients, and varicella zoster, which may be seen in pa- ter of the lesion results in the halo sign, in which the
tients with lymphoma and those undergoing steroid ground glass portion is an area of hemorrhage and the
therapy. central area is necrotic lung. This sign was thought to be
These same organisms are responsible for infections pathognomonic of invasive aspergillosis but it is also a
in patients who develop graft versus host disease. Many feature of other infections, neoplasms, and inflammato-
of these viral pneumonias have a similar appearance, in- ry diseases. CT may also reveal bronchial wall thicken-
cluding ground-glass and consolidative opacities, cen- ing, peribronchial opacities, and small centrilobular
trilobular and tree-in-bud opacities, and a frequently bi- nodules.
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IDKD 2015-2018
Imaging of Thoracic Trauma

Loren Ketai1, Caroline Chiles2
1 Department of Radiology, University of New Mexico Health Science Center, Albuquerque, NM
2 Department of Radiology, Wake Forest University Health Sciences Center, Winston-Salem, NC
Introduction receive medical attention. Radiologists, therefore, more

commonly encounter injuries to the descending thoracic
Each year, approximately 5.8 million people throughout aorta and injuries that leave the adventitia intact. Blunt
the world die as a result of injuries, accounting for 10% traumatic injury to the aorta can be classified as minimal
of the worlds deaths [1]. Approximately 25% of these are (intimal tear only or intramural hematoma), aortic
due to motor vehicle accidents. Imaging plays a key role pseudoaneurysm, and free rupture [3]. The least severe
in the diagnosis of cardiothoracic trauma, whether due to injury, intimal tear, has only been recognized in the last
blunt force or penetrating trauma. Chest radiography and two decades. It is visible on CT, transesophageal echocar-
either computed tomography (CT) or CT angiography are diography, and intravascular ultrasound. On contrast-
considered complementary in the work-up of individuals enhanced CT, intimal tear appears as either a round or tri-
with a high-energy mechanism of injury [2]. If cardiac in- angular intraluminal filling defect attached to the wall of
jury is suspected, transthoracic echocardiography is indi- the aorta, or a small (1 cm), linear filling defect,
cated. In patients with a low probability of significant thought to represent an intimal flap, with or without me-
thoracic injury, chest radiography may be sufficient. diastinal hematoma (Fig. 1). On follow-up imaging, this
lesion is typically seen to resolve by 4 weeks and may be
managed non-operatively [4]. The term minimal aortic
Mediastinum injury includes intramural hematoma, which also has a
low mortality rate even with conservative management
Thoracic Aorta Injury [5]. Intramural hematoma may involve the entire circum-
ference of the aortic wall. On axial CT images, it is seen
Thoracic aortic injury is typically the product of deceler- as a circumferential area of increased attenuation on un-
ation injury or blunt-force trauma to the chest (Table 1). enhanced CT; bleeding may also occur within a portion
The majority of cases occur as a result of motor vehicle of the aortic wall and appear crescentic in shape.
accidents. The severity of the injury depends on the loca- Injuries that involve more than the intima are regarded
tion of the injury within the thoracic aorta and the layers as severe aortic injuries. In contained rupture, or aortic
of the aortic wall involved. Injury to the ascending aorta pseudoaneurysm, the tear involves both the intima and
is often fatal, and patients rarely survive long enough to media, which bulge outwardly, held in place by the intact
Table 1. Traumatic aortic injury

Level of aortic injury Direct signs Indirect signs
Minimal aortic injury Intraluminal thrombus: round or triangular intraluminal Mediastinal/periaortic hematoma
filling defect attached to the wall of the aorta
Intimal flap: small (1 cm), thin (linear) filling defect
Intramural hematoma: High-attenuation material in the wall
of the aorta, which may appear crescentic or circumferential
Contained rupture Saccular pseudoaneurysm Mediastinal/periaortic hematoma
Fusiform pseudoaneurysm
Free rupture Extravasation of contrast material Mediastinal/periaortic hematoma
Hemopericardium if injury involves
the ascending aorta

72 L. Ketai, C. Chiles
a b
Fig. 1 a-c. Minimal aortic injury. A linear filling defect, likely rep-
resenting an intimal flap (arrows), is seen on axial computed to-
mography (CT) images (a) and on coronal reformats (b) in the de-
scending thoracic aorta in a 38-year-old man who was involved in
a motor vehicle accident. Three days after the accident, the intimal
flap appears more rounded (c), possibly due to thrombus forma-
tion. On a follow-up CT prior to hospital discharge 3 weeks later,
the intraluminal findings had resolved without intervention
adventitia. Adventitial tears may involve 360o of the aor- complete rupture of the descending thoracic aorta, medi-
tic wall, so that the pseudoaneurysm appears fusiform or astinal tissues and the periaortic hematoma can produce
barrel-shaped (Fig. 2). When the tear involves only a por- a tamponade effect, preventing rapid exsanguination.
tion of the adventitia, the pseudoaneurysm bulges eccen- This is in contrast to free rupture involving the ascending
trically from the aorta, typically in the region of the aor- aorta, when blood can rapidly fill the pericardial sac,
tic isthmus. causing cardiac tamponade and death. It is important to
The stress placed on the aortic wall during sudden de- recognize free rupture on imaging and to distinguish it
celeration may result in complete rupture, with disruption from contained rupture. Although delayed repair may be
of all three layers of the aortic wall intima, media, and considered in patients with aortic pseudoaneurysm, or
adventitia with extravasation of blood into the adjacent contained rupture, immediate repair is necessary for pa-
anatomic compartment (Fig. 3). In some patients with tients with free aortic rupture.
Imaging of Thoracic Trauma 73
In a patient with blunt trauma or deceleration injury,

mediastinal hematoma is most commonly due to small
venous injury and is therefore considered an indirect sign
of aortic injury. Mediastinal hematoma associated with
aortic injury is typically adjacent to the transverse and
descending thoracic aorta and may dissect superiorly in
the extrapleural space to form an apical cap. Mediasti-
nal hematomas not in contact with the aorta but located
in the anterior or posterior mediastinum are more likely
to be related to chest wall or spinal fractures [6].
Cardiac Herniation
Cardiac herniation as a result of a traumatic tear of the
pericardium is an uncommon occurrence but may be con-
sidered in the patient with fluctuating blood pressures af-
ter intravenous fluid administration together with tachy-
cardia and dilated jugular veins [7]. Although cardiac-
axis deviation may be apparent on a chest radiograph, more
specific signs of cardiac herniation are better seen on CT
and include the empty pericardial sac, as air fills the
space remaining once the heart is displaced into the
hemithorax, and the collar sign, resulting from the peri-
cardium pinching the heart as it herniates through the
pericardial tear. The tear is typically a longitudinal one
located along the pericardiophrenic nerve and occurs
more commonly on the left side. The mortality of patients
with cardiac herniation is high, with death resulting from
Fig. 2. Contained aortic rupture. A fusiform pseudoaneurysm has torsion along the inferior vena cava and great vessels and
formed in the proximal descending thoracic aorta. This occurs
when the intima and media are torn and the pseudoaneurysm is cardiac strangulation [8].
contained by the intact adventitia
Hemopericardium
Hemopericardium should raise suspicion of injury to the
heart, ascending aorta, or coronary arteries. It is most
commonly associated with injury to the aortic root and
ascending aorta but may also result from cardiac cham-
ber rupture, myocardial contusion, and coronary artery
laceration [8]. Simple fluid should demonstrate attenua-
tion values of 010 Hounsfield units (HU) whereas he-
mopericardium will have attenuation values in the 35-HU
range. The rapid accumulation of hemopericardium may
result in cardiac tamponade. The latter diagnosis in pa-
tients with blunt chest trauma is suggested when CT
demonstrates a triad of high-attenuation pericardial effu-
sion, distention of the inferior vena cava and renal veins,
and periportal low-attenuation fluid [8].
Esophageal Injury
Esophageal injuries caused by external, non-iatrogenic
trauma are rare but potentially catastrophic. Mortality for
undiagnosed rupture after 24 h is 1040%. Chest radio-
graphs may reveal pleural effusions, left sided if the low-
er third of the esophagus is injured, right sided if the up-
Fig. 3. Free rupture. The extravasation of contrast medium from the
transverse thoracic aorta is diagnostic of injury involving all three per two thirds is injured. Pneumomediastinum is also
layers of the aortic wall. Mediastinal hematoma is also present, an commonly seen but is nonspecific and usually not related
indirect sign of aortic injury to esophageal or tracheobronchial injury (see below):
a b
Fig. 4 a, b. Two patient with acute diffuse lung disease. a Acute respiratory distress syndrome (ARDS) with dependent consolidation and
midlung ground glass opacities. The pneumomediastinum is due to the Macklin effect (arrow). b Trauma with acute aspiration causing
tree in bud opacities and secretions in segmental bronchi (arrow)
instead, it represents alveolar rupture and the dissection of

air along bronchovascular sheaths to the mediastinum, the
so-called Macklin effect (Fig. 4). Fluoroscopic esopha-
gography is moderately sensitive (75%) for esophageal in-
jury and very specific but it can be technically difficult to
perform in critically ill patients. In a study of a small
group of patients, CT esophagography performed after the
ingestion or instillation of contrast and effervescent gran-
ules was very accurate in the detection of injury [9]. More
recent studies following a similar protocol with the ex-
ception of the effervescent granules showed a high speci-
ficity but a sensitivity of only 50% [10].
Tracheobronchial Rupture
Tracheobronchial injury as a result of blunt-force trauma
Fig. 5. Bronchial rupture. The lung lies in a dependent position
is uncommonly seen, as the majority of patients die be- within the right hemithorax, consistent with the fallen lung sign.
fore reaching the hospital. In a review of 88 surviving pa- Additional evidence of bronchial rupture in this case includes dis-
tients reported in the literature, the rupture involved the ruption of the bronchus, extensive subcutaneous emphysema, and
right main bronchus in 41 (47%), and 76% of the injuries a large pneumothorax despite satisfactory positioning of a thora-
were within 2 cm of the carina [11]. The median time un- cotomy tube
til diagnosis was 9 days. Chest radiography may show in-
direct signs of tracheobronchial rupture, including cervi- Although originally described on chest radiography, this
cal subcutaneous emphysema, pneumomediastinum, and can also be seen on CT, which may demonstrate disrup-
persistent pneumothorax despite satisfactory positioning tion in the wall of the trachea or bronchus; however, this
of a thoracotomy tube [12]. The fallen lung sign de- is more readily identified at bronchoscopy, which should
scribes a collapsed lung lying in a dependent position, be performed in any patient with suspected tracheo-
tethered to the hilum by pulmonary vessels (Fig. 5) [13]. bronchial injury.
Pleural Space on CT, manifesting as pleural fluid (3570 HU) and in

some cases demonstrating a hematocrit sign in which the
densest clot is seen in the dependent pleural space. High
Pneumothorax
attenuation within 1015 HU of vascular structures is in-
Pneumothorax is second only to rib fractures in its preva- dicative of active hemorrhage, usually arterial.
lence among patients with blunt chest trauma. Rates vary Following tube thoracostomy, pleural blood loss 250
widely, from 5 to 64%, with a recent large series report- ml/h or greater 10001500 mL often indicates the need
ing an incidence of 16%. Some patients will develop ten- for thoracotomy [17, 18]. Initial CT imaging showing a
sion pneumothorax, in which the pleural pressure rises layering hemothorax thicker than 24 mm is a relatively
sufficiently to impair venous return, causing hemo- specific indicator that blood loss will exceed this thresh-
dynamic instability. A chest radiographic finding of me- old [18]. For patients who do not undergo initial thoraco-
diastinal shift is not specific for tension pneumothorax; tomy and are instead treated with tube thoracostomy, CT
rather, the diagnosis is made on clinical grounds. is useful in detecting retained hemothorax. Most patients
Many trauma patients will receive only supine chest with a 500-mL retained hematoma require video-assisted
radiography, mandating a search for radiographic signs in thoracoscopy for its evacuation in order to prevent com-
addition to a pleural line, which may not be visible due plications, principally empyema. Due to the typical pres-
to the predilection of pleural air to collect antero-inferiorly ence of extensive associated parenchymal damage, chest
in supine patients. The deep sulcus sign, indicative of radiography is neither sensitive nor specific for identify-
an abnormally deep and widened costophrenic sulcus, is ing a retained clot. In one series, half of the cases select-
the most commonly missed finding of a pneumothorax ed for surgical intervention by radiography showed no
on supine radiographs. The presence of the double di- significant hematoma on chest CT [19].
aphragm sign, in which air outlines both the dome of the
diaphragm and the anterior costophrenic sulcus ( seen ex- Extrapleural Hematoma and Chylothorax
tending from the seventh costochondral cartilage medial-
ly to the 11th rib laterally), may increase the specificity When the parietal pleura remains intact, blood may accu-
but in general the sensitivity of supine radiographs in de- mulate in the extrapleural space rather than within the
tecting pneumothorax remains 25% [14]. pleural space. These extrapleural hematomas can be iden-
The limitations of chest radiography have stimulated the tified on CT by the inward displacement of extrapleural
use of bedside ultrasound in the detection of pneumotho- fat. They are not treated by tube thoracostomy (Fig. 6).
races [15, 16]. In the absence of a pneumothorax, high-fre-
quency probes readily demonstrate the to and fro sliding of
the parietal and visceral pleura surfaces, the sliding lung
sign. B lines, caused by echo reverberations of the air-
filled lung, appear as narrow hyperechoic ray-like opaci-
ties. While the presence of a sliding lung sign and B lines
has a very high negative predictive value, multiple sites in
the chest, and not only in the area of the ultrasound probe,
must be evaluated. In well-trained hands, the sensitivity of
ultrasound for pneumothorax is much greater than that of
supine chest radiography, ranging between 50 and 95%.
CT remains the standard for the detection of pneumo-
thoraces against which all other imaging is judged. Howev-
er, the utility of detecting occult pneumothoraces, whether
by CT or ultrasound, is tempered by the more recent sur-
gical literature showing that many of the small pneumo-
thoraces not seen on radiographs have a benign course and
may not routinely warrant tube thoracostomy drainage.
Hemothorax
Hemothorax occurs in 3050% of blunt injuries but more
commonly requires surgical intervention following pene-
trating trauma. On supine radiographs a posterior layer-
ing hemothorax can cause hazy opacity of the entire Fig. 6. Extrapleural hematoma. Blood has accumulated in the ex-
hemithorax through which the pulmonary vasculature is trapleural space following blunt force trauma to the left chest wall.
Extrapleural fat is displaced inwardly (arrow). The biconvex shape
visible. Hemothorax is more easily detected when it is ac- and the high-attenuation material within the hematoma suggest an
companied by a rim of fluid displacing the lung from the active arterial bleeding source, which may require embolization or
lateral and apical chest wall. Hemothorax is readily visible surgical intervention
Collections that are biconvex may represent an arterial that indirectly damage the lung. Other insults from trau-
bleeding source and are more likely to require surgical in- ma directly injure the lung parenchyma; these include as-
tervention [20]. piration, fat emboli, inhalation injury, near drowning, and
Chylothorax is an uncommon complication of chest smoke inhalation. When the extent of injury is severe,
trauma. It can result from penetrating trauma to the up- damage caused by most mechanisms has a similar radio-
per mediastinum that injures the thoracic duct as it as- logic appearance. CT often demonstrates consolidation in
cends to the left of the esophagus, resulting in a left sided the most dorsal lung, ground glass opacities in the mid
pleural effusion [21]. Blunt injury to the thoracic duct is lung, and nearly normal appearing lung along the ventral
often related to hyperextension of the spine and occurs surfaces (Fig. 4). Direct pulmonary insults may cause
most commonly at the level of the diaphragm, where the more extensive and asymmetric consolidation than indi-
duct is located in the right hemithorax, thus giving rise to rect injuries.
a right pleural effusion. Pleural fluid from a chylothorax In early stages or in less severe cases of alveolar dam-
may be lower in attenuation than water due to its fat con- age, the clinical history and imaging findings may suggest
tent but in many cases co-existing protein in the fluid a specific cause. For instance, in cases of acute aspiration
raises its attenuation to that of other pleural effusions. pneumonitis, tree-in-bud type centrilobular nodules may
co-exist with CT findings of diffuse alveolar damage [24].
In early or mild cases of fat embolization, CT may demon-
Pulmonary Injury strate ill-defined nodules 1 cm in size in addition to
ground glass opacities and consolidation [25]. The diag-
Contusion nosis of fat emboli, however, is not made radiologically.
The presence of bilateral parenchymal opacities is a ma-
Pulmonary contusions are defined as the leakage of jor diagnostic criteria but confirmation requires the pres-
blood into the alveoli and lung interstitium without the ence of non-radiologic major criteria (e.g., axillary or
presence of a discrete laceration. CT is more sensitive subconjunctival petechiae) or multiple minor criteria
than radiography but many of the contusions seen on CT (e.g., fat within the urine, significant hypoxemia).
alone are not clinically significant. In more extensive in- CT may be more useful in assessing prognosis than in
jury, CT is useful in differentiating contusion from aspi- identifying the etiology of lung injury. For example, in
ration or acute respiratory distress syndrome as the etiol- burn victims, CT imaging can identify those patients
ogy of acute lung injury, by showing lung opacities that most at risk for diffuse lung damage related to smoke in-
have geographic borders and cross pleural fissures. These halation. The addition of bronchoscopic inspection im-
opacities are subpleural but may demonstrate immediate proves prediction, and at least in theory could be replaced
subpleural sparing, particularly in children. If the opaci- by virtual bronchoscopy [26]. More commonly, CT can
ties continue to worsen after 24 h or do not begin to im- be useful in assessing the prognosis of patients with al-
prove after 4872 h, concurrent volume overload, atelec- ready established diffuse alveolar damage. Development
tasis, or super-infection should be suspected. of fibroproliferative changes on CT predicts prolonged
mechanical ventilation, the development of barotrauma
Laceration and ventilator-associated pneumonia [27].
Pulmonary lacerations occur with both blunt and pene-

trating trauma. When caused by blunt trauma, their loca- Diaphragm
tion in the lungs can suggest specific mechanisms of in-
jury. For instance, central lacerations are likely caused by Diaphragm injuries are less common than pneumo-
shearing forces between the lung and tracheobronchial thoraces or hemothoraces but their radiologic detection has
tree, while peripheral lesions are more commonly related become more important as the number of trauma patients
to punctures from overlying fractured ribs [22]. Lacera- managed non-operatively has increased. Missed di-
tions from blunt trauma are usually round or oval but vary aphragm injures have been reported in 20% of patients
greatly in size and may be filled by air, blood, or both. initially managed non-operatively for penetrating trauma.
Lacerations may become more evident in the first 72 h Use of positive pressure ventilation can maintain the vis-
post-trauma, as the contusion clears, and then resolve cera within the abdomen despite the presence of a di-
slowly over weeks to months. Lacerations do not usually aphragm laceration, contributing to a delayed diagnosis
require specific surgical management but can be repaired Blunt diaphragm injuries are roughly three times more
if associated with bleeding or if surgery is necessary to common on the left, are often 10 cm in length, and
treat retained hemothorax (see above) [23]. commonly occur in the posterolateral aspect of the di-
aphragm [28]. Other laceration sites are reported but the
Diffuse Lung Injury esophageal hiatus is usually spared. Chest radiograph
signs of diaphragmatic injury are more commonly appre-
Thoracic trauma can cause diffuse alveolar damage via ciated in the setting of left sided injuries. Elevation of the
systemic processes such as shock and hypertransfusion left hemidiaphragm 4 cm above the right strongly
CT signs of diaphragmatic injury include direct visu-

alization of a diaphragm defect and several different signs
based on the abnormal appearance of the upper abdomi-
nal viscera [29]. These include herniation of the abdom-
inal viscera into the chest, the collar sign, and the depen-
dent viscera sign. The collar sign describes focal narrow-
ing of an upper abdominal structure that is constricted by
the margins of a diaphragm tear (Fig. 7). The dependent
viscera sign is caused by the absence of diaphragm re-
straint on the abdominal viscera, such that the stomach,
bowel, or upper third of the liver lie in contact with the
posterior chest wall. Each of these signs carries a speci-
ficity 90% but a considerably lower sensitivity, man-
dating a search for multiple signs.
Penetrating diaphragm injuries tend to be considerably
smaller than blunt diaphragmatic injuries. Accordingly, ra-
diologic signs based on the constriction or abnormal po-
sition of abdominal viscera are generally not helpful. Di-
rect visualization of a diaphragm defect on CT is specific
but uncommonly seen. CT demonstration of contiguous
Fig. 7. Diaphragmatic rupture. The stomach has herniated through injuries on both signs of the diaphragm is the most sensi-
a left sided diaphragmatic rupture and is pinched by the di-
aphragm, producing the collar sign. Additional signs of blunt
tive CT finding (Fig. 8). Its specificity can be diminished,
force trauma in this patient include an aortic tear, hemomedi- however, if multiple wounds are present. The absence of
astinum, and laceration/contusion of the left lung this sign remains useful in ruling out penetrating di-
aphragmatic injury. The construction of double oblique
CT images along the trajectory of the knife or bullet can
suggests diaphragm injury. This may be accompanied by improve the accuracy of diagnosis. Demonstration of a
a U-shaped configuration of the gastric tube, with the ab- tract extending on both sides of the diaphragm is specific
normally placed gastroesophageal junction (the nadir of for penetrating diaphragm injury and in many cases is ad-
the U) caused by an intact esophageal hiatus. equate impetus for operative exploration [30].
a b
Fig. 8 a, b. Penetrating diaphragm injury. CT sections in a patient stabbed through the anterior chest wall. The trajectory of the knife (arrows)
can be followed inferiorly through the lung and into the liver parenchyma. The course is indicative of a focal laceration of the diaphragm
Table 2. Chest wall trauma

Fracture/Dislocation Associated injury Direct injury
Completely displaced Traumatic pericardial effusion (40%), spinal fracture (30%) NA
sternal fracture
Manubrium fracture Thoracic spine (T5T6) and the thoracolumbar junction (T12L1) NA
Type 2 sternomanubrial dislocation Hyperflexion spinal injury NA
Type 1 sternomanubrial dislocation NA Internal mammary artery
Posterior sternoclavicular NA Bracheocephalic vein, aortic
joint dislocation arch vessels
Scapulothoracic disassociation NA Subclavian/axillary artery,
brachial plexus,
pseudomeningoceles
NA, not applicable
Chest Wall Trauma Sternoclavicular Joint and Scapulothoracic Disassociation
Fracture of the chest wall bones can be clinically signif- Sternoclavicular dislocations are clinically relevant due
icant because of their correlation with overall injury to potential direct damage to adjacent structures. These
severity or because of the direct anatomic or physiologic injuries are rare because of the extensive ligamentous
impact of the fracture (Table 2). Fractures of the scapula support, such that forces transmitted along the clavicle
are an example of the former, their presence correlating are far more likely to fracture the clavicle than dislocate
with more severe chest injury. The association is stronger the joint. Anterior dislocations are more common but
if more than two separate regions of the scapula are frac- posterior dislocations are of greater clinical importance
tured (e.g., scapular body and glenoid neck, scapular due to potential impingement on adjacent structures. Di-
spine, and acromion). agnosis of this dislocation without CT is very difficult,
even if special radiographic views (e.g., serendipity view)
are taken [33].
Sternal and Rib Trauma The sternoclavicular joint may also be disrupted in
Sternal fractures are also associated with the severity of scapulothoracic disassociations; a severe injury separates
chest injury, the degree of displacement being the major the scapula and muscular attachments of the upper ex-
determinant. Less than 10% of patients with minimally tremity from the thorax but without disrupting the over-
displaced sternal fractures have spinal fractures or trau- lying skin. Radiographic diagnosis relies on detecting
matic pericardial effusions, but the incidence is much scapular displacement via the scapula index, a measure-
higher in patients with completely displaced sternal frac- ment easily distorted by differences in arm positioning
tures. The location of the fracture within the sternum is and by rotation [34]. In suspected cases CT and magnet-
also significant: those involving the manubrium have the ic resonance imaging are essential for detecting vascular
highest association with spinal fractures [31]. Sterno- and nerve injuries, respectively.
manubrial dislocations share this association with tho-
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IDKD 2015-2018
Missed Lung Lesions: Side by Side Comparison of Chest Radiography

with MDCT
Nigel Howarth1, Denis Tack2
1 Institut de Radiologie, Clinique des Grangettes, Geneva, Switzerland
2 Department of Radiology, EpiCura Hospital, Ath, Belgium
Introduction graph are not uncommon. One estimate is that nearly

30% of lung nodules may be overlooked [15]. Missing a
Missed lung lesions are one of the most frequent causes nodule that may represent malignancy will have adverse
of malpractice issues [1-4]. Chest radiography plays an consequences on patient management, essentially
important role in the detection and management of pa- through delayed diagnosis, which may carry medico-
tients with lung cancer, chronic airways disease, pneu- legal implications. A number of authors have explored
monia, and interstitial lung disease. Among all diagnos- the reasons why lesions are overlooked [16-21]. Specific
tic tests, chest radiography is essential for confirming or studies have focused on size [14, 22, 23], contrast gradi-
excluding the diagnosis of most chest diseases. However, ent [24], conspicuity [25, 26], and anatomic noise during
numerous lesions of a wide variety of disease processes imaging [27].
affecting the thorax may be missed on a chest radiograph. A more recent study [28] examined the imaging fea-
For example, the frequency of missed lung carcinoma on tures of non-small-cell lung carcinoma overlooked at dig-
chest radiographs can vary from 12 to 90%, depending on ital chest radiography and compared the performances of
study design [5]. Despite the lack of convincing evidence general and thoracic radiologists with respect to lung car-
that screening for lung cancer with the chest radiograph cinoma detection. Frontal and lateral chest radiographs
improves mortality, chest radiography is still requested from 30 consecutive patients with lung carcinoma over-
for this purpose [6, 7] The chest radiograph will also help looked during the initial reading and from 30 normal con-
in narrowing a differential diagnosis and in determining trols were submitted to two blinded thoracic radiologists
additional diagnostic measures, in addition to being of and three blinded general radiologists for retrospective
use during follow-up. The diagnostic utility of the radio- review. The location, size, histopathology, borders, pres-
graph will be maximized by integrating the radiological ence of superimposed structures, and lesion density were
findings with the clinical features of the individual pa- recorded. Interobserver agreement was calculated and de-
tient [8]. In this chapter, we review the more important tection performance between thoracic and general radio-
radiological principles regarding missed lung lesions in a logists was compared. The average size of carcinomas
variety of common chest diseases, with a focus on how missed by the thoracic radiologists was 18.1 mm (range
the correlation of missed lung lesions with subsequent 1032 mm). The average size missed by general radiolo-
multi-detector computed tomography (MDCT) can help gists was 27.7 mm (range 1260 mm). In 71% (5/7) of
improve interpretation of the plain chest radiograph. the cases, the missed lesions were obscured by anatomic
superimposition, with 43% located in the upper lobes and
63% identified as adenocarcinomas. Compared with gen-
Reasons for Missed Lung Lesions eral radiologists, the lesions missed by thoracic radiolo-
gists tended to be smaller but also had significantly low-
The conditions contributing to missed lung lesions, es- er CT density measurements and, more commonly, had
pecially carcinomas, have been extensively studied [1, 3, ill-defined margins. The clinical stage of the overlooked
5, 9-11]. Poor viewing conditions, hasty visual tracking, lesions did not differ between the two groups (p = 0.480).
interruptions, and inadequate image quality, observer in- The authors concluded that the size, location, conspicu-
experience are amongst the most important [9, 10, ity, and histopathology of the lesions overlooked on dig-
12-14]. The features of the lesions themselves, in the ital chest radiography were similar to those missed on
case of nodules, such as location, size, border character- conventional film-screen techniques. Several other stud-
istics, and conspicuity, also play a role [10, 12]. Missed ies on the subject have led to similar conclusions [8, 22,
lung nodules during the initial reading of a chest radio- 27, 29-32].

Missed Lung Lesions: Side by Side Comparison of Chest Radiography with MDCT 81
The detection of carcinoma on a chest radiograph re- standing of the overlooked lesion. There is no harm done
mains difficult, with implications for patient manage- by learning from ones mistakes!
ment. Nowadays, missed detection of a lung carcinoma is
by far the most frequent cause of malpractice suits (42%
of cases) [4]. Nonetheless, whereas overlooking chronic Missed Nodules
airways disease, pneumonia, and interstitial lung disease
may not have the same potential medico-legal implica- Nodular Lesions: Tumors
tions, the consequences for patient care could be critical.
By seeking a correlation between MDCT and plain Nodular lesions are frequently due to lung cancer, which
chest radiograph with respect to missed lung lesions, in- may be primary or secondary. Lung cancer is probably one
terpretation of the latter imaging modality can be im- of the most common lung diseases that radiologists en-
proved. During the course of clinical work, when report- counter in practice. Berbaum formulated the concept that
ing chest CT, whenever available, every effort should be perception is better if you know where to look and what to
made to review previous chest radiographs and their re- look for [33]. Our first example is that of a 53-year-old
ports, as this provides one of the best learning tools for man who complained of pain in the right axilla for 4
chest radiograph interpretation. months and underwent chest radiography. The postero-
A CT scan can be performed in patients with a nega- anterior and lateral radiographs were interpreted as showing
tive chest radiograph when there is a high clinical suspi- normal findings (Fig. 1a, 1b). Subsequent MDCT showed
cion of chest disease. CT scan, especially high-resolution a right superior sulcus mass with rib destruction (Fig. 1c,
CT (HRCT), is more sensitive than plain films for the d). Needle biopsy established a diagnosis of bronchogenic
evaluation of interstitial disease, bilateral disease, cavita- carcinoma (adenocarcinoma). Hindsight bias [34] with the
tion, empyema, and hilar adenopathy. CT is not general- information available from the MDCT makes the initial le-
ly recommended for routine use because the data it pro- sion extremely obvious. Careful scrutiny of both apices is
vides in chronic airways disease and pneumonia are lim- essential when reporting a frontal chest radiograph.
ited, the cost of imaging is high, and there is no evidence Radiological errors can be divided into two types
that outcome is improved. Thus, a chest radiograph is the [35]: cognitive, in which an abnormality is seen but its
preferred method for initial imaging, with CT scan re- nature is misinterpreted, and perceptual, or the miss, in
served for further characterization (e.g., evaluation of which a radiological abnormality is not seen by the radio-
pattern and distribution, detecting of cavitation, adenopa- logist on initial interpretation. The perceptual type is es-
thy, mass lesions, or collections). timated to account for approximately 80% of radiologi-
Many methods have been suggested for the correct in- cal errors [36].
terpretation of the chest radiograph, but there is no pre- Our second patient illustrates the complexity of the de-
ferred scheme or recommended system. The clinical ques- tection of a lung nodule located close to the hilum. A 77-
tion should always be addressed. An inquisitive approach is year-old man with known prostate cancer underwent
always helpful and being aware of the areas where mistakes chest radiography for right upper quadrant abdominal
are typically made is essential. Hidden abnormalities can pain (Fig. 2a, b). The radiographs were reported as nor-
thus be looked for. The difficult hidden areas that must mal. The coronal and sagittal reformats demonstrated the
be checked are the lung apex, areas superimposed over the position of the nodule (Fig. 2c, d), which, with the bene-
heart, around each hilum, and below the diaphragm. In the fit of hindsight, can be seen clearly on the posteroanterior
following, we concentrate on difficult areas, such as lesions and lateral chest radiographs.
at the lung apices or bases or adjacent to or obscured by the
hila or heart. For a systematic approach, we divide this re- Nodular Lesions: Infections
view into three sections addressing specific problems:
missed nodules, missed consolidations, and missed intersti- Nodular lesions attributed to pulmonary infections are
tial lung diseases. Finally, we examine some of the common most often seen in nosocomial pneumonias and in im-
signs that may help in the detection of lesions located in dif- munocompromised patients. They may be caused by bac-
ficult anatomic areas of the chest. teria such as Nocardia asteroides and Mycobacterium tu-
berculosis, septic emboli, and fungi. Nocardia asteroides
causes single or nodular infiltrates with or without cavi-
Specific Problems tation. Invasive pulmonary aspergillosis (IPA), mucor,
and Cryptococcus neoformans may present with single or
Specific problems of missed lung lesions can be divided multiple nodular infiltrates, which often progress to
into missed nodules, missed consolidations, and missed wedge-shaped areas of consolidation. Cavitation is com-
interstitial lung diseases. In the first two, the overlooked mon later in the course of the infiltrate. In the appropri-
pathology may have been detected if special attention had ate clinical setting, CT may aid in the diagnosis of IPA by
been paid to known difficult hidden areas. The follow- demonstrating the halo sign. Figure 3 shows the imag-
ing examples show how a side-by-side comparison of the ing results from a 43-year-old woman with fever after a
chest radiograph and CT images improves our under- bone marrow transplant. The posteroranterior radiograph
82 N. Howarth, D. Tack
a b c
Fig. 1 a-d. A 53-year-old man who underwent chest radiography for pain in the right axilla.
Posteroranterior (a) and lateral (b) radiographs were interpreted as normal. With hindsight
bias from MDCT, the right apical mass is obvious. MDCT coronal and sagittal images with
soft tissue (c) and bone (d) windows show a right apical mass with bone destruction
a b c
Fig. 2 a-d. A 77-year-old man with right upper quadrant pain. Posteroranterior (a) and lateral
(b) radiographs were interpreted as normal. With hindsight, the 13-mm nodule in the supe-
rior segment of the lingula can be seen. Coronal (c) and sagittal (d) reformats (lung window)
show the position of the lingular nodule, close to the hilum
a b
Fig. 3 a, b. A 43-year-old woman with fever after a bone marrow

transplant. The posteroranterior radiograph was interpreted as nor-
mal (a). With hindsight, a subtle infiltrate can be seen at the left
apex. Conspicuity is lessened by the overlying clavicle and 1st rib.
Also note the in-dwelling catheter from the left brachial vein to the
superior vena cava. Axial CT image (lung window) shows nodular
consolidation with crescentic cavitation (air-crescent sign) and a
surrounding ground-glass infiltrate (halo sign) (b)
a b c
Fig. 4 a-c. A 46-year-old woman with cough and right-sided chest pain. The posteroranterior radiograph was interpreted as normal (a). Coronal
(b) and sagittal (c) reformats showing consolidation in the anterior segment of the right lower lobe
was interpreted as normal (Fig. 3a). With hindsight, a lar carcinoma [37]. Acute airspace pneumonia is charac-
subtle infiltrate can be seen at the left apex. Conspicuity terized by a mostly homogeneous consolidation of lung
is lessened by the overlying clavicle and 1st rib. The axi- parenchyma and well-defined borders; it does not typi-
al CT image (Fig. 3b) shows nodular consolidation with cally respect segmental boundaries. An air bronchogram
crescentic cavitation (the crescent sign) and a sur- is very common. Progression to lobar consolidation may
rounding ground-glass infiltrate (the halo sign). These occur. As with lung nodules, whether consolidation is de-
characteristic findings of IPA are best identified on CT. tected or missed on the plain chest radiograph may de-
pend on a combination of the same factors of size, den-
sity, location, and overlying structures. Location is a sig-
Missed Consolidations nificant factor for missed consolidations [38, 39]. Con-
solidations in the middle lobe and both lower lobes can
Airspace Disease be difficult to diagnose, especially when only the poste-
rioranterior view is obtained [40]. Figure 4 shows the ra-
Airspace disease is usually caused by bacterial infections. diographs from a 46-year-old woman with cough and
However, it can be seen in viral, protozoal, and fungal in- right-sided chest pain. The posteroanterior radiograph
fections as well as malignancy, typically brochioloalveo- was interpreted as normal (Fig. 4a). Due to a clinical
a b c
d e
Fig. 5 a-e. A 38-year-old immunocompro-

mised man with a fever. Posteroranterior
(a) and lateral (b) radiographs show a peri-
hilar reticular infiltrate with right upper
lobe consolidation. c-e Axial CT images
show bilateral lung cysts in addition to con-
solidation in the right upper lobe with
patchy ground-glass opacification in both
lungs. Pneumocystis pneumonia was con-
firmed by bronchoalveolar lavage. Note the
retro-esophageal right subclavian artery
suspicion of pulmonary embolism, MDCT was request- of pneumonia when the chest radiograph is normal. This
ed, which showed consolidation in the anterior segment is especially true when the early diagnosis of pneumonia
of the right lower lobe. The coronal and sagittal reformats is critical, as is the case with immunocompromised and
demonstrated the extent of the consolidation (Fig. 4b, c). severely ill patients [43].
There were no signs of pulmonary embolism on the con- Figure 5 shows the imaging studies from a 38-year-old
trast medium study. A diagnosis of right lower lobe pneu- immunocompromised man with fever. The posteroanterior
monia was established and the patient was treated suc- and lateral radiographs (Fig. 5a, b) were interpreted as
cessfully with antibiotics. showing a peri-hilar reticular infiltrate with right upper
Chest radiography is the most frequently performed di- lobe consolidation. MDCT was requested to further char-
agnostic investigation requested by general practitioners acterize the infiltrate and revealed ground-glass opacifi-
in Europe [41]. Chest radiography is considered the gold cation with bilateral lung cysts (Fig. 5 c-e ). Pneumocys-
standard for the diagnosis of pneumonia. It can be used tis pneumonia was confirmed by bronchoalveolar lavage.
to diagnose pneumonia when an infiltrate is present and
to differentiate pneumonia from other conditions that
may present with similar symptoms, such as acute bron- Missed Interstitial Lung Disease
chitis. The results of the chest radiograph may in some
cases suggest a specific etiology (for example, a lung ab- Diffuse (Interstitial or Mixed Alveolar-Interstitial) Lung Disease
scess) or reveal a complication (empyema) or coexisting
abnormalities (bronchiectasis, bronchial obstruction, in- Diffuse lung disease presenting with widely distributed
terstitial lung disease). Chest radiography remains a valu- patchy infiltrates or interstitial reticular or nodular ab-
able diagnostic tool in primary-care patients with a clin- normalities can be produced by a number of disease en-
ical suspicion of pneumonia as it substantially reduces tities. An attempt is usually made to separate the group
the number of misdiagnosed patients [42]. MDCT can of idiopathic interstitial pneumonias from known causes,
help in differentiating infectious from non-infectious ab- such as infections, associated systemic disease, or drug-
normalities and may detect empyema, cavitation, and related. The most common infectious organisms are
lymphadenopathy when the chest radiograph cannot. viruses and protozoa. In general, the etiology of an un-
MDCT imaging is useful in patients with community- derlying pneumonia cannot be specifically diagnosed
acquired pneumonia when there is an unresolving or because the patterns overlap. It is beyond the aim of this
complicated chest radiograph and should be performed in chapter to discuss in detail the contribution of MDCT to
immunocompromised patients with a clinical suspicion the diagnosis of diffuse infiltrative lung disease. The
development of HRCT has resulted in markedly improved ened lateral costophrenic angle may have a sharp, angu-
diagnostic accuracy in acute and chronic diffuse infiltra- lar appearance. In the supine patient, air in the pleural
tive lung disease [44-47]. The chest radiograph remains space (pneumothorax) collects anteriorly and basally
the preliminary radiological investigation of patients within the nondependent portions of the pleural space;
with diffuse lung disease but is often non-specific. Pat- when the patient is upright, the air collects in the apico-
tern recognition in diffuse lung disease has been the sub- lateral location. If air collects laterally rather than medi-
ject of controversy for many years. Extensive disease ally, it deepens the lateral costophrenic angle and pro-
may be required before an appreciable change in radio- duces the deep sulcus sign. In Fig. 6, a deep sulcus sign
graphic density or an abnormal radiographic pattern is seen on the left, in addition to a continuous diaphrag-
can be detected on the plain chest radiograph. At least matic sign, present when there is air between the di-
10% of patients who are ultimately found to have biop- aphragm and the heart.
sy-proven diffuse lung disease have an apparently nor-
mal chest radiograph [48]. HRCT, and now MDCT, have Spine Sign
become integral components of the clinical investigation
of patients with suspected or established interstitial lung On the normal lateral chest radiograph, the attenuation
disease. These techniques have had a major impact on decreases (the lucency increases) as one progresses down
clinical practice [49, 50]. the thoracic vertebral bodies [52]. If the attenuation in-
creases, locally or diffusely, there must be a posteriorly
located lesion (Fig. 7). This lesion might not be seen on
Key Signs for Reducing the Risk of Errors on Chest the frontal view, as it might be hidden by the heart or the
X-rays hila.
Deep Sulcus Sign Silhouette Sign

The deep sulcus sign (Fig. 6) is seen on chest radiographs In a chest X-ray, non-visualization of the border of an
obtained with the patient in the supine position [51]. It anatomic structure that is normally visualized shows that
represents lucency of the lateral costophrenic angle the area neighboring this margin is filled with tissue or
extending toward the abdomen. The abnormally deep- material of the same density [53]. The silhouette sign is
an important indicator of the presence and localization of
a lesion.
Take-Home Messages
Despite the increasing use of CT imaging in the diagno-
sis of patients with chest disorders, chest radiography is
still the primary imaging method in patients with sus-
pected chest disease. The presence of an infiltrate on a
chest radiograph is considered the gold standard for di-
agnosing pneumonia. Extensive knowledge of the radio-
graphic appearance of pulmonary disorders is essential
when diagnosing pulmonary disease. Chest radiography
is also the imaging tool of choice in the assessment of
complications and in the follow-up of patients with pul-
monary diseases.
MDCT plays an increasing role in the diagnosis of
chest diseases, especially in patients with unresolving
symptoms. CT will aid in the differentiation of infection
and non-infectious disorders. The role of CT in suspect-
ed or proven chest disease can be summarized as follows:
1. CT is valuable in the early diagnosis of chest disease,
Fig. 6. A 78-year-old man with acute left chest pain and a previous especially in patients in whom an early diagnosis is
history of pneumoconiosis. Bedside chest radiograph shows a thin important (immunocompromised patients, critically ill
white line near the left chest wall (white arrows), corresponding to patients)
the left lung visceral pleura, and indicating a pneumothorax. The 2. CT may help with the characterization of pulmonary
deep lucency of the left lateral costophrenic angle extending to-
wards the abdomen is an indirect sign of pneumothorax (black ar- disorders
row). The continuous diaphragmatic sign is also seen as air sepa- 3. CT is an excellent tool in assessing the complications
rating the diaphragm from the heart (white hollow arrow) of chest disease
a b c
Fig. 7 a-d. A 69-year-old woman with chronic obstructive pulmonary disease and hemoptysis.
The posteroanterior chest radiograph (a) shows an opacity next to the right border of the
heart (arrow) and obliterating the right side of the spine. This silhouette sign of the right
posterior mediastinal border indicates that the lesion is in a posterior location in the right
lower lobe. Lateral view (b) shows an increased density (arrow) of the lower spine
compared with the upper and middle thoracic spine (spine sign). This increased density
is due to a large mass in the right lower lobe. Coronal CT image (c) shows the right lower
lobe mass obliterating the border of the mediastinum. The sagittal CT image (d) shows the
posterior location of the mass
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persistent or recurrent pulmonary infiltrate. or radiologic information on the interpretation of radiographic
examinations. Acad Radiol 2:205-208.
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IDKD 2015-2018
Plain Film and HRCT Diagnosis of Interstitial Lung Disease

Sujal R. Desai1, Jeffrey R. Galvin2
1 Kings College Hospital NHS Foundation Trust, London, UK
2 Departments of Radiology and Internal Medicine, University of Maryland School of Medicine, Baltimore, MD, USA
Introduction HRCT in Diffuse Interstitial Lung Disease

There is little doubt that imaging tests have a central role The term DILD is a convenient catch-all for a heteroge-
in the investigation of patients with suspected and estab- neous group of disorders [2]. The DILDs have been sub-
lished diffuse interstitial lung diseases (DILD). In most categorized as follows: (1) DILDs that have a known etio-
cases, physicians who manage patients with DILD will logy (e.g., secondary to exposure to certain drugs or a
request a plain chest radiograph. However, high-resolu- connective tissue disorder); (2) the idiopathic interstitial
tion computed tomography (HRCT) is usually indicated, pneumonias (which themselves have undergone classifi-
particular at initial review. HRCT, for a variety of reasons cation [12] and a more recent update [13]; (3) the granu-
discussed below, is superior to plain radiography. In many lomatous DILDs; and (4) a group of diffuse lung diseases
cases where, historically, biopsy might have been consid- that include Langerhans cell histiocytosis and lymphan-
ered mandatory, there has been a paradigm shift because gioleiomyomatosis.
of HRCT. For example, in some patients with idiopathic In patients with established diffuse lung disease,
pulmonary fibrosis (characterized by the histological pat- HRCT will not only detect but also characterize
tern of usual interstitial pneumonia), the HRCT appear- parenchymal abnormalities with greater accuracy than
ances may be characteristic enough for biopsy to be un- plain chest radiography. One important caveat is that in
necessary [13]. In instances in which a radiological di- patients with nodular infiltrates, traditional interspaced
agnosis is not possible, HRCT may provide guidance as HRCT images may mislead; on thin section images the
to the best site for surgical biopsy. More recently, HRCT dimensions of nodules and pulmonary vessels may be
has moved into the realms of prognostic evaluation and comparable, making the distinction difficult [14]. This is
disease staging [49]. unlikely to be an issue on thin-section volumetric acqui-
sitions. In practice, the range of CT features that com-
monly indicate the presence of ILD is relatively limited.
The HRCT Technique Thus, radiologists will typically encounter some combi-
nation of reticulation, ground-glass opacification, honey-
In the era of multi-detector row CT machines, a brief combing, dilatation of airways in regions of reticulation
summary of the HRCT technique is perhaps pertinent. and ground-glass opacification (traction bronchiecta-
The two technical features that differentiate HRCT imag- sis), nodules, and thickening of interlobular septa [15,
ing from conventional CT are, first, the narrow X-ray 16].
beam collimation, which significantly improves spatial Findings at HRCT generally reflect the macroscopic
resolution, and, second, the use of a dedicated recon- abnormalities seen by the pathologist. This was elegantly
struction algorithm [10]. The high-frequency algorithm demonstrated in the very early days of HRCT by Mller
effectively exaggerates the naturally high contrast milieu and colleagues, who showed that the morphologic fea-
of the lungs (i.e., aerated lung vs. more solid elements) tures in patients with idiopathic pulmonary fibrosis (at
[10]. The conspicuities of vessels, small bronchi, and in- that time still known as cryptogenic fibrosing alveolitis)
terlobular septa are increased compared to conventional reflected the histopathological changes [17]. A reticular
(thick-section) CT images [11]. An important downside pattern was seen in seven out of nine patients and corre-
of high-frequency algorithms is the increased visibility of sponded to areas of irregular fibrosis at microscopy.
image noise although, in practice, this generally does not Not surprisingly, because there is no anatomical su-
hamper radiological interpretation. perimposition, the sensitivity of HRCT is better than that

Plain Film and HRCT Diagnosis of Interstitial Lung Disease 89
of chest radiography. However, a more important issue manageably short) list of differential diagnoses. To this
than sensitivity is the confidence and accuracy with end, a proposed schema, presented in the form of ques-
which the diagnosis can be made. In the oft-quoted land- tions that the observer should ask (in roughly the order
mark study by Mathieson and colleagues, experienced given), is as follows.
chest radiologists were asked to independently indicate
up to three diagnoses based on evaluations of the chest Is There a Real Abnormality?
radiographs and CT scans of 118 patients with a variety
of biopsy-confirmed ILDs [18]. Importantly, for the first- This is a crucial first question: the radiologist must first
choice diagnosis, the readers were asked to assign a lev- determine whether what is shown on HRCT represents
el of confidence. The first important finding of this study real disease. CT features attributable to technical fac-
(which effectively put HRCT on the map) was that, com- tors/normal variation (for instance, caused by a poor in-
pared with chest radiography, a confident diagnosis was spiratory effort, inadequate mAs, regions of physiologi-
made nearly twice as often using HRCT. The second, and cally dependent atelectasis) must not be overinterpreted
perhaps more striking, message was that when experi- and reported as disease. Making the distinction between
enced radiologists were confident of the diagnosis on normality and abnormality can also be difficult when
HRCT, they were almost always correct [18]. However, a there is apparently minimal disease or, conversely, when
confident diagnosis on chest X-ray (which, incidentally, there is diffuse abnormality, as may occur with subtle but
was offered in only 25% of the cases), was associated widespread decreased attenuation (mosaicism) or in-
with a significantly lower rate of correct diagnoses. creased (ground-glass opacity) attenuation.
The results of subsequent studies have not always mir-
rored those of the initial study by Mathieson [18, 19]. If There Is an Abnormality, What Is/Are the Predominant HRCT
However, because of study design, the majority of the Pattern(s)?
comparative studies in HRCT probably undervalued its
true utility [1]. Firstly, there was no recourse to pre-test Having decided that there is a definite abnormality on
probabilities for observers in early series and, therefore, HRCT, the observer should attempt to identify the domi-
these do not accurately reflect clinical practice. Secondly, nant pattern(s) using only the standard radiological terms
radiologists (and specifically those with an interest in tho- [15]. The use of non-standard, terminology (e.g., patchy
racic disease) have become increasingly familiar with the opacification, parenchymal opacities) or descriptive terms
spectrum of HRCT patterns and disease. This, almost cer- in which there is an implied pathology (e.g., interstitial
tainly, would be associated with a proportionate increase pattern or alveolitis) is misleading and best avoided.
in the confidence of experienced observers in making
HRCT diagnoses, were such a study to be repeated today. What Is the Distribution of the Disease?
Some justification for this last statement comes from a
study that addressed the clinically vexing issue of end- Since many DILDs have a predilection for certain zones,
stage lung disease [20], in which two experienced tho- an evaluation of the dominant distribution is of diagnos-
racic radiologists independently made correct first-choice tic value. For instance, it is known that in the majority of
diagnoses in just under 90% of cases, with nearly two- patients with idiopathic pulmonary fibrosis (IPF) the dis-
thirds of those diagnoses made with high confidence. On ease tends to be most obvious in the mid- to lower zones.
first inspection, these data seem less than impressive. This contrasts with fibrosis in patients with sarcoidosis,
However, the results of open lung biopsy (the supposed which typically has a predilection for the upper lobes. In
gold-standard for a diagnosis of DILD) are not infre- addition, the radiologist should take note of the axial dis-
quently inconclusive, no doubt in part relating to the de- tribution (central vs. peripheral) which, in contrast with
gree of observer variability between pathologists [21]. chest X-ray, can readily be made on HRCT. The potential
value can be demonstrated by again using the example of
IPF and sarcoidosis: the former is commonly peripheral
An Approach to HRCT Diagnoses (subpleural) whereas in the latter the distribution tends to
be central (and bronchocentric). A final example is seen
It must be acknowledged that HRCT interpretation can in patients with organizing pneumonia, in which consol-
be difficult, even for trained thoracic radiologists! This is idations may have a striking perilobular predilection [22].
not surprising given the sheer numbers of documented
DILDs. These broad-ranging disorders manifest with a Are There Any Ancillary Findings?
relatively small number of histopathological patterns
(e.g., fibrosis, consolidation, intra-alveolar hemorrhage) Ancillary HRCT features may suggest or, indeed, exclude
which, in turn, are reflected by a similarly select group of certain diagnoses. Thus, the presence or absence of the
HRCT features (reticulation, ground-glass opacification, following may be of diagnostic value in specific cases:
nodularity, thickening of interlobular septa). However, a. Pleural thickening/effusions /plaques ( calcification)
with a systematic approach to HRCT interpretation the may suggest asbestos-related lung disease as opposed
observer should, in time, be able to offer a sensible (and to IPF as a possible cause of lung fibrosis.
90 S.R. Desai, J.R. Galvin
b. Reactive intrathoracic nodal enlargement (hilar/medi- microscopy, there is temporally heterogeneous fibrosis
astinal) is normal in fibrotic DILDs. However, sym- admixed with areas of unaffected lung [2]. In areas of fi-
metrical hilar nodal enlargement may suggest a diag- brosis, there will be characteristic honeycombing. The
nosis of sarcoidosis or occupational lung disease. In- disease has a striking basal and subpleural predilection.
trathoracic nodal enlargement is uncommon in pul- To make a diagnosis of a UIP pattern on HRCT, the
monary vasculitides (e.g., Wegeners granulomatosis). radiologist must therefore look for the following: (1) a
c. Bronchiectasis with co-existent suppurative airways reticular pattern, (2) honeycombing (with or without trac-
disease in a patient with established pulmonary fibro- tion bronchiectasis), and (3) a subpleural, basal, disease
sis may point to a diagnosis of an underlying connec- distribution [23] while ensuring that features inconsistent
tive tissue disease, such as rheumatoid arthritis. with a UIP pattern (i.e., mid/upper zone predominance, a
d. The demonstration of intrapulmonary cysts in the ap- bronchovascular distribution, ground-glass opacification
propriate clinical context suggests a range of diag- more extensive than reticulation, widespread micronodu-
noses, including Langerhans cell histiocytosis, lym- larity, multiple cysts away from areas of honeycombing,
phangioleiomyomatosis, and lymphocytic interstitial a mosaic attenuation pattern in three or more lobes, and
pneumonia. consolidation) are absent. In the absence of honeycomb-
e. Consolidation indicative of organizing pneumonia may ing (but with the other features in the list), an HRCT di-
co-exist with signs of fibrosis and parenchymal distor- agnosis of possible UIP can be made.
tion in patients with connective-tissue-disease-related The presence of a UIP pattern on HRCT is accurate
lung disease. and obviates histologic confirmation [3, 24]. However,
typical appearances may not be present in over half of pa-
What Is the Likely Pathology? tients with biopsy-proven disease [24, 25].
Knowledge of the relationships between the HRCT ap- (Cryptogenic) Organizing Pneumonia
pearances and the possible histopathological correlates is
crucial. Thus, in a patient with predominant consolidation Organization is a common response to lung injury and is
it is reasonable to conclude that the dominant pathology part of the normal process of lung repair. It is represented
involves the air spaces, whereas in a patient with reticula- on histology by plugs of fibroblastic tissue that fill the
tion the likely pathological process affects the interstitium. alveolar spaces. This same fibroblastic tissue may be iden-
tified in respiratory and terminal bronchioles, explaining
What Is the Clinical Background? the use of the older term bronchiolitis obliterans orga-
nizing pneumonia, but which has been replaced by or-
Clinical data must always be integrated when formulating ganizing pneumonia (OP) [12]. OP was first recognized
a radiological opinion. However, it is often advisable to in 1923 as a response to unresolved pneumonia [26]. Most
review the clinical information after evaluation of the ra- cases are likely to be post-infectious; however, the organ-
diological features. This is particularly true at the very ism is rarely recovered. The OP pattern is also a common
start of HRCT interpretation, when the radiologist is de- feature in a wide range of other diseases, including colla-
ciding whether or not there is a real abnormality (see gen-vascular disease, hypersensitivity pneumonitis,
above). Specific clinical features that may be of impor- chronic eosinophilic pneumonia, drug reaction, and radi-
tance in HRCT interpretation include basic demographic ation-induced lung injury. The appearance of OP on imag-
data (age, gender, ethnicity), smoking history, time ing is highly variable, depending on the prior injury and
course of the illness (i.e., have symptoms developed over the stage at which it is imaged [27]. A minority of patients
hours and days or weeks and months?), and any relevant present with solitary pulmonary nodules or focal areas of
past medical history. consolidation. However, the dominant finding in OP is bi-
lateral consolidation that is peripheral, often with sparing
of the subpleural portion of the lung. Opacities are often
HRCT Appearances in Select DILDs perilobular and may be associated with septal lines. In
some patients, OP may progress to an non-specific inter-
A working knowledge of the relationship between stitial pneumonia pattern of fibrosis (see below). Al-
histopathological changes and HRCT patterns and the though many cases of OP will clear with steroids, a sub-
typical appearance of common DILDs is of value in day- stantial minority of patients are left with significant dis-
to-day practice. The following sections briefly consider ability due to pulmonary fibrosis [27-29].
the HRCT appearances of a few DILDs.
Non-specific Interstitial Pneumonia
Idiopathic Pulmonary Fibrosis/Usual Interstitial Pneumonia
After UIP, non-specific interstitial pneumonia (NSIP) is
IPF is a chronic progressive fibrosing interstitial lung dis- the most common pattern of idiopathic interstitial pneu-
ease associated with a histologic and/or HRCT pattern of monias (IIP) and linked with a better survival [13, 24,
usual interstitial pneumonia (UIP) [23]. At low-power 30]. This pattern of IIP may be idiopathic but more
commonly it is seen in a variety of clinical contexts, in- In the final stages, the appearance may be indistinguish-
cluding connective tissue disorders (especially systemic able from severe bullous emphysema.
sclerosis) and as a consequence of drug-related toxicity. It is important to recognize that findings of RB, DIP,
At the histologic level there are varying amounts of in- PLCH and the NSIP pattern of fibrosis commonly coex-
terstitial inflammation and fibrosis, which, in stark con- ist in biopsies of dypneic smokers. Some of the histolog-
trast to what is seen in UIP, has a temporally and spatial- ic changes are reflected on imaging, while others are be-
ly uniform appearance. low the resolution of chest CT.
On HRCT, one of the key findings is ground-glass
opacification which is typically bilateral and symmetri- Cigarette Smoking-Related Fibrosis
cally distributed in the lower zones [30, 31]. In some pa-
tients, the extent of ground-glass may decrease over time The relationship between cigarette smoke and fibrosis re-
and become replaced by reticulation (i.e., with UIP-like mains contentious [36, 4550]. Niewoehners original de-
features) [32]. Reticulation (generally without significant scription of RB did not include fibrosis of the alveolar
honeycombing) is usually also present. wall [33].However, there is substantial support for a rela-
tionship between cigarette smoke exposure and a pattern
Respiratory Bronchiolitis/Respiratory Bronchiolitis Interstitial of alveolar wall fibrosis other than UIP [46, 51-55]. In
Lung Disease/Desquamative Interstitial Pneumonia and our experience there is a group of dyspneic cigarette
Pulmonary Langerhans Cell Histiocytosis smokers who, as seen on CT, present with a combination
of well-formed cystic spaces that follow the typical up-
Respiratory bronchiolitis (RB), of variable severity, is an per-lobe-predominant distribution of smoking-related
almost invariable pathologic finding in all smokers [33]. emphysema, with variable surrounding ground glass
Importantly, this lesion is asymptomatic and not associ- opacity and reticulation that may extend into the lower
ated with physiologic impairment in the vast majority of lung zones [48]. These patients commonly present with
individuals. However, in a small minority, there will be strikingly normal flows and volumes on pulmonary func-
the clinical manifestations of an interstitial lung disease. tion testing and a low diffusing capacity. The unexpect-
It is this clinico-pathologic/radiologic entity that has been edly normal flows and volumes are the result of the op-
called respiratory bronchiolitis interstitial lung disease posing effects of emphysema and fibrosis [56].
(RBILD). The cardinal HRCT signs of RB/RBILD in-
clude soft centrilobular nodules, ground-glass opacifi- Sarcoidosis
cation, smooth thickening of interlobular septa, and lob-
ular foci of decreased attenuation [34-36]. Non-caseating epithelioid-cell granulomata are the
Desquamative interstitial pneumonia (DIP) was first histopathologic hallmark of sarcoidosis [57]. Since the
described by Leibow in 1965. Dypsneic patients with DIP granulomata have a tendency to distribute along the lym-
were found to have numerous inflammatory cells in alve- phatics, the lymphatic pathways that surround the axial
olar spaces [37]. The cells were thought to be desqua- interstitium that invests bronchovascular structures and
mated pneumocytes but are now recognized as the same those located subpleurally (including the subpleural lym-
macrophages identified in patients with RB and RBILD. phatics along the fissures) are typically involved. Not sur-
The majority of patients with DIP are heavy smokers and prisingly, a nodular infiltrate (presumably reflecting con-
the disease is now considered part of the spectrum of in- glomerate granulomata) with a propensity to involve the
flammatory lung disease related to the inhalation of cig- bronchovascular elements is a characteristic CT finding
arette smoke [34]. Patients with DIP suffer an increased [58, 59]. Subpleural nodularity is also commonly seen. In
incidence of pulmonary fibrosis that fits the histologic the later stages of the disease there may be obvious signs
pattern of NSIP [38, 39]. Imaging in patients with DIP is of established lung fibrosis with upper zone volume loss,
typified by homogeneous or patchy areas of ground glass parenchymal distortion, and traction bronchiectasis. Be-
opacity in the mid and lower lung zones [39, 40]. cause of the bronchocentric nature of the disease, signs
Langerhans cell histiocytosis (LCH) is confined to the of small-airways disease are seen at CT in some patients
lungs in approximately 90% of patients. Although the with sarcoidosis [60].
pathogenesis is unknown, most if not all of the patients
are cigarette smokers. Pulmonary LCH (PLCH) is char- Hypersensitivity Pneumonitis
acterized by bronchiolocentric collections of Langerhans
cells admixed with a variety of other inflammatory cells Exposure to a range of organic antigens will cause lung
forming a stellate nodule [41]. Over time infiltration of disease in some patients, probably due to an immuno-
the airway wall results in its damage and subsequent di- logically mediated response [57]. In the subacute stage,
latation [42]. In the late stage of PLCH, small stellate there is an interstitial infiltrate comprising lymphocytes
scars are surrounded by emphysematous spaces. Imaging and plasma cells with a propensity to involve the small
reflects the histologic progression, with early bronchiolo- airways (bronchioles). Scattered non-caseating granulo-
centric nodules in the upper lobes progressing to a com- mata may be seen. Predictably, at CT, there is diffuse
bination of bizarrely shaped cysts and nodules [43, 44]. ground-glass opacification, ill-defined centrilobular
92 S.R. Desai, J.R. Galvin
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IDKD 2015-2018
A Systematic Approach to Chest Radiographic Diagnosis

Melissa L. Rosado-de-Christenson1, Jeffrey S. Klein2
1 Department of Radiology, Saint Lukes Hospital of Kansas City, MO, USA; Department of Radiology, University of Missouri-Kansas City, MO, USA
2 Department of Radiology, University of Vermont College of Medicine, VT, USA
Introduction Lungs
Chest radiographs are frequently obtained for the assess- Lung Volume
ment of patients who present with a variety of thoracic
complaints. In addition, asymptomatic patients undergo- In normal subjects, postero-anterior (PA) chest radio-
ing a physical exam, a hospital admission, or a preopera- graphs obtained at full inspiration or total lung capacity
tive assessment may also undergo chest radiography. (TLC) result in the visualization of the ten posterior ribs
Accurate interpretation of chest radiographs requires above the diaphragm. Lung volume may be increased in
knowledge of imaging anatomy, as obscuration of nor- patients with obstructive diseases such as emphysema
mally visualized structures may be the only clue to the and reduced in those with restrictive diseases such as pul-
presence of an abnormality. Radiography allows the vi- monary fibrosis.
sualization and assessment of the lungs, central airways, Atelectasis may involve the entire lung, a lung lobe, or
pulmonary vasculature, mediastinum, heart, great ves- a pulmonary segment [1]. Obstructive (resorption)
sels, and chest wall (including skeletal and soft-tissue atelectasis is characterized by the absence of intrinsic air
structures). The superimposition of complex structures bronchograms. As it may result from endoluminal ob-
of various radiographic densities (air, water, calcium, struction, a centrally obstructing neoplasm such as lung
metal, fat) makes radiographic interpretation challeng- cancer must be excluded (Fig. 1). Relaxation (passive)
ing. Radiologists must work with technologists to atelectasis often results from mass effect, commonly
achieve proper patient positioning and optimal radi- from pleural effusion. Cicatricial atelectasis is related to
ographic technique. Unusual opacities must be assessed pulmonary fibrosis. Rounded atelectasis occurs adjacent
to determine whether they are intrinsic or extrinsic to to pleural thickening in which subpleural atelectatic lung
the patient and to exclude artifacts and foreign bodies. folds upon itself.
In addition, the radiologist must carefully evaluate all Direct signs of atelectasis include fissural displace-
visualized medical devices for appropriate course and ment, bronchovascular crowding, and shift of calcified
position. granulomas. Indirect signs include increased pulmonary
opacity, ipsilateral mediastinal shift, hilar displacement,
ipsilateral hemidiaphragm elevation, and compensatory
A Systematic Assessment hyperinflation of the adjacent lung [2].
Here we present a systematic approach to the analysis of Parenchymal Opacities

chest radiographs. An orderly assessment of each
anatomic region and structure will yield a comprehensive Parenchymal opacities include alveolar and interstitial
imaging evaluation, allow identification of subtle abnor- processes. Pneumonia typically manifests with consoli-
malities, and decrease interpretive errors. The following dation due to alveolar filling by purulent material and
must be evaluated in each and every chest radiograph: pa- may be lobar or sublobar, or it may manifest with patchy
tient positioning, radiographic technique, medical de- pulmonary opacities. Consolidation often exhibits intrin-
vices (if present), lungs (volume, opacities, vasculature), sic air bronchograms and may also result from alveolar
airways, hila, mediastinum (cardiomediastinal silhouette, edema or hemorrhage (Table 1).
great vessels), pleura, and chest wall. A pulmonary nodule is defined as a round or ovoid
density 3 cm in diameter [3]. A benign pattern of in-
trinsic calcification allows the confident diagnosis of

A Systematic Approach to Chest Radiographic Diagnosis 95
a b
Fig. 1 a, b. Left upper lobe atelectasis. Postero-anterior (PA) chest radiograph (a) shows left upper lobe atelectasis manifesting as a vague left
upper lung zone opacity with elevation of the left hemidiaphragm. The lateral chest radiograph (b) shows the opaque atelectatic left upper
lobe and anterosuperior displacement of the major fissure (arrows). The etiology of the atelectasis was a left upper lobe lung cancer
Table 1. Differential diagnosis of air space opacification (ASO) A pulmonary mass is a round or ovoid pulmonary
Finding(s) Disease opacity 3 cm in diameter and is highly suspicious for
malignancy, typically lung cancer. The radiologist should
Focal/segmental ASO Pneumonia, contusion, infarct,
lung cancer (adenocarcinoma)
look for pertinent ancillary findings of malignancy in-
cluding other lung nodules, lymphadenopathy, pleural ef-
Lobar ASO Pneumonia, endogenous lipoid
pneumonia, adenocarcinoma fusion, and chest wall involvement.
Patchy ASO Infection, cryptogenic organiz-
Interstitial opacities may manifest with reticular, lin-
ing pneumonia, adenocarcino- ear, and/or small nodular opacities. As the normal inter-
ma, metastases, emboli stitium is not visible on radiography, visualization of pe-
Diffuse ASO Edema, hemorrhage, ripheral subpleural reticular opacities is always abnormal.
pneumonia A reticulonodular pattern occurs when abnormal linear
Perihilar ASO Edema, hemorrhage opacities are superimposed on micronodular opacities.
Peripheral ASO Eosinophilic pneumonia, acute
respiratory distress syndrome,
contusion Table 3. Ancillary findings in patients with interstitial lung disease
and differential diagnostic considerations
Rapidly changing/resolving ASO Edema, eosinophilic pneumo-
nia, hemorrhage Finding(s) Disease
Hilar lymph node enlargement Sarcoidosis, lymphangitic
carcinomatosis, viral pneumonia
Table 2. Differential diagnosis of the solitary pulmonary nodule Clavicular/osseous erosions Rheumatoid associated ILD
Finding(s) Disease (UIP, NSIP)
Pleural effusion Infection, edema
Granuloma
Pleural plaques Asbestosis
Primary malignancy: Lung cancer, carcinoid tumor
Solitary metastasis Hyperinflation PLCH, end-stage sarcoidosis,
lymphangioleiomyomatosis,
Hamartoma emphysema with UIP
Focal organizing pneumonia
Esophageal dilatation Scleroderma associated ILD
Hematoma (UIP, NSIP), recurrent aspiration
Conglomerate masses Silicosis, sarcoidosis, talcosis
granuloma, for which further evaluation is not required. Basilar sparing PLCH, sarcoidosis
However, many pulmonary nodules are indeterminate on Basilar predominance UIP, aspiration
radiography and require further assessment and charac- ILD, interstitial lung disease; UIP, usual interstitial pneumonia;
terization with computed tomography (CT) to exclude NSIP, nonspecific interstitial pneumonia; PLCH, pulmonary
malignancy (Fig. 2 and Table 2). Langerhans cell histiocytosis
96 M.L. Rosado-de-Christenson, J.S. Klein
a b
Fig. 2 a, b. Solitary pulmonary nodule. a PA chest radiograph shows a nodule in the left mid lung zone (arrow). b Unenhanced chest com-
puted tomography (CT) (lung window) shows a lobular soft-tissue nodule (arrow) in the left upper lobe. Typical carcinoid tumor was di-
agnosed by CT-guided needle biopsy
a b
Fig. 3 a, b. Interstitial lung disease. a PA chest radiograph of a 62-year-old man with chronic progressive dyspnea shows diffuse bilateral pe-
ripheral reticular interstitial opacities and low lung volumes. b Coronal contrast-enhanced chest CT shows subpleural reticulation, traction
bronchiectasis (arrow), and honeycomb cysts (arrowhead), consistent with usual interstitial pneumonia
Interstitial opacities frequently result from interstitial stitial opacities in diseases such as sarcoidosis, siliciosis,
edema characterized by perihilar haze, peribronchial and lymphangitic carcinomatosis.
thickening, septal thickening, and subpleural edema often The idiopathic interstitial pneumonias are a distinct
associated with cardiomegaly and pleural effusion [4]. group of disorders often characterized by basilar pre-
Associated radiographic findings can help limit the dif- dominant pulmonary fibrosis associated with volume
ferential diagnosis (Table 3). loss. The diagnosis usually requires further imaging with
Cells and fibrosis may also infiltrate the pulmonary in- high-resolution chest CT to assess for the presence or ab-
terstitium, producing reticular and reticulonodular inter- sence of honeycombing (Fig. 3).
a b
Fig. 4 a, b. Lymphadenopathy. a PA chest radiograph shows bilateral hilar, right paratracheal, and aortopulmonary window lymph node
enlargement associated with reticulonodular opacities in the upper and mid lung zones. b Contrast-enhanced chest CT shows bilateral hilar
and subcarinal lymphadenopathy and multifocal perilymphatic pulmonary nodules, consistent with suspected sarcoidosis
Airways Table 4. Etiologies of hilar enlargement

Unilateral Bilateral
The trachea and bronchi should be assessed for size, pa- Lung cancer Sarcoidosis
tency, and course. Tracheal narrowing may be focal or Infection (granulomatous) Metastatic lymphadenopathy
diffuse. Focal tracheal narrowing or stenosis often results Metastatic lymphadenopathy Pulmonary hypertension
from mucosal damage from prolonged intubation. Airway Bronchogenic cyst Lymphoma
neoplasms may manifest as endoluminal soft-tissue nod- Valvular pulmonic stenosis (left) Infection (granulomatous)
ules that may be associated with volume loss. Endotra-
cheal tumors may grow to obstruct up to 75% of the air-
way lumen before symptoms ensue. Airway neoplasms convergence sign refers to enlarged vessels coursing to-
may also manifest as focal or diffuse airway stenosis and wards the enlarged hilum and signifies a vascular etiolo-
must be differentiated from inflammatory processes that gy. The hilum overlay sign refers to visualization of the
may produce airway stenosis. Bronchiectasis is defined normal hilar vasculature through a mediastinal soft-tissue
as irreversible bronchial dilatation and may result from mass that projects over the hilum (Table 4) [6].
infection, cystic fibrosis, primary ciliary dyskinesia, or
allergic bronchopulmonary fungal disease [5].
Mediastinum
Hila The mediastinum is the space between the mediastinal

pleural reflections bound anteriorly by the sternum and
On normal frontal chest radiographs, the right hilum is posteriorly by the thoracic vertebrae. It extends from the
lower than the left in 97% of cases, and the hila are at the thoracic inlet superiorly to the diaphragm inferiorly. It
same level in 3% of cases. Alterations of these relation- contains the heart, pericardium, central great vessels,
ships should suggest volume loss. The right hilum is an- esophagus, trachea, carina and proximal mainstem
terior to the left on lateral chest radiography. The inter- bronchi, the thoracic duct, lymph nodes, and mediastinal
mediate stem line, visible on lateral chest radiography, fat. The radiologist must be familiar with the normal me-
represents the posterior walls of the right mainstem diastinal contours and its normal lines, stripes, and inter-
bronchus and bronchus intermedius and should be as- faces in order to identify subtle abnormalities.
sessed for abnormal thickening, which may be seen in in-
terstitial edema and in central malignancies. Heart
Hilar enlargement may result from a central neoplasm,
lymphadenopathy (Fig. 4), or enlarged central pulmonary The right cardiac border is formed by the right atrium,
arteries, such as in pulmonary hypertension. The hilum and the left cardiac border by the left ventricle inferiorly
and a small portion of the left atrial appendage superior- Lines, Stripes, and Interfaces
ly. The right ventricle projects anteriorly and inferiorly on
the lateral chest radiograph. The posterior cardiac border The anterior and posterior junction lines represent the in-
is formed by the left ventricle inferiorly and the left atri- terfaces between the right and left upper lobes, and may
um superiorly. be thickened by fat, lymphadenopathy, or mediastinal
The heart must be assessed for its shape and size. The masses. The paravertebral stripes may be thickened by
normal pericardium is not visible on radiography. En- lymphadenopathy or fat. An abnormal convex contour of
largement of the cardiac silhouette may result from car- the upper azygoesophageal recess may result from sub-
diac enlargement and/or pericardial effusion. When the carinal lymphadenopathy or a bronchogenic cyst, while
volume of the latter is large, a water bottle heart mor- hiatus hernia often produces convexity of the lower one-
phology may be seen on frontal chest radiographs or an third of the azygoesophageal recess. Convexity of the
epicardial fat pad sign on lateral radiography. In the aortopulmonary reflection may be caused by mediastinal
epicardial fat pad sign, the pericardial effusion appears fat, lymphadenopathy, anterior mediastinal masses, or
as a curvilinear band of soft tissue 2 mm thick and out- anomalous vasculature [7].
lined by mediastinal fat anteriorly and by subepicardial
fat posteriorly. Constrictive pericarditis may manifest Mediastinal Masses
with linear pericardial calcification. Cardiac calcifica-
tions may correspond to coronary artery, valvular, or an- Mediastinal masses include primary and secondary neo-
nular calcifications or curvilinear calcification in a left plasms, mediastinal cysts, vascular lesions, glandular en-
ventricular aneurysm secondary to myocardial infarction. largement (thyroid and thymus), and herniations (hiatus
and Morgagni). Since 10% of mediastinal masses are vas-
Systemic Arteries cular in their etiology, a vascular lesion should always be
considered in a patient with a mediastinal contour abnor-
The normal aortic arch is readily visible on radiography mality.
and characteristically produces an indentation on the left The first step in the assessment of a mediastinal mass
inferior tracheal wall. With increasing aortic atheroscle- is determining that there is indeed a mediastinal abnor-
rosis and ectasia, a larger portion of the aorta is visible mality. Focal unilateral mediastinal masses are typically
and may exhibit intimal atherosclerotic calcification. The primary neoplasms, enlarged lymph nodes, cysts, and
left para-aortic interface projects through the left heart vascular aneurysms or anomalous vessels. While diffuse
and courses vertically towards the abdomen. The left sub- symmetric mediastinal widening without mass effect can
clavian artery is seen as a concave left superior mediasti- be seen in mediastinal lipomatosis, when lobulated or
nal interface on frontal chest radiography. A right aortic asymmetric it should suggest lymphadenopathy in a pa-
arch is usually associated with a right descending tho- tient with advanced lung cancer, metastatic disease, or
racic aorta. In the absence of associated congenital heart lymphoma (Fig. 5).
disease, it is also frequently associated with non-mirror The mediastinal mass should then be localized within
image branching characterized by an aberrant left sub- a radiographic mediastinal compartment (anterior, mid-
clavian artery, which may be seen as an indentation on dle or posterior) based on the lateral chest radiograph.
the posterior trachea on lateral chest radiography [7]. Ancillary findings should be noted, such as benign pres-
sure erosion in patients with paravertebral masses (typi-
Systemic Veins cal of neurogenic neoplasms). The cervicothoracic sign
can be used to localize superior mediastinal and thoracic
The azygos arch is visible at the right tracheobronchial inlet masses. Clinical factors such as age, gender, and
angle and normally measures 1 cm in diameter when presence or absence of symptoms allow the radiologist to
the patient is in the upright position. The azygos arch may provide a focused differential diagnosis prior to proceed-
be contained within an accessory azygos fissure, as an ing to cross-sectional imaging. Mediastinal widening in
anatomic variant. Enlargement of the azygos arch may the setting of trauma may represent hemorrhage from
occur in azygos continuation of the inferior vena cava, in traumatic vascular injury (Table 5) [8].
which the vertical portion of the azygos vein manifests as
a vertically oriented right-sided mediastinal interface [7].
Pleura
Pulmonary Arteries
Pleural abnormalities are those that involve the pleural
Enlargement of the pulmonary arteries may represent space, such as gas (pneumothorax) or fluid (pleural effu-
pulmonary hypertension and is typically associated with sion), or the pleural surfaces, including thickening (pleur-
enlargement of the pulmonary trunk. The pulmonary al plaques, neoplasms) with or without pleural calcifica-
trunk is visible as a left mediastinal interface located tion (pleural plaques, fibrothorax).
above the heart and below the aortopulmonary window Pneumothorax manifests with visualization of a pleur-
on frontal radiography. al line and may be traumatic, iatrogenic, or spontaneous.
a b
Fig. 5 a, b. Mediastinal mass. a PA chest radiograph shows bilateral

lobular mediastinal widening with mass effect on the trachea
(arrow) and findings of supraclavicular lymph node involvement.
b Sagittal reformatted CT shows an anterior mediastinal mass (m).
CT-guided core tissue biopsy showed non-Hodgkin lymphoma
Table 5. Differential diagnosis of mediastinal masses Spontaneous pneumothorax is categorized as primary (no
Anterior Middle Posterior visible underlying lung disease) and secondary (underly-
ing lung disease).
Lymphoma Lung cancer Neurogenic
neoplasm
Pleural effusion is categorized as transudative or ex-
Thymic neoplasm Lymphadenopathy Aneurysm udative, and manifests as blunting of the costophrenic an-
(lymphoma, metastases) gle, producing a meniscus. Transudative pleural effusions
Germ cell neoplasm Foregut cyst Extramedullary are usually secondary to heart failure. Exudative effu-
hematopoiesis sions are often secondary to infection, malignancy, or
Thyroid goiter Hiatus hernia pulmonary infarction. Pleural effusions may exhibit loc-
ulation, which should raise the suspicion of empyema in
a b
Fig. 6 a, b. Malignant pleural mesothelioma. a PA chest radiograph

shows circumferential, nodular right pleural thickening. b Axial
contrast-enhanced chest CT shows encasement of the right lung by
a circumferential nodular pleural thickening extending into the ma-
jor fissure (arrow)
a patient with signs and symptoms of infection. An air- wall could indicate an air leak in the setting of trauma,
fluid level in the pleural space in the absence of prior in- pneumomediastinum or pneumothorax.
tervention is diagnostic of a bronchopleural fistula. Mas-
sive pleural effusions and pleural effusions with associat-
ed pleural nodules should suggest malignancy. Circum- References
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to CT. Radiographics 27:33-48.
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indicative of chest wall involvement [11]. Benign pres- 671.
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IDKD 2015-2018
Diseases of the Chest Wall, Pleura, and Diaphragm

Aine Kelly1, Nicola Sverzellati2
1 University of Michigan Hospital System, Ann Arbor, MI, USA
2 Department of Surgical Sciences, Section of Radiology, University of Parma, Parma, Italy
Introduction tinguish those originating in the pleura from those aris-

ing in the chest wall, as the shape can be similar; how-
Chest radiography is useful to evaluate the chest wall, ever, the presence of bone destruction indicates an ex-
pleura, and diaphragm, while magnetic resonance imag- trapleural origin.
ing (MRI) provide high-quality studies of the extra-
parenchymal extent of lesions residing in the superior
sulcus (apical) region. As skeletal abnormalities are very Chest Wall Disease
difficult to detect, the individual bones must be careful-
ly examined. Normal variants, unlike abnormalities, are The normal chest wall is symmetric. The most common
often bilateral and reasonably symmetric, such that a causes of asymmetry are rotation and kyphoscoliosis. On
side by side comparison is helpful. To help distinguish a chest radiography, the side to which the patient is rotated
lung mass from an extraparenchymal (pleural, diaphrag- is more radiolucent (in a left anterior oblique/right pos-
matic, or chest wall) mass, determination of the angle terior oblique position the right side is more lucent).
between the mass and the lung edge is often informative: Chest radiography is useful to evaluate skeletal disease,
acute for lung and obtuse for extraparenchymal (Fig. 1). calcifications, and subcutaneous emphysema.
With extraparenchymal lesions, it may be difficult to dis-
Calcifications
Calcifications deposited in soft tissues may be metastat-
ic or dystrophic. Metastatic calcifications occur with el-
evated serum calcium, in which case calcium hydroxy-
apatite crystals are deposited in multiple locations, includ-
ing the lung, stomach, kidney, and vascular system [1].
Dystrophic calcifications in altered, necrotic, or dead tis-
sues are seen in patients with normal serum calcium and
phosphorus levels and occur in association with connec-
tive tissue disorders, in subcutaneous tissues, muscles,
and fascial planes as calcification universalis.
Soft-Tissue Masses
These must first be differentiated from asymmetries aris-
ing from patient positioning, contralateral surgery (mas-
tectomy), and atrophy (poliomyelitis and stroke). Prima-
ry tumors are rare. Malignancies include fibrosarcoma
and malignant fibrohistiocytoma, with lipomas as the
most common benign primary tumor. Neurogenic tu-
mors, such as neurofibromas, arise from intercostal
Fig. 1. Extraparenchymal mass forms an obtuse angle with the
chest wall in a patient with a solitary plasmacytoma. Note the bone nerves or the paraspinal ganglia and can be found at mul-
destruction indicating the origin of the tumor outside the lung and tiple sites in neurofibromatosis type 1 (von Reckling-
pleura hausen disease).

102 A. Kelly, N. Sverzellati
Inflammatory Diseases of the Chest Wall and cardiac injury. Sternal fractures are very difficult to
visualize on frontal chest radiographs and may be seen on
Bacterial infection of the chest wall is rare and typically the lateral view, but nearly all are visible by CT, which
involves the ribs and sternum. Osteomyelitis can spread will demonstrate any adjacent hematoma. Significantly
hematogenously or directly from an adjacent infectious displaced sternal fractures should lead one to look for as-
process, typically Staphylococcus aureus or Pseudo- sociated cardiac injury. Lower rib fractures can be asso-
monas aeruginosa. Radiography may demonstrate soft- ciated with hepatic, renal, or splenic injury. Abdominal
tissue swelling overlying rib destruction and a periosteal radiographs are helpful to depict fractures of the lower
reaction in chronic cases but computed tomography (CT) ribs, as they are better visualized.
and MRI are much more sensitive and specific. CT is A flail chest (or segment) occurs with five or more
limited in its detection of bone marrow abnormalities, consecutive rib fractures (or three or more ribs fractured
while MRI allows the early detection of osteomyelitis by in two places). The flail segment moves paradoxically
showing bone marrow edema on T2 and marrow hypo- during respiration, with resultant ventilatory compro-
intensity on T1 images. However, CT is more sensitive mise. Fractures of the thoracic spine account for 1530%
than MRI in showing cortical destruction and a periosteal of all spinal fractures. The most vulnerable segment is at
reaction. the thoracolumbar junction (T9T12). Most (~70%) tho-
Chest wall involvement with tuberculosis (TB) is un- racic spine fractures are visible on radiographs, but CT
common, occurring via hematogenous spread or, more shows almost all of them and, more importantly, will
rarely, by direct extension from the underlying lung or demonstrate the displacement or retropulsion of bone
pleura; the latter is referred to as empyema necessitans. fragments into the spinal canal and cord.
Chest wall involvement in TB manifests as osseous and
cartilaginous destruction and soft-tissue masses with cal- Bone Masses
cifications and rim enhancement [2]. Fungal infections of
the chest wall occur in immunocompromised patients, The most common non-neoplastic tumor of the thoracic
with Aspergillus accounting for 8090% of cases [3]. In skeleton is fibrous dysplasia, which accounts for 30%
15% of the cases of thoracic actinomycosis, the fungus of the benign bone tumors of the chest wall [7]. These
invades the chest wall, creating fistulas and empyema ne- slow-growing tumors often occur in the posterolateral
cessitans. Postoperative patients are at risk of Nocardia ribs and are usually asymptomatic unless pressure
infection. symptoms or pathologic fractures occur. Fibrous dys-
plasia manifests as an expansile lytic lesion with a hazy
Congenital Diseases of the Chest Wall or ground glass appearance. Plasmacytoma and multiple
myeloma are the most common malignant neoplasms of
Poland syndrome is characterized by aplasia of the the thoracic skeleton and can present as extraparenchy-
pectoralis major muscles, and occasionally by hypopla- mal masses with bone destruction, similar in appear-
sia of the ipsilateral chest wall, scapula, and ribs. Imag- ances to other metastases [8]. Bone lesions are well de-
ing reveals a smaller and more lucent hemithorax, fined; they have a punched out appearance. In advanced
while cross sectional imaging demonstrates the absence cases there is marked erosion as well as areas of expan-
of the pectoral muscles and a smaller, hypoplastic sion and destruction of bone cortex, sometimes with
hemithorax [4]. thick ridging around the periphery, giving a soap bub-
ble appearance.
Pectus Excavatum
Thalassemia
In this variant in chest wall development (incidence
1/4001/1000), the sternum is depressed relative to the With extramedullary hematopoiesis, hematopoietic tis-
anterior chest (ribs) and often tilts rightward, with the sues outside the bone marrow produce blood cells. This
mediastinum leftward [3, 5]. In most cases, it is a cos- occurs mostly in the chronic hemolytic anemias, with
metic issue only, but in severe cases, it can lead to pain, thalassemia being the most common. Normal marrow
dyspnea, and restrictive lung disease. On radiographs, the tissue can expand outside the medulla through perme-
right side of the mediastinum is indistinct, simulating ative erosions or by the reactivation of previously dor-
middle lobe airspace disease. The depressed sternum is mant hematopoietic tissues [9]. Ineffective erythro-
visible on the lateral projection [3]. poiesis leads to expansion of the bone marrow space in
the ribs, long bones, vertebral column, skull, and, char-
Injuries to the Thoracic Skeleton, Rib Fractures, and Trauma acteristically, facial bones, and may lead to osteoporo-
sis. Paravertebral and rib lesions are most often seen in-
Upper rib fractures suggest severe trauma, and a search cidentally but can occasionally cause mass effect on the
should be made for associated injury of the aorta, great spinal canal and cord compression. On radiography, bi-
vessels, and brachial plexus [6]. Fractures of the medial lateral lobulated paravertebral masses and rib expansion
clavicle and sternum are also associated with vascular are seen.
Diseases of the Chest Wall, Pleura, and Diaphragm 103
Pleural Disease surgically. Congestive heart failure effusions are usually

bilateral and typically symmetric, although occasionally
When assessing for pleural effusion or pneumothorax, they are unilateral or more asymmetric, with the right
the patients positioning for the radiograph should be tak- larger than the left. With unilateral effusions (or left larg-
en into account, as air moves upwards and fluid moves er than the right) in a non-surgical patient, other causes
downwards within the pleural space. In the critically ill include pneumonia, infarction, neoplasm, trauma, and
supine patient, air will rise to be anterior and fluid will connective tissue disorders (especially systemic lupus
layer posteriorly and over the apex as a cap. Intraperi- erythematosus and rheumatoid arthritis). With pulmonary
toneal gas rises to the highest point, under the diaphragm embolus, radiographs may reveal small unilateral or bi-
dome on upright radiographs. Even ill patients can roll lateral hemorrhagic pleural effusions and atelectasis.
onto their side for a decubitus view; in those with effu- Adjacent upper abdominal abnormalities can cause ef-
sions place the effusion side down to allow the fluid to fusion (most often unilateral), with the most common etio-
layer along the ribs. For suspected pneumothorax, the ab- logies including splenic trauma, subdiaphragmatic ab-
normal side should be up, to allow the air to rise. scess, pancreatitis, and ascites. Here, the clinical history
is very helpful, while thoracentesis can be diagnostic
Pleural Effusion (e.g., elevated amylase with pancreatitis). With ascites
(e.g., due to liver failure), pleural effusions can develop
On upright studies, pleural fluid produces a meniscus because of ascites leaking through the diaphragm. When
sign, displacing the affected lung away from the a right subdiaphragmatic abscess is suspected, ultrasound
costophrenic sulci and blunting the angle. Evaluate the can be very helpful, but for suspected left upper quadrant
posterior costophrenic sulcus (the lowest point) on upright fluid collections CT is better.
chest radiographs for small pleural effusions. On the Trauma can result in pleural effusion, more common-
frontal view, evaluate the lateral costophrenic angle or sul- ly unilateral. This is obvious with multiple rib fractures
cus, keeping in mind that a subpulmonic effusion may be but less apparent with, for example, aortic laceration in
present with the lateral costophrenic angle unblunted. the absence of fractures. Another less obvious case is a
With subpulmonic fluid, the ipsilateral hemidiaphragm malpositioned vascular catheter or feeding tube. Inadver-
will be of uniform attenuation. There will be a lack of vis- tent placement of a feeding tube into the lung is usually
ibility of the posterior lung vessels through the hemi- benign, as long as it is discovered before a feeding is giv-
diaphragm on the frontal view, and lateral displacement of en. However, pleural placement is not similarly benign, as
the apparent dome of the hemidiaphragm (with a more tension pneumothorax and empyema are among its im-
sharply sloping lateral aspect). On supine radiographs, portant consequences.
free flowing pleural fluid layers posteriorly, possibly ob-
scuring the meniscus or borders (with lung or normal Empyema
pleura). If the effusion is large enough, there may be an
apical pleural cap, as fluid caps the apex of the lung. Pneumonia patients commonly have uninfected pleural
Pleural fluid may be loculated in the presence of ad- fluid (sympathetic effusion). Infection of the pleura
hesions or scars. It can track into fissures even if not loc- (empyema) can occur as a complication, with organisms
ulated and is often recognizable because of its tapering such as TB and fungi having a particular predilection for
cigar-shaped appearance. A pseudotumor can occur the pleural space. The differentiation of empyema from
when the fluid has a more rounded shape; a homogeneous lung abscess can generally be accomplished by chest X-
density with a different shape on two orthogonal projec- ray alone and corroborated by thoracic ultrasound.
tions is a clue to its nature (as is a comparison between Empyemas typically make right or obtuse angles with the
old and follow up radiographs showing a change in size). adjacent chest wall, while lung abscesses usually demon-
With large pleural effusions, mediastinal structures strate acute angles only. In addition, empyemas are usu-
will deviate to the opposite side. Another important effect ally oval or lenticular in shape and therefore are larger on
of large pleural effusions is diaphragmatic inversion. one of two orthogonal projections, while lung abscesses
When this occurs, the two hemidiaphragms move in op- are more spherical in shape and thus more similar in size
posite directions during respiration. As a result, air may on two orthogonal projections. CT can help by demon-
move over and back between the two lungs (pendelluft or strating the empyema as more mass-like, deflecting ves-
pendulum respiration), with the net effect being increased sels and bronchi in its path, while lung abscess is more
dead space and significant dyspnea. Thoracentesis with destructive of lung structures but less mass-like. The
removal of enough fluid to restore the affected hemi- smoother margins of a pleural abnormality and the CT
diaphragm to its normal position may provide marked re- split pleura sign of enhancing visceral and parietal
lief of symptoms. Left hemidiaphragm inversion is easi- pleura around an empyema can also aid in the differential
er to diagnose, since it results in mass effect in the left diagnosis (Fig. 2).
upper quadrant, displacing the gas-filled stomach. Neither chest X-ray nor CT alone can establish the
In hospitalized patients, pleural effusions may arise as presence or absence of infection in the lung or pleural
a consequence of congestive cardiac failure or post- space; rather, clinical findings (such as fever and elevated
The differential diagnosis for pneumothorax is far

less extensive than that for pleural effusion. Most cases
follow trauma but can occur secondary to ruptured
blebs, with the latter typically found in aesthenic young
males. Interstitial lung disease is another potential cause
and honeycombing or lung cysts increase the risk of
pneumothorax, particularly in males with eosinophilic
granuloma and in females with lymphangioleiomyo-
matosis.
Other potential causes, in which the radiograph is nor-
mal, include subpleural abnormalities that tend to cavi-
tate, such as tuberculosis and metastases. Squamous pri-
mary neoplasms account for most cavitary metastases,
but cavitation is also a feature of sarcomas. Increased in-
trathoracic pressure (e.g., asthma or pregnancy) is anoth-
er potential explanation for pneumothorax with an other-
Fig. 2. Right pleural effusion with thickened visceral and parietal wise normal or nearly normal radiograph. A persistent
pleura (split pleura sign)
pneumothorax after chest tube insertion and suction sug-
gests either a malfunctioning chest tube, bronchial injury,
or bronchopleural fistula.
white blood cell count) are important in raising the pos- A special category of pneumothorax is the pneumo-
sibility of infection. The role of imaging is to localize the thorax ex vacuo, which is a complication of lobar collapse
infection to the lung or pleura. The final etiology of [10]. In this condition, the collapse results in a sudden
pleural effusion is sometimes established on clinical increase in negative intrapleural pressure surrounding
grounds alone. In difficult cases, diagnosis generally re- the collapsed lobe. As a result, gas from the ambient tis-
lies on thoracentesis and an analysis of the pleural fluid. sues and blood is drawn into the pleural space while the
Ultrasound imaging and marking of the adjacent chest seal between the visceral and parietal pleura of the adja-
wall can be helpful to guide thoracentesis. cent lobe or lobes remains intact. The pneumothorax re-
solves as soon as the bronchial obstruction is relieved
Pneumothorax and the collapsed lobe re-expands. Recognition of this
entity is critical as appropriate treatment is to relieve the
Air can enter the pleural space as a result of lung, tra- bronchial obstruction rather than insert a pleural
cheobronchial or esophageal injury. Pneumothorax is drainage catheter.
seen in 15-40% of acute chest trauma patients. Upright
frontal radiography is preferred for detecting pneumo- Hemothorax
thorax, as air tends to rise up within the pleural space.
However, lateral decubitus radiography with the suspect- Bleeding from low-pressure pulmonary vessels is usu-
ed side of the pneumothorax up is an alternative. Many ally self-limiting; however, injury to large central pul-
small and even moderate-sized pneumothoraces not visi- monary vessels, systemic thoracic veins or arteries, or
ble on supine radiographs are readily identified at CT. lacerated viscera can lead to a large, potentially life-
Pneumothorax is best diagnosed by visualization of threatening hemothorax requiring surgical intervention.
the lung edge outlined by pleural air. Apical lucency and As for pneumothorax, hemothorax can be difficult to
absence of vessels are less reliable and can be produced detect on supine radiographs, due to dependent posteri-
by bullae. As for pleural effusions, the detection of pneu- or layering. Signs of hemothorax on a supine chest ra-
mothorax becomes difficult with supine patients, with the diograph include apical cap, hazy increased opacity
non-dependent portion of the pleural space near the ante- projected over the hemithorax, and confluent lateral
rior hemidiaphragm. Lucency near the lung bases should pleural thickening. A hemothorax should always be
raise suspicion, particularly in the presence of the deep considered when rib fractures are found. CT is the most
sulcus sign, even when no lung edge is visualized. Pneu- accurate way to detect even small amounts of pleural
mothorax can track into fissures with air in the minor fis- fluid. On CT, hemothorax is suggested when the pleur-
sure considered as another sign of supine pneumothorax. al fluid measures 3540 HU. In some cases, depen-
A tension pneumothorax is a medical emergency, as dent layering of the higher-attenuation hematocrit can
mediastinal structures can be compressed, causing de- be seen in the pleural space. The delayed or late ap-
creased venous return to the heart and hemodynamic in- pearance of pleural fluid that continues to slowly accu-
stability. With increasing intrapleural pressure, mediasti- mulate over several days, particularly following a pen-
nal structures deviate contralaterally, with ipsilateral etrating injury or recent thoracic surgery, raises the
hemithorax hyperexpansion and hemidiaphragm depres- possibility of a chylous effusion secondary to thoracic
sion. duct disruption.
With chronic pleural hematoma, dependent layering of

the higher-attenuation hematocrit component may occur.
It is usually visible on CT, simulating a malignant effu-
sion. Malignant thymoma often causes unilateral multi-
focal pleural implants, but these are generally not associ-
ated with effusion.
Benign fibrous tumor of the pleura (benign mesothe-
lioma) often presents as a single pleural mass, ranging in
size from small to enormous [12]. Lesions may be pe-
dunculated, such that the mass may change position by
twisting around its pedicle. Even large benign fibrous tu-
mors are generally distinguishable from malignant
mesothelioma by their focal nature (malignant mesothe-
lioma being typically more widespread) and the lack of
associated pleural effusion. Benign fibrous tumors are
generally easily recognized as pleural lesions by their
shape, except when located in a pleural fissure, in which
case the lesion may be round and sharply marginated.
This lesion might raise concern for malignancy but CT
Fig. 3. Holly leaf appearance of bilateral calcified pleural localization of the mass to the pleural fissure makes
plaques, seen en face, in a patient with a history of asbestos expo- benign fibrous tumor the more likely diagnosis. Clinical
sure (he had worked in a shipyard). Note the calcified plaques also clues are sometimes also useful in diagnosing benign fi-
on the hemi-diaphragmatic surface
brous tumor, such as associated hypertrophic pulmonary
osteoarthropathy and, less commonly, hypoglycemia. In a
third of cases, malignant degeneration occurs, necessitat-
Pleural Plaques or Thickening ing excision.
Pleural metastases are far more common than primary
Unlike pleural fluid or air, pleural implants or plaques are pleural neoplasms. Many neoplasms metastasize to the
often better seen with CT than on chest X-ray. Pleural pleura, with those closest more likely (bronchogenic and
plaques are common in patients exposed to asbestos (as- breast). In a patient with a pleural mass and a known pri-
bestos-related pleural plaques), are usually bilateral, and mary neoplasm elsewhere, metastases should still be con-
are sometimes visibly calcified. A characteristic location sidered even if the malignancy is not frequently associat-
is at the diaphragmatic domes and under the lower posed with pleural disease. Ovarian cancer frequently
terolateral ribs [11]. With plaques visualized en face, the spreads to the peritoneum and can give rise to pleural ef-
imaging appearances are often irregularly shaped, poorly fusions when malignant ascites passes through hemidi-
marginated opacities. Calcified pleural plaques en face aphragm defects. Pleural metastases from ovarian cancer
often have scalloped outlines, giving a holly leaf -like are referred to as Meigs syndrome. Patients with pleural
appearance (Fig. 3). A clue to their extraparenchymal metastases may have unilateral or bilateral effusions.
(pleural) location is that the long axis of pleural plaques Malignant mesothelioma is the most common primary
is not parallel that of the underlying pulmonary vascula- neoplasm, typically appearing as lobulated pleural mass-
ture. es associated with pleural effusion, often unilateral. A
Unilateral pleural plaques can also occur with asbestos history of asbestos exposure (or bilateral calcified pleur-
exposure, but in this setting other possibilities, such as al plaques) can be a helpful clue but asbestos exposure is
prior empyema or trauma, should be raised. Untreated he- only documented in about half of mesothelioma patients.
mothorax or TB may result in a small hemithorax with In some patients, the lack of mediastinal shift away from
extensive pleural calcification (fibrothorax). the side of extensive pleural abnormality is a clue to the
diagnosis of malignant mesothelioma [13, 14]. Metastatic
Pleural Implants and Masses adenocarcinoma closely mimics malignant mesothe-
lioma, with circumferential nodular pleural masses often
Pleural implants may be seen with metastatic disease but including the medial pleura (Fig. 4).
metastatic disease more commonly causes pleural effu-
sion. Many pleural masses are obscured on chest radio-
graphy (and even on CT) by surrounding pleural effusion. Diaphragmatic Disease
However, not all pleural masses are accompanied by ef-
fusions. In these cases, CT may reveal soft-tissue im- The right hemidiaphragm is usually a rib interspace high-
plants, suggesting the malignant nature of the effusion. er than the left, with its upper border at the 5th anterior rib
Contrast-enhanced CT is generally better able to distin- through the 6th7th anterior rib interspace level on the
guish solid elements of pleural masses from effusion. posteroanterior radiograph. The diaphragm is inseparable
Bochdalek hernia include discontinuity of the posterior

or posteromedial diaphragm with protrusion of peritoneal
or retroperitoneal fat through the defect. Less commonly,
colon, small bowel, liver, spleen, or kidney may also her-
niate into the thoracic cavity. On CT, discontinuity of the
diaphragm is usually easily visualized [15]. On chest ra-
diography, the differential diagnosis will include lipomas,
lung or diaphragmatic tumors, neurogenic tumors, pul-
monary sequestrations, or intrathoracic kidney.
Morgagni Hernia
Less than 10% of congenital hernias are Morgagni hernias.
They arise anteromedially due to the failed fusion of the
sternal and costal portions of the hemidiaphragm [18, 19].
They are more common in females and occur more fre-
Fig. 4. Nodular thickening of the left pleura, including the mediasti- quently on the right, possibly due to greater support pro-
nal aspect, in a 43-year-old patient with malignant mesothelioma
vided by the pericardial attachments on the left. In adults,
protrusion of omentum is the most common form, and on-
ly rarely, bowel, stomach or liver. On imaging, Morgagni
hernia will appear as a fatty mass in the right cardiophrenic
from the abdominal structures on radiographs. Multipla- angle that can be difficult to differentiate from a prominent
nar CT is ideally suited to visualize the diaphragm due to epicardial fat pad. The differential diagnosis will include
its differential attenuation from adjacent intraperitoneal lipoma, teratoma, thymoma, thymolipoma, or liposarcoma.
fat and aerated lung. CT shows the diaphragm as a smooth Detection of displaced curvilinear omental vessels within
soft-tissue attenuation band-like structure that is thicker the mass or coursing across the diaphragmatic defect,
at the edges and thinner (sometimes imperceptibly) to- characteristic of Morgagni hernia, is best appreciated on
wards the central tendon [15]. Folds or bundles of muscles coronal CT or MRI.
(slips) run obliquely along the inferior surface, are often
asymmetric, and can have a mass like appearance if they Diaphragmatic Eventration
are seen in cross-section, especially in males, where they
are more prominent. Multiple slips can give the dia- An eventration is a congenital circumscribed area of di-
phragm a scalloped appearance where the muscle bulges aphragmatic muscular aplasia or thinning that allows
upwards on either side of them. Defects and hernias may bulging of the abdominal contents towards the thorax,
be congenital (Bochdalek, Morgagni or eventration) or ac- due to the relative pressure gradient between the peri-
quired (hiatus hernia, trauma, or paralysis). Predisposing toneum and the thorax [17]. Unlike a true hernia, the ab-
conditions for all abdominal hernias include pregnancy, dominal contents are still confined by a layer of pleura,
trauma, obesity, chronic constipation, and chronic cough. diaphragmatic tendon and peritoneum [15]. Symptoms
are rare and include tachypnea, dyspnea, recurrent pneu-
Bochdalek Hernia monia, and failure to thrive. These cases can be treated
with surgical plication (folding or tucking and suturing).
In adults, 90% of congenital hernias are Bochdalek her- Eventration occurs most commonly on the right side an-
nias. These hernias are more common on the left because teromedially and can become more pronounced with in-
of the protective effect of the liver on the right posterior- creasing intra-abdominal pressure, usually as a result of
ly [16]. Bochdalek hernias occur posterolaterally due to obesity. Imaging shows an anterior elevation of the
the persistence of a gap between the costal and vertebral hemidiaphragm, since the thinning and weakening in-
portions of the diaphragm, through which peritoneal fat volve this portion, with a normal posterior position. With
and, less commonly, kidney and other solid organs or diaphragmatic paralysis, the posterior portion will also be
bowel protrude [17]. Neonates and young children under elevated. On CT, there may be relative thickening of the
a year may present with respiratory symptoms, while old- muscle at the edge of the eventration. In some cases the
er children and adults more likely present with acute or edges are undercut, with upwards ballooning of the even-
chronic gastrointestinal symptoms, if any. Rarely, patients trated portion [17].
can present with bowel incarceration, strangulation, per-
foration, or shock. However, nowadays, most Bochdalek Esophageal Hiatus Hernia
hernias are discovered incidentally on CT imaging, as
small defects, particularly in patients with longstanding The esophageal hiatus is at the T10 level and contains the
obstructive lung disease. For incidentally discovered her- esophagus, vagus nerve, and sympathetic nerve branches
nias, no further action is needed. Imaging appearances of [16]. This ring functions as an anatomic sphincter by
constricting upon inspiration and helping to prevent gas-

troesophageal reflux. In hiatal hernia, there is herniation
of part of or, rarely, the entire stomach, or another ab-
dominal organ or fat. Obesity, aging, and general weak-
ening of the musculofascial structures may cause en-
largement of an esophageal hiatus. Esophageal hiatal
hernias can be sliding or rolling (para-esophageal) or a
combination of these two. Sliding hernias comprise 90%
of esophageal hernias, with displacement of the gastroe-
sophageal junction and a portion of (or the entire) stom-
ach upwards into the thoracic cavity, with loss of the usu-
al anti-reflux mechanism. With the para-esophageal type,
a portion (or all) of the stomach or other abdominal con-
tents, such as the spleen or intestines, roll up past the
gastroesophageal junction into the thoracic cavity. On
chest radiography, herniation of the stomach will be vis-
ible as an opacification behind the heart on the lateral
view and obliteration of the azygoesophageal line on a
frontal view [19].
Traumatic Diaphragmatic Rupture or Hernia

Diaphragmatic rupture occurs in about 5% of patients
with blunt trauma [20]. Mechanisms of injury include lat-
eral impact, which distorts the chest wall with shearing
forces across the diaphragm, and frontal impact, which
causes increased intra-abdominal pressure and blows Fig. 5. Unusual configuration and elevation of the left hemidiaphragm
out the diaphragm. Most diaphragmatic ruptures are as- in a trauma patient. A large tear in the left hemidiaphragm was found
sociated with significant intra-abdominal injuries. Left at surgery
and right diaphragmatic ruptures are thought to occur
equally frequently, but right sided ruptures may be more
clinically occult due to protection from the liver. Left rup- irregularity/obscuration (Fig. 5) or discontinuous con-
tures tend therefore to be reported in most (7590%) cas- tour; contralateral mediastinal shift; air-containing vis-
es, with the majority of tears occurring posterolaterally, cera above the hemidiaphragm; and basilar opacification
at the musculotendinous junction, i.e., the weakest por- and an abnormal U-shaped configuration of a gastric tube
tion. Most diaphragmatic tears resulting from blunt trau- with an elevated tip. However, these signs are non-
ma are 2 cm in length with many left tears being 10 specific and can also be seen with atelectasis, lung contu-
cm long. sion, subpulmonic pleural effusion, post-traumatic lung
Visceral organ herniation occurs in about half of the cysts, pneumothorax, hiatal hernia, and phrenic nerve
cases of diaphragmatic rupture, with the stomach and paralysis. Diaphragmatic eventration can also simulate
colon herniating most commonly on the left side, and injury, in which case comparison with old radiographs
sometimes small bowel, spleen, and kidney. On the right may be helpful. CT is better than radiography, with the
side, the liver most commonly herniates and occasional- advantage of multiplanar viewing. CT signs of diaphrag-
ly the colon. Herniation can be complicated by strangu- matic injury include: focal discontinuity of the dia-
lation, leading to ischemia, infarction, or obstruction. In phragm; non-visualization of the diaphragm (absent
some cases, herniation can be delayed after diaphragmat- hemi-diaphragm sign) or a large gap between the torn
ic rupture, but the relatively increased intra-abdominal ends of the diaphragm (perhaps with muscular contrac-
pressure will cause the defect to increase in size, increas- tion at torn ends; the curled diaphragm sign; Fig. 6);
ing the likelihood of herniation of the intra-abdominal herniation of peritoneal fat, omentum, bowel, or an or-
contents into the thorax. The progression may be pre- gan; focal constriction of bowel or an organ at the site of
vented if patients need positive pressure ventilation after herniation (collar sign) and herniated organs or bowel
their injury, which eliminates or reverses the pressure not supported posteriorly because of the ruptured dia-
gradient. The delay period between injury and herniation phragm falling dependently, abutting the posterior ribs
is known as the latent phase and can go for months or (dependent viscera sign). Other signs include concomi-
years, but most cases of strangulation declare themselves tant pneumothorax and pneumoperitoneum and/or hemo-
within 3 years of the trauma. thorax and hemoperitoneum. Coronal T2-weighted MRI
Chest radiography can show the secondary signs of can be used to document diaphragmatic injuries in the
herniation including: apparent hemidiaphragm elevation; non-acute setting.
Linear atelectasis may also be present, usually at the lung

bases. The differential diagnosis of bilateral diaphrag-
matic elevation includes poor inspiratory effort, obesity
with decreased chest wall compliance, subpulmonic
pleural effusions, subdiaphragmatic processes such as as-
cites, ileus, and organomegaly, and pleural adhesions.
With a unilateral elevated hemidiaphragm, the left
hemidiaphragm may lie at the level of or above the right,
or the right hemidiaphragm will lie more than the usual
one interspace higher than the left side. A paralyzed
hemidiaphragm will be elevated in its entirety, including
the posterior take off point, which helps differentiate it
from eventration.
Fluoroscopic sniff testing can be helpful in cases of
unilateral diaphragmatic weakness or paralysis, with
the weak side moving more slowly downwards (caudal)
or paradoxically upwards (with paralysis) during quiet
inspiration, deep inspiration, and sniffing [21]. The
sniff test can be falsely positive in normal individuals
Fig. 6. Coronal contrast-enhanced computed tomography. Traumat- and it is not as useful in patients with bilateral paraly-
ic left hemidiaphragmatic hernia, through which the spleen and sis. Ultrasonography has also been used to diagnose
vessels are partially herniating. The thickened medial portion of
the left hemidiaphragm is visible
paralysis, following the same principles as the fluoro-
scopic sniff test to assess diaphragmatic movement. CT
is very useful to evaluate processes that can contribute
to dysfunction or cause diaphragmatic elevation, in-
Penetrating injuries of the diaphragm are more com- cluding obstructive airways disease, pleural effusion,
mon than blunt injuries. The site of injury is more ran- subdiaphragmatic abscess, ascites, organomegaly, or
dom, depending on the trajectory of the penetrating ob- ileus. Dynamic T2-weighted MRI in the coronal (or
ject. These injuries tend to be smaller, most being 2 sagittal) plane can be used to assess paralysis, with the
cm and many 1 cm, related to the size of the pene- diaphragm depicted as a low-T2-signal structure. MRI
trating object. Visceral herniation is uncommon with can also allow quantitative evaluation, including the ex-
these smaller injuries. Penetrating injuries are usually cursion, synchronicity, and velocity of diaphragmatic
diagnosed clinically, relying on the entry site and direc- motion.
tion of the wound. Patients with these injuries com-
monly undergo exploratory surgery, at which time the Tumors of the Diaphragm
diaphragmatic injury is diagnosed and repaired. Imag-
ing findings include pneumothorax, hemothorax, or Primary tumors are rare and more than half are benign
radiopaque material associated with the projectile near [22]. Benign tumors are resected if they are symptomatic
the diaphragm or indicating the path through the dia- or if there is diagnostic doubt [22, 23]. The most common
phragm. primary malignant lesion is rhabdomyosarcoma, followed
by fibrosarcoma [8]. Direct involvement of the dia-
Diaphragmatic Weakness or Paralysis phragm from lung cancer and other intra-abdominal or
intrathoracic tumors, including mesothelioma and
There are many causes of weakness or paralysis, includ- esophageal and hepatic carcinomas, can occur. Drop
ing central nervous disease or phrenic nerve damage metastases may also be seen in thymoma and, with in-
from thoracic surgery or invasion by tumors [21]. Tho- traperitoneal spread, in ovarian cancer. The diaphragm
racic imaging is not usually rewarding when it comes to can also be involved by metastases due to benign process-
diagnosing the causes, except for direct invasion by tu- es such as endometriosis.
mors in the chest. Bilateral diaphragmatic paralysis is
usually symptomatic, often presenting with respiratory
failure. Diaphragmatic paralysis is more commonly uni- Conclusion
lateral, often asymptomatic, and usually discovered inci-
dentally on imaging. For evaluation of the chest wall, pleura, and diaphragm,
On radiography, bilateral paralysis manifests as the a combination of different imaging modalities coupled
smooth elevation of the hemidiaphragms and decreased with a good clinical history (especially trauma and
lung volumes. The costophrenic and costovertebral sulci known malignancy) and knowledge of imaging principles
will be deep and narrow. The lateral view reveals a (air, water, blood and soft tissue) can give valuable diag-
smooth contour and elevated diaphragmatic position. nostic clues.
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3. Baez JC, Lee EY, Restrepo R, Eisenberg RL (2013) Chest wall nant pleural mesothelioma: role of CT, MRI, and PET/CT in
lesions in children. AJR Am J Roentgenol 200:W402-419. staging evaluation and treatment considerations. Semin
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Radiol Clin North Am 44:213-224, viii. 18. Anthes TB, Thoongsuwan N, Karmy-Jones R (2003) Morga-
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9. Orphanidou-Vlachou E, Tziakouri-Shiakalli C, Georgiades CS 21. Kharma N (2013) Dysfunction of the diaphragm: imaging as a
(2014) Extramedullary hemopoiesis. Semin Ultrasound CT diagnostic tool. Curr Opin Pulm Med 19:394-398.
MR 35:255-262. 22. Kim MP, Hofstetter WL (2009) Tumors of the diaphragm. Tho-
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IDKD 2015-2018
Pulmonary Manifestations of Systemic Diseases

Cornelia Schaefer-Prokop1, Brett M. Elicker2
1 Department of Radiology, Meander Medical Centre, Amersfoort en Radboud University, Nijmegen, The Netherlands
2 Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA, USA
Introduction lution often occurring in 2 years. Mortality is between

1 and 5%.
Lung involvement in systemic disease may be a manifes- Staging (Siltzbach classification) is based on chest X-
tation of the underlying pathological process, a compli- ray findings, described in the following:
cation of the underlying disease, or related to treatment.
In certain diseases, such as sarcoidosis or Wegeners Stage 0 normal chest radiograph
granulomatosis, lung involvement is a predominant fea- Stage I bilateral hilar and paratracheal lymphadeno-
ture where in others, such as Henoch-Schnlein purpura, pathy
it is only rarely present. Stage II lymphadenopathy and nodular opacities
Lung involvement has a profound effect on progno- Stage III nodular opacities without lymphadenopathy
sis but it may be challenging to accurately diagnose. or signs of fibrosis
Imaging often plays a central role when it is suspected Stage IV fibrosis.
clinically. In the following, we focus on the more com-
mon systemic disorders in which pulmonary abnormal- This classification scheme is purely descriptive and
ities develop, including sarcoidosis, connective tissue does not indicate disease activity.
diseases, and vasculitis. While a comprehensive review Pulmonary findings include small, well-defined
of the lung manifestations of all systemic diseases is nodules in a characteristic perilymphatic distribution in
not possible, a few selected rare disorders (inflamma- relation to the subpleural surface, adjacent to the major
tory bowel disease, amyloidosis, Erdheim-Chester dis- fissures, along thickened interlobular septa, and adja-
ease, and IgG4-related sclerosing disease) are also dis- cent to vessels in the lobular core. The nodules may be
cussed. evenly distributed throughout both lungs, predominant-
ly in the upper and middle lung zones; however, they
may be also clustered in the perihilar and peribron-
Pulmonary Sarcoidosis chovascular regions with relative sparing of the lung
periphery, or they may be grouped in small areas. The
Sarcoidosis is a systemic disorder of unknown origin. It confluence of granulomas results in larger nodules (1-
is characterized by non-caseating epithelioid cell granu- 4 cm, nodular sarcoid, galaxy sign) or ill-defined
lomas in multiple organs, but morbidity and mortality are opacities (ground glass or consolidations, up to 10 cm,
closely related to pulmonary manifestations, occurring in alveolar sarcoidosis). On CT, lymphadenopathy is seen
90% of patients. The computed tomography (CT) ap- in up to 50% patients and is accompanied by calcifica-
pearance of pulmonary sarcoidosis varies greatly and tions, either eggshell or with an amorphous cloudlike
mimics that of many other diffuse lung diseases; con- pattern.
versely, the CT features of several diseases can resemble Up to 25% of patients develop irreversible pulmonary
those of sarcoidosis. fibrosis with architectural distortion, septal displacement,
The histology of pulmonary sarcoidosis consists of traction bronchiectasis, honeycombing, and bullae (stage
noncaseating granulomas with a rim of lymphocytes and IV). Conglomerate masses occur mostly in a perihilar lo-
fibroblasts in a perilymphatic distribution, which may ei- cation and represent areas of fibrosis with characteristic
ther resolve or cause fibrosis. The disease can occur at traction bronchiectasis. Volume loss of the upper lobes is
any age, but mostly affects individuals between 20 and 40 associated with hilar retraction.
years of age and only rarely occurs in those over 65 years Airway abnormalities include airway compression,
of age. The prognosis is mostly good, with disease reso- caused by the surrounding lymphadenopathy, and traction

Pulmonary Manifestations of Systemic Diseases 111
Table 1. Typical and atypical features of pulmonary sarcoidosis at The latter results in a mosaic pattern on expiration CT
high-resolution computed tomography that may even precede the appearance of other parenchy-
Typical features mal abnormalities and is considered an early sign of ex-
Lymphadenopathy: hilar, mediastinal, bilateral symmetric, well de- tralymphatic disease spread.
fined Sarcoidosis may present with very characteristic high-
Nodules: micronodules (2- to 4-mm), well defined, larger coalesc-
ing nodules
resolution CT (HRCT) features that secure the diagnosis
Perilymphatic distribution: subpleural, interlobular septa, peri- and obviate further invasive procedures. However, sar-
bronchovascular coidosis is also known to present with less typical fea-
Fibrosis: reticular densities, architectural distortion, traction tures (Table 1).
bronchiectasis, volume loss Especially in advanced disease stages with fibrosis,
Distribution: predominance of parenchymal abnormalities in upper
lobes and perihilar areas the differential diagnosis between sarcoidosis and other
fibrosing diseases can be very challenging. Table 2 sum-
Atypical features marizes the imaging findings that are helpful in differen-
Lymphadenopathy: unilateral, isolated, in atypical mediastinal lo-
cations tiating several diseases.
Airspace consolidations: conglomerate masses, confluent alveolar Complications include the development of aspergillo-
opacities (alveolar sarcoidosis) mas and pulmonary hypertension. Mycetomas are a typ-
Linear opacities: interlobular septal thickening ical complication of stage IV sarcoidosis: they present as
Fibrocystic changes: cysts, bullae, honeycomb like opacities, up- a soft-tissue mass located in a preexisting cavitation in
per lobe predominance
Airway involvement: atelectasis, mosaic pattern patients with fibrotic sarcoidosis. Life-threatening
Pleural disease: effusion, chylo/hemothorax, pneumothorax, pleur- hemoptysis may require immediate interventional thera-
al plaques py (embolization of the bronchial arteries). Pulmonary
hypertension occurs in patients with end-stage fibrosis
but may be also caused by mediastinal fibrosis, extrinsic
bronchiectasis, due to the surrounding fibrosis. Granulomas compression of the pulmonary arteries by lym-
within the bronchial walls lead to irregular bronchial wall phadenopathy, or intrinsic sarcoid vasculopathy, includ-
thickening with narrowing of the large and small airways. ing features of pulmonary veno-occlusive disease.
Table 2. Diseases with imaging features that overlap with sarcoidosis

Differential diagnosis Overlapping finding Suggestive of sarcoidosis
Lymphangitic carcinomatosis Irregular beaded thickening Upper lobe predominance
of the interlobular septa Absence of pleural effusion
Less central bronchial cuffing
Silicosis/Pneumoconiosis Pleural pseudoplaques No calcifications in pseudoplaques
Eggshell calcifications of lymph nodes Pseudoplaques consist of confluent nodules
Perihilar fibrotic masses The perihilar fibrotic masses extend directly from the hi-
lar structures and move posteriorly (upper lobe volume
loss)
Chronic EAA/chronic HP Honeycombing UIP pattern predominantly in upper lobes
and UIP/IPF Traction bronchiectasis or perihilar region
Architectural distortion Thickened interlobular septa
Lobular distribution of areas with air Lymph node calcifications
trapping (in the presence of obliterative Fibrosis and traction bronchiectasis tend to run
bronchiolitis) and fibrosis from the hilar structures dorsolaterally
Lymphoproliferative disorders Lymphadenopathy Usually but not always symmetric
Presence of typical parenchymal findings
(caveat: biopsy may be necessary)
Chronic beryllium disease Nodular pattern Large hilar lymphadenopathy
No exposure to beryllium
Other organ involvement
Tuberculosis Nodular pattern Egg shell or disperse calcifications as opposed
(normally random versus perilymphatic to rough TB calcifications
nodules, however, sarcoidosis may Symmetric calcifications (in TB frequently asymmetric)
occasionally show a random pattern) Clinical symptoms of acute infection in patients
with miliary TB
CVID Nodules in perilymphatic distribution Different clinical history (in CVID recurrent bacterial
Ill-defined nodules in mid-lower infection)
predominance Different histological features
EAA, exogenic allergic alveolitis; HP, hypersensitivity pneumonitis; UIP; usual interstitial pneumonia; IPF, idiopathic pulmonary fibrosis;
TB, tuberculosis; CVID, common variable immune deficiency
112 C. Schaefer-Prokop, B.M. Elicker
Collagen Vascular Diseases (NSIP). Of all connective tissue diseases, RA is the most
common to present with a UIP pattern. The CT findings
Collagen vascular diseases are characterized primary on in interstitial pneumonia associated with RA are often in-
clinical grounds, namely, typical clinical complaints and distinguishable from those of the idiopathic varieties;
physical examination findings. The presence of specific however, other findings, such as nodules, pulmonary ar-
autoantibodies may greatly assist in the correct diagnosis. terial enlargement, or pleural abnormality, may provide a
Involvement of the respiratory system is often seen in clue to the underlying diagnosis. UIP and NSIP both typ-
collagen vascular diseases and results in significant mor- ically demonstrate a subpleural and basilar distribution of
bidity and mortality. It is important to note that lung ab- findings. A confident diagnosis of UIP may be made
normalities may precede the other clinical manifesta- when honeycombing and reticulation is also present. In
tions, sometimes by more than 5 years. NSIP there is an absence of honeycombing and sub-
Lung injury from collagen vascular disease can affect pleural sparing is present.
each portion of the lung, the pleura, alveoli, interstitium, The introduction of a new generation of biologic
vasculature, lymphatic tissue, and both the large and agents used to treat RA has resulted in a new array of po-
small airways. Commonly, more than one compartment is tential pulmonary side effects. The most important of
involved. Many of the parenchymal manifestations of these is the impaired immunity related to the use of anti-
collagen vascular disease are similar to those of the idio- tumor necrosis factor (TNF) antibodies (etanercept, in-
pathic interstitial pneumonias and can be classified using fliximab, and adalimumab), which has resulted in a sub-
the same system. stantially increased incidence of tuberculosis (sometimes
Lung biopsy is rarely obtained in patients with a de- disseminated or extraarticular) and of nontuberculous
fined connective tissue disease. For this reason, HRCT of- mycobacterial infection.
ten determines the predominant pattern of injury, which in Low-dose methotrexate may be associated with suba-
turn is important in determining treatment and prognosis. cute hypersensitivity pneumonitis in 25% of patients.
While many patterns of injury are associated with the Pre-existing radiographic evidence of interstitial lung dis-
particular collagen vascular diseases, certain patterns are ease in patients with RA suggests a predisposition to the
more representative than others. For instance, nonspecif- development of methotrexate pneumonitis. Infections,
ic interstitial pneumonia is the most common pattern in such as pneumocystis pneumonia, are another potential
patients with scleroderma. It is also important to note that complication of therapy.
more than one pattern of injury may be present in the
same patient. Scleroderma (Progressive Systemic Sclerosis)
Rheumatoid Arthritis Parenchymal lung involvement is very common in pa-

tients with scleroderma. At autopsy, the lungs are abnor-
Most patients with rheumatoid arthritis (RA) have abnormal in at least 80% of cases. Lung fibrosis is the most
malities on HRCT. However, CT-detected abnormalities common pattern of abnormality, with NSIP being much
are often not associated with symptoms. Airways abnor- more common (90%) than UIP. Pulmonary hyperten-
malities such as bronchial wall thickening (1292%) or sion, either isolated or in association with lung fibrosis,
bronchial dilation (3040%) are more common than is another frequent finding. Pulmonary hypertension de-
parenchymal changes, including reticular abnormality velops especially in patients with limited scleroderma
(1020%), ground-glass opacity (1525%), honeycomb- (CREST syndrome). Esophageal dilation is seen on CT
ing (10%), and consolidation (5%). Nodular changes and in up to 80% of cases.
pleural disease, the latter preceding parenchymal The CT findings in scleroderma reflect the dominant
changes, are also seen. NSIP histology. Cellular NSIP presents with ground glass
Airways disease appears to be the earliest manifestation opacity and/or a fine reticular pattern, often in posterior
of RA in the lung. Bronchiectasis and air trapping are com- and subpleural distributions. Fibrotic NSIP shows irregu-
mon findings. There is a recognized association between lar reticulation and traction bronchiectasis as the predomi-
rheumatoid disease and obliterative bronchiolitis (constric- nant findings. Honeycombing is often absent, but when
tive bronchiolitis), in which the bronchioles are destroyed present it is limited in extent. Cellular and fibrotic NSIP
and replaced by scar tissue. The characteristic CT finding often co-exist such that the findings may overlap. Sub-
is mosaic perfusion with expiratory air trapping often as- pleural sparing is particularly suggestive of a NSIP pattern.
sociated with bronchial dilation. Follicular bronchiolitis is The lung fibrosis associated with scleroderma is asso-
a second type of small-airway disorder recognized in ciated with a much better prognosis than that found in id-
rheumatoid lung disease. The major CT finding is cen- iopathic lung fibrosis, probably due in part to the pre-
trilobular nodules and areas of ground glass opacity. dominant NSIP histology. Fibrotic changes may remain
Rheumatoid lung fibrosis is substantially more com- stable for many years. In a large treatment study, the ex-
mon in males than in females. The two most frequently tent of lung fibrosis identified on baseline CT was an im-
occurring patterns of lung fibrosis are usual interstitial portant independent predictor of physiologic progression
pneumonia (UIP) and nonspecific interstitial pneumonia and of the response to treatment.
Pulmonary arterial hypertension usually causes en- superimposed on a background of reticular abnormality
largement of the main and proximal pulmonary arteries, with traction bronchiectasis. This pattern reflects the
as seen on chest radiograph or CT, but normal-sized pul- characteristic histologic combination of OP and fibrotic
monary arteries do not exclude the diagnosis. The pres- NSIP. On serial evaluation, the changes of consolidation,
ence of pericardial thickening or fluid in patients with ground glass abnormality, reticular abnormality, and trac-
scleroderma is also a strong predictor of echocardio- tion bronchiectasis may all be partially reversible with
graphic pulmonary hypertension. treatment. Consolidation may also progress to reticular
There is an increased prevalence of lung cancer in pa- abnormality.
tients with scleroderma, especially in those with lung fibro- PM/DM can be associated with other collagen vascular
sis. The relative risk of malignancy ranges from 1.8 to 6.5. diseases (SLE, scleroderma, RA, Sjgren syndrome).
There is an increased risk for malignancy (especially breast
Systemic Lupus Erythematosus lung, ovary, and stomach malignancies), which in up to
20% of patients is concurrently diagnosed within 1 year of
Pleuritis is the most commonly seen pleuropulmonary follow-up.
manifestation of systemic lupus erythematosus (SLE),
found in 4060% of patients, and may or may not be as- Sjgren Syndrome (SS)
sociated with pleural effusion.
Fibrotic interstitial lung disease is less frequent in SLE CT provides substantial information regarding the pat-
than in the other collagen vascular diseases. While pul- terns of pulmonary involvement by Sjgren syndrome
monary infection is said to be the most common pul- (SS). These may be divided into airway abnormality, in-
monary complication of lupus, acute pulmonary hemor- terstitial fibrosis, pulmonary hypertension, and those
rhage is also an important pulmonary complication of suggestive of lymphoid interstitial pneumonia.
this condition, characterized radiologically by diffuse or Airway-related abnormalities consist of bronchial wall
patchy consolidation and ground glass abnormality. thickening, bronchiectasis, bronchiolectasis, and the tree-
In patients with lupus, acute lupus pneumonitis is a in-bud pattern. Small-airway disease may manifest as a
poorly defined entity, characterized by a variable degree mosaic attenuation pattern and expiratory air trapping.
of respiratory impairment accompanied by focal or dif- NSIP and lymphoid interstitial pneumonia (LIP) are
fuse pulmonary consolidation. It is now believed that the most common patterns of parenchymal lung disease.
most cases previously identified as lupus pneumonitis NSIP resembles that seen in scleroderma. LIP is charac-
probably represented acute interstitial pneumonia with or terized by ground glass abnormality due to the homoge-
without pulmonary hemorrhage. It is mostly associated neous lymphocytic infiltration. Peribronchovascular, cen-
with renal infiltration and multi-organ failure. trilobular, and subpleural nodules may also be seen, and
Other complications of lupus may include diaphrag- cysts measuring 530 mm are often present. These cysts
matic dysfunction, pulmonary hypertension, and pul- frequently contain thin septa; they may be associated with
monary thromboembolism, which may be related to the soft-tissue nodules sitting either close to them or in their
presence of antiphospholipid antibodies. Diaphragmatic walls. Similar cysts may be found in follicular bronchio-
dysfunction, thought to be due to a diaphragmatic myo- litis. These changes are ascribed to bronchiolar obstruc-
pathy, is manifested by reduced lung volumes (shrinking tion on the basis of lymphocytic wall infiltration. Cysts
lungs with plate-like atelectasis). are helpful in distinguishing LIP from lymphoma.
Lymphoma should be suspected if consolidation, large
Polymyositis/Dermatomyositis nodules (1 cm), mediastinal lymphadenopathy or effu-
sions are present. However, similar large, pseudo-alveo-
The presence of interstitial lung disease (ILD) in poly- lar, poorly defined nodules were found in four patients
myosistis/dermatomyositis (PM/DM) correlates strongly with combined amyloidosis and LIP. In contrast to other
with the presence of anti-Jo-1 antibodies. Between 50% cystic lung diseases, such as lymphangioleiomyomatosis,
and 70% of patients who are anti-Jo-1 positive have ILD the cysts of LIP show a peribronchovascular and lower
whereas the frequency of ILD falls to about 10% if anti- lung predominance.
bodies are absent. ILD may antedate myositis in patients
with anti-Jo-1 antibodies. Mixed Connective Tissue Disease
The most common pathological findings are NSIP and
organizing pneumonia (OP), often occurring in combina- Mixed connective tissue disease (MCTD) is an overlap
tion. As with other collagen vascular diseases, the occur- syndrome that is a distinct clinicopathological entity. The
rence of interstitial pneumonia may precede the develop- principal characteristics are the presence of: (1) features
ment of clinical myositis. of SLE, scleroderma, and PM/DM, occurring together or
Lung disease associated with PM/DM or with the evolving sequentially during observation; and (2) anti-
antisynthetase syndrome, a closely related entity, often bodies to an extractable nuclear antigen (RNP).
has a typical CT appearance consisting of confluent Pulmonary involvement is common in MCTD. A study
ground glass opacity and consolidation in the lower lobes of 144 unselected patients found CT evidence of infiltrative
Table 3. The most recent classification of systemic vasculitis: from the 2012 Chapel Hill Consensus conference
Vasculitis Pulmonary-renal Pulmonary Pulmonary
syndrome hemorrhage hypertension
Small-vessel vasculitis, GPA Pulmonary involvement 90% In about 10%
ANCA-associated (formerly Wegeners) Renal involvement 80%
Eosinophilic granulomatous up to 25% Rare
vasculitis with polyangiitis
GPA(Church Strauss)
Microscopic polyangiitis Frequently associated Frequent
with necrotizing
glomerulonephritis
Small vessel vasculitis, Cryoglobulinemic IgA
immune-complex type (Henoch Schoenlein)
HUV
Anti-GBM
(formerly Goodpastures)
Medium-vessel vasculitis PAN Very rare idiopathic,
associated with hepatitis B;
part of RA, SLE
Large-vessel vasculitis Kawasaki syndrome
GCA Rare, focal Rare
Takayasu arteritis Rare, focal Rare
Collagen vascular diseases RA Very rare, diffuse Up to 60%
SS Rare, diffuse with necrotizing 1060%
vasculitis
MCTD Rare, diffuse Up to 45%
SLE Up to 60%, late In at least 4%, diffuse 545%
ANCA, anti-neutrophil cytoplasmic antibody; GPA, granulomatous vasculitis with polyangiitis; HUV, hypocomplementemic vasculitis;
GBM, glomerular basement membrane; PAN, polyarteritis nodosa; GCA, giant cell arteritis; RA, rheumatoid arthritis; SS, Sjgren syn-
drome; MCTD, mixed connective tissue disease; SLE, systemic lupus erythematosus
lung disease in 67%. Many affected patients are asympto- established collagen vascular diseases is not yet known.
matic. The pulmonary abnormalities resemble those seen in The term lung-dominant CTD has been proposed for
SLE, SS, and PM/DM. Thus, pleural thickening and pleur- the subgroup of patients with: (1) NSIP, UIP, LIP, OP, or
al and pericardial effusions are common. Ground glass at- diffuse alveolar damage in the lung determined by his-
tenuation is the most frequent parenchymal abnormality. tology or HRCT; (2) insufficient extrathoracic features of
The CT pattern corresponds most closely to that of NSIP. a definite collagen vascular disease but a combination of
Less frequent findings include honeycombing, consolida- serologic features suggesting an autoimmune process;
tion, and poorly defined centrilobular nodules. and (3) no identifiable alternative cause for interstitial
Other important complications of MCTD are pul- pneumonia.
monary arterial hypertension, and esophageal dysmotili-
ty, with sequelae of recurrent aspiration.
Pulmonary Vasculitis/Diffuse Alveolar Hemorrhage
Undifferentiated Connective Tissue Disease (or Interstitial
Lung Disease with Autoimmune Features) The pulmonary vasculitides encompass a clinically, radio-
logically, and histopathologically heterogeneous group of
Not all patients with interstitial lung disease meet the cri- diseases that are usually associated with a systemic vas-
teria of having a collagen vascular disease. Among patients culitis. The clinical symptoms and radiologic signs sug-
with histologically proven UIP or NSIP whose disease was gestive of pulmonary vasculitis include diffuse alveolar
originally diagnosed as idiopathic, because it did not ful- hemorrhage (DAH), acute glomerulonephritis, upper-air-
fill the criteria of one of the established collagen vascular ways disease, lung or cavitary nodules, mononeuritis
diseases, subgroups of patients with one or more serolog- multiplex, and palpable purpura.
ical features of an autoimmune process have been subse- The classification of systemic vasculitis remains con-
quently identified. Several terms have been suggested to troversial. In the most recent classification, the Chapel Hill
describe the condition detected in these subgroups, includ- Consensus Conference (CHCC) of 2012 (Table 3), the
ing undifferentiated connective tissue disease (UCTD), in- main consideration remained the predominant vascular
terstitial lung disease with autoimmune features, and lung- size involved, but the presence of ANCA (anti-neutrophil
dominant CTD. Whether these patients have a better prog- cytoplasmic antibody) was newly added. Small vessel vas-
nosis than patients without these autoimmune features culitis (SVV) is divided into ANCA-associated vasculitis
or even a prognosis comparable to that of patients with (AAV) and immune complex SVV. AAV represents necro-
tizing vasculitis with only few or no immune deposits pre- tem (up to 50%). Involvement of the peripheral nerves is
dominantly affecting the small vessels; patients are MPO- more frequent while glomerulonephritis (GN) and pul-
ANCA or PR3 ANCA positive but in a minority of cases monary hemorrhage are less common than in GPA.
ANCA-negative. ANCA specificity should be indicated Up to 30% of patients are ANCA-positive, mostly
because it appears to identify distinct categories of disease. MPO-ANCA. Histology demonstrates small vessel (ar-
The combined involvement of the lungs and kidneys teries and veins) vasculitis with eosinophilic infiltrates,
by some of these diseases accounts for their description and vascular and extravascular granulomas. Five-year
as pulmonary-renal syndrome. Note that capillaritis/ survival is reported in up to 80% of patients; 50% of the
vasculitis can also manifest in the setting of the various deaths are related to cardiac involvement.
collagen vascular diseases. Upper-airways disease and pulmonary abnormalities
are seen in up to 70% of patients with CSS. The most
ANCA-Associated Granulomatous Vasculitis with Polyangiitis common pulmonary findings include transient, multifo-
(GPA, Formerly Wegeners Disease) cal, and non-segmental consolidations without zonal
predilection. The presence of (non-cavitating) small nod-
Granulomatous vasculitis with polyangiitis is the most ules or diffuse reticular densities has also been reported.
common of the AAV. It affects the sinuses, kidneys, and If located subpleurally, the consolidations mimic
lungs, resulting in the classic triad of symptoms com- eosinophilic pneumonia. Diffuse consolidations or
prising sinusitis and/or tracheobronchitis, pathological ground glass attenuation reflect hemorrhage.
chest X-ray (with or without hemoptysis), and micro- Airway abnormalities are also an important thoracic
hematuria. However, any part of the body may be in- manifestation and include wall thickening, dilatation, small
volved. Females and males are affected equally and at nodules, and mosaic perfusion. Increased interlobular septa
any age (mostly age 4055 years). Airway involvement may reflect edema caused by cardiac and/or renal involve-
is more frequent in males. The most common cause of ment or eosinophilic infiltration of the septa. Eosinophilic
death is renal failure. With treatment, the 24-month sur- pleural effusion is seen in up to 50% of patients.
vival is 80%. The factors initiating disease are unknown, Airway changes consisting of tree-in-bud, bronchial
but current data support the involvement of (recurrent) wall thickening, and bronchial dilatation are likely relat-
infection for GPA. Up to 80% of patients are (in the ed to asthma and develop in almost patients. Wall thick-
course of disease) ANCA-positive (mostly PR3-AN- ening can also be caused by eosinophilic involvement.
CA). Histologic findings include necrotizing granulo-
matous vasculitis of the small to medium vessels with- Microscopic Polyangiitis/Diffuse Alveolar Hemorrhage
out associated infection.
The most frequently seen pulmonary abnormalities are Microscopic polyangiitis is a systemic necrotizing small-
multiple nodules with or without a CT halo sign (peri- vessel vasculitis with granulomatous inflammation. Clin-
nodular hemorrhage). They tend to involve the subpleur- ically, it is characterized by a long prodromal phase with
al regions, but there is no predilection for upper or lower weight loss and fever followed by a rapidly progressive
lung zones. Although the nodules can be as large as 10 GN. Microscopic polyangiitis is the most common cause
cm, most are smaller. Cavitations have thick walls. Pe- of pulmonary-renal syndrome: rapidly progressive GN is
ripheral wedge-shaped consolidations resemble infarcts seen in up to 90%, pulmonary involvement in up to 50%.
and may also cavitate. Diffuse consolidations or ground More than 75% of patients are ANCA-positive in the
glass opacities represent pulmonary hemorrhage. Fibrot- course of disease, mostly MPO ANCA.
ic changes reflect preexisting disease. Microscopic polyangiitis is characterized by the com-
In addition there may be a concentric thickening of the bination of GN and diffuse alveolar hemorrhage (DAH).
tracheal or bronchial walls with diameter reduction, po- Imaging findings include patchy, bilateral, or diffuse air-
tentially causing atelectasis. Bronchial abnormalities space opacities. The opacity can show features of consol-
mainly involve the segmental and subsegmental bronchi. idations and ground glass, depending on the amount of
Involvement of the subglottic trachea is most typical. alveolar filling by blood. The opacifications may be dif-
fuse or more pronounced in the dependent lower parts of
Churg-Strauss Syndrome the lungs. A halo surrounding a consolidation or nodule
underlines the character of the hemorrhage. During the
Eosinophilic granulomatous disease with polyangiitis phase of resorption, interlobular lines (crazy paving)
(Churg-Strauss syndrome, CSS) is caused by a small-ves- are increasingly seen.
sel systemic vasculitis that almost exclusively occurs in Repeated hemorrhage leads to fibrosis, with honey-
patients with asthma and is characterized by a marked combing, reticulation, and traction bronchiectasis.
serum eosinophilia. Clinically, radiologically, and patho-
logically it combines features of GPA and eosinophilic Goodpasture Syndrome/DAH
pneumonia (allergic granulomatosis and angiitis). Many
other organs may be involved including the heart (up to Goodpasture syndrome describes the clinical triad of
47%), the skin (up to 40%), and the musculoskeletal sys- circulating anti-glomerular basement membrane anti-
body, DAH, and (necrotizing) GN. Presenting symp- Three radiographic manifestations of amyloidosis are
toms comprise an acute onset of dyspnea and hemo- described: nodular parenchymal, diffuse alveolar septal,
ptysis. and tracheobronchial. The nodular parenchymal form
Histologically, there is a linear deposition of IgG along presents radiographically as one or more solid lung nod-
the glomerular basement membranes, such that renal ules, often found incidentally. These may be confused
biopsy is used to establish the diagnosis. The serology with malignancy, particularly when spiculated borders
comprises c-ANCA or p-ANCA positivity in 30% and are present. A slow growth rate is typical, and calcifica-
anti-basement membrane antibodies in 90% of patients. tion may be present. The diffuse alveolar septal form is
Young males are more often affected than females characterized by the presence of widespread deposits
(M:F9:1), although the condition is also seen in elder- throughout the lungs. The most common findings are
ly females. With treatment, the prognosis is good. Recur- small nodules (typically in a perilymphatic distribution),
rent episodes cause pulmonary fibrosis. consolidation, ground glass opacity, and reticulation. The
Imaging features consists of diffuse or patchy ground presence of calcification associated with these abnormal-
glass or consolidations based on alveolar hemorrhage ities may be particularly suggestive. The tracheobronchial
that typically resolve within days. The subpleural space is form shows extensive thickening of the trachea and/or
usually spared, with predominance instead of the peri- bronchi with or without calcification.
hilar areas in the mid and lower lung zones. Pleural effu- The imaging findings of light-chain deposition disease
sion is uncommon. After recurrent episodes, traction are less well described. There are two types: nodular and
bronchiectasis, a reticular pattern, and honeycombing diffuse. The nodular type presents with scattered solid
may evolve. nodules, often associated with cysts. The nodules are typ-
DAH caused by pulmonary capillaritis (Table 3) needs ically located within or adjacent to the wall of the cysts.
to be differentiated from bland pulmonary hemorrhage The diffuse type may show diffuse small nodules, resem-
(e.g., coagulation disorders, mitral stenosis, drug- bling the diffuse alveolar septal type of amyloidosis.
induced, etc.) and hemorrhage associated with diffuse
alveolar damage (drug-induced, acute respiratory distress Erdheim-Chester Disease
syndrome, bone marrow transplantation, or crack cocaine
inhalation). Erdheim-Chester disease is an infiltrative disorder in
which non-Langerhans cell histiocytes are found in one
or more organ systems. The primary organs affected in-
Miscellaneous Systemic Disorders clude bones, brain, kidneys, and the cardiovascular sys-
tem. Middle-aged males are most commonly affected.
Inflammatory Bowel Disease While pathology is helpful in excluding lymphoprolifer-
ative malignancies, the pathological findings may be non-
Ulcerative colitis and Crohn disease are associated with specific; thus typical radiographic features are a key to
a wide variety of pulmonary complications, which may the correct diagnosis. Characteristic imaging findings in
precede the diagnosis of inflammatory bowel disease the chest include peri-adventitial aortic soft-tissue thick-
(IBD) or may occur years after the initial diagnosis, and ening that may involve the aorta and its main branches
even after complete colectomy for ulcerative colitis. In- diffusely, giving rise to the term coating of the aorta.
deed there is some suggestion that pulmonary complica- The most common lung finding is smooth interlobular
tions may be more common after surgical treatment, per- septal thickening, resembling pulmonary edema. The
haps because anti-inflammatory treatment is withdrawn. most characteristic finding outside of the chest is cir-
Both Crohn disease and ulcerative colitis can be associ- cumferential perinephric soft tissue, resembling lym-
ated with tracheobronchitis and airway stenosis. phoma.
Bronchiectasis and bronchial wall thickening are also
common. Small-airway involvement can have a pattern of IgG4-Related Sclerosing Disease
panbronchiolitis. Parenchymal abnormalities associated
with IBD include OP, pulmonary hemorrhage, and, in This disorder was originally thought to be isolated to the
Crohn disease, granulomatous infiltration. pancreas and thus was previously called lymphoplasmo-
cytic sclerosing pancreatitis. However, it is now realized
Amyloidosis and Light-Chain Deposition Disease that IgG4-related sclerosing disease is a systemic order
associated with IgG4 plasma cells and with fibrosclero-
These rare disorders are characterized by the extracellu- sis in multiple organ systems. The primary organs in-
lar deposition of proteins in one or more organs. They volved include the pancreas, hepatobiliary system, sali-
share clinical, radiographic, and pathological features. vary glands, and lymph nodes. The findings in the chest
The main difference between these two entities is the are variable and may include nodules, lymphadenopathy,
Congo red staining pattern and the fibrillar structure seen airway thickening, and pleural abnormalities. IgG4-related
on electron microscopy of amyloidosis. Both entities may sclerosing disease may account for a proportion of the
be associated with a plasma cell dyscrasia. idiopathic interstitial pneumonias.
Acknowledgment. D.A. Lynch, Dept. of Radiology, NJH Remy-Jardin M, Remy J, Cortet B et al (1994) Lung changes in
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this manuscript. Tanaka N, Kim JS, Newell JD et al (2004) Rheumatoid arthritis-re-
lated lung diseases: CT findings. Radiology 232:81-91.
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IDKD 2015-2018
CT Evaluation of Chest Pain: Acute Coronary Syndrome and Acute Aortic

Syndrome
Dominik Fleischmann1, Udo Hoffmann2
1 Department of Radiology, Stanford University School of Medicine, Stanford, CA, USA
2 Department of Radiology, Massachusetts General Hospital, Harvard School of Medicine, Boston, MA, USA
Background presence of significant coronary artery stenosis, their

specificities are only moderate when compared to that of
Chest pain is a common presenting symptom among pa- coronary angiography (ETT: 60%, SPECT: 64%, Echo:
tients visiting emergency departments (EDs) in the US 77%) [12-14]. Moreover, these tests are time-consuming
and is responsible for over 5.5 million visits annually, (e.g., SPECT: 23 h) and usually not available around the
second only to abdominal pain [1]. However, the number clock. Thus, the standard evaluation of patients with chest
of patients ultimately diagnosed with an acute coronary pain to rule out myocardial ischemia requires hospital ad-
syndrome (ACS), either ST-elevation myocardial infarc- mission for 2436 h [15]. The remarkable inefficiency of
tion (MI), unstable angina, or a non-ST elevation MI, is current evaluation strategies is also documented by the
20% [2]. The prevalence of acute aortic chest pain is fact that 10% of the six million patients admitted each
one to two orders of magnitude less than chest pain due year in the US ultimately receive a diagnosis of ACS at
to ACS [3]. For every 130 patients with ACS, there is on- discharge [16, 17]. In-patient care for negative evalua-
ly one patient with an aortic cause of chest pain. tions is a significant economic burden, in excess of $8
In the evaluation of patients in the ED who present billion annually for the US healthcare system [18-20].
with chest pain, the goals include the rapid recognition of The rapid development and dispersion of modern com-
conditions that require emergent care, such as ACS as puted tomography (CT) technology have resulted in the
well as the far less common acute aortic syndromes, and ability to acquire high-resolution three-dimensional
risk stratification for these conditions to allow for rapid datasets, with the elimination of cardiac motion artifacts
treatment and triage decisions. However, the accurate in coronary CT and the reliable suppression of pulsation
triage of individuals presenting with acute chest pain to artifacts in the ascending aorta [21]. These developments
the ED remains difficult because neither the chest pain have substantially changed the triage of patients present-
history [1, 2], nor a single set of established biochemical ing with acute coronary or aortic chest pain. Recent data
markers for myocardial necrosis (troponin I, troponin T, have confirmed the ability of early coronary CT angio-
creatine kinase, MB-type) [4, 5] nor initial 12-lead graphy (CTA) to allow the safe triage patients with sus-
echocardiography (ECG), either alone or in combination pected ACS. Our experience over more than a decade al-
(acute cardiac ischemia time-insensitive predictive in- so confirms the benefits of modern ECG-gating technol-
strument), identifies a group of patients that can be safe- ogy in the setting of acute aortic syndromes. Here we re-
ly discharged home without further diagnostic testing view the clinical context and state-of-the art of ECG-
[6-8]. As a result, the threshold to admit chest pain patients gated CT in the imaging of patients presenting to the ED
remains low, and over six million patients are admitted with acute coronary and aortic chest pain.
annually to US hospitals [2, 9-11]. The standard rule
out MI protocol consists of serial ECG and cardiac bio-
marker measurements and usually requires a noninvasive Acute Coronary Syndrome: Definition and Classification
stress test. These tests, whether exercise treadmill ECG
testing (ETT), stress echocardiography (Echo), or rest or The American Heart Association/American College of
stress myocardial perfusion imaging with Tc-99m Cardiology (AHA/ACC) guidelines [22-24] define ACS
(SPECT), require the exclusion of myocardial necrosis as follows: (1) STEMI (ST-segment elevation myocardial
with negative serial biomarkers and are performed to rule infarction): a new finding of ST-segment elevation of
out the presence of a hemodynamically significant coro- 0.1 mm in at least two anatomically contiguous limb
nary stenosis. While these tests have good sensitivities leads and/or 2 mm in at least two anatomically contigu-
(ETT: 76%, SPECT: 83%, Echo: 85%) for detecting the ous precordial leads in conjunction with elevated serial

120 D. Fleischmann, U. Hoffmann
levels of cardiac troponin-I (0.09 ng/ml); (2) NSTEMI Table 2. Stanford conceptual classification of acute aortic syn-
(non-ST-segment elevation myocardial infarction): a new dromes
finding of ST-segment depression of 1 mm or T-wave in- 1. Aortic dissection and dissection variants (diseased media)
version of at least 3 mm in at least two anatomically con- 1.a Classic aortic dissectiona
tiguous leads and elevated serial levels of troponin-I 1.b Intramural hematoma variant
1.c Limited intimal tear (limited dissection)a
(0.09 ng/mL); (3) UAP (unstable angina pectoris): clini- 2. Penetrating atherosclerotic ulcer (diseased intima)a
cal symptoms suggestive of ACS, such as typical chest dis- 3. Rupturing thoracic aortic aneurysma
comfort or the equivalent, with an unstable pattern of chest a Classic aortic dissection, limited intimal tear, penetrating athero-
pain (at rest, new onset, or crescendo angina), optimally sclerotic ulcer and rupturing aneurysm are lesions that can occur
with a markedly positive stress test (SPECT, Echo, or with or without associated intramural hematoma.
treadmill testing) and/or an invasive coronary angiogram
demonstrating a 50% epicardial coronary stenosis.
derlying pathology and allows for a broader spectrum of
manifestations, particularly within the dissection category.
Acute Aortic Syndrome: Definition and Classification We also consider symptomatic thoracic aortic aneurysms
as an acute aortic syndrome, and treat IMH as a dissection
Acute aortic syndrome is a contemporary clinical term, variant or as an unspecific imaging finding rather than as
analogous to acute coronary syndrome and referring to a a separate disease entity (Table 2).
spectrum of acute life-threatening abnormalities of the aor-
ta associated with intense chest or back pain [25]. Acute
aortic syndromes are much less common than acute car- ECG-Gated CT: Improved Chest Pain Triage in Patients
diac events, with an estimated annual incidence of approx- with Acute Coronary and Acute Aortic Syndromes
imately 6 per 100,000 for acute aortic dissection [3] (the
most common acute aortic condition requiring emergency Nowadays, fast scanner technology combined with
operative repair) versus more than 400 per 100,000 for heart-rate-reducing medication has made it possible to
acute MI. While the presumptive diagnosis of acute MI is image the coronary arteries without motion artifacts in
usually considered first, excluding acute thoracic aortic most patients. Indeed, state-of-the-art scanners acquire
disease is imperative to expedite appropriate treatment, 64320 cross-sections per rotation, depicting vascular
avoid deleterious thrombolysis, and circumvent unneces- details with a spatial resolution of 0.5 mm. ECG-syn-
sary delays associated with emergency coronary angiogra- chronized, contrast-enhanced images of the heart and
phy. The clinical picture of an acute aortic syndrome can coronary arteries can be acquired in one to five heart cy-
be caused by a wide range of aortic lesions and predispos- cles. The diagnostic performance of coronary CTA has
ing conditions. Traditionally, acute aortic syndromes have been investigated extensively in patients with stable
been ascribed to three main abnormalities [25]: (1) aortic coronary artery disease (CAD). Using invasive angio-
dissection, (2) intramural hematoma (IMH), and (3) pene- graphy as a reference, coronary CTA is more sensitive
trating atherosclerotic ulcer (PAU). Although poorly re- (98100%) than any other noninvasive technique [30].
flecting the underlying pathology and without including Because of its high negative predictive value (99100%),
the full spectrum of acute aortic diseases, these categories coronary CTA is recommended in patients with a low to
are almost universally used in the literature [26-28]. They intermediate probability of CAD and in patients with an
are also at the core of the current classifications of acute inconclusive functional test [31]. A normal cardiac CT
aortic diseases by the European and American Heart As- examination is associated with a low adverse cardiac
sociations (Table 1), with added subcategories for limited event rate in the following years [32] The reported per-
tears and iatrogenic/traumatic dissections [28, 29]. patient specificity (85%) is lower because stenosis
At our institution we use a conceptually different clas- severity is overestimated, often due to the presence of
sification of acute aortic disorders that is based on the un- calcifications, but it is not inferior to that of other non-
invasive techniques. In addition, radiation exposure has
decreased dramatically over the past years, such that dos-
Table 1. ESC Task force, and ACCF/AHA/AATS/ACR/ASA/SCA/
SCAI/SIR/STS/SVM guidelines for the diagnosis and management es of 5 mSv are now common practice using state-of-
of aortic diseases the-art technology; moreover, very recent innovations
permit doses under 1 mSv in selected patients [33]. Giv-
ESC/AHA/ACC/AATS classification
en the practical limitations of functional testing in the
Class 1 Aortic dissection ED setting and the relatively low prevalence of CAD in
Class 2 Intramural hematoma
Class 3 Discrete/Subtle dissection/Limited tear
patients visiting EDs, direct coronary visualization by
Class 4 Penetrating atherosclerotic ulcer CTA offers an attractive diagnostic alternative for the
Class 5 Iatrogenic and traumatic dissection early triage of ACS patients.
ESC, European Society of Cardiology; AHA, American Heart As-
CTA of the thorax and abdomen is a well-established
sociation; ACC, American College of Cardiology; AATS, Ameri- imaging technique for many acute abnormalities of the
can Association for Thoracic Surgery aorta. Even without the use of ECG gating, CTA of the
aorta has high sensitivity and specificity for the detection mentation of ECG gating for acute coronary CTA pro-
of acute thoracic aortic diseases and it has largely re- grams.
placed conventional diagnostic angiography [34]. How-
ever, over the last decade it has become clear that the Combined Triple-Rule-Out Protocol
spectrum of acute aortic abnormalities also includes sub-
tle yet important aortic lesions that evade nearly all cross- While it is technically possible to build CT protocols that
sectional imaging techniques, including non-gated CTA. allow imaging and interpretation of the entire aorta, the
Conversely, using ECG-gated CTA, the aortic root, coro- coronary arteries, and the pulmonary vasculature, such
nary arteries, and valve apparatus can be accurately as- studies are not performed at our institutions. A complete
sessed preoperatively. Finally, modern endovascular triple-rule-out protocol would require a longer injection
treatment options require much higher degrees of accu- of contrast agent (to opacify systemic and pulmonary ar-
racy in the delineation of pathology and treatment plan- teries simultaneously), resulting in artifacts from the su-
ning: both the exact size and location of a primary inti- perior vena cava and the right heart. To perform a guide-
mal tear and the branching pattern of the aortic arch are line-conforming work-up for aortic dissection, the scan-
affected by cardiac pulsation artifacts, and their suppres- ning range would have to include not only the entire chest
sion is highly desirable. but also the entire abdominal aorta and iliofemoral access
vessels, which implies greater radiation exposure. While
it is possible to detect an aortic dissection using coronary
CT Protocols in Patients with Acute Chest Pain CTA, and acute coronary abnormalities or abnormal myo-
cardial enhancement can be identified on a gated CTA for
The CT techniques used for the assessment of CAD are evaluation of acute aortic syndrome, these situations tend
different from those used in patients with acute aortic dis- to be rare. Some studies have suggested the limited effi-
eases; thus, selection of the correct protocol is the first cacy of these protocols since they are likely to be ordered
step in any CT imaging procedure and is based on clini- in patients with undifferentiated chest pain, who have a
cal judgment by ED physicians. very low event rate for any of the syndromes [35]. Con-
trary to common belief, there is not a wide clinical over-
Coronary CTA lap between ACS and acute aortic syndromes.
The assessment of coronary stenosis requires coronary

CTA of the highest quality. The scan range is restricted to Challenges to the Implementation of a Coronary CT
the heart. Premedication of the patient with nitroglycer- Program
ine and, above a prespecified heart rate (typically 65
bpm), with beta-blockers is necessary. The entire work- While the potential diagnostic value of cardiac CT in the
flow needs to be well established, as the introduction of a ED seems evident, there are practical obstacles that in-
coronary CTA program is not without substantial effort, terfere with its widespread implementation. CT equip-
even when all the technology is available. A guide on pa- ment with sufficient cardiac imaging capabilities (mini-
tient preparation, CT imaging protocols, CT imaging as- mally a single-source 64-slice system), fully-trained
sessments, and reporting is provided below. technologists, and experienced cardiac CT readers are
essential. Not all patients are eligible for cardiac CTA,
ECG-Gated CTA of the Aorta including those with known CAD, cardiac arrhythmia,
tachycardia, or severe obesity (typically BMI 40
In the evaluation of patients with acute aortic syndromes kg/m2). CTA is associated with risks due to radiation ex-
the goal in imaging is to eliminate or at least reduce pul- posure, although doses have decreased substantially over
sation artifacts. This can be achieved routinely even with- the past decade. The use of iodine-containing contrast
out beta-blockage. Nitroglycerine is also not required. media is contraindicated in patients with renal dysfunc-
The scan range always needs to include the entire aorta tion or related allergies. The guidelines emphasize that
and iliofemoral access vessels as a road-map for en- the choice of test, whether CT or another modality,
dovascular treatment. Use of ECG-gating does not pose a should be based on local expertise and the individual
major change of workflow for an established CT system characteristics of the patient that affect eligibility [36].
operating around the clock. While routine use of ECG More advanced CT technology, i.e., dual-source CT sys-
gating in the setting of acute aortic syndromes has sever- tems or wider detector arrays, can improve image quali-
al advantages, it may be an unnecessary effort outside of ty in somewhat less suitable patients. Presently, few cen-
centers with large surgical and endovascular programs. If ters have a sufficient number of experienced personnel
ECG gating is not routinely used for patients with acute to offer cardiac CT around the clock. Current published
aortic syndromes, a gated protocol should nevertheless be guidelines on the practice of cardiac CT in the ED spec-
available to further evaluate indeterminate findings on a ify the requirements for and maintenance of certification
non-gated scan. Another benefit of routine ECG gating for imaging centers, interpreting physicians, and medical
for thoracic aortic CTA is that it facilitates the imple- staff [36].
Suggested Coronary CTA Approach Important: In patients abstaining from phosphodi-

esterase inhibitors 48 h before the test, no nitrates should
The following sections provide guidance based on profes- be given during CT scan acquisition.
sional society standards and encourage the use of the rec-
ommended practices [36]. Cardiac CT should be performed CT Imaging Protocol
and interpreted in accordance with best practice standards
as delineated in the imaging guidelines of the Society of 1. Iodinated contrast agent with at least 320 (or 300) mg
Cardiovascular Computed Tomography (SCCT), using at iodine/mL.
least 64-slice technology and interpreted by physicians at a. Injection rate of contrast agent: minimum of 5 ml/s
least Core Cardiology Training Symposium (COCATS) and up to 8 mL/s in obese patients.
level 2 or equivalent, SCCT level 2, or certified by the Cer- 2. Determination of optimal contrast timing using either
tification Board of Computed Cardiovascular Tomography a test bolus or a bolus trigger technique
(CBCCT) [29]. Below is a summary of the standards that 3. Amount of contrast: duration of scan but at least a
should be considered at every institution: 10-s injection.
4. Minimizing the radiation exposure by choosing an ap-
Patient Preparation propriate field of view (at the level of the carina to the
dome of the diaphragm).
Contraindications
Steps
1. Absolute: Iodinated contrast allergy not amenable to
pre-treatment, pregnancy 1. Scout: Topogram anteroposterior and/or lateral
2. Relative: Renal insufficiency, multiple myeloma/ 2. Coronary calcium assessment
radioactive iodine therapy, untreated hyperthyroidism, a. Prospective ECG-gated/triggered, low-dose non-
inability to perform breath-hold for 15 s, cardiac contrast CT scan to determine coronary artery cal-
rhythm (frequent ectopy/arrhythmia), unwillingness to cification
abstain from metformin for 48 h after the CT exami- b. An Agatston score of 800
nation. c. No contrast-enhanced CTA
3. Assessment of coronary atherosclerotic plaque and
Prior to Arrival stenosis: Prospective ECG-triggered or retrospective
ECG-gated CT imaging using tube modulation tech-
1. Discontinue phosphodiesterase inhibitors for 48 h be- nique
fore the test. a. Maximal temporal and spatial resolution of the
2. Consider abstaining from nonsteroidal anti-inflamma- equipment
tory agents. b. Candidates for prospective triggering: regular heart
3. Consider 48-h abstention from metformin after the CT rate 62 bpm during breath-hold after beta-block-
examination. ade, no cardiac arrhythmias or premature beats pri-
4. Continue medications other than phosphodiesterase in- or to or during test breath-hold and 400 AS
hibitors/nonsteroidal anti-inflammatory drugs. 4. Adjusting kvp to BMI:
5. No solids 4 h prior to the scan, but otherwise may con- a. 100 kvp if BMI 30 kg/m2 AND body weight
tinue usual intake of liquids and solid foods. 220 pounds
b. 120 kvp if BMI 30 kg/m2
In the Scanner c. For retrospective gating: use radiation safety op-
tions according to the manufacturers guidelines
1. Patient positioning (i.e., tube current modulation, width of the full tube
a. Heart centered within the gantry current according to heart rate, hybrid techniques
b. Appropriate placement of ECG leads such as padding)
2. Patient preparation 5. Image reconstruction
a. A test breath-hold to monitor heart rate to decide on a. ECG editing in patients with premature beats
beta-blocker requirement and usage of prospective b. Reconstruction with approximately 50% overlap
vs. retrospective gating (e.g., 0.75-mm slice thickness with 0.4-mm incre-
b. Use of i.v. or oral beta blockers if heart rate is 60 ment or 0.6 mm slice thickness with 0.3-mm over-
bpm, e.g., 520 mg metoprolol i.v. or 50100 mg lap)
atenolol 1 h before (exceptions can be made for CT c. Reconstruction of the number of series necessary
scanners with high temporal resolution such as to eliminate motion artifacts, typically two data
dual-source or flash) sets, but more if required (i.e., for the right coro-
c. Use of nitroglycerin for coronary vasodilation, e.g., nary artery) in mid-diastole (6580%) and end
400800 g sublingual nitroglycerin (one to two systole (3545%) if retrospective technique was
tabs). used.
Left Ventricular Function Evaluation of the Left Ventricle

1. For either prospective (extending the gate) and ret- 1. Regional left ventricular (LV) dysfunction including
rospective ECG gating, data on global and regional wall motion and wall thickening of the myocardium
left ventricular function should be collected and as- assessed qualitatively based on the American Heart
sessed. Association, American College of Cardiology, Ameri-
2..Typically 1.5- to 2-mm-thick axial images are recon- can Society of Echocardiography (AHA/ACC/ASE)
structed at 10% increments (10 phases) for single- 17-segment model.
source CT scanners or 5% increments (20 phases) for 2..Whether the location of regional dysfunction matches
dual-source CT scanners throughout the cardiac cycle the stenosis location.
with a reduced pixel matrix of 256256. 3. Regional LV dysfunction has to be present in at least
two contiguous myocardial segments or in one seg-
Full Field of View ment visualized in two different views to be consid-
ered a true-positive finding.
1. If incidental findings are assessed: reconstruction of a 4. Each LV segment is graded as normal, hypokinetic
data set of 3-mm-thick axial images, covering the por- (impaired contraction), akinetic (absent contraction),
tions of the thorax acquired during the cardiac CT scan dyskinetic (paradoxical outward wall motion during
2. Reconstruction of a field of view optimized for cover- systole without aneurysm formation in diastole) or
age of the heart. aneurysmal.
5. Global LV function as normal, mildly, moderately or
Documentation of Radiation Exposure severely impaired.
6. Non-cardiac finding assessment should include aortic
Radiation exposure should be reported as the CT dose in- dissection, pulmonary embolism, pulmonary nodules,
dex per volume (CTDIvol), expressed in mGy, for a giv- pneumonia, pneumothorax, pericardial effusion, hiatal
en anatomic coverage (e.g., the heart) with or without the hernia, rib fractures.
corresponding dose-length product (in mGy per cm) for
each diagnostic acquisition (e.g., for the calcium score
and the CT angiographic acquisition), together with a to- Coronary CTA in Patients with Suspected ACS
tal dose length product (DLP).
The absence of plaque on CTA excludes ACS (sensitivi-
CT Parameters To Be Reported ty 100%), while obstructive CAD (50% stenosis) does
not (sensitivity 77%); only half of the patients with ob-
A diagnostic testing report should contain information on structive CAD on CTA have acute coronary disease. Sev-
beta-blocker and nitrate administration, imaging se- eral randomized controlled trials have investigated the
quences performed, overall contrast administration, in- safety and economic performance of cardiac CT in acute
cluding the contrast agent used, and the overall radiation chest pain (Table 3) [3739]. Taken together, the three tri-
dose. als comprised more than 3000 patients. Follow-up analy-
sis demonstrated that, based on the CTA results, not a sin-
Report on the Coronary Arteries gle patient was discharged with a missed diagnosis of
ACS. These trials demonstrated the efficiency of CTA
1. Arterial distribution (right or left dominant, co-domi- compared to the standard of care (SOC) as evidenced by
nant) a reduction in length of stay, hospital admissions, and ED
a. Rate overall image quality as interpretable/uninter- cost, while overall hospital costs remained similar to
pretable; specify non-evaluable segments/arteries those of the SOC, driven by a higher rate of invasive an-
and reason giography and revascularizations. Across the trials, pa-
2. Presence and extent of coronary atherosclerotic plaque tients randomized to CTA more often underwent cardiac
(none, calcified, non-calcified, both) according to catheterization (8.4% vs. 6.3%) and percutaneous coro-
American Heart Association (AHA) classification per nary intervention (4.6% vs. 2.6%). Unfortunately, the tri-
vessel and optionally per 17 coronary segments, in- als were not powered to prove that higher sensitivity for
cluding presence and severity of a significant coronary the detection of obstructive CAD by CTA, with subse-
stenosis (70% luminal narrowing) per vessel and op- quently increased revascularization rates, also results in a
tionally per 17 coronary segments. better clinical outcome. Additionally, radiation exposure
a. Degree of luminal narrowing should be as follows: will be higher for CTA when the SOC consists of exer-
normal: 0%, non-significant/minor disease: 149%, cise tests and stress echocardiography. In summary, these
moderate disease: 5069% (except left main, where trials have established cardiac CT as a viable alternative
50% is considered significant), significant dis- to functional testing in the triage of low-risk patients with
ease: 7099%, occluded: 100%. acute chest pain. Several studies demonstrated that CTA
findings of plaque, stenosis, and ventricular function
Table 3. Randomized controlled trials comparing coronary CTA with the standard of care in the evaluation of acute chest pain
Study CT-STAT ACRIN ROMICAT II
(2011) (2012) (2012)
Population 699 1370 985
TIMI risk score 04 TIMI risk score 02 Lowintermediate risk
MI 0.9% MI 1% MI 2.5%
Randomization 1:1 2:1 1:1
Control group SPECT MPI Usual care Usual care
CTA Controls CTA Controls CTA Controls

ACS diagnosis 1.1% 2.4% 1% 1% 9% 6%
ED discharge 50% 23% 47% 12%
ICA rate 8.0% 7.4% 5% 4% 12% 8%
Revascularization 4.3% 2.7% 3% 1% 6% 4%
Time to diagnosis 2.9 ha 6.3 h
(median, range) (2.1-4.0) (4-19)
Length of stay 18.0 h 24.8 h 23.2 ha 30.8 h
(median, range) (8-27) (19-31)
1 month MACE 0%a 0% 0.4% 1.2%
6-month MACE 0.8% 0.4%
Cost (US$) 2137b 3458 4026c 3874
TIMI, Thrombolysis in myocardial infarction; CTA, computed tomography angiography; ACS, acute coronary syndrome; ED, emergency
department; ICA, invasive coronary angiography; MACE, major adverse cardiac event; MI, myocardial infarction.
Statistically significant results are shown in italic.
a Primary endpoint of the study.
b Represents only emergency department costs.
c Represents index hospitalization including angiograms and interventions.
accurately predict adverse cardiac events over the next 6 incorporation of morphologic plaque assessment and by
months to 2 years. While patients without CAD remain applications to assess the functional relevance of CAD
virtually event-free, those with non-obstructive CAD on CTA. Additionally, high-sensitive-troponin assays
have a slightly increased risk, and those with obstructive may allow the safe exclusion of ACS without the need
CAD are at the highest risk [32]. for further diagnostic testing in a proportion of patients.
Hence, early triage by cardiac CT may re-focus efforts
towards those patients with (conflicting) low elevations
Current Recommendations and Future Expectations in high-sensitive-troponins.
Several guideline documents discuss the role of cardiac

CT in the management of acute chest pain, including the Potential of CCTA Beyond the Coronary Lumen
2010 Cardiac CT Appropriateness Criteria, which in-
cluded representation by the ACC, AHA, and SCCT, the Resting myocardial ischemia or MI can be identified on
2011 ESC Non-STE-ACS management guidelines [39], CTA datasets as myocardial hypo-enhancement. The
and the 2014 SCCT guidelines for CCTA in acute chest presence of resting myocardial enhancement defects on
pain [32, 36], suggest cardiac CT as appropriate in pa- CTA has a sensitivity and specificity of around 90% to
tients with low to intermediate risk for ACS, defined as identify MI patients. The hemodynamic severity of
a non-diagnostic ECG and serum biomarkers. The 2014 CAD can also be determined by calculation of the frac-
SCCT recommendations have been informed by the tional flow reserve (FFR) from CT angiograms using
ACRIN (American College of Radiology Imaging Net- computational fluid dynamics. CTA-derived FFR can
work) and ROMICAT (Rule Out Myocardial Ischemia/ confidently exclude hemodynamically significant
Infarction Using Computer Assisted Tomography) II CAD. Neither of these applications is currently the
results, published in 2012. It is important to emphasize clinical standard but they add much needed information
that information from cardiac CT needs to be interpret- on functional testing. Moreover, they have the potential
ed in the context of all clinical and diagnostic informa- to improve the efficacy of CCTA by improving its
tion available (Table 4). In the future, the diagnostic specificity, thereby reducing unnecessary referrals to
value of cardiac CT may be further strengthened by the invasive angiography and other downstream testing.
Table 4. Clinical interpretation of cardiac CT in the emergency department

Immediate evaluation of life-threatening conditions Management recommendation
Coronary arteries 70% stenosis (myocardial hypo-enhancement) Hospital admission, catheterization if symptoms
suggestive of ACS
Moderate stenosis (4070%) Observation (admission), second troponins,
consider stress testing
Atherosclerotic plaque, 40% stenosis ACS ruled out after second negative troponins,
no stress testing, (clinical) observation
depending on clinical presentation, consider
non-cardiac causes
No or minimal atherosclerotic plaque ACS ruled out, consider non-cardiac conditions
Other cardiac Pericardial effusion, aortic valve disease, myocardial scar As indicated
Thoracic aorta Acute aortic syndrome (within scan range) As indicated
Pulmonary arteries Pulmonary emboli (as far as scan range As indicated
and opacification allows)
Extravascular Pulmonary disease (pneumonia, pneumothorax) Appropriate referral
Other Relevant, but not acutely relevant, cardiac and non-cardiac
abnormalities (which may be evaluated during office hours) Appropriate referral
ACS, Acute coronary syndrome.
Simplified diagnostic algorithm, depending on local conditions and practices. Management also affected by risk profile and other findings.
Cardiac CT does not exclude ACS by functional coronary artery disease (spasm).
CT Evaluation of Acute Aortic Syndromes simply due to the much faster helical acquisition with
short rotation times and detector bank widths of at least
The sensitivity and specificity of non-gated CT for acute 4 cm.
aortic abnormalities have been reported to approach The following guiding principles may help in the deci-
100%. CTA can reliably assess complications of aortic sion to implement ECG gating for acute aortic syndromes:
diseases and guide treatment decisions. However, there Suppression of pulsation artifacts is highly desirable in
are subtle lesions of the aorta that can be missed with the ascending aorta
non-gated CT [40]. Cardiac pulsation artifacts may also Dynamic (time resolved) visualization is intriguing but
mimic disease, particularly in younger individuals. While may not provide critical information beyond an arti-
ECG gating clearly improves both assessment of the aor- fact-free static dataset
tic root, including the coronary artery origins and the Assuming a prevalence of 5% of limited tears (dissec-
valve apparatus, and visualization of subtle aortic lesions, tion variant) that might be missed without gating and
the superiority of gated versus non-gated CT acquisitions those cases in which pulsation artifacts mimic aortic
in acute aortic disease has yet to be assessed in a prospec- lesions or do not allow their exclusion, a reasonable es-
tive trial. The possibility of reconstructing time-resolved timate for the proportion of patients benefitting from
datasets to display dynamic changes in the position of a gating is probably in the order of 510%
dissection flap or the size of a true or false lumen pro- If ECG-gating can be achieved at no or minimal addi-
vides intriguing insights into the hemodynamic conse- tional dose and without an unreasonably complicated
quences of a given pathology. The best CT protocol for workflow, it is the opinion of the authors that gating
the evaluation of acute aortic syndromes depends on sev- should be implemented
eral factors, including the scanner generation, patient If ECG-gating is not routinely used, e.g., in a setting
population, and expected prevalence of acute aortic dis- with a low prevalence of patients with acute aortic dis-
eases, the comfort and training level of night- and week- ease, a dedicated gated protocol should still be avail-
end technologists, as well as the expertise of readers. able for problem solving (e.g., in the 510% of cases
ECG-gating technologies include retrospective gating, in which it is deemed necessary) following an incon-
which allows 4D reconstructions but comes with a slight clusive non-gated study.
radiation-dose penalty. Prospective triggering involves a
lower dose of radiation but requires larger detectors if the
entire thoracic aorta is to be covered. High-pitch helical Aortic Dissection and Its Variants
scans (so-called flash mode) are an intriguing alternative,
but require high-power X-ray tubes or small patient size. Our conceptual approach to acute aortic syndromes
It is also worth mentioning that improved scanner tech- groups all the manifestations of a diseased aortic media
nology reduces pulsation artifacts even without gating, into the dissection group. The common pathologic
denominator of these diseases is the presence of an ab- penetrating ulcer, or even trauma blood can extend in-
normal aortic medial layer, traditionally (albeit not com- to the neighboring aortic wall and result in IMH. These
pletely accurately) described as cystic medial necrosis. local hematomas typically do not extend far along the
Cystic medial necrosis is the common pathologic end- aorta or its branches when associated with a PAU, but are
point of several underlying acquired and inherited condi- typically local.
tions, ranging from severe hypertension and normal ag- While IMH can occur in underlying cystic medial
ing to familial aortic diseases, vasculitis, and connective necrosis as well as in PAUs, this does not make these le-
tissue diseases such as Ehlers-Danlos, Loeys-Dietz, or sions the same entity, and the notion that PAUs can be-
Marfan disease. come dissections and vice versa does not reflect our ex-
Classic dissection (class I) is characterized by a pri- perience. The one patient group in which overlapping and
mary intimal tear (in which blood enters the false lumen), indistinguishable features of PAU, IMH, and elements of
a false channel, or a lumen within the aortic media that dissection may occur in the same individual are typically
is separated from the true lumen by a dissection flap older individuals with moderate atherosclerotic burden
made of intima and a considerable portion of the media. and presumed coexisting cystic medial necrosis, which is
A common variant of aortic dissection manifests as an a known manifestation of normal aging as well. In this
IMH (class II). The abnormal space within the aortic me- particular situation the overlapping imaging features may
dia enabled by the underlying cystic medial necrosis is reflect coexisting intimal (atherosclerotic) and medial
filled by thrombus rather than by flowing blood. It is im- (cystic degeneration) disease in the same patient.
portant to realize that elements of classic dissection and
its IMH variant may coexist in the same individual. For Penetrating Atherosclerotic Ulcer (Class IV)
example, it is not uncommon to find areas of intramural
blood in patients who otherwise have features of classic The pathologic definition of a PAU is a deep ulcerated
dissection. At the same time, in most patients with IMH plaque that penetrates the internal elastic lamina into the
it is now recognized that small primary intimal tears as medial layer of the aorta [42]. PAU is therefore a mani-
well as other small communications between the true lu- festation of atherosclerosis (and not of cystic medial dis-
men flow channel of the aorta and portions of the throm- ease). The risk profile of patients with PAU is different
bosed false channel do exist [41]. from that of patients with aortic dissection. Patients are
A so-called limited tear of the aorta, or limited dissec- typically older, with several other atherosclerotic comor-
tion (class III), is a rare lesion characterized by a partial- bidities, including a history of stroke, peripheral vascular
thickness tear of the aortic wall, extending from the inti- disease, CAD, and aortic aneurysms. CT images fre-
ma into part or all of the media [40]. This lesion could be quently show extensive atherosclerotic changes, often
regarded as a very large primary intimal tear but without with more than one ulcer-like lesion.
development of a separate flow channel in the media Given the multiplicity of lesions and the common ob-
(false lumen) as in classic dissection. Limited tears occur servation of atherosclerotic ulcers in non-symptomatic pa-
more often in the ascending aorta than more distally and tients, it is important to try to distinguish between non-
are associated with dilated or aneurysmal aortic diame- penetrating ulcers (i.e. ulcerated plaque confined to the
ters. The underlying pathology, typically with cystic me- thickened intima), chronic healed penetrating ulcers
dial degeneration, and risk profiles of patients with lim- (which are re-endothelialized and not an acute threat), and
ited tears are similar to those with classic dissection. those lesions that acutely penetrate the aortic wall with a
high risk of complications such as perforation and rupture.
Intramural Hematoma (Class II) The key distinguishing features of acute lesions are intra-
mural blood and periaortic stranding, which can help iden-
While the term intramural hematoma simply means tify a culprit lesion. Acute PAUs without IMH do exist,
blood in the aortic wall, it has been used misleadingly though, and in the setting of acute aortic pain a CT scan
(class II lesion) to describe an entity on the same level as without IMH or periaortic stranding near an identifiable
an aortic dissection or penetrating atherosclerotic ulcer, ulcer-like lesion does not exclude an acute aortic condi-
which has resulted in considerable confusion and incon- tion. In these cases, follow up imaging is recommended.
sistent classification of aortic diseases in the literature.
We do not consider IMH as a specific disease entity, but Iatrogenic and Traumatic Dissection (Class V)
instead as an important imaging finding, because it is un-
specific to the underlying pathology or etiology. Intra- Aortic and other arterial dissections can occur as a com-
mural blood can be seen to variable degrees in any acute plication of diagnostic and interventional catheter-based
aortic condition: if fresh clot fills the entirety of the dis- procedures, as well as a complication of cardiac or vas-
section plane in patients with cystic medial necrosis, it is cular surgery. While patients with iatrogenic dissections
best considered a variant manifestation of aortic dissec- may have underlying vascular diseases that predispose
tion. Intramural blood is also typically associated with them to aortic dissection, even the non-diseased aortic
PAUs: any communication between the aortic lumen and wall can be mechanically dissected by subintimal ad-
the media be it through a primary intimal tear, a focal vancement of endovascular wires and catheters.
Acute traumatic injuries of the aorta typically occur in References

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IDKD 2015-2018
Incidental Findings on Thoracic and Cardiac CT

Lynn S. Broderick1, Shawn D. Teague2
1 University of Wisconsin-Madison, Madison, WI, USA
2 Indiana University School of Medicine, Indianapolis, IN, USA
Introduction
With the ever-increasing use of computed tomography
(CT) for imaging, there is always the possibility of find-
ing something on the exam that was not anticipated and is
not related to the primary indication for obtaining the ex-
am. These unanticipated findings have been labeled inci-
dentalomas and, depending on their significance, a cas-
cade of additional imaging exams can result. Care must be
taken to limit unnecessary downstream imaging due to
these unanticipated findings. In a patient with an inciden-
tal finding, the first task of the radiologist is to determine
its stability. An active search of the patients prior imaging
exams in the picture archiving and communication sys-
tems is critical. Appropriate comparison exams may in- Fig. 1. Axial image shows a right axillary lymph node with a fatty
hilum (arrow) indicating a benign lymph node
clude prior abdominal, renal, or virtual colonoscopy CT
exams, magnetic resonance (MR) or ultrasound exams of
the liver or biliary tree, or a thoracic or cardiac CT in intravenous contrast. As with other incidental lymph
which the organs of the upper abdomen were incidentally nodes in the mediastinum and hilum, assessment for clin-
included. For lesions of the thoracic inlet, a prior neck or ical significance should include a short-axis measure-
cervical spine CT may be helpful. If the patient is new to ment as well as evaluation of the lymph node density. In
your institution, comparison exams from other institutions general a short-axis measurement of 1.0 cm suggests a
can often be electronically transferred and thus obtained benign lymph node [1]. However, a lymph node may be
with relatively little effort, and are of great value. Obtain- enlarged secondary to reaction to local infection or to a
ing prior exams can save the patient the significant cost, neoplastic process. The density of the lymph node is also
radiation exposure, and anxiety associated with repeat ex- important since lymph nodes containing a fatty hilum
ams. If the incidentaloma is new or there are no com- (Fig. 1) are considered benign regardless of size. Diffuse,
parisons to determine stability, a decision must be made central, or peripheral eggshell calcifications also indicate
regarding the overall significance of the finding, which a benign etiology. However, eccentric calcification
often has yet to be fully assessed. We have included some should not be considered a benign feature.
of the incidental findings that may be encountered on rou- The thyroid gland is usually at least partially included
tine thoracic and cardiac CT imaging, with a focus on on a chest CT exam. Thyroid nodules are extremely com-
their management. mon in the adult population and the vast majority are be-
nign. Recent guidelines have been published by Hoang et
al. [2] to diminish the number of unnecessary follow-up
Thoracic Inlet exams. (Fig. 2). For adults 35 years of age, a follow-up
ultrasound is recommended if the nodule is 1.5 cm. In
Coronal reconstructed images can be helpful in detecting adults 35 years of age, a follow-up ultrasound is rec-
supraclavicular lymph nodes, which may be more diffi- ommended if the nodule is 1 cm. In addition, any nod-
cult to differentiate from adjacent vascular structures on ule in the pediatric age group or any nodule regardless of
axial images, especially if the exam is performed without patient age that is fluorodeoxyglucose-avid on positron

130 L.S. Broderick, S.D. Teague
Incidental Thyroid Lesion
18 years old Adult 35 years old 35 years old
Ultrasound Ultrasound if 1 cm Ultrasound if 1.5
Fig. 2. The exact guideline for the evaluation of incidental thyroid

nodules depends on the age of the patient and the size of the lesion
emission tomography (PET) or with evidence of invasion

or adjacent lymphadenopathy should be assessed by
ultrasound.
Chest Wall
Coronal and sagittal reformatted images are useful in Fig. 3. Sagittal image demonstrating a compression fracture of the
evaluating skeletal structures. The ribs are problematic T9 vertebral body; the fracture was not present on the prior exam
because a single rib is not visualized on a single axial
image. The use of bone windows improves visualization
of the lateral aspects of the ribs on sagittal images; pos- Upper Abdomen
terior aspects are best visualized on coronal reformatted
images. Rib lesions will be more obvious while Liver
scrolling through the data set than if each image is in-
dependently reviewed. Sternal fractures can be missed Although commonly encountered, most liver lesions are
on axial images because of the plane of imaging but are benign, even in patients with known malignancy. Berland
very well depicted on sagittal views. Likewise, the ver- et al. [3] published guidelines for the management of in-
tebral column is ideally suited for review on sagittal cidental liver findings on CT (Fig. 4). They categorized
views, where compression fractures (Fig. 3) and lytic liver lesions based on the size and appearance of the le-
and sclerotic lesions may be more obvious than on axi- sion and the relative risk of the patient. Hepatic cysts are
al images. very common and present as sharply marginated, low-
CT is not ideal for breast imaging. However, assess- attenuation lesions of 20 Hounsfield units (HU). Typical
ment of breast tissue should be included in the search hemangiomas show peripheral, nodular enhancement that
pattern. Breast cancer may be visible as an asymmetric fills in centrally on delayed images (Fig. 5). Findings that
soft-tissue mass that sometimes shows enhancement with are more concerning include low-attenuation lesions with
the administration of intravenous contrast. Skin thicken-
ing from tumor or radiation can also be visualized, as
well as evidence of prior surgery such as lymph node dis-
section. The presence of collateral vessels in the chest 0.5 cm in low or Any size lesion with
wall may alert the clinician to the presence of vascular average risk patient benign imaging features
pathology elsewhere, such as a stenosis or occlusion at
the thoracic inlet.
Subcutaneous nodules such as metastases occur more No follow-up required
commonly with lung cancer, breast cancer, or melanoma.
However, soft-tissue nodules of the chest wall are more
typically related to benign etiologies such as sebaceous
cysts, or, when involving the anterior upper abdominal Robust enhancement in low- or
wall, injection sites from subcutaneous administration of average-risk patient
medication. Occasionally, abnormalities such as calcifi- Fig. 4. Liver lesions do not always require follow-up imaging;
cations in patients with scleroderma or neurofibromas in rather, the decision depends on the imaging features and size of the
patients with neurofibromatosis will be present. lesion and the risk to the patient
Incidental Findings on Thoracic and Cardiac CT 131
Fig. 6. Axial image shows a soft-tissue mass (asterisk) in the

spleen, consistent with metastasis
Fig. 5. Axial image demonstrates a lesion in the right lobe of the
liver with peripheral contrast enhancement (arrow) and a central
low density. The findings are consistent with the peripheral pud-
dling contrast enhancement pattern seen in hemangiomas uation of 20 HU, lack of contrast enhancement, and
smooth margins. Features that should raise suspicion of a
neoplasm include heterogeneous contrast enhancement,
ill-defined margins, enhancement 20 HU, and hetero- irregular margins, necrosis, and evidence of invasion
geneity. These lesions will require additional imaging (Fig. 6). When suspicious features are present, follow-up
and/or intervention. Hyperenhancing liver lesions may be imaging or intervention is warranted [3].
encountered particularly on CT angiogram for the di-
agnosis of pulmonary embolism or evaluation of the aor- Adrenal Glands
ta and may represent a transient hepatic attenuation dif-
ference (THAD) flow artifact or focal nodular hyperpla- The most important parameter for incidental adrenal
sia. For lesions measuring up to 1.5 cm, in patients with gland nodules is the density of the lesion. Lesions that
a low or average risk of malignancy, hyperenhancing le- show homogeneous macroscopic fat attenuation are con-
sions can be considered benign and no further imaging is sistent with myelolipoma. If the lesion does not visually
recommended [3]. appear to be a fatty lesion but has a density of 10 HU,
it is consistent with a benign, lipid-rich adenoma. For le-
Kidneys sions 20 HU and 4 cm in diameter in patients with-
out symptoms and without a personal history of malig-
Renal cysts are very common. The features consistent nancy, a 1-year follow-up CT or MR study is recom-
with a cyst on unenhanced CT scans include a well-de- mended. If the lesion measures 4 cm in size, dedicated
fined margin, homogeneous attenuation of 020 HU, ab- MR or CT imaging of the adrenal glands is recommend-
sence of nodularity, septa, wall thickening, and nodular or ed (Fig. 7) [3].
thick calcification. Thin calcification of the wall is an ac-
ceptable benign feature of a cyst. If these features are pre- Stomach
sent, no further work-up is necessary. A homogeneously
dense lesion, with an intensity 70 HU and measuring A hiatal hernia is a common finding in routine thoracic
3 cm in diameter, is most likely a hyper-dense cyst. Le- imaging. It is important to recognize because patients
sions that do not demonstrate these benign imaging fea- with hiatal hernias may have chest pain secondary to as-
tures will require additional work-up [3]. sociated reflux. At echocardiography, hiatal hernia can
sometimes be misinterpreted as a mass adjacent to or in-
Spleen volving the cardiac atria.
Incidental splenic lesions are not as common as inciden-

tal hepatic lesions but they do occur. If the lesion is con- Incidental Cardiovascular Findings on Non-Cardiac CT
sistent with a splenic cyst, i.e., imperceptible wall, near-
water attenuation (10 HU), and lack of contrast en- Cardiovascular structures are always included on a tho-
hancement, no further work-up is necessary. If these cri- racic CT exam and should be evaluated much the same as
teria are not met, the lesion may still be benign when it one evaluates the mediastinum for lymph node enlarge-
has the following imaging features: homogeneous atten- ment. One of the most common incidental cardiac find-
132 L.S. Broderick, S.D. Teague
Incidental adrenal lesion
10 HU?
Yes No
Benign
14 cm 4 cm
Benign Consider PET,

features? biopsy
or resection
Yes No
Fig. 8. Axial image shows an enlarged ascending aorta, measuring
4.9 cm at the level of the main pulmonary artery. Orthogonal mea-
surements require double-oblique reformatted images.
Consider Needs further
CT or MRI work-up
in 12 months [4, 5]. Surgery is usually not contemplated until the as-
cending aorta measures 5 cm, unless the patient is
Fig. 7. The guidelines for incidental adrenal lesions depend on the
density and size of the lesion
symptomatic or has a connective-tissue disorder such as
Marfans syndrome. If the ascending aorta appears en-
larged on axial images, it is important to perform double-
oblique reformats to create a true transaxial image of the
ings on CT scans of the chest is coronary artery calcifi- aorta, perpendicular to the axis of blood flow, so that an
cation, which is often seen in combination with athero- accurate measurement can be made. It is also important to
sclerotic disease of the aorta. Numerous studies have evaluate the size of the pulmonary artery. If the main pul-
shown that the more extensive the coronary artery calcifi- monary artery diameter is 3.0 cm, then pulmonary hy-
cation, the greater the risk of cardiac events, especially in pertension becomes a consideration, especially if there is
younger patients. Whenever coronary artery calcification concomitant right ventricular hypertrophy and/or dilata-
is detected, the association with coronary artery disease tion. Among the normal variant vascular anomalies are a
merits further attention. Subjective assessment of the persistent left superior vena cava (SVC), which may occur
amount of calcification relative to the patients age can al- in isolation or in combination with a right SVC, and par-
so be made. Calcification of the aortic valve is also com- tial anomalous pulmonary venous return, most common-
monly encountered. It is important to distinguish calcifi- ly with the left upper lobe pulmonary vein draining into
cation of the aortic wall from calcification of the aortic the left innominate vein or the right upper lobe pulmonary
valve leaflets. If the distinction is not obvious due to the vein draining directly into the SVC. When right heart en-
orientation of the aortic valve plane relative to the imag- largement is present, the pulmonary venous drainage
ing plane, oblique multiplanar reformatted images are of- pathways should be reviewed so that this diagnosis is not
ten helpful. The significance of aortic valvular calcifica- overlooked.
tion depends on the amount of calcification and the pa-
tients age. In patients 65 years of age, aortic valve cal-
cification should raise suspicion of aortic stenosis, usual- Lung Parenchyma
ly in association with a bicuspid aortic valve. As patients
age, the presence of aortic valve calcification is more In the lungs, there are endemic areas where certain in-
common and may be related to aortic valve sclerosis fections, such as histoplasmosis, coccidiodomycosis and
rather than aortic valve stenosis. In sufficiently calcified even tuberculosis, are common and result in benign cal-
valves, the leaflets may be apparent on non-enhanced cified pulmonary nodules. Recently, however, incidental
scans. The size of the great vessels should be assessed rou- non-calcified pulmonary nodules have received signifi-
tinely, including a measurement of the ascending aorta at cant attention as they may indicate early stage lung can-
the level of the main pulmonary artery (Fig. 8), ensuring cer, which is potentially treatable. In 2005, the Fleischn-
that an aortic aneurysm is not overlooked. There are no er Society published guidelines for the evaluation of pul-
strict size criteria for the ascending aorta since the aortic monary nodules in asymptomatic patients, with guidelines
size is related to the patients body habitus. However, as a for the evaluation of subsolid pulmonary nodules pub-
general rule, size should be reported if the ascending aor- lished in 2013 [6, 7]. A recent review by Truong et al. sum-
ta measures 4.0 cm (measured from the external walls) marized these guidelines and offered tips on technique and
Incidental Findings on Thoracic and Cardiac CT 133
emphysema. These patients will need to be referred to

pulmonology for further work-up.
Conclusion
In the routine practice of interpreting thoracic and cardiac
CT exams, there will be frequent incidental findings that
are not related to the patients indication for the exam and
may not be symptomatic [9]. The majority of these inci-
dental lesions will be benign in etiology and not require
additional attention. However, in patients with incide-
nalomas, it is key that we, as radiologists, make efforts
to compare current and prior examinations to determine
Fig. 9. Axial image shows a pure ground glass opacity nodule the chronicity of the abnormality, in order to avoid un-
(arrow) in the right lower lobe
necessary additional work-up. Conversely, when a new
finding is significant, it is important that we recommend
appropriate follow-up management, including additional
evaluation to ensure that patients are adequately treated imaging or specialty consultation. Appropriate manage-
[8]. The follow-up of solid nodules includes determination ment is critical for patient safety as well as for the over-
of their average of the length and width and of the pres- all resource utilization of the medical system.
ence of known risk factors for lung carcinoma. It should
be noted that these guidelines do not apply to patients
who are suspected of having, or who have, a known ma- References
lignancy, patients 35 years of age, and patients with un- 1. Onuma Y, Tanabe K, Nakazawa G et al (2006) Noncardiac
explained fever. The guidelines for the follow-up of sub- findings in cardiac imaging with multidetector computed to-
solid (ground glass or part solid/part ground glass) nod- mography. J Am Coll Cardiol 48:402-406.
ules (Fig. 9) are based on the size of the lesion [8]. Only 2. Hoang JK, Langer JE, Middleton WD et al (2014) Managing
subsolid nodules 5 mm in diameter require follow-up. incidental thyroid nodules detected on imaging: white paper of
the ACR incidental thyroid findings committee. J Am Coll Ra-
Solid nodules are followed for a period of 2 years, at diol pii: S1546-1440 (14) 00627-9 [E_pub a head to print].
which time a lack of change is considered to be evidence 3. Berland LL, Silverman SG, Gore RM et al (2010) Managing
of a benign process; subsolid nodules require at least 3 incidental findings on abdominal CT: white paper of the ACR
years of surveillance, as the malignancies that demon- incidental findings committee. J Am Coll Radiol 7:754-773.
strate this pattern are typically slow-growing. When a 4. Elefteriades JA, Farkas EA (2010) Thoracic aortic aneurysm:
clinically pertinent controversies and uncertainties. J Am Coll
lung nodule is identified, it should also be assessed on Cardiol 55:841-857.
sagittal or coronal reformatted images. Nodules that ap- 5. Hiratzka LF, Bakris GL, Beckman JA et al (2010) ACCF/
pear discoid are likely benign, regardless of their con- AHA/AATS/ACR/ASA/SCA/SCAI/SIR/STS/SVM Guide-
spicuity on axial images. Likewise, triangular or polygo- lines for the diagnosis and management of patients with tho-
racic aortic disease. J Am Coll Cardiol 55:e27-e129.
nal nodules that are intimately associated with the lung 6. MacMahon H, Austin JH, Gamsu G et al (2005) Guidelines for
fissures most likely represent intrapulmonary lymph nodes. management of small pulmonary nodules detected on CT
Emphysema is usually related to smoking and is commonly scans: a statement from the Fleischner Society. Radiol
found in the same patient population undergoing CT exams 237:395-400.
for smoking-related pathologies. In emphysema, there is 7. Naidich DP, Bankier AA, MacMahon H et al (2013) Recom-
mendations for the management of subsolid pulmonary nod-
destruction of lung parenchymal tissue resulting in focal ules detected at CT: a statement from the Fleischner Society.
lucencies. It is important to distinguish emphysema from Radiol 266:304-317.
cystic lung disease, which is often managed differently. 8. Truong MT, Ko JP, Rossi SE et al (2014) Update in the evalu-
The key finding to distinguish emphysema from cystic ation of the solitary pulmonary nodule. RadioGraph 34:1658-
lung disease is the ability to identify a discernible wall 1679.
9. Teague SD, Rissing S, Mahenthiran J, Achenbach S (2012)
around the focal lucency in the lung parenchyma, which Learning to interpret the extracardiac findings on coronary CT
indicates the latter (i.e., pulmonary Langerhans cell his- angiography examinations. J Cardiovasc Comput Tomogr
tiocytosis or lymphangioleiomyomatosis) rather than 6:232-245.
IDKD 2015-2018
Cardiac Magnetic Resonance

Didier Revel1, David A. Bluemke2
1 Department of Radiology, Universit Claude Bernard Lyon 1, Bron, France
2 Radiology and Imaging Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA
Introduction Turbo Spin-Echo Imaging

Magnetic resonance (MR) imaging is widely recognized Fast or turbo spin-echo images are a fundamental MR
for its ability to provide accurate and reliable assessments pulse sequence. In all parts of the body except the heart,
of the function and anatomy of the heart and great ves- a complete examination often consists of T1 images,
sels. With the recent development of more specialized which typically clearly display the anatomy, and/or T2
cardiovascular MR scanners, cardiac MR applications images, which accentuate pathologic changes, such as
have expanded and are now utilized on a routine basis. In edema from infarction or the relationship of a tumor to
this chapter, the technical aspects of MR scanning of the the pericardium. The advantages of spin echo are the ex-
cardiovascular system are outlined, followed by brief dis- cellent signal to noise ratio and excellent contrast be-
cussions of its applications to several diseases involving tween the heart, epicardial fat, and adjacent structures.
the heart in adults. A separate chapter in this volume Fast or turbo spin-echo imaging reduces acquisition times
specifically covers the use of cardiac MR for the diagno- by an acceleration factor typically ranging from 16 to 32.
sis of coronary artery disease. Parallel imaging can further accelerate speed by a factor
of 23. Essentially all spin-echo imaging of the cardio-
vascular system is now done with fast/turbo spin-echo
Understanding the Basic Pulse Sequences imaging, usually during a single breath-hold.
The primary disadvantage of fast/turbo spin-echo
It is extremely helpful to understand the strategy under- imaging is that these are very time-consuming sequences,
lying the selection of a particular MR pulse sequence. typically one or two slices per breath-hold of 1015 s. In
This allows the user to determine the acquisition time and so-called black-blood images, the blood is made to ap-
the corresponding imaging strategy to be employed. A pear dark. Cine information is not routinely obtained. De-
fundamental characteristic of all pulse sequences is that spite these drawbacks, spin-echo images are important
the image is generated in the frequency domain, also refor imaging congenital anomalies and in evaluations of
ferred to as k-space. Fourier reconstruction is used to the pericardium, right ventricular cardiomyopathy, and
generate the image. The k-space representation of the im- cardiac tumors.
age is a pixel array generated one line at a time, typical-
ly 128256 lines. To obtain a repetition time (TR) of
1000 (or 1 s, approximately one heart beat), each line of Cine MR Imaging
the image requires the duration of one heart beat for the
acquisition (e.g., if 256 lines are generated, 256 heart Cine-gradient echo images are used to evaluate motion
beats at 60 beats per minute requires 256/60 = 4.3 min gated to the cardiac cycle. Information from 412 cardiac
per image). However, new techniques incorporate fast (or cycles is used to obtain cine information during the en-
turbo) imaging modes as well as parallel imaging tech- tire cardiac cycle, referred to as segmented k-space cine
niques that greatly accelerate imaging times. For exam- MR imaging (MRI). Older MR scanners used so-called
ple, cine images of the heart are now routinely obtained conventional gradient-echo pulse sequences together with
in 6- to 12-s breath-holds. Real-time cine imaging is also gradient moment nulling, or flow compensation, to make
possible. The most useful pulse sequences are discussed blood bright (bright-blood images). In nearly all new
below. MR scanners however, steady-state free precession
(SSFP, also known as TrueFISP, Fiesta, balanced fast
field echo) images are now used with a segmented

Cardiac Magnetic Resonance 135
k-space acquisition. SSFP images provide very rapid MRI is the method of choice for longitudinal follow-
imaging, with blood having very high signal intensity up in patients who are undergoing therapeutic interven-
compared to the ventricular wall. Because there is a large tions. For example, in cardiac stem cell trials MRI was
amount of signal available, the SSFP technique is often the test of choice to assess changes in LV size, function,
combined with parallel imaging, which improves imag- and mass [2, 3]. From a research perspective, the sample
ing speed by two- to three-fold. A single cine slice of the size needed to detect LV parameter changes in a clinical
heart with a 40-ms temporal resolution is acquired in trial is far smaller, in the range of one order of magnitude,
about 6 s on a modern MR scanner. when MRI rather than 2D echocardiography is used, thus
markedly reducing the time and cost of patient care and
pharmaceutical trials [4, 5].
T1 and T2 Mapping A unique MR technique, myocardial tagging (spatial
modulation of magnetization, SPAMM technique), has
The detection of myocardial fibrosis using contrast-en- been developed, in which heart muscle is labeled with a
hanced cardiac MR depends on differences in signal in- dark grid and cardiac rotation, strain, and the displace-
tensity between scarred regions and adjacent normal my- ment and deformation of different myocardial layers dur-
ocardium. However, in diffuse myocardial fibrosis these ing the cardiac cycle are analyzed in 3D (Fig. 1).
differences in signal intensity are lacking. Measurement SPAMM technique helps in assessing regional myocar-
of myocardial T1 times (T1 mapping) using non-contrast dial wall motion but it requires sophisticated software to
or gadolinium-enhanced inversion recovery prepared se- extract local function parameters such as 2D or 3D myo-
quences has the potential to identify diffuse myocardial cardial strains [6, 7].
fibrosis that correlates well with ex vivo fibrosis content.
T1 mapping calculates myocardial T1 relaxation times
using image-based signal intensities and can be per- Assessment of Cardiomyopathies
formed using standard cardiac MR scanners and radiolo-
gy workstations. Current studies show that a myocardium In the visualization of left and right ventricular morphol-
with diffuse fibrosis will have greater retention of con- ogy and function, MRI is a noninvasive tool that has a
trast and thus shorter T1 times than normal myocardium. high degree of accuracy and reproducibility. It is also su-
Amyloidosis is a deposition disease in which the T1 time perior to echocardiography in the determination of ven-
of the myocardium is likewise altered. These observations tricular mass and volumes [8] and has become the gold
suggest the utility of T1 mapping in the detection of dif- standard for the in vivo identification of the phenotypes
fuse myocardial fibrosis and amyloidosis. of cardiomyopathies [9].
T2 and T2* maps of the myocardium may also be cal-
culated. T2* maps have clinical utility in the assessment Dilated Cardiomyopathy
of iron content of the myocardium (e.g., hemochromato-
sis). T2 mapping has been used to evaluate diseases that In dilated cardiomyopathy, MRI is useful to study ventric-
have associated myocardial edema, such as myocarditis ular morphology and function (Fig. 2), by analyzing wall
and acute myocardial infarction. thickening, impaired fiber shortening, and end-systolic
The different clinical and emerging applications of wall stress, which is a very sensitive parameter of a change
cardiac MRI are described below. in LV systolic function. It can also accurately assess the
morphology and function of the right ventricle (RV),
which is frequently affected in dilated cardiomyopathy.
Assessment of Ventricular Function Late contrast-enhanced T1-weighted images are helpful in
detecting the changes that occur in acute myocarditis. In
MRI is a very accurate and highly reproducible technique this setting, increased gadolinium accumulation is thought
for measuring ejection fraction and ventricular volumes to be due to inflammatory/hyperemia-related increased
noninvasively in three dimensions. For this reason, it has flow, slow wash-in/wash-out kinetics, and diffusion into
become the gold standard to which other modalities are necrotic cells [10]. There is evidence of similar changes in
compared [1]. Simpsons rule is applied to determine chronic dilated cardiomyopathy [11]. Contrast-enhanced
ejection fraction and volumes. In assessments of volumes MRI may also increase the sensitivity of endomyocardial
and mass, bright-blood SSFP sequences are typically biopsy by revealing inflamed areas, which aids in deter-
used, with 3040 phases per cardiac cycle. Breath-hold- mining the appropriate biopsy site. Moreover, the presence
ing techniques with acquisition times of 612 s reduce and extent of myocardial late enhancement has been
blurring of the endocardial border. Generally, for accurate shown to predict clinical outcome [12, 13].
measurement of volume and mass, entire coverage of the
left ventricle (LV) with short-axis views from the mitral Hypertrophic Cardiomyopathy
plane are recommended. Slice thickness is typically 810
mm, but in the evaluation of subtle changes the thickness Due to its high accuracy, MRI is increasingly used to as-
should be reduced appropriately. sess morphology, function, tissue status, and degree of
136 D. Revel, D.A. Bluemke
a b
Fig. 1 a, b. Cardiac magnetic resonance (MR) tagging. Magnetic strips are placed in the heart before contraction (diastole, a) and then
followed throughout the cardiac cycle (systole, b) to measure the regional contraction of different portions of the heart. Note that in the left
image the tag lines are curved, representing deformation of the myocardium. Cardiac MR is considered the reference standard for the
measurement of regional function of the heart compared to other imaging modalities
LV outflow tract (LVOT) obstruction in patients with hy- bulent jet during systolic LVOT obstruction is easily de-
pertrophic cardiomyopathy (HCM) (Fig. 3). In addition, tected using suitable echo times (about 4 ms). MRI also
it is very accurate in assessing a LV mass, regional hy- detects the systolic anterior motion of the mitral valve, in
pertrophy patterns, and the different phenotypes of HCM a four-chamber or a short-axis view on the valvular plane
(e.g., apical HCM) [7]. Post-surgical changes after myo- [15], and can be used to document quantify mitral regur-
mectomy can also be reliably monitored [14]. The tur- gitation. A newer technique is to measure the effective
LVOT area by MR planimetry during systole, which over-
comes the problem of interstudy variability of the LVOT
gradient due to its independence from the hemodynamic
status. There are preliminary data showing that assess-
ment of diastolic function using MRI may be superior to
the determination of conventional parameters by echocar-
diography. Analysis of the early untwisting motion of the
myocardium could be helpful in assessing diastolic func-
tion [16]. Other functional changes that make use of myo-
cardial tagging include a reduction in posterior rotation,
reduced radial displacement of the inferoseptal my-
ocardium, reduced 3-D myocardial shortening, and het-
erogeneity of regional function. With late enhancement
imaging after the injection of gadolinium chelates (Fig.
4), MRI may help to detect areas of fibrosis, the prog-
nostic value of which has been demonstrated [17, 18].
MRI also easily detects the acute and chronic changes af-
ter septal artery ablation [14, 19].
Arrhythmogenic Right Ventricular Cardiomyopathy/Dysplasia

Arrhythmogenic right ventricular cardiomyopathy/
dysplasia (ARVC/D) is a rare disorder characterized by
Fig. 2. Bright-blood cine image (SSMP) shows the vertical long-
axis view of the left ventricle. There is an aneurysm at the base of fibrofatty replacement of the RV free wall. MRI is usual-
the left ventricle; the thickened dark tissue in the aneurysm is the ly the diagnostic imaging technique of choice for
thrombus (arrow) ARVC/D (Fig. 5) [20, 21] as it visualizes the ventricular
Fig. 3. Morphologic patterns in hyper-

trophic cardiomyopathy. A, a normal LV;
B, b sigmoid septum; C, c reversed septal
contour; D, d mid-ventricular hypertro-
phy; E, e apical and F, f symmetric hyper-
trophic cardiomyopathy
cavities and walls, with excellent depiction of the my- Restrictive Cardiomyopathy
ocardial anatomy. Although T1-weighted spin-echo im-
ages may reveal fatty infiltration, thinned walls, and dys- Primary infiltration of the myocardium by fibrosis or
plastic trabecular structures, these particular findings are other tissues leads to the development of restrictive car-
actually quite infrequent. Moreover, the subjective as- diomyopathy, which is characterized by normal LV size
sessment of RV wall thinning, wall motion abnormalities, and systolic function, severe diastolic dysfunction, and
and fatty infiltration of the myocardium by cardiac MR biatrial enlargement. Restrictive cardiomyopathy needs
may be problematic. Thus, the international Task Force to be differentiated from constrictive pericarditis, which
proposed revised criteria for the clinical diagnosis of is a primary disease of the pericardium rather than the
ARVC/D. Major and minor criteria defined by cardiac myocardium. LV size and thickness are quantified us-
MR contribute to the final diagnosis. Regional RV dys- ing gradient-echo sequences. Atrial enlargement is as-
function associated with an increase of RV end-diastolic sessed in a four-chamber view. Mitral regurgitation
volume (110 mL/m2 for males and 100 mL/m2 for fe- should be assessed as well. The restrictive diseases that
males) and RV ejection fraction 40% are considered to can be effectively assessed using MRI are described be-
be major criteria for the diagnosis of ARVC/D [22]. low [23, 24].
Fig. 4. Delayed gadolinium short-

axis images of the heart in a pa-
tient with a history of myocardial
infarction. The bright, high-sig-
nal portion of the anterior and an-
terolateral walls (arrows) of the
left ventricle is the area of prior
infarction. At the apex (lower
right corner) the infarct involves
the entire circumference of the
heart; a small thrombus (thin
arrow) is present at the apex as
an area of dark tissue
a b
Fig. 5 a, b. Axial black-blood image of the heart. The T1 image (a) shows replacement of the myocardium by fat signal (arrows) in the left
and right ventricles. The fat suppression T1-weighted image (b) shows dark signal at the corresponding sites of fat deposition
Sarcoidosis cases of familial amyloidosis. MRI is the modality of

choice for evaluating cardiac amyloidosis, by demonstrat-
Cardiac involvement in sarcoidosis produces symptoms ing LV wall thickening, reduced systolic function with de-
in only 5% of patients but has been found in 2050% of creased ejection fraction, and disproportionate atrial en-
sarcoidosis patients at autopsy. During acute myocardial largement. The more specific finding, obtained on late-
inflammation, sarcoid infiltrates are visible on MRI as in- enhanced images, is a diffuse, heterogeneous pattern of in-
tramyocardial, epicardial, or endocardial hyperhancement creased signal intensity on delayed contrast-enhanced in-
in a non-ischemic pattern with increased signal intensity version recovery T1 images. During the selection of the
on both T2-weighted and gadolinium-enhanced images most appropriate inversion time to null the normal myo-
[25, 26]. Occasionally, MRI may be useful in guiding en- cardium signal intensity, the null point for the myocardium
domyocardial biopsy. is often reached before the blood pool is nulled [30]. The
shorter T1 of myocardium than of blood reflects the ac-
Hemochromatosis, Iron Overload Conditions cumulation of amyloid material. This finding is of impor-
tant value for the final diagnosis of cardiac amyloidosis.
Extensive iron deposits leading to wall thickening, ven- Most recently, T1 mapping of the myocardium has
tricular dilatation, congestive heart failure, and death char- been performed prior to gadolinium administration to de-
acterize cardiac hemochromatosis. Usually, the iron determine native T1 times. In patients with cardiac amy-
posits are subepicardial; hence, endomyocardial biopsy loidosis, the native T1 time is longer than in normal sub-
may fail to confirm the diagnosis of hemochromatosis. jects (e.g., average 1140 ms vs. 958 ms) [31].
MRI is able to detect the iron deposits because of the very
strong paramagnetic properties of iron, which lead to ex-
tensive signal loss in native T1- and T2-weighted images. Assessment of Pericardial Disease
The pattern of focal signal loss in a dysfunctional myo-
cardium associated with an abnormally dark liver might MRI is ideally suited to evaluating the pericardium (Fig.
be sufficient to confirm the diagnosis of systemic he- 6). T1-weighted spin-echo imaging demonstrates the nor-
mochromatosis. However, iron loading in the myocardium mal pericardium as a thin band (2 mm) of low signal,
does not always correlate with the degree of disease in- bordered by epicardial and pericardial fat, which have a
volvement. A particular sequence acquisition that allows high signal. Because pericardial thickness varies at dif-
T2* calculation (T2* mapping) has been established for the ferent levels, the thickness should be measured in axial
determination of cardiac iron concentrations. T2* values images at the level of the right atrium, RV, and LV. A
2025 ms indicate myocardial iron overload [27-29]. thickness 4 mm is considered abnormal and suggests
fibrous pericarditis, either acute or chronic (due to
Amyloidosis surgery, uremia, tumor, infection or connective tissue dis-
ease) [32]. Contrast-enhanced MRI may help to better de-
Infiltration of the heart by amyloid deposits is found in al- lineate the pericardium in cases of effusive-constrictive
most all cases of primary amyloidosis and in 25% of the pericarditis. Breath-hold or real-time cine gradient echo
a b
Fig. 6 a, b. Black-blood image of the heart in long (a) and short (b) axis reveals a thickened pericardium (arrows) and fluid (b, arrows).
Pericardial effusion and thickening 4 mm is abnormal
images of the ventricles and phase-velocity mapping of

the cardiac valves may be helpful in assessing the signif-
icance of pericardial pathology. The same approach is
useful to detect other disorders, such as congenital ab-
sence of the pericardium, pericardial cysts, or pericardial
effusion undetected by other modalities.
Myocarditis
In patients in whom myocarditis is suspected, cardiac MR
has become the primary tool for the noninvasive diagno-
sis of myocardial inflammation. Myocarditis is defined as
the inflammation of myocardial tissue and is an important
underlying etiology of other myocardial diseases, such as
dilated cardiomyopathy. The definitive diagnosis is fre-
quently confirmed based on the clinical history, the clin-
ical assessment, and non-invasive test results, in which
case cardiac MR is nowadays crucial. Pericardial effusion
has been reported in 3257% of patients with myocardi-
tis although it is not specific for the diagnosis. T2- Fig. 7. Black-blood image of the heart in a long-axis view shows a
mass (arrow) in the right atrium that was subsequently diagnosed
weighted or T2 mapping images sensitively detect tissue as lipoma
edema because of the long T2 values of edematous tissue.
However, the definitive diagnosis is usually based on the
observation on late enhanced images of focal signal in-
crease typically localized to the subepicardial regions of MRI is generally reserved for use when other modalities
the LV and possibly extension through the ventricular fail or provide suboptimal information. Double inversion
wall. Late enhancement may be multifocal or diffuse in recovery sequences can show valve morphology as well
distribution but with no coronary artery disease distribu- as evidence of associated secondary changes (chamber
tion. Consensual diagnostic criteria using cardiac MR dilatation, myocardial hypertrophy, post-stenotic changes
have been proposed (Lake Louise Consensus Criteria) in the great vessels, or thrombus in any of the chambers).
for the diagnosis of acute myocarditis [33]. Semi-quantitative assessment of valvular stenosis or re-
gurgitation can be obtained by measuring the area of sig-
nal void on gradient-echo images. The duration or extent
Evaluation of Cardiac and Paracardiac Masses of the signal void correlates with the severity of the aor-
tic stenosis, and the total area of signal loss with the
Primary cardiac tumors are rare (0.0020.3% incidence) severity of mitral regurgitation. This technique has a very
and the majority (75%) are benign. Metastatic tumors are high sensitivity (98%), specificity (95%), and accuracy
20- to 40-fold more common than primary tumors. MRI (97%) for diagnosing aortic and mitral regurgitation. The
is ideal for delineating the morphologic details of a mass signal void, however, is dependent upon certain scan pa-
(including extent, origin, hemorrhage, vascularity, calci- rameters, such as echo time, voxel size, and image orien-
fication, and effects on adjacent structures). Protocols in- tation relative to the flow jet. Phase-contrast MRI can be
clude the combined use of axial black-blood sequences used to assess the severity of valvular stenosis (by mea-
and axial bright-blood cine images. Functional MRI is suring the peak jet velocity) by calculating the valve ori-
useful to study the pathophysiologic consequences of a fice area and the transvalvular pressure gradient.
cardiac mass. Specifically, benign myxomas (the most
common cardiac tumor) appear brighter than myocardi-
um on T2 weighting; cine images may reveal the charac- Evaluation of Myocardial Perfusion and Ischemia
teristic mobility of the pedunculated tumor. Lipomas
(Fig. 7) appear brighter on spin-echo T1-weighted im- MRI has been validated as a reliable and useful tool in
ages. The diagnosis is verified by a decrease in signal in- the assessment of regional left ventricular perfusion [35].
tensity using a fat suppression technique [34]. In this setting, MRI relies upon monitoring the first pass
of a contrast agent. After a rapid intravenous contrast in-
jection, there is marked signal enhancement first in the
Evaluation of Valvular Diseases right ventricular cavity, then in the left ventricular cavity,
and finally in the left ventricular myocardium. This is
Echocardiography with color Doppler is usually the first- completed within 2030 s. Peak signal intensity is relat-
line imaging modality for diagnosing valvular diseases. ed to the concentration of the contrast agent in the local
tissue and is directly proportional to coronary blood flow. and the wide variety of tools that the imaging physician
A comparison between perfusion MRI at rest and after must thoroughly understand in order to appropriately de-
the infusion of pharmacologic agents (adenosine, re- ploy them.
gadenoson, and persantine) and standard methods (an-
giography or radionuclide scintigraphy) has shown that
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IDKD 2015-2018
An Integrative Approach to the Imaging of Ischemic Heart Disease

Albert de Roos1, Danilo Neglia2
1 Department of Radiology, Leiden University Medical, Leiden, The Netherlands
2 Institute of Clinical Physiology, CNR National Research Council, Pisa, Italy
Introduction method of reference, the pressure gradient across a coro-

nary stenosis, is measured as a means to estimate the
A multitude of invasive and non-invasive imaging tech- functional significance of a coronary stenosis. The frac-
niques are available to evaluate coronary artery disease tional flow reserve, as measured by the pressure wire, in-
(CAD) and its effect on the myocardium [1]. Traditional- dicates whether a coronary stenosis causes downstream
ly, invasive coronary X-ray angiography is the mainstay ischemia in response to stress. This functional knowledge
for diagnosing coronary artery stenosis. To a large extent, is crucial for the optimization and timing of revascular-
coronary computed tomography angiography (CCTA) ization therapy by stent placement or surgery. Coronary
has reached a high level of sophistication for performing interventions guided by the fractional flow reserve have
coronary angiography non-invasively. CCTA is, in partic- been shown to improve outcome in treated patients.
ular, highly successful for excluding coronary artery Even more relevant information on the presence of
stenosis. Coronary magnetic resonance (MR) angiogra- functionally significant CAD and the related risk can be
phy is still hampered by a lack of robustness and consis- gathered non invasively by stress myocardial perfusion
tent image quality. CT and MR techniques to image the imaging (MPI) or wall motion imaging. The preferred
coronary wall, even before the development of overt imaging technique varies between countries, regions, and
plaques, are still being tested. Plaque imaging is techni- hospitals, partly because of local expertise and customs
cally challenging, such that there is interest in improving and partly because guidelines do not specify one tech-
the reliability and robustness of non-invasive techniques. nique over another. Among the non-invasive tests, func-
Plaque characterization by CT largely involves the visual tionally significant CAD can be detected by assessing
inspection and grading of plaques (calcified, non-calci- stress-induced changes in myocardial perfusion by MPI,
fied and partly calcified). So-called soft plaques seem to as single photon computed emission tomography
be more prone to rupture than those that are fully calci- (SPECT), positron emission tomography (PET), or car-
fied. Other plaque characteristics that may relate to worse diac magnetic resonance (CMR), or by detecting stress-
outcome include expansive or positive remodeling with- induced changes in regional myocardial function by wall
out high-grade narrowing, small or spotty calcifica- motion imaging using echocardiography or CMR. Previ-
tions localized in soft plaques, and adventitial high den- ous studies have compared the diagnostic accuracy of
sity (ring sign). Currently, post-processing software is some of these modalities but a large multi-center study
available to extract the coronary tree and quantify the providing definitive evidence on the best imaging choice
plaque components from CT images. However, the tradi- in specific patient groups has yet to be conducted.
tional calcium (Agatston) score is still useful for quanti-
fying the amount of coronary calcium as a risk factor for
all-cause mortality. CCTA may improve the prediction of Non Invasive Imaging in Patients with Suspected
coronary events especially when used together with the Stable CAD
calcium score. The evaluation of comprehensive plaque
burden integrates information from calcified and non- Based on recent European guidelines, patients with sus-
calcified components. pected stable CAD should be managed using non-inva-
The limited information (i.e. vessel narrowing) pro- sive cardiac imaging, to select patients for invasive coro-
vided by luminography using either invasive X-ray an- nary angiography (ICA) and to determine medical and
giography or non-invasive CT or MR angiography has possibly interventional treatments. Non-invasive imaging
become apparent and has paved the way for functional is not only used to recognize the presence of anatomical-
imaging. In invasive X-ray angiography, the current ly obstructive coronary disease but, more importantly, to

144 A. de Roos, D. Neglia
Fig. 1. Hybrid PET-CCTA imaging in a

patient with stable angina. Perfusion PET
images were acquired at rest and during
dipyridamole stress, using 13N-ammonia
as the flow tracer. Absolute myocardial
blood flow (MBF) (mL/min/g) was quanti-
fied under two different conditions.
Myocardial flow reserve (MFR) was com-
puted as the ratio of dipyridamole/resting
MBF. PET images show a critical down-
stream stenosis of the right coronary
artery, documented at CCTA (arrow) and a
large inducible perfusion defect during
dipyridamole stress corresponding to a
severely depressed MFR at quantitative
analysis. This is an example of high-risk
findings detected during imaging, which in
this patient, indicated invasive coronary an-
giography and possible coronary revascu-
larization
stratify future cardiovascular risk. Only patients at high- have no significant stenoses [3, 6]. Conversely, non-inva-
er risk will be referred to interventional procedures, with sive testing does not always guide clinical management
the final goal of improving their outcome [2]. since 27% of patients with high-risk imaging results do
The management of patients with stable chest pain not undergo ICA [7].
starts with an estimation of the pre-test probability (PTP)
of CAD, based on age, sex, and type of symptoms ac-
cording to an updated predictive model [3]. Patients with Nuclear Myocardial Perfusion Imaging (MPI) and
a PTP score 15% should not undergo further testing Hybrid CCTA-MPI Imaging for the Diagnosis of Stable CAD
while in patients with a PTP 85% non invasive testing
is not indicated for diagnosis but only for risk stratifica- Stress MPI by SPECT and PET is an established and
tion [2]. According to international guidelines, patients widely used approach in the diagnostic and risk assess-
with an intermediate PTP should preferably undergo ment of patients with suspected CAD. These techniques
stress MPI rather than exercise echocardiography [2, 4]. provide information on the presence, extent, and severity
CCTA is considered a reasonable alternative in interme- of myocardial perfusion abnormalities, which define the
diate-low likelihood patients or in case of doubtful stress functional significance of coronary disease and are relat-
tests results. ed to event risk. Since CCTA is able to depict anatomical
Only in the presence of high-risk findings at non inva- abnormalities of the vessel wall and has a high predictive
sive imaging should patients be referred to invasive in- value in excluding significant coronary stenoses and in
vestigation and possible coronary intervention [2, 5]. identifying high-risk coronary anatomy, a combination of
High-risk findings are defined by the presence of left functional and anatomical information, obtained either
main or proximal left anterior descending arterial disease by side-by-side interpretation of stress MPI and CCTA
and/or three-vessel disease as determined by CTCA images or by using a hybrid approach, has recently been
and/or by the documentation of significant inducible my- proposed as a more accurate strategy in patients with
ocardial ischemia (10% of the left ventricular myo- known or suspected CAD [8] (Fig. 1).
cardium) at stress testing. ICA in patients with stable Large observational studies have demonstrated that a
CAD is not recommended as a first testing method, al- normal MPI yields a favorable prognosis, with an annu-
though in current practice as many as 30% of patients alized event-rate of 0.6%, while an abnormal scan im-
with no symptoms (including no angina) and 16% of pa- plies a 3- to 7-fold increase in annual cardiac events, es-
tients without non-invasive testing, and 15% of those pecially those related to the extent and severity of perfu-
with prior normal non-invasive testing (resting electro- sion defects [9-11]. Additional prognostic data on left
cardiography, echocardiography, CT, or a stress test) un- ventricular volumes and function (e.g., ejection fraction)
dergo ICA [3]. Perhaps as a consequence, 62% of stable at baseline and possible evidence of transient left ven-
patients without known CAD who undergo elective coro- tricular dysfunction after stress are provided by the gated
nary angiography in the USA and 42% of those in Europe acquisition of SPECT data [12].
An Integrative Approach to the Imaging of Ischemic Heart Disease 145
The demonstration by SPECT imaging of significant Non Invasive Imaging of the Heart and Large Vessels
inducible myocardial ischemia not only defines a high
cardiovascular risk for a specific patient but also guides Cross-sectional CT and MR imaging are well suited to
treatment to modify that risk and improve outcome. assess the gross morphology of the heart and large ves-
Hachamovitch et al. [13] demonstrated that revascular- sels. CT is currently routinely applied to evaluate acute
ization procedures have a beneficial impact on outcome chest pain (life-threatening coronary occlusion, aortic
only in the presence of ischemia involving 10% of the dissection, and pulmonary embolism should initially be
left ventricular myocardium at SPECT imaging. In a excluded). However, it should be noted that the differen-
prospective nuclear substudy of the COURAGE trial, a tial diagnosis of acute chest pain is quite extensive and
better prognosis was related to the extent of ischemia re- many other causes may be incidentally diagnosed by CT
duction evidenced by SPECT [14]. These data justify the (e.g., pneumonia, lung disease, chest wall disease, peri-
use of SPECT as one of the techniques recommended by cardial disease). In many hospitals excluding pul-
the European Society of Cardiology (ESC) guidelines to monary embolism is a very common and sometimes
diagnose CAD, stratify risk in patients with suspected misused indication for urgent CT of the chest. In the
disease, and guide further management and treatment of emergency setting, CT is a preferred technique due to its
the patient to improve outcome. speed, availability, robust image quality, and ease of use
In analogy to SPECT, the presence and extent of myo- in acutely ill patients who may require assisted ventila-
cardial perfusion defects demonstrated by PET provide tion and direct supervision. The complications of is-
strong prognostic information [15]. PET allows measure- chemic heart disease may be well shown by CT and/or
ment of absolute myocardial blood flow and flow reserve MR imaging (e.g., scar, aneurysm, contained rupture,
(MFR) and has incremental prognostic value compared to thrombus).
the evaluation of perfusion defects alone. A blunted MFR MR imaging is a versatile technique for evaluating
is an independent predictor of risk compared to more many aspects of ischemic and non-ischemic heart dis-
common prognostic indicators, such as transient regional ease. In stable patients with suspected CAD, imaging
perfusion defects, previous myocardial infarction, and will mostly focus on the detection of coronary stenosis
left ventricular ejection fraction [16]. Interestingly, high- and defining the functional significance of the stenosis.
risk, diffuse anatomical CAD may manifest as apparent- The focus of imaging will be different in patients with
ly normal regional perfusion images with homogeneous suspected acute coronary syndromes (acute infarction,
tracer distribution; however, it may be recognized by unstable angina pectoris). In the acute setting it will be
global reductions of myocardial blood flow and MFR at important to use imaging tools to diagnose or exclude
quantitative PET imaging [17]. coronary occlusion, especially when the clinical signs
Improved risk stratification is obtained by combining and symptoms are inconclusive. CCTA is an excellent
the anatomical information of CCTA with the functional gatekeeper for excluding CAD in the emergency room
data of MPI. The likelihood of diagnosing obstructive setting and thereby decrease the length of stay of pa-
CAD by ICA is highest when both CCTA and MPI are tients in the hospital. MR MPI has also successfully
abnormal [18]. The hybrid approach is also useful to been employed as a gatekeeper in the emergency room
stratify risk in patients with doubtful results at either setting for the exclusion of ischemia due to coronary
functional or anatomical evaluation. Accordingly, a com- artery stenosis. After coronary artery occlusion, the de-
bined anatomical and functional assessment provides pendent myocardium distal from the occluded coronary
complementary rather than overlapping diagnostic and artery is at risk of necrosis, thus mandating early and
prognostic information. timely intervention. The area at risk may be visualized
on T2-weighted MR sequences, which will show a re-
gion of high signal intensity due to developing edema in
CT and CMR Imaging in the Diagnosis of Stable CAD the area at risk. Early intervention may prevent myocar-
dial necrosis in the area at risk (aborted infarction).
CT and MRI techniques have also been developed to The necrosis develops over several hours, starting as a
evaluate myocardial perfusion. Currently, in MPI, MR is wavefront at the endocardial site within the confines of
more widely used than CT. Both are performed with the the area at risk that, when not halted by intervention,
patient at rest and the results are compared to perfusion then progresses over time and may fill the entire area at
under adenosine stress. MR perfusion imaging provides risk. There is some discussion as to whether T2-weighted
dynamic information on the wash-in of gadolinium-based techniques are reliable enough for quantification of the
contrast agents into the myocardium. Ischemia will be vi- risk area, because of potential imaging artifacts.
sualized during stress MR perfusion as a perfusion defect Nonetheless, MR-based estimates of the area at risk
(cold spot). CT perfusion is more static and provides have been incorporated as end-points in several cardiol-
perfusion information mostly at a fixed time point in a ogy trials.
non-dynamic manner. The difference between ischemic The wave front of progressing necrosis can be defined
and normal myocardium is far greater on MR than on CT very accurately by late gadolinium enhancement (LGE).
imaging. Combining LGE and T2-weighted MR images is an
option to assess the infarct:risk ratio as an important clin- sive differential diagnosis of its own. Primary (idiopath-
ical parameter. LGE has been used for over 25 years to ic), secondary (toxic, infiltration, etc.), and complex ge-
characterize myocardial necrosis, in both the acute setting netic forms of cardiomyopathy may present with the di-
and chronic setting. T2-weighted MR techniques may be lated phenotype. The idiopathic form of dilated car-
useful to distinguish acute from chronic infarcts. Acute diomyopathy is diagnosed after excluding secondary
infarcts will show LGE in conjunction with high my- forms. Idiopathic dilated cardiomyopathy may be further
ocardial signal (acute edema) in the area at risk, whereas characterized by LGE. Among the LGE patterns ob-
chronic infarcts will show LGE in the absence (no edema served in dilated cardiomyopathy are the so-called mid-
present) of high signal intensity in the myocardium at wall stripe as well as patchy, diffuse, and subepicardial
risk. enhancement. Interestingly, LGE has prognostic implica-
tions in idiopathic dilated cardiomyopathy, as the mid-
wall stripe pattern may herald arrhythmias and sudden
CT and CMR Imaging in Patients with Heart Failure death. LGE patterns may be helpful for risk stratification
and guiding treatment options (e.g., implantable car-
The epidemic growth of the number of patients suffer- dioverter-defibrillator).
ing from heart failure constitutes a diagnostic and ther- The differential diagnosis of hypertrophic phenotypes
apeutic challenge. CT and MR imaging are playing an starts with the exclusion of arterial hypertension and aor-
increasingly important role in the work-up and follow- tic stenosis as the underlying causes of pressure overload
up of patients with heart failure. The diagnostic chal- on the left ventricle. It is also important to distinguish
lenge in heart failure is to identify its most likely cause. global or diffuse hypertrophy from local hypertrophy
First and foremost, it is important to exclude CAD, e.g., (lumps and bumps, as seen in genetic forms of hyper-
by using CCTA to exclude coronary stenosis and trophic cardiomyopathy). The diffuse hypertrophic phe-
plaques. However, it may also be important to evaluate notype has a differential diagnosis that should be consid-
the myocardium directly, to assess the presence of myo- ered from the imaging perspective. Genetically deter-
cardial scar and infarction, because in a small number mined hypertrophic (obstructive) cardiomyopathy may
of patients infarction may be present after recanalization present as diffuse global hypertrophy, although localized
of a previously occluded coronary artery. In this respect forms are more common (e.g., classic asymmetric septal
LGE by MR imaging has a central role in the identifi- hypertrophy). Many common, but also uncommon, infil-
cation of ischemic myocardial scar (i.e., subendocardial trative myocardial diseases may present with the hyper-
LGE). trophic phenotype (e.g., amyloid, storage diseases, Fab-
The MR protocol in the evaluation of patients with rys disease, inflammatory processes such as sarcoid,
heart failure includes functional imaging (global and re- medication such as amiodarone and chloroquine). Genet-
gional function), velocity-encoded MR to assess mitral ically determined hypertrophic cardiomyopathy has many
flow, T2-weighted sequences to assess edema, T1-weighted additional morphological features that may be a clue for
sequences (T1 mapping with techniques such as Look- the correct diagnosis, such as the appearance and length
Locker technique or modified Look-Locker inversion re- of the mitral leaflets, the systolic anterior motion of the
covery sequences) to assess diffuse fibrosis and other dif- anterior leaflet of the mitral valve, secondary mitral in-
fuse myocardial infiltration unseen with LGE, and LGE sufficiency and atrial enlargement, crypts in the myocar-
sequences to assess scar location, size, and distribution. dial wall as an early sign of hypertrophy in a mutation
The combined assessment of the location and extent of is- carrier, and various patterns of LGE. Hypertrophic car-
chemic scar, the presence and severity of secondary mi- diomyopathy is a common cause of sudden death in ath-
tral regurgitation, and precise estimates of left ventricular letes and apparently healthy young people, although the
volumes provide a surgical road-map for planning scar death rate may be lower than previously suggested. The
resection in conjunction with mitral valve repair (e.g., risk of arrhythmias and sudden death may be related to
Dor procedure). the presence and extent of scar tissue as demonstrated by
These combined techniques constitute a comprehen- LGE. Typical LGE enhancement occurs at the right ven-
sive set of tools with which to obtain a specific diagno- tricular attachment points, although the scar can be wide-
sis of underlying ischemic cardiomyopathy. They also of- ly distributed in various patterns. A transmural infarct-
fer a wide array of diagnostic features that may be help- like pattern in an aneurysmatical apical scar may imply a
ful in differentiating ischemic from non-ischemic car- worse prognosis.
diomyopathy and in further differentiating the multitude Finally, amyloid cardiomyopathy may present as a hy-
of common and uncommon causes of non-ischemic car- pertrophic phenotype. The LGE pattern may demonstrate
diomyopathies. In the differential diagnosis of non- a typical diffuse subendocardial pattern throughout the
ischemic cardiomyopathy it may be useful to make an left ventricle, possibly also involving the right ventricle
initial distinction between dilated (i.e., globally dilated and atrial walls. T1 mapping techniques are currently
left ventricle, thin walls) and hypertrophic (thick walls, used to characterize diffuse myocardial involvement to
locally or diffuse) phenotypes. The dilated phenotype is better advantage, such as in amyloid cardiomyopathy. T1
a quite common cause of heart failure and has an exten- mapping is a promising tool for characterizing diffuse
An Integrative Approach to the Imaging of Ischemic Heart Disease 147
myocardial fibrosis in many forms of cardiomyopathy 5. ACCF/SCAI/AATS/AHA/ASE/ASNC/HFSA/HRS/SCCM/

presenting as heart failure. The occurrence of diffuse SCCT/ SCMR/STS (2012) 2012 appropriate use criteria for
diagnostic catheterization: a report of the American College
myocardial fibrosis may be an important turning point in of Cardiology Foundation Appropriate Use Criteria Task
the natural history of aggravating heart disease, but it Force, Society for Cardiovascular Angiography and Interven-
may also be a target for specific medical therapy. tions, American Association for Thoracic Surgery, American
Heart Association, American Society of Echocardiography,
American Society of Nuclear Cardiology, Heart Failure Soci-
ety of America, Heart Rhythm Society, Society of Critical
Myocardial Perfusion Imaging in Patients with Heart Care Medicine, Society of Cardiovascular Computed Tomog-
Failure Who Are Candidates for Revascularization raphy, Society for Cardiovascular Magnetic Resonance, and
Society of Thoracic Surgeons. J Am Coll Cardiol 59:1995-
2027.
The 2012 ESC guidelines for the diagnosis and treat- 6. Patel MR, Peterson ED, Dai D et al (2010) Low diagnostic
ment of heart failure recommend the consideration of yield of elective coronary angiography. N Engl J Med 362:
MPI in heart failure patients with suspected CAD, to de- 886-895.
termine the extension of ischemia and the presence of vi- 7. Hachamovitch R, Nutter B, Hlatky MA et al; SPARC Investi-
ability before revascularization [19]. The assessment of gators (2012) Patient management after noninvasive cardiac
imaging results from SPARC (Study of myocardial perfusion
myocardial viability has been an important step in thera- and coronary anatomy imaging roles in coronary artery dis-
peutic decision-making in patients with left ventricular ease). J Am Coll Cardiol 59:462-474.
dysfunction who are candidates for coronary revascular- 8. Flotats A, Gutberlet M, Marcassa C et al; Cardiovascular
ization. In a classical meta-analysis, patients with myo- Committee of the EANM, the ESCR and the ECNC, Hybrid
cardiac imaging: SPECT/CT and PET/CT. A joint position
cardial viability had a better outcome than those with- statement by the European Association of Nuclear Medicine
out myocardial viability [19]. However, in a sub-study of (EANM), the European Society of Cardiac Radiology (ESCR)
the STICH (Surgical Treatment for Ischemic Heart Fail- and the European Council of Nuclear Cardiology (ECNC). Eur
ure) trial, the presence of myocardial viability in patients J Nucl Med Mol Imaging 1:201-212.
with ischemic severe heart failure randomized to revas- 9. Shaw LJ IA (2003) Prognostic value of gated myocardial per-
fusion SPECT. J Nucl Cardiol 2:171-185.
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all-cause mortality [20]. Conversely, in the presence of nosis after a normal exercise stress Tc-99m sestamibi SPECT
extensive viability (10% of the myocardium), early study. J Nucl Cardiol 10:261-266.
revascularization was associated with improved survival 11. Klocke FJ, Baird MG, Lorell BH et al (2003) ACC/AHA/AS-
compared with medical therapy [21]. Indeed, current NC guidelines for the clinical use of cardiac radionuclide
imagingexecutive summary: a report of the American Col-
heart failure guidelines recommend the consideration of lege of Cardiology/American Heart Association Task Force on
noninvasive imaging for the assessment of both inducible Practice Guidelines (ACC/AHA/ASNC Committee to Revise
ischemia and viable myocardium in the heart failure pop- the 1995 Guidelines for the Clinical Use of Cardiac Radionu-
ulation. clide Imaging). Circulation 1404-1418.
12. Abidov A, Bax JJ, Hayes SW et al (2003) Transient ischemic
dilation ratio of the left ventricle is a significant predictor of
future cardiac events in patients with otherwise normal my-
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IDKD 2015-2018
Acute Aortic Syndrome: State-of-the-Art Diagnostic Imaging

Thomas Grist1, Geoffrey D. Rubin2
1 Department of Radiology, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
2 Department of Radiology, Duke University School of Medicine, Durham, NC, USA
Introduction each cardiac contraction. The remaining arteries of the

body are muscular arteries, with a paucity of elastin and
The accurate detection and evaluation of acute aortic syn- a predominance of smooth muscle that allows the regula-
drome is one of the radiologists most important and im- tion of regional blood flow throughout the body. The
mediately impactful opportunities to improve human boundary between the intima and media is not readily de-
health. Acute aortic syndrome is often a clinical emer- fined but is recognized histologically as being formed by
gency and a situation that demands accurate radiologic the internal elastic lamina, which represents the inner-
diagnosis and intervention to provide lifesaving care. The most of the many elastic lamellae within the aortic me-
diagnosis of acute aortic syndrome has evolved signifi- dia. The adventitia lacks elastic lamellae and is predomi-
cantly over the last two decades, from an arteriographic nantly composed of loose connective tissue and blood
diagnosis to a diagnosis based upon multi-detector com- vessels, the so-called vasa vasorum.
puted tomography (CT) angiography [1] and, to a limited Anatomically, the aorta can be divided longitudinally
extent, magnetic resonance imaging (MRI). With the ad- into five zones: the aortic root, ascending thoracic aorta,
vent of these new techniques for diagnosis, investigators aortic arch, descending thoracic aorta, and abdominal
have revisited the questions and pathologies surrounding aorta. Although acute aortic syndromes can involve any
acute aortic syndromes. of these five anatomic zones, they only rarely originate
within the abdominal aorta. An important principle in the
management of acute aortic syndromes is the classifica-
Anatomic and Pathological Considerations tion of lesions into Stanford type A or type B. Type A le-
sions, defined as those involving the ascending aorta or
Acute aortic syndromes are principally diseases of the aortic root, demand urgent surgical intervention, with re-
aortic wall. As a result, their categorization is aided by an placement of the diseased ascending aortic segment. The
understanding of the fundamental pathological features rationale for this urgent intervention is the high risk of
of the aortic wall. aortic rupture, which can lead to pericardial tamponade
The aorta is composed of three layers. From inner to or frank exsanguination. Type B lesions do not involve
outer, they are the intima, media, and adventitia. The in- the ascending aorta and thus can occur within the aortic
tima is made up of a single layer of flattened endothelial arch or the descending thoracic aorta. If there is evidence
cells with a supporting layer of elastin rich collagen, fi- for active aortic rupture, then these patients should like-
broblasts, and myointimal cells. As humans age, the myo- wise be referred for urgent surgical intervention. Howev-
intimal cells tend to accumulate lipid resulting in inti- er in the absence of active bleeding, they are typically
mal thickening which is the earliest sign of atherosclero- managed with blood pressure reduction and regular mon-
sis. The majority of the aortic wall thickness is composed itoring to assess the evolution of aortic dimension and
of the media, which is broad and elastic and made up of disease extension.
concentric fenestrated sheets of elastin, collagen, and
sparsely distributed smooth muscle fibers. The predomi-
nance of elastin arrayed as elastic lamina reflects the fact Definitions and Classifications
that the aorta together with the pulmonary arteries are the
only elastic arteries of the body. Because the aorta and Collectively, acute aortic syndromes represent life-threat-
the pulmonary arteries receive the entirety of the cardiac ening conditions that are associated with a high risk of aor-
output, they undergo substantial deformation in order to tic rupture and sudden death. The typical presentation is
accommodate the large volume changes that occur with the sudden onset of chest pain, which may be accompanied

150 T. Grist, G.D. Rubin
by signs or symptoms of hypoperfusion or ischemia to the cause of IMH has never been definitively proven. IMH is
distal organs, extremities, or brain. treated similar to dissections in terms of initial diagnosis
Traditionally, acute aortic syndromes have been cate- as well as clinical management. Most IMHs occur in the
gorized as aortic dissection, intramural hematoma, and descending thoracic aorta and can be associated with se-
penetrating atherosclerotic ulcer. vere pain. The imaging features vary depending on the
Aortic dissection (AD) is characterized by a separation amount of blood accumulated in the wall of the aorta, but
of the aortic media, creating an intimal-medial complex typically the normal wall measures <7 mm in thickness.
that separates from the remaining aortic wall. Blood The natural history of IMH can be quite variable. Rough-
flowing between the intimal-medial complex (intimal ly one-third of them will progress to AD, one third will
flap), and the remaining wall is considered to be within a be stable, and one third will resolve [3]. The mortality for
false lumen, whereas blood flow bounded by the intima patients with IMH involving the ascending aorta is simi-
is considered to be within a true lumen. Multiple com- lar to that of patients with classic dissection; therefore
munication points can be observed between the true and these patients are treated as though they have a classic
false lumens. The most proximal communication is de- AD, with emergent surgery [4]. Patients with IMH in-
fined as the entry tear and the remaining points of com- volving the descending thoracic aorta can initially be giv-
munication as the exit tears, implying flow directional- en appropriate therapy for hypertension and then fol-
ity from true to false lumen and from false to true lumen, lowed.
respectively. The actual incidence of AD is difficult to de- Penetrating atherosclerotic ulcer (PAU) is a condition
fine, since AD involving the ascending aorta is often fa- that originates with atherosclerotic plaque involvement of
tal and patients frequently die prior to hospitalization. the aorta, primarily the descending thoracic aorta (Fig. 1).
Likewise, AD is sometimes misdiagnosed on initial pre- As the plaque evolves, the ulceration penetrates the in-
sentation; consequently, these patients are also at risk for ternal elastic lamina into the media of the aortic wall.
death outside of the hospital. Nevertheless, various pop- Over time, the PAU may extend through all three layers
ulation-based studies suggest that the incidence of AD of the aortic wall to form a false or pseudoaneurysm. A
ranges from 2 to 4 case per 100,000 patients [2]. finding of PAU does not necessarily imply the existence
The temporal definition of acute AD is a dissection of an acute aortic syndrome. Signs of IMH or extravasa-
that is identified less than 2 weeks after the onset of tion indicate acuity.
symptoms, while sub-acute ranges from 2 to 6 weeks fol- There are two limitations to this traditional classifica-
lowing an initial painful episode. Chronic AD is defined tion. The first concerns the omission of a rupturing true
as a dissection identified >6 weeks after the onset of pain. aortic aneurysm, as the nature of the presentation and the
Intramural hematoma (IMH) is an entity that was first severity of the event are similar in PAU and the other
described approximately 25 years ago as a stagnant col- acute aortic syndromes. The second limitation is that
lection of blood within the aortic wall. The common as- IMH, defined as a stagnant intramural collection of
sociation of IMH with pathologically detected intimal de- blood, can be observed in the setting of AD, PAU, and
fects led to the hypothesis that most are sequelae of pen- rupturing aortic aneurysm. As such, it is a feature or char-
etrating atherosclerotic ulcer. An alternative cause of acteristic associated with any of the acute aortic syn-
IMH, typically invoked in the absence of an intimal de- dromes, reflecting degradation of the aortic wall as a har-
fect, is rupture of the vasa vasorum. This hypothetical binger of impending aortic rupture.
a b c
Fig. 1 a-c. Rupturing thoracic aortic aneurysm. a Unenhanced computed tomography (CT) demonstrates a high-attenuation hematoma in the
right pleural space and middle mediastinum. There is an aneurysm of the descending aorta. b Unenhanced CT section 5 cm inferior to (a),
reveals an intramural hematoma (IMH) at the inferior margin of the aneurysm, with extravasation of blood into the middle mediastinum.
Note the displacement of intimal calcium along the inner wall of the IMH. c Following the administration of intravenous contrast materi-
al, the IMH is harder to visualize because of the wider window used to display the CT angiogram.
Acute Aortic Syndrome: State-of-the-Art Diagnostic Imaging 151
a b
Fig. 2 a, b. Type B aortic dissection. a The true lumen is completely collapsed posteri-
orly and only the true lumen fills with contrast material. The entry tear was (not shown)
in the proximal descending aorta. b Because of their supply from the aortic true lumen,
the renal arteries do not opacity and the kidneys are not perfused
In consideration of these two points, a new classifica- 5. The presence of IMH, PAU, or calcification.
tion scheme has been proposed based upon the primary 6. Extension of the aortic abnormality to include inter-
location of the lesion within the aortic wall. In this new branch vessels, including dissection and aneurysm,
classification scheme, there are three pathological enti- and secondary evidence of end-organ injury (e.g., re-
ties: AD, PAU, and rupturing aortic aneurysm [5]. These nal or bowel hypoperfusion).
three entities are differentiated by the fact that AD prin- 7. Evidence of aortic rupture, including periaortic and me-
cipally involves the aortic media, PAU originates within diastinal hematoma, pericardial and pleural fluid, and
the aortic intima, and aortic aneurysm is a disease of all contrast extravasation from the aortic lumen (Fig. 2).
three layers. The presence of IMH is an observation or 8. When a prior examination is available, direct image-
epi-phenomenon to be applied to any of these three fun- to-image comparison to determine whether there has
damental pathologies. In the setting of an isolated IMH been any increase in lesion diameter.
without PAU, non-communicating dissection has been
proposed as a descriptor, although the term IMH is
more commonly associated with this lesion. CT-Based Imaging Approaches to Acute Aortic
Syndromes
Essential Elements of Aortic Imaging Reports High-quality and comprehensive aortic and end-organ as-
sessment is performed using multi-detector row CT with
In 2010, a group of medical organizations representing at least 16 detector rows. This scanner configuration al-
the disciplines of cardiology, radiology, thoracic surgery, lows for imaging from the neck through the pelvis, ac-
and anesthesia published guidelines for the diagnosis and quiring 1.5-mm-thick transverse sections during the ar-
management of patients with thoracic aortic diseases. In terial phase of enhancement from an intravenous contrast
this report, the authors identified eight essential elements administration. It also allows for the use of electrocar-
that should be addressed in aortic imaging reports [2]. diographic (ECG) gating of the scan when appropriate, as
While these guidelines are not comprehensive, nor do described below.
they imply the necessity of reporting every element in
every case, they are a useful construct from which to Unenhanced CT
build any formalized description of the imaging findings
of an acute aortic syndrome. They are the following. An unenhanced scan prior to the administration of intra-
1. The location at which the aorta is abnormal. venous contrast can be valuable for the detection of intra-
2. The maximum diameter of any dilation, measured mural and periaortic blood, which is often subtle. It can al-
from the external wall of the aorta, perpendicular to so be useful for mapping the specific regions of the aorta
the axis of flow, and the length of the aorta that is ab- that are abnormal and thus guide the mode of subsequent
normal. CT angiographic acquisition. While an associated increase
3. For patients with genetic syndromes who are at risk for in radiation exposure results from this approach, the po-
aortic root disease, measurements of the aortic valve, tential value of the information almost always outweighs
sinuses of Valsalva, the sinotubular junction, and the the risk. Using dual-energy scanning, a virtual unenhanced
ascending aorta. scan might obviate the need for a separate unenhanced ac-
4. The presence of internal filling defects consistent with quisition. However, this approach has not been compre-
thrombus or atheroma. hensively validated in acute aortic syndromes. Moreover,
it eliminates the possibility of using the preliminary unen- the presence of unrelated but important abdominal aorto-
hanced acquisition to guide the decision to gate the CT an- iliac pathology, the value of assessing the caliber of a
giogram. transfemoral delivery route to intra-aortic repair devices,
and the possibility of abdominal visceral ischemia, scan
CT Angiography ranges that extend through the abdomen and pelvis are
highly recommended as a routine approach to imaging
While unenhanced imaging can reveal aortic dilation, in- acute aortic syndromes. By beginning the scan in the
tramural and extra-aortic hemorrhage, and in uncommon neck and extending inferiorly below the lesser trochanters
circumstances directly visualize an intimal flap, the use of of the femurs, the scan range will comfortably include
intravenously administered contrast medium is required for several centimeters of the cervical carotid arteries
a complete assessment in patients in whom acute aortic through the bifurcation of the femoral artery. Scan ranges
syndrome is suspected (Fig. 3). The volume and flow rate that include less anatomy risk the possibility that impor-
of the contrast material should be adjusted based on patient tant observations will be missed, such that additional CT
size. A concentrated iodine solution containing 350 mg scans with further injections of iodinated contrast mater-
of iodine/mL will assure adequate intravenous delivery of ial may be required.
iodine with a safe and reliable flow rate of the contrast
material into the peripheral vein. Typical volumes and Electrocardiographic Gating
injector flow rates for iodinated contrast range between 60
and 115 mL at flow rates between 3.5 and 6 mL/s. When the ascending aorta is involved by an acute aortic
To assure diagnostic aortic enhancement throughout syndrome, electrocardiographic (ECG) gating can be
the CT acquisition, the duration of the contrast injection valuable. ECG gating allows for clear delineation of the
should exceed the scan duration by 510 s, and initiation position of the intimal flap across the cardiac period,
of the CT angiographic acquisition should be based on distinction of the involvement of the structures of the aor-
the active monitoring of the arrival of iodine within the tic root including the coronary artery ostia and the aortic
descending thoracic aorta. annulus, elimination of pulsation-related artifacts that can
blur the aortic wall, and subtle regions of extravasation.
Imaging the Abdominal Aorta and Iliac Arteries Unlike the use of ECG gating in the setting of coronary
artery disease assessment, the strategy for using ECG gat-
Because of the likelihood of direct extension of thoracic ing in acute aortic syndromes does not rely upon the ma-
aortic disease into the abdominal aorta and iliac arteries, nipulation of heart rate or coronary artery dimension us-
ing -blockers or nitrates. Regardless of the basal heart
rate, the placement of ECG leads and the acquisition of a
retrospectively gated CT scan (with judicious use of ECG
directed X-ray tube current pulsing to minimize radiation
exposure) allow for a four-dimensional assessment of the
aortic root, aortic valve, coronary arteries, and ascending
aorta. It is sufficient to reconstruct 10 phases every 10%
of the R-R interval. Gating is only beneficial through the
thoracic aorta. The abdomen and pelvis are imaged after
the chest acquisitions, using a non-gated acquisition with
a minimization of the delay between the two scans so that
only one contrast injection is required.
MRI-Based Imaging Approaches to Acute Aortic

Syndromes
Clinical Indications for MRI

While CT remains the mainstay for the initial diagnosis
of patients with acute aortic syndrome, MRI does play a
limited role in patients with contraindications for CT, as
well as in the follow-up of patients for complications fol-
lowing prior AD. First, in patients who cannot tolerate io-
dinated contrast associated with CT, MRI may play a use-
ful role in the diagnosis of acute AD. Investigators have
Fig. 3. Penetrating atherosclerotic ulcer with pseudoaneurysm for- demonstrated the value of cardiac-gated steady-state free
mation in the proximal descending aorta precession (SSFP) MRI in detecting the intimal flap
associated with dissection [6]. These scans are performed pression of branch vessels, especially the coronary arter-
with minimal MRI table time and by using fast acquisi- ies. Likewise, cine MRI can be used to further character-
tion techniques. In patients who are stable, contrast-en- ize the relationship of a type A dissection flap to the aor-
hanced magnetic resonance angiography (MRA) may be tic valve and any resultant aortic valve insufficiency. T1-
used to further diagnose and characterize the configura- and T2-weighted imaging is typically performed with fast
tion of the intimal flap and the involvement of branch spin-echo technique (Table 1).
vessels in acute AD. Finally, gadolinium contrast-enhanced MRA is used to
In the setting of acute dissection with thrombosis lu- characterize the luminal pathology associated with acute
men and intramural hematoma, SSFP MRI alone may be aortic syndrome [7]. Contrast-enhanced MRA is usually
inadequate for detecting hemorrhage in the wall of the acquired during the arterial phase of contrast as well as
aorta. In this clinical scenario, T1- and T2- weighted during the delayed steady state phase of contrast en-
spin-echo technique is typically necessary for diagnosis. hancement. Some authors describe the use of time-re-
MRI using these techniques may be useful in detecting solved 3D MRA during a small initial bolus of gadolinium-
and characterizing the age of the intramural hematoma, based contrast agent, thus allowing the dynamic de-
with typical characteristics such as a transition of the he- lineation of the filling pathways of the true and false lu-
morrhage from deoxyhemoglobin in the early stage of men and branch vessels [8]. These images are typically
IMH to extracellular methemoglobin in its late stage. followed by high-resolution 3D images for more precise
In the setting of aortic aneurysm with suspected rup- anatomic characterization.
ture, patients typically are unstable and therefore far more Extracellular contrast agents are typically the primary
complicated to image with MRI; in these cases, CT is the diagnostic enhancement agents. Contrast agents with
preferred imaging modality. MRI has been used, howev- higher relaxivities are preferred because of their greater
er, to evaluate stable patients with suspected complica- signal at a lower dose as well as their protein binding,
tions of aneurysm and can be particularly helpful in pa- which facilitates delayed imaging in the steady state. For
tients with suspected inflammatory or infectious causes delayed imaging, a fat-suppressed post-contrast T1-
of the aneurysm, due to the exquisite sensitivity of MRI weighted gradient echo image, with spoiling of the trans-
to inflammation in the tissues surrounding the aorta. In verse magnetization, is typically acquired. The delayed
this setting, the use of gadolinium-based contrast agents, images are particularly helpful in evaluating extraluminal
especially those with prolonged blood-pool retention, can pathology affecting the aorta, including aortic leaks, ar-
be particularly informative. teritis, and infection, and in characterizing the size and
extent of hematoma outside the aortic wall (Fig. 3). The
MRI Technique arterial phase of contrast-enhanced images is used to de-
lineate branch vessel involvement of the intimal flap,
Evaluation of thoracic pathology with MRI begins with characterizing the size of aortic enlargement in dissection
rapid SSFP imaging of the aorta and its major branches. and/or dissecting aneurysm, and determining the nature
This technique, in which high-performance gradients are of the intraluminal pathology associated with acute aor-
applied to acquire images using a short repetition time tic syndrome, such as an intimal flap, associated throm-
(TR) and short echo time (TE), are especially useful for bosis, or an atherosclerotic aortic plaque causing in-
imaging aortic vascular pathology in the absence of creased risk of distal atheroembolization.
gadolinium contrast medium (Table 1) [6]. The images
are typically initially acquired in axial and oblique sagit- MRI Findings in Acute Aortic Syndrome
tal projections, and gated to the diastolic phase of the car-
diac waveform. For a more complete characterization of MRI findings in classic AD are similar to those identified
intimal flap motion in the setting of AD, cine SSFP MRI on CT, including a displaced intimal flap, thrombosed lu-
can be used to further delineate the entry and exit zones men, and demonstration of entry and exit tears [9]. One
of the intimal flap, as well as potential dynamic com- key finding on CT that is not reliable on MRI is the
Table 1. Magnetic resonance imaging techniques for the diagnosis and monitoring of acute aortic syndromes
Sequence Plane TR/TE (MS) Matrix Acceleration factor Gating
SSFP 2D axial/sagittal 3/1.5 256192 12 Yes
Time-resolved CE-MRA 3D TRICKS sagittal 3/1 19212832 3
High-resolution CE-MRA 3D sagittal 3/1 320256128 4 No
T1 fast spin echo 2D axial 600/10 256192 n/a No
T2 fast spin echo 2D axial 2500/60 256192 n/a No
4D flow phase contrast 3D sagittal 10/4 25612864 610 Yes
TR, repetition time; TE, echo time; SSFP, steady-state free precession; CE, contrast-enhanced; MRA, magnetic resonance angiography;
TRICKS, time-resolved imaging of contrast kinetics; n/a, not applicable
a b
Fig. 4 a, b. a T1-weighted magnetic resonance imag-

ing demonstrating an IMH with mixed signal inten-
sity components, including low signal intensity cor-
responding to deoxyhemoglobin and high signal in-
tensity extracellular methemoglobin, suggesting an
IMH of subacute or chronic duration. b T2-weighted
image demonstrating high signal intensity asso-
ciated with extracellular methemogolobin due to
chronic IMH
a b
Fig. 5 a, b. Penetrating aortic ulcer. a Early arterial phase and b delayed steady state phase magnetic resonance angiogram (MRA) demon-
strating penetrating aortic ulceration involving the superior surface of the aortic arch (arrows). Note the excellent delineation of the
aortic adventitia on the delayed images due to contrast enhancement during the steady-state imaging phase
displaced intimal calcifications associated with a dis- T1- and T2-weighted images in the chronic phase (Fig. 4).
placed intimal flap. Contrast-enhanced MRA can demon- The exquisite soft-tissue contrast obtained on delayed
strate filling patterns in AD and may be helpful in delin- contrast-enhanced MRI may be helpful in delineating
eating branch-vessel and end-organ perfusion. penetrating aortic ulceration. The immediate arterial-
Spin-echo MRI may allow characterization of the age phase images on contrast-enhanced MRI may show the
of the intramural hematoma associated with an AD or size and extent of ulceration, whereas delayed images en-
penetrating aortic ulceration. Classic features of aortic in- hance visualization of the aortic adventitia and the sur-
tramural hematoma include intermediate to low signal in- rounding soft tissues, thus allowing a more definitive
tensity in the acute phase on both T1- and T2-weighted se- characterization of the aortic enlargement and associated
quences, with gradual transition to high signal intensity on structures in penetrating aortic ulceration (Fig. 5).
a b
Fig. 6 a, b. CT angiography (CTA)

and phase-contrast MRA in type
B aortic dissection. a Reformat-
ted CTA demonstrates a dissec-
tion flap with fenestration but
does not reveal the cause of the
patients persistent abdominal
pain and organ hypo-perfusion.
b Pressure gradient image calcu-
lated from phase-contrast MRA
4D flow imaging demonstrates a
significant pressure gradient and
the dynamic obstruction of flow
to the distal aorta due to com-
pression of the true lumen by the
false lumen
Finally, phase-contrast MRI typically delineates the References

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IDKD 2015-2018
Interventional Techniques in the Thorax of Adults

Dierk Vorwerk
Department of Radiology, Klinikum Ingolstadt, Ingolstadt, Germany
Introduction cantly higher (p0.005) in group A (17%) than in group

B (2.6%). For a specific diagnosis of benignity, no sta-
Interventional radiology in the thorax is somewhat ill- tistically significant difference was found between the
defined, as nonvascular interventions such as lung biopsy two groups (44% vs. 26%) but the automated biopsy de-
tend to be more common. However, many nonvascular as vice provided fewer indeterminate cases. There was no
well as vascular interventions are performed within tho- difference between the two groups concerning the pneu-
racic structures, some of which, such as radiofrequency mothorax rate (20% in group A and 15% in group B) or
ablation of lung tumors, are gaining in importance. the hemoptysis rate (2.4% in group A and 4% in group
B). The authors concluded that, for a diagnosis of ma-
lignancy, automated biopsy devices have a lower rate of
Nonvascular Interventions false-negative results than FNA and a similar complica-
tion rate.
Lung Biopsy Richardson et al. [2] carried out a survey of 5444 lung
biopsy in the UK. Complications included pneumothorax
In the nonvascular field, CT-guided lung biopsies are the (20.5% of biopsies), pneumothorax requiring a chest
most well known and frequently performed intervention drain (3.1%), hemoptysis (5.3%), and death (0.15%). The
in this part of the body. Both fine-needle aspiration timing of post-procedural chest radiography was variable.
(FNA) for cytology as well as miniaturized cutting nee- Centers that performed predominantly cutting-needle
dles (not exceeding 1820 G) for histology are used for biopsies had similar pneumothorax rates to those per-
this purpose. Automated biopsy guns have several advan- forming mainly fine-needle biopsies (18.9% vs. 18.3%).
tages, including excellent sampling quality and the possi- There is great variation in practice throughout the UK
bility to perform repeated biopsies using a single access. and most procedures are performed on an outpatient ba-
FNA is more often recommended if a lesion for biopsy is sis. Small pneumothoraces are common but infrequently
located close to central and vascular structures, in order require treatment. Chojniak et al. [3] carried out a retro-
to avoid major bleeding complications. spective study of 1,300 consecutive CT-guided biopsies
Laurent et al. [1] compared the accuracy and the performed within 6 years. Nodules or masses were sus-
complication rate of FNA and an automated biopsy de- pected as the primary malignancy in 845 cases (65%) and
vice. Two consecutive series of 125 (group A) and 98 as metastases in 455 (35%); 628 of the lesions were tho-
(group B) biopsies performed using 20- to 22-gauge racic. For any site, sample adequacy and specific diagno-
coaxial FNA (group A) and an automated 19.5-gauge sis rate were always better for cutting-needle biopsy.
coaxial biopsy device (group B) were investigated. Among 530 lung biopsies, there were 84 cases of pneu-
Among the patients in groups A and B were 100 (80%) mothorax (16%) and 2 cases of hemothorax (0.3%), with
and 77 (79%) with malignant lesions and 25 (20%) and thoracic drainage in 24 cases (4.9%).
18 (21%) with benign lesions, respectively. The two Postbiopsy pneumothorax is a rather frequent compli-
groups did not significantly differ with respect to pa- cation but in most cases can be treated relatively simply.
tient-, lesion-, and procedure-related variables. Howev- In asymptomatic patients we recommend not evacuating
er, for a diagnosis of malignancy, the difference in sen- the pneumothorax earlier than 4 h after biopsy, in order
sitivity (group A: 82.7%, group B: 97.4%) between the to achieve a durable success. In symptomatic patients or
results obtained with the automated biopsy device vs. those with drainage failures with a single needle ap-
FNA were significant. For a diagnosis of malignancy, proach, the use of percutaneously introduced Heimlich
the false-negative rate of the biopsy result was signifi- valves is recommended.

158 D. Vorwerk
Minimally invasive thoracoscopic procedures have Survival

gained widespread acceptance and offer a valid alterna-
tive in patients with only a single pulmonary nodule that Survival data for patients treated with RFA are scarce and
can be removed both for diagnostic and therapeutic rea- still preliminary, with few series achieving survival be-
sons. In such cases, CT-guided hook marking of the nod- yond 3 years [5]. Accordingly, there are as yet no com-
ule allows easy identification of the nodule during thora- parative studies of RFA and surgery, either for small
coscopy and facilitates its removal. (stage I) non-small-cell carcinomas (NSCLCs) or for
Poretti et al. [4] described their experience with percu- lung metastases. There are also no studies comparing
taneous CT-guided placement of hook-wires to localize RFA and other local ablative therapies. Although in early
nodules before video-assisted thoracoscopy (VATS). In reports survival rates after RFA have been close to the
their report, 19 patients with newly diagnosed intrapul- rates after surgery, the data are preliminary. Ideally, com-
monary nodules underwent CT-guided hook-wire local- parative randomized studies are needed in patients treat-
ization using a X-Reidy set, followed by a VATS resection ed with curative intent.
of the lesion within a mean time of 30 min (range: 1048 Gillams et al. [6] recently published survival data for 122
min). In all cases, resection of the nodules was success- patients with 256 procedures and metastatic disease. The
ful. Eight patients developed an asymptomatic pneu- initial number of metastases ablated was 2.3 (range 18);
mothorax. In four patients, in whom the tumor was hit di- the total number was 3.3 (range 115). The maximum tu-
rectly by the needle, local bleeding occurred. In one case, mor diameter was 1.7 (range 0.54) cm, and the number of
hemoptysis was present. There were no cases of disloca- procedures was 2 (range 110). The major complication
tion of the hook-wire system. rate was 3.9 %. Overall median and 3-year survival rates
were 41 months and 57%. Survival was better in patients
Abscess Drainage with smaller tumors: a median of 51 months, with a 3-year
survival of 64% for patients with tumors 2 cm vs. 31
Percutaneous drainage of pleural, pulmonary, and medi- months and 44% for those with tumors 2.14 cm (p0.08).
astinal abscesses is a commonly employed technique that The authors concluded that, among patients with inopera-
is available in almost all radiological departments. Suc- ble colorectal lung metastases, a 3-year survival of 57% is
cess depends on the size of the drainage catheters, the better than would be expected with chemotherapy alone.
composition of the drained material, the organization of Schlijper et al. [7] performed a systematic review com-
the pseudomembrane, and the access routes, especially paring surgery, RFA, and stereotactic body radiation
into mediastinal locations. (SBRT) as treatment options for metastases from colo-
rectal cancer. The review included 27 studies matched
Radiofrequency Ablation of Lung Lesions according to the a priori selection criteria, the most im-
portant being 50 patients and a follow-up period of
Primary and metastatic lung neoplasms with indications 24 months. Since there were no eligible SBRT studies,
close to those of surgical resection can be treated by ra- the review was conducted on four RFA series and 23 sur-
diofrequency ablation (RFA) [5]. Thus, RFA is performed gical series. Four of the surgical studies were prospective,
with curative intent in nonsurgical or borderline surgical all others were retrospective. There were no randomized
candidates. Inoperability is most often due to poor respi- trials. The reporting of data differed between the studies,
ratory function in relation to chronic obstructive pul- which led to difficulties in the analyses. Treatment-related
monary disease in patients with primary tumors, and it- mortality rates for RFA and surgery were 0% and
erative surgery in patients with metastatic disease. Be- 1.42.4%, respectively, whereas morbidity rates were re-
cause the intent is curative, a pre-ablation imaging ported inconsistently but seemed to be lowest for surgery.
workup must be equivalent to a pre-surgical workup. In According to the authors [7] due to the lack of phase
addition, the size and number of the tumors matter not III trials, no firm conclusions can be drawn, although
only for the oncologic indication but also for the techni- most evidence supports surgery as the most effective
cal possibilities. It is generally agreed that the number of treatment option. High-quality trials comparing currently
tumors per hemithorax should not be more than 5, and the used treatment modalities such as SBRT, RFA and
largest diameter should be 5 cm, ideally 3.5 cm. surgery are needed to inform treatment decisions.
In a microsimulation model, Tramontano et al. [8] cal-
Local Efficacy culated a survival gain of 2.02 years for patients with
stage I inoperable NSCLC undergoing RFA for peripher-
In a review of 17 recent publications, the median report- al tumors and SBRT for central tumors, compared to uni-
ed rate of complete ablation was 90%, although there was versal radiation.
high variability between publications, as ranges between
38% and 97% were reported [5]. Tumors 2 cm in size Technical Considerations
can be ablated in 7896% of cases, according to several
reports of CT-guided RFA in which there was a lengthy The delivery of RFA therapy must be adapted to tumor lo-
imaging follow-up of treated patients. cation because impedance before ablation is significantly
Interventional Techniques in the Thorax of Adults 159
different among tumors, depending on whether 50% or artery, which should not be covered without performing
50% of the tumor abuts the pleura, or whether the tumor a carotid-carotid bypass; and the celiac trunk. Elongation
does not abut the pleura at all. A tumor surrounded by of the aortic arch can make an exact and easy placement
lung parenchyma is highly electrically and thermally in- of the stent graft difficult. Paraplegia is a rare but serious
sulated by the air-filled lung parenchyma compared to a side effect in case the descending aorta is treated but is a
tumor with pleural contact and will require less energy de- less common occurrence than in open surgery.
position. Matsumura et al. [9] evaluated the safety and effec-
tiveness of thoracic endovascular aortic repair (TEVAR)
with a contemporary endograft system compared with
Vascular Interventions open surgical repair of descending thoracic aortic
aneurysms and large ulcers. They included 230 patients
Vascular interventions can be divided into arterial and ve- and compared 16 TEVAR subjects treated with a single
nous interventions. Among the former are balloon angio- type of stent graft with 70 patients undergoing open
plasty of the supra-aortic arteries, such as the subclavian surgery. The 30-day survival rate was non-inferior
artery, implantation of thoracic endografts, and em- (p0.01) for the TEVAR group compared with the open
bolization of bronchial arteries. Rarely performed inter- group (98.1% vs. 94.3%). Cumulative major morbidity
ventions include transarterial techniques for tumor treat- scores were significantly lower at 30 days in the TEVAR
ment, such as chemoperfusion of the lateral thoracic, group than in the open group (1.33.0 vs. 2.3.6,
mammarian, and bronchial arteries in the treatment of p0.01). TEVAR patients had fewer cardiovascular, pul-
bronchial or breast cancer. Vascular interventions involv- monary, and vascular adverse events. No ruptures or
ing the pulmonary artery include the occlusion of arteri- conversions occurred in the first year after the proce-
oportal fistulas, particularly in patients with hereditary dure. Reintervention rates were similar in both groups.
hemorrhagic telangiectasia. Local thrombolysis or throm- At 12 months, aneurysm growth was identified in 7.1%
bodestruction of pulmonary emboli is another rare inter- (8/112), endoleak in 3.9% (4/103), and migration (10
vention but it is a promising alternative in emergency mm) in 2.8% (3/107); other device-related problems
cases involving pulmonary embolism (PE). were infrequent. At 1 year of follow-up, they concluded
Venous interventions in the thorax include central ve- that thoracic endovascular aortic repair with the Zenith
nous stents, either to treat malignancies or to recanalize TX2 endovascular graft (William Cook Europe, ApS,
central venous stenoses in order to allow successful Bjaeverskov, Denmark) is a safe and effective alternative
drainage in dialysis patients, the placement and mainte- to open surgical repair for the treatment of anatomically
nance of central venous catheters, fibrin sheath stripping, suitable aneurysms and ulcers of the descending tho-
and the removal of foreign bodies. racic aorta.
Only some of these interventions merit further discussion In a prospective trial, Nienaber et al. [10] investigated
in the following. However, embolization of the bronchial 140 patients with stable type B aortic dissection who
arteries and treatment of malignant venous stenoses, were randomly assigned to elective stent-graft placement
while uncommon, might be helpful in treating patients in addition to optimal medical therapy (n72) or to opti-
with acute symptoms and are considered below. mal medical therapy (n68) with surveillance. There was
no difference in all-cause mortality: cumulative survival
Arterial Interventions was 97.0%3.4% with optimal medical therapy vs.
91.3%2.1% with thoracic endovascular aortic repair
Stent Graft Implantation (p0.16). Aorta-related mortality was not different
(p0.42), and the risk for the combined end point of aor-
The routine commercial availability of stent grafts for the ta-related death (rupture) and progression (including con-
thoracic aorta has drastically changed the treatment of version or additional endovascular or open surgical inter-
traumatic or iatrogenic pseudoaneurysms, true vention) was similar (p0.86). Three neurologic adverse
aneurysms, intramural hematomas, and symptomatic events occurred in the thoracic endovascular aortic repair
type B aortic dissections. There has been a change of group (one case each of paraplegia, stroke, and transient
strategy for some types of thoracoabdominal aneurysms paraparesis) vs. one episode of paraparesis with medical
but they still present a challenging but luckily small treatment. It was concluded that in survivors of uncom-
group of cases. There is currently no good endoluminal plicated type B aortic dissection, elective stent-graft
alternative for type A aortic dissections or other placement does not improve 1-year survival and adverse
aneurysms of the ascending thoracic aorta. events.
Technically, stent graft implantation into the thoracic The same group recently published their long-term re-
aorta is straightforward, as it involves the insertion of a sults [11], reporting that patients with best medical treat-
simple tube graft or several tube grafts. Important land- ment but no TEVAR had an aortic-related mortality of
marks are the left subclavian artery, which can be usual- 3.6% while those with TEVAR did not show late aortic
ly covered by a stent graft in case the right vertebral events between 2 and 5 years. This difference was signif-
artery is patent; sometimes the left common carotid icant although the overall mortality was not different
160 D. Vorwerk
between the two treatment approaches. However, the au- group of 51 patients with isolated subclavian artery oc-
thors did find stabilization of the dissection in patients clusive disease treated with CSBG using polytetrafluo-
with TEVAR beyond 1 year of follow-up, while patients roethylene grafts. The mean follow-up for the PTA/stent
with optimal medical therapy had a constant progression group was 3.4 years vs. 7.7 years for the CSBG group.
over time. Paraplegia after TEVAR is a significant risk, The technical success rate for the CSBG group was 100%
requiring immediate treatment with corticosteroid and vs. 98% (119/121) for the PTA/stent group. The overall
spinal drainage. perioperative complication rate in the stent group was
15.1% (18/119: 11 minor and 7 major complications) vs.
Percutaneous Transluminal Angioplasty of Supra-aortic 5.9% (3/51: 2 phrenic nerve palsies and 1 myocardial in-
Vessel Origins farction) in the bypass group (p0.093). There was no
perioperative stroke or mortality in the CSBG group. The
Supra-aortic percutaneous transluminal angioplasty major perioperative complications in the stent group in-
(PTA) is mainly performed on the left subclavian artery, cluded four thromboembolic events, one case of conges-
but in some cases on the brachiocephalic trunk, the prox- tive heart failure, one case of reperfusion arm edema, and
imal carotid arteries, and the right subclavian artery. one of pseudoaneurysm. The 30-day patency rate was
Stenosis or occlusions may be caused mainly by athero- 100% for the bypass group and 97% (118/121) for the
sclerosis and less by inflammatory processes such as PTA/stent group. The primary patency rates at 1, 3, and
Takayasu arteritis. Indications for interventions are em- 5 years were 100%, 98%, and 96% for the CSBG group
bolic events, neurological symptoms due to steal or vs. 93%, 78%, and 70% for the stent group, respectively
malperfusion, or brachial claudication. Dilatation of the (p0.0001). Freedom from symptom recurrence was al-
left subclavian artery is relatively safe, with a low rate of so statistically superior in the bypass group vs. the stent
vertebral embolization. However stent placement is fre- group (p0.0001). The authors concluded that
quently necessary due to an insufficient post-PTA result. PTA/stenting of the subclavian artery should be the pro-
Sixt el al. [12] retrospectively analyzed 108 interven- cedure of choice for high-risk patients, but CSBG should
tions of atherosclerotic lesions in subclavian arteries or be offered to good-risk surgical candidates who may be
the brachiocephalic trunk, representing 92% of the pa- seeking a more durable procedure.
tients treated for subclavian artery obstructive disease dur-
ing a 10-year period. The primary success rate was 97%: Bronchial Artery Embolization
100% for stenoses (78/78) and 87% for total occlusions
(26/30). Treatment modalities included PTA alone (13%; Bronchial artery embolization (BAE) is not a simple inter-
n14) or stenting (87%; n90) with balloon-expandable vention for several reasons. First, the anatomy of the
(n61) or self-expanding (n17) devices, or both bronchial artery is variable and the arteries are frequently
(n12). The 1-year primary patency rate of the 97 pa- very small, which often makes their cannulation difficult.
tients eligible for follow-up was 88%: 79% for the PTA Feeders to bronchial artery bleeding sources mainly ar-
subgroup and 89% for the stenting subgroup (p0.2). teriopulmonary fistulae due to tumoral or inflammatory
Babic et al. [13] reported a reasonably high technical changes may originate not only from the bronchial artery
success of 82% and a complication rate of 7% in 56 pa- but also from many other arteries in the thorax, such as the
tients treated for chronic total occlusions of the subcla- subclavian artery, the thyrocervical trunk, or the mammar-
vian artery. Patency after 3 years was 83%. ian or costal arteries. Moreover, there is variation in col-
Van Hattum et al. [14] evaluated the results of PTA and laterals in the region, including the spinal arteries.
stent placement in isolated brachiocephalic trunk lesions Particles, glue and coils are used as embolization ma-
in 30 patients with isolated clinically significant stenoses terials but a golden rule requires that the artery is sealed
(n25) or occlusions (n5) of the brachiocephalic as close as possible to the bleeding source, to avoid re-
artery. The initial technical success rate was 83% (occlu- currence via collateral feeders shortly thereafter.
sions, 60%; stenoses, 88%), and the clinical success rate Benign reasons for bronchial bleeding include
81%. Two patients had major complications, and four ex- bronchiectasis, chronic bronchitis, aspergillosis, tubercu-
perienced minor complications. At a median follow-up of losis, pneumonia, and abscesses. Malignant sources are
24 months (4 weeks to 92 months), the primary clinical predominantly bronchial cancers.
patency rate was 79% (95% confidence interval (CI): The results of percutaneous intervention are relatively
57%, 104%), with 83% (95% CI: 60%, 105%) for arter- good. Kato et al. [16] treated 101 patients and achieved a
ies with stents and 67% (95% CI: 13%, 120%) for those technical success of 100%, a 1-year success of 77.7%, and
without stents (p0.11). The primary technical patency a 5-year success of 62.5%. A better outcome was observed
rate was 50% (95% CI: 24%, 76%). in patients with tuberculosis and bronchitis and a less
AbuRahma et al. [15] compared the results of a large favorable one in those with pneumonia and abscesses.
series of PTA/stenting procedures in the subclavian artery Lee et al. [17] described their experience with BAE
with the results of a series of carotid-subclavian bypass in 54 patients that were treated for massive hemoptysis
grafts (CSBG). Subclavian artery PTA/stenting was in a 5-year period. The underlying pathologies included
performed in 121 patients, who were compared with a bronchiectasis (n31), active tuberculosis (n9),
pneumoconiosis (n3), lung cancer (n2), and pul- Recently, an Italian group described a a single cohort
monary angiodysplasia (n1). Surgery was considered if study in which a combination of segmental pulmonary
the patient had acceptable pulmonary reserve and a bleed- artery embolization and RFA was used in 17 patients
ing source was clearly identified. If the patient was not with 20 nodules. The technical success rate was good
considered fit for surgery, BAE was attempted. Hemopty- and a clinical complete response was achieved in 65%
sis ceased with conservative management only in seven [22].
patients (13%). In the 27 (50%) patients who underwent
surgical resection, the procedures included lobectomy Pulmonary Artery Embolectomy
(n21), bilobectomy (n4), and pneumonectomy (n2).
In-hospital mortality after surgery was 15%. Postoperative Treatment of acute symptomatic PE by catheter-directed
morbidity occurred in eight patients, including prolonged methods has long been a goal of interventional radiolo-
ventilatory support, bronchopleural fistulae, empyema, gists but its realization has been hampered by two prob-
and myocardial infarction. BAE was also used in 21 pa- lems in particular. First, massive PE may lead to relative-
tients not eligible for surgery. The procedure was success- ly mild symptoms not necessitating aggressive treatment.
ful in 17 patients, without any complications. Second, intravenous thrombolysis is usually effective in
Woo et al. [18] retrospectively compared BAE with most patients. Moreover, those patients who are candi-
particles vs. bucrylate glue. In a considerably large co- dates for a percutaneous approach die early or are in very
hort (293 procedures with particles, 113 with glue), they poor clinical condition, as most are hemodynamically un-
achieved a technical success of 94% vs. 97%. The com- stable and require emergency treatment but are not trans-
plication rate was similar but freedom from rebleeding portable. This logistical aspect has prevented the wide-
was better: at 1, 3, and 5 years, 88%, 85%, and 83% with spread use of catheter-based interventions. Nonetheless,
glue vs. with 77%, 68%, and 66% particles. among the small cohorts of patients treated with this ap-
Witt et al. [19] performed BAE using platinum coils proach, the results have been encouraging.
with Dacron fibers in 30 consecutive patients with bleed- Kuo et al. [23] retrospectively analyzed 70 consecutive
ing from bronchial carcinoma. The aim of that study was patients over a 10-year period with suspected acute PE
to compare immediate results with respect to bleeding who had been referred for pulmonary angiography and/or
cessation as well as recurrence, and survival rates with intervention. The criteria for study inclusion were pa-
BAE vs. conservative management. Active bleeding tients who received catheter directed intervention (CDI)
stopped immediately in all patients. A comparison of the due to angiographically confirmed massive pulmonary
BAE group with the controls showed that the cessation of embolism and hemodynamic shock (shock index 0.9).
first-time hemoptysis was 100% in the BAE group vs. CDI involved suction embolectomy and fragmentation
93% in the non-BAE group. The rates of bleeding recur- with or without catheter thrombolysis. Twelve patients
rence were similar in the two groups (BAE 50% vs. non- were treated with CDI. Seven patients (58%) were re-
BAE 47%). In case of recurrent bleeding, repeated BAE ferred for CDI after failing to respond to systemic infu-
led to a definite cessation of pulmonary hemorrhage in sion with 100 mg of tissue plasminogen activator, and
every case. By contrast, all patients with recurrent he- five patients (42%) had contraindications to systemic
moptysis without a repeated BAE (8 patients, 27%) and thrombolysis. Catheter-directed fragmentation and em-
all patients with bleeding recurrence who were in the bolectomy were performed in all patients (100%) and
non-BAE group died from pulmonary hemorrhage (8 pa- catheter-guided thrombolysis in eight patients (67%).
tients, 53%). The mean survival time of the BAE group Technical success was achieved in all 12 cases (100%).
was significantly longer than that of the non-BAE group There were no major procedural complications. Signifi-
The authors therefore concluded that BAE was beneficial cant hemodynamic improvement (shock index: 0.9)
in patients tumoral pulmonary bleeding. was reported in 10 of the 12 patients (83%). The remain-
ing two patients (17%) died secondary to cardiac arrest
Venous Interventions within 24 h. The authors concluded that CDI is poten-
tially a life-saving treatment for patients who have not re-
Pulmonary Artery Embolization sponded to or cannot tolerate systemic thrombolysis.
Lin et al. [24] evaluated the treatment outcome in pa-
Pulmonary artery embolization is an infrequently used tients with massive PE who were treated with either ultra-
tool to treat traumatic damage to the pulmonary artery in- sound-accelerated thrombolysis using the EkoSonic En-
duced by catheters or trauma and to treat pulmonary dovascular System (EKOS; EKOS; Bothell, WA) or
artery-vein shunts. In single institutions it has been mod- catheter-directed thrombolysis (CDT). Twenty-five pa-
ified as chemoembolization and used in the palliative tients underwent 33 CDI for massive pulmonary embolism
treatment of patients with lung cancer [20]. There are no during the study period. Among them, EKOS was per-
clinical randomized data on pulmonary artery emboliza- formed in 15 (45%) and CDT in 18 (55%). In the EKOS
tion, only an experimental study in rats [21] that showed group, complete thrombus removal was achieved in 100%
a significant reduction of tumor size compared to intra- cases. In the CDT cohort, complete or partial thrombus
venous chemotherapy. removal was accomplished in 7 (50%) and 2 (14%) cases,
162 D. Vorwerk
respectively. Comparing treatment success based on Benign Venous Stenoses and Occlusions
thrombus removal, EKOS resulted in an improved treat-
ment outcome compared with the CDT group (p0.02). Partial venous obstruction usually does not become clin-
The mean time of thrombolysis was 17.45.23 h and ically evident as long as there is a collateral network. In
25.37.35 h in the EKOS and CDT groups, respectively patients with dialysis fistulas, however, high venous flow
(p0.03). The mortality rate was 9.1% and 14.2% (not sig- may result in severe venous congestions in case the ipsi-
nificant). Treatment-related hemorrhagic complication lateral venous outflow is obstructed. These obstructions
rates in the EKOS and CDT group were 0% and 21.4%, re- are frequently sequelae of an earlier placement of venous
spectively (p0.02). A significant reduction in Miller dialysis catheters into the subclavian vein. However,
scores was noted in both groups following catheter-based since over time the policy has changed to a jugular access
interventions. for those catheters, there are fewer central venous outflow
problems.
Malignant Venous Obstruction (Superior Vena Cava Syndrome) Treatment of benign venous stenoses is not simple, as
balloon angioplasty usually fails to gain long-term im-
Another percutaneous procedure that has become in- provement. Stent placement yields excellent short-term
creasingly popular is the placement of metallic stents to results but is burdened by a high rate of recurrent
treat superior vena cava syndrome (SVCS). Unlike emer- stenoses due to massive neointimal tissue growth within
gency radiation, stenting gives rapid relief of symptoms the stents, thus requiring frequent reinterventions. Poly-
within a few hours or even immediately. The technique is mer-covered stent grafts may be more promising in pre-
relatively simple and can be achieved from either a venting recurrent stenoses but the results of larger stud-
brachial or a transfemoral approach. If the obstruction is ies are still pending.
associated with thrombus, stenting can be combined with Haage et al. [27] analyzed the effectiveness of stent
thrombolysis. placement as the primary treatment for central venous
Lanciego et al. [25] used stent placement as the first- obstruction in 50 patients undergoing hemodialysis. Stent
choice treatment for the relief of symptoms in 52 can- deployment (n57, Wallstent stents) was successful in all
cer patients who were diagnosed with SVCS confirmed patients, with early rethrombosis (within 1 week) noted
by cavography or phlebography. Wallstent prostheses in only one patient (2%). Among the 73 episodes of re-
(n73) were inserted in all patients. A single stent was obstruction, 54 (74%) were treated percutaneously with
sufficient in 37 patients, two stents were required in 11, angioplasty alone and 19 (26%) necessitated additional
three stents in 2, and four stents in another 2 patients. stent placement. The 3-, 6-, 12-, and 24-month primary
Contraindications for the procedure were severe car- patency rates were 92%, 84%, 56%, and 28%, respec-
diopathy or coagulopathy. Resolution of symptoms was tively. Cumulative overall stent patency was 97% after 6
achieved in all patients within 72 h. At follow-up, six and 12 months, 89% after 24 months, and 81% after 36
obstructions, one partial migration to the right atrium, and 48 months.
two incorrect placements, and four stent shortenings Bakken et al. [28] compared the outcomes of primary
were noted. All were successfully resolved by repeat angioplasty (PTA) vs. primary stenting (PTS) in a dialy-
stenting. Symptom-free survival ranged from 2 days to sis access population. PTS was used to treat 26 patients
17 months (mean: 6.4 months). The authors concluded (26 stenoses) and PTA in 47 patients with 49 central ve-
that the Wallstent vascular endoprosthesis is an effective nous stenoses. The PTS group underwent 71 percutaneous
initial treatment in patients with SVCS of neoplastic interventions (average, 2.72.4 interventions per steno-
origin. sis), and the PTA group 98 interventions (average,
Nagata et al. [26] retrospectively investigated the util- 2.01.6 interventions per stenosis). Primary patency was
ity of metallic stent placement, mainly the spiral Z-stent equivalent between the two groups by Kaplan-Meier
(S-Z-stent), for the treatment of malignant obstruction of analysis, with 30-day rates of 76% for both and 12-month
the SVC in 71 patients with SVCS. The 71 patients who rates of 29% for the PTA group and 21% for the PTS
underwent stent placement were followed until death. group (p0.48). Assisted primary patency was also equiv-
The technical success rate was 100%, the initial clinical alent (p0.08), with a 30-day patency rate of 81% and a
success rate was 87% (62/71), the primary clinical pa- 12-month rate of 73% for the PTA group, vs. 84% at 30
tency rate was 88% (57/65), and the secondary clinical days and 46% at 12 months in the PTS group. Ipsilateral
patency rate was 95% (62/65). Stent obstruction oc- hemodialysis access survival was equivalent in the two
curred at a rate of 12% (8/65), requiring secondary stent- groups. The authors concluded that PTS does not improve
ing. The survival times of the 57 patients in whom there the patency rates compared to PTA and does not add to
was no SVCS recurrence ranged from 1 week to 29 the longevity of ipsilateral hemodialysis access sites.
months (mean: 5.4 months). The S-Z-stent was consid- Jones et al. [29] used a stent graft (Viabahn) to treat 30
ered to be suitable for the treatment of malignant ob- patients with central venous stenosis. Surveillance was
struction of the SVC. Unilateral stent placement was ef- carried out at 3, 6, 9, 12, 18, and 24 months using diag-
fective for relief of SVCS in patients with bilateral bra- nostic fistulography. The technical success rate was 100%.
chiocephalic vein obstruction. Primary patency rates were 97%, 81%, 67%, and 45%;
primary assisted patency rates were 100%, 100%, 80%, and automated cutting needles using a coaxial technique. Car-
and 75% at 3, 6, 12, and 24 months, respectively. Twelve diovasc Intervent Radiol 23:266-272.
2. Richardson CM, Pointon KS, Manhire AR, Macfarlane JT
patients required further stent-grafts to maintain patency. (2002) Percutaneous lung biopsies: a survey of UK practice
Ferguson et al. [30] used stents in six patients with fi- based on 5444 biopsies. Br. J Radiol 75:731-735.
brosing mediastinitis with venous obstruction. Four pa- 3. Chojniak R, Isberner RK, Viana LM et al (2006) Computed to-
tients were treated with intravascular stents placed percu- mography guided needle biopsy: experience from 1,300 pro-
taneously. One patient underwent surgical intravascular cedures. Sao Paulo Med J 124:10-14
4. Poretti FP, Brunner E, Vorwerk D (2002) Simple localization
stent placement and one patient declined surgical therapy. of peripheral pulmonary nodules - CT-guided percutaneous
The right pulmonary artery was treated in three patients, hook-wire localization. Rofo Fortschr Geb Rontgenstr Neuen
the SVC in one patient, and three pulmonary veins in the Bildgeb Verfahr 174:202-207.
fifth patient. Each intervention resulted in hemodynamic 5. de Bare T., Farouil G, Deschamps F (2013) Lung Cancer Ab-
improvement with subsequent clinical improvement. Rein- lation: What is the evidence? Semin Intervent Radiol 30:
151-156.
tervention was required within 12 months in two of the 6. Gillams A, Khan Z, Osborn P, Lees W (2013) Survival after
four percutaneously treated patients. The authors conclud- radiofrequency ablation in 122 patients with inoperable colo-
ed that stents are an effective option in improving short- rectal lung metastases. Cardiovasc Intervent Radiol 36:
term vascular patency. In-stent stenosis was a frequent 724-730.
complication in patients with fibrosing mediastinitis. 7. Schlijper RC, Grutters JP, Houben R et al (2014) What to
choose as radical local treatment for lung metastases from co-
Riley et al. [31] investigated the treatment of SVCS as lo-rectal cancer surgery or radiofrequency ablation? Cancer
a complication of pacemaker implantation, carrying out a Treat Rev 40:60-67.
Pubmed search to identify cases of symptomatic SVCS 8. Tramontano AC, Cipriano LE, Kong CY (2013) Microsimula-
that developed following the implantation of permanent tion model predicts survival benefit of radiofrequency ablation
and stereotactic body radiotherapy vs. radiotherapy for treating
pacemakers or implantable cardioverter defibrillators. Pa- inoperable stage I non-small cell lung cancer. AJR Am J
tients in the study had been treated with one of five differ- Roentgenol 200:1020-1027.
ent modalities: anticoagulation, thrombolysis, venoplasty, 9. Matsumura JS, Cambria RP, Dake MD; TX2 Clinical Trial In-
stenting, and surgical reconstruction. The literature search vestigators (2008) International controlled clinical trial of tho-
identified 74 publications reporting 104 eligible cases in racic endovascular aneurysm repair with the Zenith TX2 en-
dovascular graft: 1-year results. J Vasc Surg 47:247-257.
which SVCS presented at a median of 48 months after de- 10. Nienaber CA, Kische S, Akin I et al (2010) Strategies for sub-
vice implantation. Anticoagulation, thrombolysis, and acute/chronic type B aortic dissection: the Investigation Of
venoplasty alone were all associated with high recurrence Stent Grafts in Patients with type B Aortic Dissection (IN-
rates. Surgery and stenting were more successful, with re- STEAD) trial 1-year outcome. J Thorac Cardiovasc Surg 140(6
currence rates of 12% and 5% over a median follow-up of Suppl):S101-108.
11. Nienaber CA, Kische S, Rousseau H et al; INSTEAD-XL tri-
16 (range: 2179) and 9.5 (range: 260) months, respec- al (2013) Endovascular repair of type B aortic dissection: long-
tively. Based on our own observations, over the last 40 term results of the randomized investigation of stent grafts in
years conservative treatments have been replaced by surgi- aortic dissection trial. Circ Cardiovasc Interv 6:407-416.
cal reconstruction, and most recently by stenting, as the 12. Sixt S, Rastan A, Schwarzwlder U et al (2009) Results after
most common therapeutic modality employed. balloon angioplasty or stenting of atherosclerotic subclavian
artery obstruction. Catheter Cardiovasc Interv 73:395-403.
There is some evidence [32] that covered stents with 13. Babic S, Sagic D, Radak D et al (2012) Initial and long-term
an expanded polytetrafluoroethylene coating are more ef- results of endovascular therapy for chronic total occlusion of
fective in preventing restenosis than PTA alone, but bare the subclavian artery. Cardiovasc Intervent Radiol 35:
stents have yet to be compared with stent grafts. Limita- 255-262.
14. van Hattum ES, de Vries JP, Lalezari F et al (2007) Angio-
tions in size and diameter and the problem of overriding plasty with or without stent placement in the brachiocephalic
collateral veins restrict the wide-spread use of stent grafts artery: feasible and durable? A retrospective cohort study. J
in the thoracic venous circulation. Vasc Interv Radiol 18:1088-1093.
15. AbuRahma AF, Bates MC, Stone PA et al (2007) Angioplasty
and stenting vs. carotid-subclavian bypass for the treatment of
isolated subclavian artery disease. J Endovasc Ther 14:
Conclusion 698-704.
16. Kato A, Kudo S, Matsumoto K et al (2000) Bronchial artery
The great variation of vascular and nonvascular proce- embolization for hemoptysis due to benign diseases: immedi-
dures in the thorax offers a vast opportunity for the use of ate and long-term results. Cardiovasc Intervent Radiol 23:
351-357.
many different therapeutic techniques, some rarely per- 17. Lee TW, Wan S, Choy DK (2000) Management of massive he-
formed or restricted to just a few centers, and others with moptysis: a single institution experience. Ann Thorac Cardio-
a relevance and general importance for many patients. vasc Surg 6:232-235.
18. Woo S, Yoon CJ, Chung JW et al (2013) Bronchial artery em-
bolization to control hemoptysis: comparison of N-butyl-2-
cyanoacrylate and polyvinyl alcohol particles. Radiology
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19. Witt Ch, Schmidt B, Geisler A et al (2000) Value of bronchial
1. Laurent F, Latrabe V, Vergier B, Michel P (2000) Percutaneous artery embolisation with platinum coils in tumorous pul-
CT-guided biopsy of the lung: comparison between aspiration monary bleeding. Eur J Cancer 36:1949-1954.
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20. Vogl TJ, Wetter A, Lindemayr S, Zangos S (2005) Treatment of treatment of a malignant obstruction of the superior vena ca-
unresectable lung metastases with transpulmonary chemoem- va. Cardiovasc Intervent Radiol 30:959-967.
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21. Schneider P, Kampfer S, Loddenkemper C et al (2002) modialysis-related central venous stenosis or occlusion: results
Chemoembolization of the lung improves tumor control in a of primary Wallstent placement and follow-up in 50 patients.
rat model. Clin Cancer Res 8:2463-2468. Radiology 212:175-180.
22. Gadaleta CD, Solbiati L, Mattioli V et al (2013) Unresectable 28. Bakken AM, Protack CD, Saad WE et al (2007) Long-term
lung malignancy: combination therapy with segmental pul- outcomes of primary angioplasty and primary stenting of cen-
monary arterial chemoembolization with drug-eluting micros- tral venous stenosis in hemodialysis patients. J Vasc Surg
pheres and radiofrequency ablation in 17 patients. Radiology 45:776-783.
267:627-637. 29. Jones RG, Willis AP, Jones C et al (2011) Long-term results of
23. Kuo WT, van den Bosch MA, Hofmann LV et al (2008) stent-graft placement to treat central venous stenosis and oc-
Catheter-directed embolectomy, fragmentation, and thrombol- clusion in hemodialysis patients with arteriovenous fistulas. J
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failure of systemic thrombolysis. Chest 134:250-254. 30. Ferguson ME, Cabalka AK, Cetta F, Hagler DJ (2010) Results
24. Lin PH, Annambhotla S, Bechara CF et al (2009) Comparison of intravascular stent placement for fibrosing mediastinitis.
of percutaneous ultrasound-accelerated thrombolysis vs. Congenit Heart Dis 5:124-133.
catheter-directed thrombolysis in patients with acute massive 31. Riley RF, Petersen SE, Ferguson JD, Bashir Y (2010) Manag-
pulmonary embolism. Vascular 17 Suppl 3:S137-147. ing superior vena cava syndrome as a complication of pace-
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26. Nagata T, Makutani S, Uchida H et al (2007) Follow-up results balloon angioplasty for failing dialysis-access grafts. N Engl J
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IDKD 2015-2018
Nonvascular Interventional Radiology of the Thorax

Albert A. Nemcek, Jr.
Department of Radiology, Northwestern Memorial Hospital, Chicago, IL, USA
Percutaneous Transthoracic Needle Biopsy thoracentesis, an aliquot of collected fluid is sent to labora-
tory analysis to try to more specifically identify the cause
Transthoracic biopsy of pulmonary and mediastinal le- of pleural fluid accumulation. In therapeutic thoracentesis,
sions is a commonly performed diagnostic procedure. It fluid is withdrawn to relieve symptoms such as dyspnea
is used to confirm malignancy in anticipation of appro- (most often) or hemodynamic compromise.
priate therapy or to spare patients with benign disease The benefits of real-time ultrasonography in improv-
from unnecessary surgery. In the following, space limita- ing the success and safety of thoracentesis (as well as
tions prohibit a detailed discussion of techniques and chest tube placement) have been clearly documented,
complications; instead, the reader is referred to several such that its use is now strongly recommended [13, 14].
reviews of this topic for details [1-5]. Current areas of Ultrasound evaluation confirms the presence and location
interest include the use of alternate image-guidance of fluid, improves the characterization of fluid collec-
methods, such as real-time ultrasound for peripheral lung tions, and helps to avoid puncture of the lungs or other
lesions and cone-beam computed tomography (CT) organs during the procedure.
[6, 7]; integrated navigational systems for guidance [8]; Hemorrhagic complications may occur as a result of
methods to decrease the rate of post-procedural pneu- thoracentesis, although the degree of risk relative to var-
mothorax [9]: and the procurement of tissue for genomic ious coagulation parameters is controversial [13]. Since
analysis [10]. the intercostal neurovascular bundle is typically on the
undersurface of the rib, it is prudent to try to enter the
pleural space above the rib. However, there is consider-
Lung Tumor Localization able variability in the position of the intercostal artery
and its branches based on age and relative thoracic posi-
Pulmonary nodule localization may be requested in tion. The British Thoracic Society therefore recommends
patients scheduled for thoracoscopic resection of small, that unless fluid is loculated posteriorly, thoracentesis
peripheral pulmonary nodules, in order to confidently lo- should be performed in the triangle of safety, bordered
calize these lesions [11]. Several methods of localization anteriorly by the lateral edge of the pectoralis major mus-
have been described, including hook-wire localization, cle, laterally by the lateral edge of the latissimus dorsi, in-
image-guided dye injection, the placement of fiducials or feriorly by the fifth intercostal space, and superiorly by
clips, intraoperative ultrasound of the deflated lung, and the base of the axilla [14].
radionuclide injection. A method using microcoil deploy- Pneumothorax may also develop during thoracentesis,
ment through the nodule and trailing to the pleural surface with lower rates generally associated with the use of ul-
has been described that appears to have several advantages trasound guidance. In pneumothorax resulting simply
compared to previously described methods [12]. from the leakage of air via the needle or catheter there is
no clinical significance. However, pneumothorax may al-
so develop due to direct injury to the visceral pleural sur-
Drainage of Thoracic Fluid Collections face, although this should be largely avoidable with good
technique and imaging guidance. Finally, air may leak in-
Thoracentesis to the lung as an ex-vacuo phenomenon in cases of
trapped lung. In these instances, as fluid is aspirated the
One of the most common image-guided interventions in lung fails to expand, and air may leak from the lung as
the thorax is thoracentesis. Thoracentesis is performed for the intrapleural pressures decrease. This has been report-
two main, sometimes overlapping indications: In diagnostic ed as the primary cause of pneumothorax following

166 A.A. Nemcek, Jr.
therapeutic thoracentesis [15], but patients with these Pleuroperitoneal shunts, placed surgically or percuta-
types of pneumothorax rarely require therapy. neously, allow patients to actively treat their dyspnea on
Another potential complication of therapeutic thora- their own. The disadvantages include obstruction or in-
centesis is re-expansion pulmonary edema. This compli- fection of the device and the need to pump the device
cation is rare, generally mild, and responds to conserva- multiple times per day.
tive measures including oxygen administration and di- Another option, unavailable as a percutaneous tech-
uresis. It seems more common in younger patients, those nique, is surgical stripping of the pleura. Although very
with more chronic effusions, and those in whom large effective, this method carries high morbidity and an ap-
amounts of fluid are removed [16]. The latter considera- proximately 10% mortality rate.
tion has led to recommendations of maximal fluid
amounts during thoracentesis (usually 10001500 mL). Empyema and Parapneumonic Effusion
However, it has also been argued that larger volumes of
pleural fluid can be safely withdrawn as long as the pa- Pleural effusions associated with infection (parapneu-
tient does not develop vague chest discomfort or exces- monic effusion and empyema) tend to evolve in stages. In
sively negative (20 cm H2O) intrapleural pressures, as the initial, exudative stage, the fluid is thin and sterile and
measured by pleural manometry [17]. associated with a low white blood cell (WBC) count. In
the fibropurulent stage, bacteria invade the pleural space,
Malignant Pleural Effusions the WBC count increases (an empyema is defined as
grossly purulent fluid), and fibrin begins to be deposited
Malignant pleural effusions are the second most common on pleural surfaces and as septae within the fluid. Final-
cause of exudative pleural effusions and the most com- ly, in the organization stage, a thick peel of fibrous tissue
mon cause of such effusions in patients over 60 years of encapsulates the pleural space. Chest-tube drainage is
age. While malignant pleural effusions can occur with most effective in the earlier stages but ineffective in the
virtually any primary tumor, they are most often the re- organization stage. Intuition would suggest that elimina-
sult of lung cancer, breast cancer, or lymphoma. Patients tion of the fibrin while fluid is being drained would fa-
tend to present with dyspnea (over 50% of patients), chest cilitate drainage. Indeed, encouraging studies in this re-
pain (usually dull in nature), cough, and generalized sys- gard appeared as early as the 1940s [21] although inter-
temic symptoms that reflect advanced metastatic disease. est waned partly due to allergic reactions to streptokinase,
There are many techniques for the management of ma- the primary fibrinolytic agent used at that time. A recent
lignant effusions [18-20], depending on the type and multicenter trial [22] compared patients with pleural in-
stage of malignancy. In advanced malignancy, the goal is fection (purulent pleural fluid, pleural fluid with pH 7.2,
palliative and is directed primarily toward relieving the and signs of infection, or proven bacterial infection of the
dyspnea, with the exception of the pharmacologic man- pleural space) in a double-blind trial. The 454 patients
agement of pain. Indeed, opiate therapy, in combination were randomly assigned to treatment with intrapleural
with oxygen, is often underutilized in patients with a streptokinase or placebo. There were no significant dif-
short life expectancy but may be quite helpful in reliev- ferences between the groups with regard to endpoints of
ing dyspnea. Therapeutic thoracentesis is a first step in death or requirement for surgery. More recent studies
more definitive therapy as it is important to determine have also looked at deoxyribonucleases in combination
whether fluid removal does, in fact, result in improve- with fibrinolytic agents [23]. In one such study, 210 pa-
ment in dyspnea. However, thoracentesis rarely provided tients with pleural infection were randomly assigned to
lasting control of dyspnea, with fluid reaccumulating in receive one of four treatments: (1) double placebo; (2) in-
98100% of patients within 30 days. trapleural tissue plasminogen activator (t-PA) and a
Indwelling tunneled catheters, placed with imaging DNase; (3) t-PA and placebo; (4) DNase and placebo.
guidance, are another management option in patients with The combined treatment group was associated with im-
malignant pleural effusions. These catheters are well-ac- proved fluid drainage, reduced frequency of surgical re-
cepted by patients, provide good palliation of dyspnea, and ferral, and a shorter hospital stay compared to the place-
result in auto-pleurodesis in over 50% and as high as bo group. The use of either agent alone did not differ sig-
70% of patients, thus allowing eventual catheter removal. nificantly from placebo. Thus, the efficacy of these
Tube thoracostomy can be combined with chemical agents remains controversial [22-24].
pleurodesis, with the aim of causing inflammation and
the adherence of the visceral and parietal pleural sur-
faces. Talc is a commonly used agent, although its opti- Thoracic Ablation Procedures
mal dosage and formulation remain uncertain; in addi-
tion, patients may require prolonged hospitalization dur- While surgical resection remains the standard of care for
ing this form of therapy. Pleurodesis can also be per- early-stage lung cancer, a variety of ablative techniques
formed thoracoscopically; while more invasive, this ap- have shown promise in the treatment of select primary and
proach can provide excellent distribution of the scleros- metastatic pulmonary malignancies [25, 26]. The largest
ing agents and be combined with mechanical abrasion. reported experience is with radiofrequency ablation,
Nonvascular Interventional Radiology of the Thorax 167
although experience with microwave ablation, cryoabla- 11. Tamara M, Oda M, Fujimori H et al (2010) New indication for
tion, and other techniques is accumulating as well. Le- preoperative marking of small peripheral pulmonary nodules
in thoracoscopic surgery. Interact Cardiovasc Thorac Surg
sions most amenable to successful ablation are small 11:590-593.
(3 cm), solitary, and remote from critical structures. 12. Mayo JR, Clifton JC, Powell TI et al (2009) Lung nodules: CT-
Complications are similar to, although greater in frequen- guided placement of microcoils to direct video-assisted thora-
cy than, percutaneous lung biopsy. Few studies have, as coscopic surgical resection. Radiology 250:576-578.
yet, compared either the various ablative techniques or 13. Sachdeva A, Shepherd RW, Lee HJ (2013) Thoracentesis and
thoracic ultrasound: state of the art. Clin Chest Med 34:
ablation with surgery vs. stereotactic radiation therapy. 1-9.
14. Havelock T, Teoh R, Laws D et al (2010) Pleural procedures
and thoracic ultrasound: British Thoracic Society pleural dis-
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IDKD 2015-2018
Dose-Lowering Strategies in Computed Tomography Imaging of the

Lung and Heart
Andr Euler1, Zsolt Szucs-Farkas2, John R. Mayo3, Sebastian T. Schindera1
1 Clinic of Radiology and Nuclear Medicine, University of Basel Hospital, Basel, Switzerland
2 Institute of Radiology, Hospital Centre of Biel, Biel, Switzerland
3 Department of Radiology, Vancouver General Hospital, Vancouver, BC, Canada
Introduction the acceptance of higher image noise. In addition, CT

technical advances have facilitated dose reduction while
Since its first introduction by Hounsfield and Cormack maintaining image quality. This chapter summarizes the
in 1972, computed tomography (CT) has become one of currently available methods for dose reduction/optimiza-
the most important imaging modalities in diagnostic tion in cardiothoracic CT.
imaging, because of its strong impact on patient out-
come. As a result, CT utilization has risen 10% per year
during the last 15 years in the USA [1] and 142% be- Practical Methods for Dose Reduction
tween 1998 and 2008 in Switzerland [2]. In 2008, CT
was responsible for 68% of the yearly Swiss medical ra- Practical methods for dose reduction are independent of
diation exposure while accounting for only 6% of the the CT scanner and are controlled by the operator.
ionizing radiation examinations [2]. Current knowledge
on the attributable risk of cancer induction by low level Limitation of the Enhancement Phases
medical imaging radiation exposure (100 submillisiev-
ert, mSv) is largely based on longitudinal studies of A first and simple step in dose reduction is the limitation
atomic bomb survivors [3]. These data were recently of the number of acquisition phases dependent on the
augmented by two large, retrospective, epidemiologic clinical question. An additional pre-contrast phase in a
cohort studies that showed a correlation between CT ra- chest CT is indicated only in a few clinical situations;
diation exposure and a slightly increased cancer risk in e.g., to assess an intramural aortic hematoma or an aortic
children and young adults [4, 5]. However, the disease stent graft endoleak. Two-phase scanning for these indi-
status of these patients represents a confounding factor cations may be eliminated by the use of dual-energy CT,
in the interpretation of these data. which derives a virtual non-contrast image from a con-
Given the rapid rise in CT frequency and the potential trast-enhanced dual energy acquisition [6]. However, to
risk of cancer induction, it is the responsibility of the ra- realize a reduction in the radiation dose, the dual-energy
diologic community (radiologists, technologists, medical CT protocol needs to be optimized.
physicists, CT manufacturers) to optimize radiation dose.
In addition to ensuring CT examination justification, su- Reduction of Scan Length
pervising radiologists are responsible for using the low-
est diagnostic CT radiation dose, in accordance with the In general, the scanned volume should be adapted to the
ALARA (as low as reasonable achievable) principle. In clinical question. For example, in suspected pulmonary
chest examinations, the reasons for rigorous dose opti- embolism, the radiation dose in CT pulmonary angio-
mization include highly radiosensitive organs (breast tis- graphy can be reduced by up to 30% by only scanning
sue, bone marrow, lung) within the scanned volume and to the level of the subsegmental pulmonary arteries and
the frequent scanning of radiosensitive young adults (e.g., excluding the lung apex and base [7] (Fig. 1), which
to query pulmonary embolism). harbor distal vessels that will not impact clinical treat-
The radiation dose in a chest CT can be reduced with- ment in most cases. The negative impact of this dose
out degradation of the diagnostic accuracy by taking ad- reduction strategy is the potential to miss a clinically
vantage of the large differences in attenuation between air significant alternative diagnosis, such as a malignant
and soft tissue. The intrinsic high subject contrast allows lung nodule.

Dose-Lowering Strategies in Computed Tomography Imaging of the Lung and Heart 169
Fig. 1. Simulation of reduced scan length

and estimated organ doses in pulmonary
CT angiography to rule out pulmonary em-
bolism, in which the lung apex and base
are excluded. A reduction of the effective
dose by about one third compared with the
original scan volume is estimated by the
dose management software (Radimetrics,
Bayer, Germany)
Positioning of the Arms ners. These filters modify beam strength by strongly at-
tenuating the peripheral projections and weakly attenuat-
In thoracic CT, the patients arms should be raised over ing central ones. This evens the X-ray fluence at the de-
his or her head to achieve a dose-efficient thoracic CT tector and reduces the radiation dose to less-attenuating
scan with acceptable image quality. The increased atten- peripheral structures. Incorrect centering defeats the pur-
uation by the arms in the x-axis forces the automatic tube pose of the bowtie filter, leading to an increased radiation
current modulation to increase the radiation dose to dose to peripheral structures and a decreased image qual-
maintain constant image quality, thus increasing the radi- ity [10]. Clinical studies have found that up to 95% of pa-
ation dose to most organs. Furthermore, with the arms tients receiving a thoracic or abdominal CT scan are not
next to the thorax, beam-hardening artifacts are in- centered properly in the vertical plane [10], with an aver-
creased, degrading image quality (Fig. 2). Compared to age error of 2.6 cm. Li et al. quantified this effect, there-
arm-down positioning, placing the arms above the head by demonstrating that a vertical mis-centering of 3 cm re-
increases subjective and objective image quality [8] and sults in an increase in the peripheral radiation dose of up
leads to a dose reduction of up to 45% in CT of the tho- to 18%, with a 6% increase in image noise [10]. Thus,
rax and abdomen [9]. If a patient is unable to lift one arm, technicians should be trained to meticulously center pa-
the technician should still position the other arm above tients such that the bowtie filters are utilized optimally.
the head.
Patient Positioning in the Isocenter of the CT Scanner Technical Advances for Dose Reduction
The detrimental radiation dose effect of mis-centering pa- In the last 10 years, CT manufacturers have introduced a
tients within the scanner gantry is often not appreciated by number of effective tools that reduce the radiation dose
technicians and radiologists. The increased radiation dose while maintaining or improving image quality. The clinical
associated with mis-centering arises from the pre-patient consequence of impaired image quality associated with
X-ray beam bowtie filters installed in all modern CT scan- dose reduction has been demonstrated in experimental
170 A. Euler, Z. Szucs-Farkas, J.R. Mayo, S.T. Schindera
a b
Fig. 2 a, b. Localizer radiograph and transverse CT slice of the lung base in a patient who underwent two CT examinations, one in which
the arms were raised over the head (a) and the other with the arms placed next to the thorax due to immobility (b). The second CT scan
resulted in an increase of beam hardening artifacts and reduced image quality in the lung bases
studies using computer-simulated low-dose scans [11]. In cal task specified on the clinical requisition. Therefore,
the experimental design, intra-observer agreement was the effectiveness of ATCM dose reduction is dependent
lower when noisy, low-dose rather than higher dose ex- on the radiologist. Each manufacturer uses a proprietary
ams were interpreted [12]. The authors concluded that op- method to define the desired image quality (e.g., refer-
timal dose reduction should be achieved without sacrific- ence mA by Siemens, noise index by GE, standard devi-
ing image quality. Since CT manufacturers use diverse ation by Toshiba, reference images by Philips). In chest
technical approaches for dose reduction, there are some CT, a dose reduction of 2026% can be achieved in aver-
differences in the technical implementations and their re- age-size patients using ATCM rather than fixed tube cur-
sultant effectiveness. rent [16]. However, in very large patients, ATCM can re-
sult in increased radiation doses [17] because the system
Automatic Tube Current Modulation attempts to maintain uniform image quality almost inde-
pendently of body size. Thus, the operator needs to be
Since radiation dose is linearly related to tube current at aware of this important caveat and to adjust the image
constant kVp, a decrease in the tube current results in quality level in obese patients.
dose reduction. Although image noise is impacted by A few years ago, organ-based tube current modulation
dose reduction, there is no impact on the CT numbers was introduced by one manufacturer with the goal of re-
(Hounsfield units) of the body tissues scanned. The aim ducing the tube current (xy plane) when the X-ray tube
of automatic tube current modulation (ATCM) is to main- was positioned over radiosensitive organs, including the
tain operator-selected image quality throughout the scan female breast, the thyroid gland, and the lens of the eye.
while reducing the radiation dose to the patient. State-of- Long term follow-up data from the Life Span Study have
the-art ATCM modulates the tube current in three dimen- shown that the radiation sensitivity of female breast tis-
sions (x-, y-, and z-axes) for every slice of the scan, based sue is higher than previously thought. Consequently, in
on the X-ray attenuation within the slice. Tube current the 2007 ICRP (International Commission on Radiologi-
modulation is implemented based on either: cal Protection) publication [18], the tissue weighting fac-
1. attenuation measurements obtained from the topogram tor of the female breast was increased. Because in chest
or scout views: This approach is used by all manufac- CT the breasts are included in the scan range but are not
turers for z-axis (longitudinal) ATCM modulation, but the target organ of the imaging procedure, it is important
is used by GE and Toshiba for the x- and y-axes (trans- to decrease the radiation dose to these radiosensitive tis-
verse or angular) [13, 14]; sues. Organ-based tube current modulation reduces the
2. tube current adjustment on the fly using the mea- tube current in the anterior 120 arc of the rotation by up
sured attenuation of the previous one-half gantry rota- to 25% of the tube current, while increasing the tube cur-
tion: This approach is used by Siemens for x, y (trans- rent to 125% over the remaining 240 of the rotation to
verse or angular) ATCM modulation [15]. maintain constant image quality in the center of the pa-
The noise level or desired image quality is user-pro- tient [19] (Fig. 3). In phantom studies, an average reduc-
grammable and typically adjusted according to the clini- tion of the breast dose up to 37% was achieved [20].
Further refinement of this technique will be required to

better protect radiosensitive breast tissue.
Adjustment of the Tube Voltage for Pulmonary CT Angiography

Increasing attention is being paid to the use of lower tube
voltages (80100 kVp) in contrast-enhanced CT. In the
chest, pulmonary CT angiography to rule out an em-
bolism is well suited for a low tube voltage technique for
two reasons (Fig. 4): while the radiation dose decreases
at a more than linear rate, the iodine contrast enhance-
ment increases substantially (by a factor of 2, for exam-
ple, when the tube voltage is decreased from 140 to 80
kVp). The increased attenuation of contrast medium at re-
duced kVp (70100) is secondary to the enhanced pho-
toelectric effect at a lower kVp. Two publications demon-
strated that image quality did not decrease when the peak
tube voltage for pulmonary CT angiography was lowered
to 100 kVp, while resulting in a dose reduction of up to
50% [22, 23]. Furthermore, Schueller-Weidekamm et al.
reported an increase in analyzable segmental pulmonary
arteries at 100 kVp compared to 140 kVp [23]. The first
large-scale prospectively randomized study (REDOPED)
investigating the accuracy of low-dose pulmonary CT an-
giography provided clear evidence that, in patients up to
Fig. 3. Principle of organ-based tube current modulation: to protect 100 kg body weight, an 80-kVp protocol yields very sim-
radiosensitive organs such as the female breasts, the tube current ilar accuracy, diagnostic confidence, and image quality
is reduced during the anterior 120 of the gantry rotation. To main- but with a dose that is 30% lower than in a 100-kVp pro-
tain image quality in the center of the image, the tube current is tocol [24]. The estimated effective dose was only 2.25
augmented for the remaining 240 of rotation mSv at 80 kVp. The study also suggested the potential for
further dose reduction since it employed a dated CT tech-
Nevertheless, recent clinical studies showed that in a ma- nology using slow scan times and no iterative recon-
jority of women (up to 99%) parts of the glandular breast struction.
tissue are located outside the dose-reduced sector and Reduced tube voltage can be implemented either man-
therefore might be at increased risk of overexposure when ually or using an automated technique. We employ a
organ-based tube current modulation is used [20, 21]. manual technique based on clinical observation and
a b
Fig. 4 a, b. Examples of lowering the tube voltage in pulmonary CT angiography to rule out pulmonary embolism. a A transverse slice in a
male patient (95 kg body weight) who was scanned with 80 kVp [150 mA; volume CT dose index (CTDIvol) of 4.2 mGy]. b An obese
male patient (150 kg body weight) scanned with 100 kVp (100 mA, CTDIvol of 9.3 mGy). Both images were acquired on a 16-slice MDCT
scanner and reconstructed with filtered back projection. The images clearly demonstrate that, even with dated CT technology, lowering of
the tube voltage in pulmonary angiography is possible without impairing diagnostic accuracy
measurements; specifically, an 80-kVp protocol is ap- the use of IR techniques for dose reduction in general, ra-
plied for patients with a body weight up to 100 kg and a diologists are advised to pay extra attention to the diag-
100-kVp protocol for patients with a body weight 100 nostic accuracy with respect to the detection of small pul-
kg (Fig. 4). At least two manufacturers offer automatic monary nodules on the IR images. This advice is given
tube voltage selection, which selects an optimal tube volt- against the background of the substantially decreased im-
age based on patient size, selected CT protocol, and op- age noise achieved with IR but no impact of improved le-
erator-defined image quality [25]. In a prospective study, sion detectability [28].
Niemann et al. demonstrated a dose reduction of 39% in
pulmonary CT angiography using automatic tube voltage
selection [25]. Instead of the standard tube voltage of 120 Special Indications
kVp, in 28% of the cases a tube voltage of 100 kVp and
in 69% of the cases a tube voltage of 80 kVp were auto- Pulmonary CT Angiography in Pregnancy
matically selected.
Low-dose pulmonary CT angiography is a valuable al-
Iterative Reconstruction Technique ternative for a ventilation/perfusion scan to exclude pul-
monary embolism in a pregnant woman with elevated D-
While the commonly used filtered back-projection image dimer level and negative compression sonography of the
reconstruction technique is computationally efficient, it veins of the lower extremities. The use of tube voltages
suffers from noise and artifact limitations. Despite their of 80 or 100 kVp and limiting the scan range from the
availability over 20 years ago, iterative reconstruction aortic arch to the diaphragm will effectively reduce the
(IR) techniques never gained acceptance due to their radiation dose. The increased radiosensitivity of the glan-
computational intensity and slow image reconstruction dular breast tissue during pregnancy deserves particular
speed. The advent of faster computer platforms and the attention. Although the impact of using breast shields in
demand for a reduction of the radiation dose without an preventing higher absorbed breast dose is controversial
increase in image noise has spurred research into IR. The [29, 30], a reduction of tube current in the anterior part
nomenclature of IR techniques is not yet standard. Man- of the thorax with organ-based tube current modulation
ufacturers have developed a number of proprietary tech- might offer a partial solution, as mentioned earlier.
niques involving different strengths and varying in re-
construction speed, spatial resolution, and image noise. In Lung Cancer Screening
general, in IR an initial image is formed that is then used
to generate simulated raw scan data, which are compared Recent US and Japanese lung cancer screening trial data
to the acquired scan data. A new image is then generated have shown a statistically significant (p0.05) reduction
based on the difference. This process is repeated, or iter- in lung cancer mortality when lung cancers are diagnosed
ated, to further improve the image. IR can operate either at an early stage [31, 32]. Ultra low dose lung cancer
with image and raw scan data space (Adaptive Statistical screening is possible because the large contrast differ-
Iterative Reconstruction, ASIR, GE Healthcare; Adaptive ences between the pulmonary nodules and surrounding
Iterative Dose Reduction 3D, AIDR 3D, Toshiba, Sino- air-filled lung allows the use of images with very high
gram Affirmed Iterative Reconstruction, SAFIRE, noise levels; however, mediastinal images will have re-
Siemens Healthcare; and iDose, Philips Healthcare) or duced diagnostic accuracy with these techniques. The im-
raw scan data space alone (MBIR or Veo, GE Healthcare; age quality and diagnostic accuracy for the lung
Advanced Modeled Iterative Reconstruction, ADMIRE, parenchyma using low mA values have been investigated
Siemens Healthcare). IR is a powerful tool to either im- [12, 33]. Results from phantom studies showed that 80 or
prove image quality in large patients or to maintain diag- 100 kVp can be combined with 25 mA with no deterio-
nostically adequate noise while decreasing radiation dose ration in the detection of small lung nodules [33]. A re-
in small or intermediate sized patients. cent phantom study achieved high image quality and sen-
There are numerous reports of substantial dose reduc- sitivity in pulmonary nodule detection at an effective
tions using IR rather than standard filtered back projec- dose of 0.06 mSv using a novel IR technique and tin fil-
tion while maintaining image quality [26, 27]. However, tration for spectral shaping [34].
radiologist applying IR techniques have to be aware of
the fact that images thus reconstructed tend have a Cardiac CT Dose Reduction
blotchier and more pixilated appearance, impacting the
evaluation of normal anatomic lung structure such as the In cardiac CT, the requirement for scan acquisition to be
interlobular fissures, subsegmental bronchial walls, and synchronized to the phase of the cardiac cycle leads to
small peripheral blood vessels [27]. This occurs particu- specialized dose reduction strategies [35]. The initial ap-
larly with very aggressive noise reduction in order to proach to cardiac gating was retrospectively gated helical
achieve sub-mSv chest CT scans. Moreover, the image acquisitions that used low pitch values (approximately
quality of sub-mSv chest CT is suboptimal for diagnos- 0.20.5 depending on heart rate and single vs. dual tube
ing mediastinal structures such as lymph nodes [27]. In gantry configuration) to provide raw scan data at all
spatial locations in all phases of the cardiac cycle. Initial for the most motion-free time point for the coronary ar-
retrospective helical acquisition allowed the reconstruc- teries. In some cases, motion-free visualization of differ-
tion of low-noise images at multiple cardiac phases. The ent parts of the vessels (e.g., proximal vs. distal portion
images were typically reconstructed at 5 or 10% incre- of the right coronary artery) occurs at different time
ments of the R to R interval. These image sets provided points. However, these additional projections are associ-
visualization of the coronary arteries and the motion of ated with an increased radiation dose such that some au-
the ventricular walls and valves but at the cost of a high thors recommend against the routine use of padding [36].
radiation dose (932 mSv). Moreover, this acquisition
technique was radiation dose wasteful for pure coronary
artery imaging, as the arteries are only motion free at Conclusion
6080% of the R to R interval for heart rates below 80
beats per minute. This review has outlined a number of practical methods
The dose efficiency of retrospective helical acquisition for dose reduction that are independent of the CT scan-
was improved by 50% with the implementation of EKG ner make and model. Other very effective scanner-spe-
tube current modulation, which reduces tube current by cific technical innovations are also available on current-
5090% during high-motion portions of the cardiac cy- generation scanners. They require that radiologists are
cle. This provides low-noise coronary artery images in di- aware of the benefits and limitations of their use. When
astole and noisier wall and valve motion images at se- all current dose reduction strategies are utilized, sub-mSv
lected increments through the remaining cardiac cycle. cardiothoracic CT is achievable in non-obese patients.
The use of tube current modulation is recommended for
all retrospective cardiac-gated acquisitions.
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Eur Radiol 23:2643-2651.
NUCLEAR MEDICINE SATELLITE COURSE
DIAMOND
IDKD 2015-2018
FDG-PET Imaging for Advanced Radiotherapy Treatment of

Non-Small-Cell Lung Cancer
Matthias Guckenberger, Leonie Rudofsky, Nicolaus Andratschke
Department of Radiation Oncology, University Hospital Zrich (USZ), Switzerland
Introduction leaf collimators enabled the faster delivery of these mul-

tiple-field treatment plans. Randomized controlled trials
Radiation oncology has benefited from the enormous have demonstrated the clinical benefit of 3D-CRT com-
progress that followed rapid technical developments over pared to conventional radiotherapy, e.g., in the treatment
the last few decades. Until the 1980s, large volumes of prostate cancer [5].
were unnecessarily irradiated during radiotherapy, due to In the last 10 years, intensity-modulated radiotherapy
the lack of imaging techniques to identify tumor exten- (IMRT) has become broadly available. IMRT has im-
sion, the lack of technologies to accurately conform the proved radiotherapy of complex-shaped target volumes.
radiotherapy dose with the tumor, and the inability to ac- Imaging technologies (electronic portal imaging, X-ray,
curately deliver radiotherapy over a prolonged fraction- cone-beam CT, magnetic resonance) have been integrat-
ated course of treatment. Consequently, in many solid tu- ed into radiation treatment delivery machines to accu-
mors, the radiation tolerance of the surrounding normal rately visualize and target the tumor on a daily basis. Ad-
tissue limited the maximum irradiation dose that could ditionally, imaging and treatment-delivery technologies
be delivered safely. have been expanded to the fourth dimension, meaning
In non-small-cell lung cancer (NSCLC) for example, that intra-treatment motion, e.g., breathing-induced, of
radiation-induced pneumonitis limited the irradiation the tumor can be compensated in real time. Irradiation
dose in many patients to a maximum of 6066 Gy, which with particles, for example, protons and carbon ions, in-
achieved local tumor control in fewer than 50% of the stead of photons, has further improved the physics of ra-
cases [1]. Simultaneously, studies had shown that sub- diotherapy. Together, these technologies allow the pre-
stantially higher irradiation doses (80 Gy) were neces- cise targeting of virtually every tumor within the brain or
sary to locally control locally advanced NSCLC [2] and body of the patient, with nearly sub-millimeter accuracy.
that higher irradiation doses with improved local tumor As a result of these technological advances, the
control also translated into increased overall survival process of target-volume definition, that is, what to treat
(OS) [3]. In prostate cancer, irradiation doses were lim- with which irradiation dose, has become the limiting
ited to a similar dose of 6066 Gy because of the prox- factor in the overall accuracy of radiotherapy. Soft-tis-
imity of the prostate to the rectum, and therefore a risk sue contrast is limited, especially in CT, and the value
of radiation-induced proctitis [4]. of magnetic resonance imaging (MRI) is limited, espe-
Research in radiation oncology thus focused on the cially in the thoracic region. Nodal and distant staging
development of technologies aiming at accurately confin- are suboptimal using CT and MRI only. Response as-
ing the irradiation dose to the tumor while simultane- sessment during and after radio(chemo)therapy is re-
ously minimizing the exposure of adjacent normal tis- stricted to an evaluation of volume and not of function
sue. By broadening the therapeutic ratio, escalated irra- and biology.
diation doses could be delivered without the risk of in- Therefore, functional imaging using positron emis-
creased toxicity. sion tomography (PET) is now the standard of care in
The first major step was the integration of computed radiation oncology. This chapter summarizes the current
tomography (CT) into target-volume definition and applications of PET imaging in radiation oncology and
treatment planning, thus enabling a patient-tailored as- provides an outlook on its future applications. It focus-
sessment of tumor location and tumor size. The devel- es first on the use of 18F-fluorodeoxyglucose (FDG)-
opment of powerful computers allowed for three-dimen- PET for lung cancer and then briefly discusses novel
sional conformal radiotherapy (3D-CRT) while multi- tracers.

178 M. Guckenberger, L. Rudofsky, N. Andratschke
FDG-PET Imaging in NSCLC FDG-PET staging [10]. After systematic lymph node dis-
section in the majority of the patients, 14.3% had occult
FDG-PET for Staging in NSCLC nodal (N1 or N2) metastasis. Total N1 and N2 involve-
ment was detected in 9.5% and 4.8%, respectively. Mul-
Selection of the appropriate patients for radical local tivariate analysis demonstrated that a primary tumor with
treatment, whether surgery, radiotherapy, or multimodal a SUVmax 7.3 was an independent predictor of occult
treatment, is essential. Today, FDG-PET for the staging nodal metastasis. In the retrospective study by Stiles et al.
of nodal and distant metastases is the standard of care, of 266 patients with stage IA disease according to CT-
based on international guidelines. In a prospective study and FDG-PET-based staging, mediastinal lymph node
of NSCLC patients with mostly locally advanced disease, dissection detected N1 and N2 disease in 6.8% and 4.9%
initial staging was performed using CT and with FDG- of the patients, respectively [11]. Tumor size 2 cm and
PET thereafter. FDG-PET led to a change from curative FDG-PET positivity were risk factors for understaging by
to palliative therapy by upstaging the disease extent in FDG-PET.
25% of the patients [6]. A similar study was performed Overall mediastinal staging accuracy was evaluated in
in a patient cohort referred for radical radiotherapy based a meta-analysis. For CT staging, the median sensitivity
on CT staging [7]. The 76 patients were mostly cN. Af- and specificity of mediastinal staging were 61% and
ter FDG-PET staging, radical radiochemotherapy was 79%, respectively. For FDG-PET, the corresponding val-
performed in only 66% of the patients, with palliative ues were 85% and 90. However, the specificity of FDG-
treatment in the remaining 34% mostly because of the de- PET staging was lower when CT showed enlarged lymph
tection by FDG-PET imaging of distant metastases or of nodes [12]. Consequently, all positive nodal findings in
more extensive nodal disease considered too extensive FDG-PET need to be confirmed pathologically, using en-
for successful radical radiochemotherapy. At 4 years af- dobronchial ultrasound or mediastinoscopy.
ter treatment with curative and palliative intent, OS was
35.6% and 4.1%, respectively, thus confirming the accu- Consequences of Improved Staging Accuracy Using FDG-PET
rate selection of a high-risk population using FDG-PET
staging. In patients with stage I NSCLC based on FDG-PET stag-
The timely performance of FDG-PET staging, before ing, stereotactic body radiotherapy (SBRT) of the prima-
the start of radical treatment, is crucial. If the interval be- ry tumor only, without elective treatment of the hilar or
tween staging and the start of radical treatment is too mediastinal lymph node regions, is the guideline-recom-
long, FDG-PET needs to be repeated. Everitt et al. eval- mended standard of care in all patients who are medical-
uated two sequential FDG-PET/CT images acquired from ly inoperable [13]. The omission of elective nodal irradi-
82 patients with a median interval of 24 days prior to the ation combined with other high-precision technologies
start of treatment [8]. Interscan disease progression (respiration correlated imaging, image guidance, intra-
(TNM stage) was detected in 11 (39%) patients. Treat- fractional motion management) allows for irradiation
ment intent changed from curative to palliative in 8 with escalated irradiation doses, which are delivered in a
(29%) because of the detection of newly developed dis- hypo-fractionated manner: biological equivalent doses
tant metastases in the second FDG-PET/CT; in 7 of these (BED) 100 Gy are delivered in 18 fractions.
patients the change in treatment was based on the PET Local tumor control in SBRT is significantly improved
image component. The average standardized uptake val- compared to conventionally fractionated radiotherapy
ue (SUV) increased by 16%. and reaches 90% in the majority of studies. This im-
In patients with NSCLC, FDG-PET is especially use- proved local control translates into significantly im-
ful for nodal staging, which is of fundamental importance proved OS [14], which is mainly limited by the comor-
in therapeutic decision-making (curative vs. palliative; bidities of the patients as well as systemic progression of
surgical vs. non-surgical; conventionally fractionated ra- the disease. Regional failures are rare after FDG-PET
diotherapy vs. stereotactic body radiotherapy) and for tar- staging. Senthi et al. reported a 7.8% regional failure rate
get-volume definition in radical radiotherapy. It is well at 2 years in a large cohort of 676 patients [15].
documented that nodal staging using CT imaging is of In locally advanced NSCLC, involved-field irradiation
low sensitivity and specificity. This is especially true in without elective nodal irradiation is currently practiced in
patients with cN0 disease. DCunha et al. reported the re- most studies and centers, if FDG-PET had been per-
sults of the CALGB 9761 study of 502 patients with clin- formed for staging purposes. Involved-field irradiation
ical stage I disease as determined by CT staging [9]. Af- reduces the irradiated volume substantially, thus allowing
ter surgical resection and mediastinal lymph node dissec- either a reduction of toxicity or iso-toxic escalation of the
tion, 14% of the patients were shown to have had patho- irradiation dose [16]. Early studies confirmed low rates
logic stage II disease and another 13.5% stage III disease. of isolated regional failures in un-irradiated hilar and me-
Two studies evaluated the value of FDG-PET staging diastinal regions [17], with only 1 out of 44 patients treat-
in patients with clinical stage IA disease based on CT ed with involved-field irradiation developing an isolated
staging. Park et al. reported a retrospective study of 147 nodal failure. The value of involved-field irradiation af-
patients who had clinical stage IA disease according to ter FDG-PET staging is currently being evaluated in a
FDG-PET Imaging for Advanced Radiotherapy Treatment of Non-Small-Cell Lung Cancer 179
prospective randomized multi-center trial (PET-Plan, tumor had a significantly worse survival than patients
NCT00697333). with a complete metabolic response. Most importantly,
the location of residual metabolic-active areas within the
FDG-PET as a Prognostic Marker in NSCLC primary tumor after therapy correlated with the initially
high FDG uptake areas determined pre-radiotherapy.
The correlation of pre-treatment, intra-treatment, or ear- Consequently, pre-treatment FDG-PET imaging could be
ly post-treatment FDG-PET characteristics with outcome used to identify subvolumes of the primary tumor at risk
could be used for patient stratification and subsequent for incomplete response after definitive radiotherapy.
treatment adaptation. However, whether FDG-uptake is a A similar study was performed by a group from the
prognostic maker in NSCLC is discussed controversially University of Michigan [22]. In 15 stage IIII NSCLC
in the literature. The uncertainty is at least partially ex- patients treated with a definitive dose of fractionated ra-
plained by differences in the methodology of outcome diotherapy, pre-treatment (2 weeks), intra-treatment (after
modeling. Firstly, different endpoints have been used to approximately 45 Gy), and post-treatment (34 months)
determine a correlation with FDG-PET characteristics: FDG-PET/CT images were acquired. A significant corre-
local tumor control, progression-free survival, and OS. lation between metabolic tumor response during radio-
Secondly, different metrics of FDG-PET images have therapy and metabolic tumor response 3 months post-
been used for outcome correlation: SUVmax, metabolic radiotherapy was determined.
tumor volume, and, more recently, texture characteristics
such as coarseness, contrast, and busyness. Additionally, Consequences of FDG-PET as a Prognostic Marker
tumor volume is a well known independent prognostic
marker, which could confound analysis using FDG-PET If either the pre-treatment or the intra-treatment FDG-
as a prognostic marker [18]. Another matter of contro- PET characteristics of the tumor correlate with local tu-
versy is whether or to what extent inflammatory reactions mor control and/or survival, the appropriate strategy
during or shortly after radio(chemo)therapy influence the would then be to adapt radiotherapy to these tumor-indi-
value of FDG-PET for outcome modeling. vidual functional and biological characteristics. This con-
The prognostic value of pre-treatment FDG-PET was cept of adaptive radiotherapy was first proposed more
evaluated in a meta-analysis of 21 studies by Paesmans et than 10 years ago [23] and is currently under clinical in-
al. [19]. The endpoint was OS. Data from individual da- vestigation.
ta patients were not available; instead, the median SUV Key questions in adaptive radiotherapy remain unan-
value of each study was used as a threshold. The study swered, which has prevented its board adaptation. A dis-
detected a poor prognosis for patients with a high vs. a cussion of these issues in detail is beyond the scope of
low SUV, with an overall combined hazard ratio of 2.08. this chapter but the questions include: Which functional
However, it did not find an optimal SUV threshold but imaging modality, PET tracer, and image characteristics
only that higher SUVs resulted in worse outcome. This are most appropriate for tumor characterization? What
may have been a consequence of the limitations of the are the relevant time points for image acquisition and
meta-analysis or that rather than two groups of patients subsequent treatment adaptation? What are the dynamics
there was a continuous increase in the hazard with in- of functional and biological tumor characteristics and is
creasing SUV. multiple-step adaptation required? Are biological charac-
Matchay et al. reported one of the largest prospective teristics representative for one patient and one tumor as a
studies, in which the pre- and post-treatment FDG-PET whole, or can tumors be subdivided into areas of differ-
characteristics of 250 patients with locally advanced ent biology and function? How can biology, treatment,
NSCLC treated with conventional concurrent platinum- and outcome be correlated with one another? How can
based radiochemotherapy without surgery were analyzed biological information be translated into a robust radio-
[20]. The 2-year survival rate for the entire population therapy plan? How can the outcome of adaptive radio-
was 42.5%. Neither pre-treatment SUVpeak nor SUVmax therapy be evaluated? And how can functional and bio-
correlated with OS, which is in contrast to the meta- logical markers other than imaging, e.g., genomic mark-
analysis described above. In contrast, SUVpeak and ers and RNA expression, be integrated into treatment?
SUVmax in FDG-PET images acquired approximately 14 Despite these uncertainties, the most advanced studies
weeks after treatment correlated with OS. Patients with on adaptive radiotherapy for locally advanced NSCLC
higher residual FDG-PET uptake had a significantly are summarized below.
worse OS. The University of Michigan group reported a pilot
In a further analysis, Aerts et al. analyzed the spatial study in which radiotherapy was adapted after the deliv-
correlation between pre- and post-treatment SUV in 55 ery of 4050 Gy based on FDG-PET/CT [24]. Among the
patients treated with chemoradiation for locally advanced 14 patients with stages IIII NSCLC, the mid-treatment
NSCLC [21]. Pre- and post-treatment FDG-PET images FDT-PET/CT showed a metabolic complete response in
were acquired about 2 weeks and 12 weeks prior to and two and increased FDG uptake in the adjacent lung tissue
after radiotherapy, respectively. The authors reported that in another two. In the remaining 10 patients, CT-mor-
patients with residual metabolic-active areas within the phological and FDG-PET metabolic volumes decreased
by 26% (range, 15% to 75%) and 44% (range, 10% sis was that pre-treatment inflammation in the lungs
to 100%), respectively. Re-planning of radiotherapy makes pulmonary tissue more susceptible to radiation
based on a reduced metabolic volume was then per- damage. The authors reported that the 95th percentile of
formed in six patients and allowed a substantial intensi- FDG uptake in the lungs, excluding clinical tumor vol-
fication of radiotherapy of 30102 Gy (mean 58 Gy) ume, correlated significantly with the risk of developing
without an increased risk of toxicity compared to a sce- radiation-induced pneumonitis. Pre-treatment FDG-PET
nario without mid-treatment plan adaptation (iso-toxic could therefore be used for risk stratification and in the
dose escalation approach). Even this small study by Feng selection of patients for closer follow-up. Even more im-
et al. [24] clearly demonstrated that: (1) adaptive radio- portant from a radiotherapy perspective is the finding that
therapy is not feasible in all patients; (2) not all patients the fraction of the 5%, 10%, and 20% highest SUV vox-
will benefit from adaptive radiotherapy; but that (3) the els that received irradiation doses 25Gy improved the
potential benefit of normal tissue sparing or treatment in- correlation with radiation-induced lung toxicity. Sparing
tensification is considerable in some patients. This con- these lung areas from low-dose irradiation could there-
cept of adaptive radiotherapy using mid-treatment FDG- fore decrease the risk of lung toxicity.
PET/CT is currently being investigated in a randomized
phase II trial (NCT01507428). Gross Tumor Definition Using FDG-PET Imaging
Another study based on the experiences of Aerts et al.
[21] is underway. In this randomized phase II study of pa- Target-volume definition of peripheral early-stage
tients with inoperable stage IB to stage III NSCLC NSCLC is associated with small inter- and intra-observer
(NCT01024829) [25], patients are randomized to con- variability. However, the accurate analysis of breath-
ventional radiotherapy with a total dose of 66 Gy given ing-induced tumor motion and its integration into target-
in 24 fractions of 2.75 Gy with an integrated boost to the volume definition are essential steps in the treatment
primary tumor as a whole (Arm A) or with an integrated process. Respiration-correlated 4D-CT is the current
boost to the 50% SUVmax area of the primary tumor method of choice, despite its limitations due to residual
(from the pre-treatment FDG-PET scan) (Arm B). The motion artifacts and the short image acquisition time.
primary endpoint of this study is progression-free sur- FDG-PET imaging, with its long image acquisition time,
vival. No results have been published so far. may provide a tool similar to slow CT scanning to evalu-
ate tumor motion. Although this concept appears straight-
Normal Tissue Characterization Using FDG-PET Imaging forward, studies have shown only a poor correlation be-
tween PET and the gold-standard of 4D-CT [28]. FDG-
FDG uptake in inflammatory processes may negatively PET for the assessment of tumor-motion amplitude and
influence tumor imaging and characterization but at the motion patterns is therefore not recommended.
same time may help in the visualization, quantification, Several 4D technologies have been developed to ac-
or prediction of inflammatory radiation-induced toxicity. quire and/or reconstruct respiration-correlated 4D PET
Pneumonitis is the most relevant toxicity in patients un- images [29]. Using these technologies should allow for
dergoing radiotherapy for lung cancer. Its development more precise tumor characterization and delineation even
correlates with the radiotherapy dose, i.e., the mean lung in the presence of large tumor motion.
dose and the volume of the lung exposed to 20 Gy, but Definition of the target volume is associated with sub-
the correlation is rather weak. stantial uncertainties especially in locally advanced-stage
A group from Melbourne correlated post-treatment NSCLC. These uncertainties have been quantified in sev-
(median 70 days) FDG uptake in the lungs with the de- eral studies that evaluated inter-observer variability in tar-
velopment of radiation-induced pneumonitis [26]. The get-volume definition and the variability in the target con-
authors reported a significant association between the tours between multiple experts in lung cancer treatment. In
worst Radiation Therapy Oncology Group (RTOG) grade the study of Steenbackers et al. based on 22 patients with
of pneumonitis occurring at any time after radiotherapy early and locally advanced stage NSCLC [30], 11 experts
and the severity of FDG uptake in the lung. No associat- delineated the gross tumor volume using CT images only
ed between FDG uptake and the duration of pneumonitis and then, 1 year later, on matched FDG-PET/CT images.
was found. The authors concluded that FDG-PET may be The variability between the experts was reduced from 1
useful in the prediction, diagnosis, and therapeutic mon- cm (one standard deviation) to 0.4 cm, clearly showing the
itoring of radiation pneumonitis. added value of the FDG-PET imaging component. Two
However, the post-treatment prediction of pneumonitis clinical situations have been identified in which FDG-PET
or lung toxicity has no value in terms of modifying ra- makes a relevant difference compared to CT imaging on-
diotherapy to reduce the risk of pneumonitis, e.g., by rely: The difficulties of nodal staging were described above,
distribution of the radiotherapy dose or dose de-escala- and FDG-PET is essential for defining the nodal target
tion. Petit et al. [27] reported promising results from a volume, especially in cases of involved-node irradiation.
study in which pre-treatment FDG uptake in the lungs The other situation in which FDG-PET can reduce uncer-
was shown to correlate with the post-radiotherapy devel- tainties in target-volume definition is the differentiation
opment of radiation-induced lung toxicity. The hypothe- between macroscopic tumor and atelectasis.
FDG-PET Imaging for Advanced Radiotherapy Treatment of Non-Small-Cell Lung Cancer 181
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IDKD 2015-2018
Staging, Restaging and Response Evaluation of Non-Small-Cell Lung

Cancer
Lars Husmann, Paul Stolzmann
Division of Nuclear Medicine, Department of Medical Radiology, University Hospital of Zurich, Switzerland
Introduction pathobiology, therapy, and prognosis. The former in-

cludes squamous carcinomas and non-squamous carcino-
Lung cancer is the most common cancer in terms of in- mas, such as adenocarcinomas and large cell carcinomas,
cidence and it is associated with the highest mortality as the major histopathological subtypes.
worldwide. The 5-year survival rate of all lung cancer pa- Squamous cell carcinoma is associated with smoking.
tients is only 15%. However, progress has been made in It has the best prognosis, due to a slow growth rate and
the last years, especially regarding screening, minimally a low incidence of distant metastases. Squamous cell
invasive techniques for diagnosis, treatment, and targeted carcinomas tend to become large tumors, often with a
therapies. central necrosis; regional lymph nodes metastases are
Treatment approaches for non-small cell lung cancer common. They are the most common cause of Pancoast
(NSCLC) include surgery, radiation therapy, and tumors.
chemotherapy. They are used as stand-alone treatments or Large-cell carcinomas are also associated with smok-
in combined therapies depending not only on the stage of ing, tend to grow rapidly, metastasize early, and are thus
disease but also on individual patient characteristics such associated with a poor prognosis.
as patient performance status. Treatment concepts are Adenocarcinoma is the most common type of lung
considered as being either curative or palliative. In ad- cancer in nonsmokers and its incidence is rising [1]. The
vanced tumor stages, treatment may be shifted from stan- subclassification of pulmonary adenocarcinoma has re-
dardized to personalized strategies, as targets for specif- cently been revised. This is important for the daily work
ic molecular tumor characteristics have been identified of radiologists and nuclear medicine physicians as use of
and can be used for new and effective treatment. the term bronchioloalveolar cell carcinoma (BAC) is no
Appropriate staging of lung cancer is critical prior to longer recommended. New histological subtypes com-
treatment. Computed tomography (CT) and positron prise adenocarcinoma in situ, lepidic predominant inva-
emission tomography/computed tomography with 18F- sive adenocarcinoma, or invasive mucinous adenocarci-
fluorodeoxyglucose (FDG-PET/CT) are the key imaging noma [2]. However, some radiologists continue to use
modalities in the staging of disease. CT has significant the old terminology in their reports, referring to lesions
limitations in differentiating between normal or malig- as formerly called BAC; others have decided to call
nant tissue regarding both organ and lymph node status. these lesions adenocarcinomas with lepidic growth, or
FDG-PET/CT has been shown to be superior to CT in simply adenocarcinomas. Adenocarcinomas may be
lung cancer staging, despite the known limitation of difficult to diagnose by imaging alone, as they may ap-
FDG-PET/CT as being non-specific for malignant tis- pear as a pneumonia-like consolidation, as a solitary pul-
sue. Thus, false-positive findings may occur in inflam- monary nodule, or as multiple nodules throughout the
matory processes. Generally, all imaging findings and lung. These adenocarcinomas may or may not be meta-
patient factors should be evaluated by a multidiscipli- bolically active in FDG-PET/CT. Additionally, not only
nary team prior to initializing therapy in a patient with is the imaging diagnosis difficult but now also the ter-
lung cancer. minology. All adenocarcinomas should be tested for the
epidermal growth factor receptor (EGFR) mutation and
for anaplastic lymphoma kinase (ALK) rearrangements
Classification for further classification, as new targeted tumor thera-
pies exist for these tumors (such as EGFR kinase in-
The WHO divides lung cancer into two major classes: hibitors gefitinib/erlotinib and ALK kinase inhibitor
NSCLC (85%) and small cell lung cancer, based on crizotinib) [3].

184 L. Husmann, P. Stolzmann
Staging The T descriptor has been reclassified according to

size of the primary tumor (Table 1):
Lung cancer staging guides patient management and pro- T1 (3 cm) is now split into T1a (2 cm) and T1b
vides prognostic information. The TNM staging system is (23 cm).
used to classify NSCLC and is based on the characteris- T2 is split into T2a (35 cm) and T2b (57 cm).
tics of the primary tumor (T), the degree of lymph node T3 includes tumors 7 cm.
involvement (N), and the presence or absence of metas- Additional pulmonary nodules are reclassified as either
tasis (M) (Table 1). In detail, the addition of a c to the T3, with location in the same lobe
term cTNM means clinical staging and includes all imag- T4, with nodules in another lobe on the same side
ing findings whereas pTNM describes the pathological M1a, with nodules in the contralateral lung.
staging. The combination of T, N, and M descriptors are The N descriptor remains unchanged [5] (Tables 1 and 3):
used to identify the overall stage group (Table 2). N1 disease refers to peribronchial and ipsilateral hilar
The 7th revision of the TNM system for lung cancer metastases, including direct extension. All N1 nodes
staging was published in 2010 [4] (Table 1). Significant lie distal to the mediastinal pleural reflection and with-
changes from the 6th edition aim to provide a stronger in the visceral pleura [5].
correlation between the TNM stage and survival data. N2 disease refers to ipsilateral paratracheal and/or sub-
carinal lymph node metastases.
N3 disease refers to contralateral mediastinal, con-
tralateral hilar, and ipsilateral or scalene or supraclav-
Table 1. Definition of T, N, and M (TNM staging) icular nodal metastases.
T Primary Tumor Notably, for paratracheal lymph nodes, the left lateral
T1 Tumor 3 cm in greatest dimension, surrounded by lung border of the trachea and not the midline differentiates
or visceral pleura, without bronchoscopic evidence of in- left from right. Thus, a pretracheal lymph node metas-
vasion more proximal than a lobar bronchus (i.e., not in the
main bronchus) tases may be N2 disease in lung cancer of the right lung,
T1a Tumor 2 cm in greatest dimension
T1b Tumor 2 cm but 3 cm in greatest dimension
T2 Tumor 3 cm but 7 cm or tumor with any of the fol- Table 2. Resultant stage groupings (TNM staging)
lowing features:
Involves main bronchus, 2 cm distal to the carina Stage grouping TNM
Involves visceral pleura Stage IA T1a,b N0 M0
Associated with atelectasis or obstructive pneumonitis that Stage IB T2a N0 M0
extends to the hilar region but does not involve the entire Stage IIA T2b N0 M0
lung T1a,b N1 M0
T2a Tumor 3 cm but 5 in greatest dimension T2a N1 M0
T2b Tumor 5 cm but 7 cm in greatest dimension Stage IIB T2b N1 M0
T3 Tumor 7 cm that directly invades any of the following: T3 N0 M0
chest wall (including superior sulcus tumors), diaphragm, Stage IIIA T1-2a,b N2 M0
phrenic nerve, mediastinal pleura, parietal pericardium, or T3 N1-2 M0
tumor in the main bronchus 2 cm distal to the carina but T4 N0-1 M0
without involvement of the carina or associated atelectasis Stage IIIB T4 N2 M0
or obstructive pneumonitis of the entire lung or separate tu- any T N3 M0
mor nodule(s) in the same lobe Stage IV any T any N M1
T4 Tumor of any size that invades any of the following: medi-
astinum, heart, great vessels, trachea, recurrent laryngeal
nerve, esophagus, vertebral body, carina, separate tumor
nodule(s) in a different, ipsilateral lobe Table 3. Lymph node map: Definitions of nodal stations
N Regional Lymph Nodes N2 nodes - all N2 nodes lie within the mediastinal pleural envelope
N0 No regional lymph node metastasis 1 Highest mediastinal nodes
N1 Metastasis to ipsilateral peribronchial and/or ipsilateral hi- 2 Upper paratracheal nodes
lar lymph nodes, and intrapulmonary nodes including in- 3 Prevascular and retrotracheal nodes
volvement by direct extension 4 Lower paratracheal nodes
N2 Metastasis in ipsilateral mediastinal and/or subcarinal 5 Subaortic nodes (aorto-pulmonary window)
lymph node(s) 6 Para-aortic nodes (ascending aorta or phrenic)
N3 Metastasis in contralateral mediastinal, contralateral hilar, 7 Subcarinal nodes
ipsilateral or contralateral scalene, or supraclavicular 8 Paraesophageal nodes (below carina)
lymph node(s) 9 Pulmonary ligament nodes
M Distant Metastasis N1 nodes - all N1 nodes lie distal to the mediastinal pleural
M0 No distant metastasis reflection and within the visceral pleura
M1 Distant metastasis 10 Hilar nodes
M1a Separate tumor nodule(s) in a contralateral lobe, tu- 11 Interlobular nodes
mor with pleural 12 Lobar nodes
Nodule(s) or malignant pleural (or pericardial) effusion 13 Segmental nodes
M1b Distant metastasis 14 Subsegmental nodes
Staging, Restaging and Response Evaluation of Non-Small-Cell Lung Cancer 185
b c
d e
Fig. 1 a-e. FDG-PET/CT in a 76-year-old man. Images display an FDG-avid squamous cell carcinoma in the right upper lobe (a, b) as well
as pretracheal (c), right paratracheal (d), and subcarinal (e) lymph node metastases. The classification pT1B pN2 cM0 was proven by his-
tology. Notably, the left lateral border of the trachea differentiates left from right paratracheal lymph nodes. Thus, the pretracheal lymph
node metastases (c) would not mean N2 but N3 disease if the lung tumor was in the left lung. Subcarinal lymph node metastases (e) are
always considered N2 disease regardless of the location of the primary lung tumor
but N3 disease if the primary is located in the left lung is no longer in line with current treatment guidelines. For
(Fig. 1). instance, stage IIIA with N2 lymph node metastasis may
The M descriptor has been divided into M1a and M1b, be considered inoperable if lymph node metastases are
for intrathoracic and distant spread, respectively. Patients bulky or in multiple lymph node levels that lie in the ip-
with malignant pleural effusions have been up-staged silateral mediastinum. A curative operation may be con-
from T4 to M1 (Table 1). sidered if down-staging of N3 disease with neoadjuvant
The labeling of stages also was revised between the 6th chemotherapy is successful. In stage IV disease, curative
and 7th editions (Table 2). For example, T2bN0 has treatment approaches may be considered today even if
moved from stage IB to stage IIA, and T2aN1 from stage oligometastatic disease is found with involvement of the
IIB to stage IIA. Patients with tumors 7 cm move from adrenal glands or the brain. Last but not least, standard-
IB to IIB if there is no lymph node metastasis, and from ized treatment strategies are to be defined in adenocarci-
IIB to IIIA if they have N1 lymph nodes. Patients with- nomas with EGFR mutations or ALK rearrangements.
out N3 lymph nodes but with an additional nodule in the This brief summary demonstrates the complexity of
same lobe have been moved from stage IIIB to stage IIIA. tumor staging in lung cancer and thus shows the need for
The new TNM staging system for lung cancer directly a multidisciplinary approach.
impacts treatment algorithms. Treatment approaches for
NSCLC are being constantly adapted and may be shifted T Staging
from standardized to personalized strategies. Formerly,
stages I to IIIA were considered operable, while stages CT and FDG-PET/CT are important imaging modalities
IIIB and VI were considered not to be operable. This in the evaluation of the primary tumor (T staging). CT is
known to have a low accuracy in the evaluation of inva- FDG-positive lymph nodes, suspicious for metastases,
sion of the pleura, the chest wall, and/or the medi- should generally be confirmed by biopsy, if relevant for
astinum, and the correct differentiation between tumor patient management.
and peritumoral atelectasis is often difficult [6, 7]. FDG-
PET/CT may improve accuracy in the detection of tu- M Staging
mor invasion into the chest wall [8-10]. This is important
particularly in patients with a poor cardio-pulmonary re- Distant metastatic disease is already present in 1836%
serve, since the preoperative determination of chest wall of patients with newly diagnosed NSCLC [17]. The abil-
infiltration is desirable in order to avoid extended en ity to detect distant metastases with a high sensitivity,
bloc resection. specificity, and accuracy (94%, 97%, and 96%, respec-
To evaluate infiltration of the mediastinum (T4), con- tively) [18] is the main advantage of FDG-PET/CT and
trast-enhanced CT may be employed but it has a relative- renders PET/CT superior to other imaging modalities.
ly low sensitivity, specificity, and accuracy (68%, 72%, The high sensitivity of FDG-PET/CT to detect distant
and 70%, respectively) [7]. According to our experience, metastases changes patient management in a consider-
PET/CT is not accurate in clearly identifying direct inva- able number of patients, mostly by the up-staging of dis-
sion of the mediastinal vasculature and airways even if ease. Thus, FDG-PET/CT becomes a cost effective imag-
the CT component of FDG-PET/CT is performed with ing modality despite its high operational cost due to a
contrast medium. significant reduction of morbidity though undesired
FDG-PET/CT is helpful for the differentiation be- surgeries [19-21].
tween tumor and peritumoral atelectasis. This allows for The American National Comprehensive Cancer Net-
a more precise determination of the T stage and thereby work guidelines advocate FDG-PET/CT for all patients
impacts surgical planning as sleeve lobectomy is pre- with newly diagnosed NSCLC provided that there is no
ferred over pneumonectomy and radiotherapy plan- evidence of distant metastases. An additional magnetic
ning as the accurate information of tumor extent pro- resonance imaging (MRI) study of the brain is recom-
vided by FDG-PET/CT contributes to a change in the ra- mended in patients with stage II-IV disease to complete
diation field in 3040% of patients [11]. accurate whole-body tumor staging. This is mandatory
because the ability to detect brain metastases is low in
N Staging FDG-PET/CT (see below).
Accurate lymph node staging in patients with NSCLC is

particularly important for patient management. Surgical False Negative and False Positive FDG-PET/CT Results
resection is the treatment of choice for early stages (stage
I or a subset of stage II T1-2, N1). Patients with ipsilat- False-negative results in FDG-PET/CT may occur in
eral mediastinal lymph nodes metastases (N2 disease) are small lesions since the spatial resolution is limited; PET
still considered to have potentially resectable disease if is usually not able to detect metastases 46 mm. Carci-
lymph node metastases are not bulky, multilevel, or tech- noid tumors and adenocarcinomas with lepidic growth
nically unresectable. Induction chemotherapy is usually (formally called BAC) [22, 23] may be false-negative on
recommended with or without combined radiation thera- FDG-PET/CT, as these tumors often metabolize only
py. Surgery is generally not indicated if contralateral me- small amounts of FDG. Finally, false-negative findings
diastinal scalene or supraclavicular lymph node metas- may occur in organs with a high metabolic turn-over,
tases are present (N3). such as the kidneys or the brain.
Both the sensitivity and specificity of CT in the de- False-positive results may occur in states of inflamma-
termination of lymph node metastases from NSCLC are tion and other neoplasms [24] (Fig. 2). For example, sar-
between 60% and 70% [6, 12]. Thus, CT scanning will coidosis often presents with FDG-positive lym-
erroneously suggest the presence of mediastinal lymph phadenopathy that may be interpreted as lymph node
node metastases but miss lymph node metastases in as metastasis or rarely that will imitate distant metastasis
many as 3040% of cases. Several studies have demon- [25]. If there is doubt, the findings must be confirmed
strated that FDG-PET/CT is significantly more accurate histologically if considered relevant for patient manage-
than CT in the determination of lymph node metastases ment.
[13-15]. State-of-the-art PET scanners have a fairly
high spatial resolution (4-6 mm), and even small lesions
with an increased FDG uptake may be detected. A Therapy Monitoring
meta-analysis of FDG-PET/CT and CT in the mediasti-
nal staging of NSCLC demonstrated an accuracy of Quantitative assessment of therapy-induced changes has
86% for FDG-PET/CT and of 73% for CT. Sensitivity, shown that tumoral FDG uptake predicts both response
specificity, positive and negative predictive values were and outcome [26]. Moreover, cancer therapy may be ad-
73%, 91%, 71%, and 90% for FDG-PET/CT and 74%, justed according to the chemosensitivity of the primary
73%, 52%, and 88% for CT, respectively [16]. Thus, tumor as assessed on follow-up FDG-PET/CT (Fig. 3).
Staging, Restaging and Response Evaluation of Non-Small-Cell Lung Cancer 187
b c
d e
a
Fig. 2 a-e. FDG-PET/CT in a 69-year-old woman with an FDG-avid adenocarcinoma of the left lower lobe (a-c). FDG-PET/CT shows not
only N2 disease (a, e) but also an FDG-avid pneumonia in the right upper lobe (d, e), which may be misinterpreted as metastasis, result-
ing in upstaging to T4 disease (i.e., nodule in another lobe on the same side) and thus in total pneumonectomy. Final tumor classification
after resection of the left lower lobe and mediastinal lymphadenectomy was pT1B pN2 cM0
a b c
Fig. 3 a-c. FDG-PET/CT in a 58-year-old woman with an FDG-avid adenocarcinoma in the left lung. Initial staging (a) shows extensive lymph
node metastases (N3); TNM stage was cT1 pN3 cM0. First follow-up (b) 2 months after the scan in (a) shows the complete metabolic re-
sponse of both the lung cancer and all lymph nodes metastases after first line chemotherapy with cisplatin and alimta. Second PET/CT fol-
low-up (c) 5 months after the scan in (b) and while the asymptomtic patient was on maintenance therapy with alimta. The recurrence of hi-
lar and mediastinal lymph nodes metastases and new abdominal lymph nodes metastases are seen. Chemotherapy with taxotere was started
Hence, FDG-PET/CT has the potential to reduce side ef- 13. Steinert HC, Hauser M, Allemann F et al (1997) Non-small
fects and costs when therapy is ineffective [27]. cell lung cancer: nodal staging with FDG PET versus CT with
correlative lymph node mapping and sampling. Radiology
202:441-446.
14. Vansteenkiste JF, Stroobants SG, De Leyn PR et al (1998)
Recurrent Lung Cancer Lymph node staging in non-small-cell lung cancer with FDG-
PET scan: a prospective study on 690 lymph node stations
Patients with NSCLC who have been treated with curative from 68 patients. J Clin Oncol 16:2142-2149.
15. Pieterman RM, van Putten JW, Meuzelaar JJ et al (2000) Pre-
intent are usually followed up with CT every 612 months. operative staging of non-small-cell lung cancer with positron-
FDG-PET/CT is used to evaluate equivocal CT findings, emission tomography. N Engl J Med 343:254-261.
due to its very high accuracy in distinguishing recurrent 16. Chao F, Zhang H (2012) PET/CT in the staging of the non-
disease from benign treatment effects. If tumor recurrence small-cell lung cancer. J Biomed Biotechnol 2012:783739.
is suspected or confirmed, a FDG-PET/CT for restaging is 17. Quint LE (2007) Staging non-small cell lung cancer. Cancer
Imaging 7:148-159.
indicated to differentiate local from distant recurrence, and 18. Hellwig D, Ukena D, Paulsen F et al (2001) [Meta-analysis of
thus to plan local or systemic treatment [28, 29] (Fig. 3). the efficacy of positron emission tomography with F-18-fluo-
Moreover, initial data suggests that FDG-PET/CT is useful rodeoxyglucose in lung tumors. Basis for discussion of the
in the detection of recurrences in asymptomatic NSCLC German Consensus Conference on PET in Oncology 2000].
patients after potentially curative operations [28-30]. Pneumologie 55:367-377.
19. van Tinteren H, Hoekstra OS, Smit EF et al (2002) Effective-
ness of positron emission tomography in the preoperative as-
sessment of patients with suspected non-small-cell lung can-
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IDKD 2015-2018
How To Approach Incidental Findings on Computed Tomography Images

of the Lungs Obtained in Hybrid Imaging
Jeffrey P. Kanne
Department of Radiology, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
Cross-sectional imaging has become an important com- Lung Nodules

ponent in nuclear medicine, as it can be used for more
precise anatomic localization as well as attenuation cor- A lung nodule is defined as a rounded or ovoid soft-tis-
rection. Positron emission tomography (PET) performed sue opacity in the lung, surrounded by air, and measuring
in conjunction with computed tomography (CT) is com- no more than 30 mm in maximum diameter. Nodules can
monly used in staging and restaging malignancies and oc- have mineral (calcium), soft tissue, fat, or mixed attenu-
casionally used for other imaging purposes such as eval- ation. Subsolid nodules, or those containing ground-glass
uating larger lung nodules and for myocardial imaging. opacity, are extremely difficult to detect or fully charac-
Single photon emission computed tomography (SPECT) terize on CT performed as part of nuclear imaging stud-
is also performed in conjunction with CT to improve ies and are best evaluated with dedicated thin-section
anatomic localization. Very recently, hybrid imaging with chest CT.
PET and magnetic resonance imaging (MRI) has become
available and may prove to have many applications be- Calcified Nodules
yond oncologic imaging.
Interpreting hybrid imaging studies requires not only Calcified nodules (Fig. 1) are usually the result of remote
an understanding of nuclear imaging but also knowledge granulomatous infection, particularly histoplasmosis (in
of cross-sectional anatomy. Furthermore, the individual North America) and tuberculosis (the rest of the world).
interpreting hybrid imaging studies must be aware of the Larger nodules may be only partially calcified. To be con-
range of incidental findings encountered on hybrid imag- sidered benign, a partially calcified nodule should fall in-
ing studies. Some incidental findings may have important to one of the following four patterns: diffusely calcified,
clinical significance whereas others may require no fur- centrally calcified, lamellated (concentric rings) calcifi-
ther attention. cation, or dystrophic (popcorn) calcification. Eccentric
This chapter focuses primarily on the incidental tho- or stippled patterns of calcification are considered inde-
racic findings encountered in the chest on PET/CT. terminate. In patients with a history of matrix-forming
sarcoma (osteosarcoma or chondrosarcoma) or adenocar-
cinoma (especially mucinous), metastases can present on
Lungs CT as calcified nodules. Comparison to previous imag-
ing and correlation with metabolic imaging are usually
Although CT performed for attenuation correction with sufficient to determine the nature of these nodules.
PET or SPECT is typically not optimized to evaluate the
lungs, many incidental findings are still encountered on Soft-Tissue Attenuation Nodules
nuclear medicine hybrid studies. Optimal imaging of the
lungs is performed with thin-section (1.5 mm) volu- Most soft-tissue attenuation nodules on CT are indeter-
metric helical CT of the chest during full inspiration. minate. In the absence of a known malignancy, the vast
Coronal and sagittal reformations are often generated and majority of tiny (5 mm) solid nodules are benign. The
reviewed. This technique provides high spatial resolution rate of malignancy increases with size. Guidelines exist
and a detailed anatomic evaluation of the lungs. Typical- for the management of incidental small solid nodules.
ly, attenuation correction CT is performed with thick (~5 However, they are not applicable to patients with known
mm) contiguous (non-helical) sections acquired during malignancy. In most cases, if not recently performed, a
quiet breathing. This results in decreased spatial resolu- dedicated non-contrast chest CT is warranted to fully
tion and artifact from respiratory motion. characterize incidental nodules on hybrid imaging.

190 J.P. Kanne
Pattern Schematic Behavior undergoing hybrid imaging for esophageal carcinoma or

head and neck malignancies. Clues to the diagnosis in-
Diffuse Benigna clude a gravitationally dependent distribution as well as
ancillary findings such as a large hiatus hernia or fluid in
the esophagus.
Central Benign Emphysema

Emphysema (Fig. 2) is the process of airspace expansion
and alveolar destruction with minimal fibrosis. Most em-
physema is the result of cigarette smoking. Emphysema
Lamellated Benign is frequently encountered in patients undergoing hybrid
imaging for lung cancer staging. Emphysema is classi-
fied based on its histopathologic morphology, but strong
correlation with CT appearances allows for use of the
same classification scheme.
Dystrophic Benign
(popcorn)
Centrilobular Emphysema
Centrilobular emphysema occurs in the central portion of
the pulmonary lobule, around the lobular bronchiole and
Eccentric Indeterminate
lobular pulmonary artery. It is almost always the result of
cigarette smoking and has a predilection for the upper
lobes and superior segments of the lower lobes. On CT,
centrilobular emphysema appears as round foci of low at-
Stippled Indeterminate tenuation. A punctate opacity may be visible within the
emphysematous lesion, representing the lobular artery.
Pattern Schematic Distribution

aExcept in the setting of matrix-forming sarcoma or metastatic
adenocarcinoma. Centrilobular Upper lobe
predominant, patchy
Fig. 1. Patterns of lung nodule calcification
Fat-Attenuation Nodules
Nodules with macroscopic fat apparent on chest CT of-
ten represent pulmonary hamartomas (mesenchymomas).
These nodules can be purely fat, primarily soft tissue, or Panlobular Lower lobe, diffuse
contain coarse popcorn calcification. Hamartomas typ-
ically show no increased metabolic activity on nuclear
imaging, although they can grow slowly over several
years.
Diffuse Micronodules
The differential diagnosis of diffuse micronodules (10
mm diameter) depends on their distribution in the lungs. Paraseptal Upper and mid lungs,
The spatial resolution of CT technique used in hybrid subpleural
imaging is typically not sufficient enough to fully char-
acterize the morphology and distribution of diffuse mi-
cronodules. However, occasionally, small branching
(Y- or V-shaped) opacities (tree-in-bud) may be apparent
on hybrid imaging studies. Tree-in-bud opacities are a CT
finding of bronchiolitis and nearly always reflect infec-
tion. Occasionally, tree-in-bud opacities reflect bronchi-
olitis from aspiration and may be encountered in patients Fig. 2. Patterns of emphysema
How To Approach Incidental Findings on Computed Tomography Images of the Lungs Obtained in Hybrid Imaging 191
Panlobular Emphysema septal thickening from lung edema is typically bilateral,

symmetric, and gravitationally dependent, septal thicken-
Panlobular emphysema reflects emphysematous destruc- ing from lymphangitic carcinomatosis is more often ran-
tion of an entire pulmonary lobule and often affects most domly distributed. In the setting of a centrally obstruct-
if not all of an entire segment or lobe. Panlobular em- ing mass (usually lung carcinoma), septal thickening may
physema is most commonly associated with alpha-1 an- be observed in the affected lobe(s) as a result of central
titrypsin deficiency and predominates in the lower lobes. lymphatic and venous obstruction.
CT shows large foci of low attenuation, hyperinflation,
and attenuated pulmonary vasculature. Intralobular Lines
Paraseptal Emphysema Intralobular lines occur within a pulmonary lobule and
are nearly always the result of pulmonary fibrosis. These
Paraseptal emphysema occurs in the periphery of the pul- irregular lines may be more difficult to detect on attenu-
monary lobule and usually develops along pleural spaces. ation correction CT but can be seen when fibrosis is more
It may occur in isolation but more often in conjunction extensive. Most pulmonary fibrosis occurs in the lung
with centrilobular emphysema. Large (10 mm) para- bases. Other findings associated with pulmonary fibrosis
septal emphysematous lesions are termed bullae and can include traction bronchiectasis and honeycomb cysts.
become quite large. Pulmonary fibrosis may be encountered in patients with
a history of cigarette smoking and in those with collagen
Linear Opacities vascular diseases. If clinically appropriate, full character-
ization can be performed with dedicated noncontrast
Fine linear (or reticular) opacities (Fig. 3) may be identi- thin-section chest CT.
fied on CT performed as part of hybrid imaging studies.
These opacities can be described as interlobular (or sep- Cysts
tal) or irregular (intralobular).
Lung cysts (Table 1) are low attenuation foci in the lungs
Interlobular Septal Thickening surrounded by a thin, smooth wall. Single or a small
number of cysts can be found in healthy patients and re-
Interlobular septal thickening occurs when fluid, cells, or quire no further evaluation. However, some lung diseases
fibrosis fill and expand the normal septum that sur- can primarily manifest by the development of extensive
rounds the pulmonary lobule. It is usually apparent on CT lung cysts.
performed in conjunction with PET. Septal thickening
most commonly reflects lung edema and may be seen in Pulmonary Langerhans Cell Histiocytosis
patients with congestive heart failure or other causes of
lung edema. The primary differential diagnosis is lym- Pulmonary Langerhans cell histiocytosis (PLCH) occurs
phangitic carcinomatosis, which occurs when tumor cells almost exclusively in adult smokers and is characterized
invade and obstruct the pulmonary lymphatics. Whereas by the formation of nodules and cysts that predominate in
the upper lungs. With progressive disease, the number and
Pattern Schematic Causes size of cysts increase as the profusion of nodules dimin-
ishes. Larger cysts may have bizarre shapes. PLCH may
Interlobular Edema
Lymphangitic
be encountered in hybrid imaging in patients being staged
carcinomatosis for lung cancer and should not be mistaken for metastases.
Central venous and
lymphatic Lymphoid Interstitial Pneumonia
obstruction
Lymphoid interstitial pneumonia (LIP) is part of the spec-
trum of pulmonary lymphoproliferative disorders and is
characterized by infiltration and expansion of the pul-
Intralobular Fibrosis monary interstitium by a polyclonal mix of lymphoid cells.
In adults, it is most commonly associated with Sjgren
syndrome and thus may be encountered on hybrid imag-
ing performed for staging of lymphoma. On CT, LIP is
characterized by the presence of basal-predominant cysts,
ranging up to approximately 30 mm in diameter. Fre-
quently, a vessel can be observed coursing along the wall
of the cyst. Other CT features of LIP include nodules (soft
tissue or calcified, the latter often reflecting amyloid depo-
Fig. 3. Fine linear (reticular) opacities sition), septal lines, and ground-glass opacity.
192 J.P. Kanne
Table 1. Causes of lung cysts

Disease Distribution Other features and associationss
Pulmonary Langerhans cell histiocytosis Upper lungs Bizarre shapes
Nodules
Cigarette smoking (97%)
Lymphoid interstitial pneumonia Basal predominant Perivascular
Nodules ( calcification)
Septal lines
Ground-glass opacity
Collagen-vascular disease (especially Sjgren syndrome)
Birt-Hogg-Dub syndrome Basal predominant Bilenticular
Renal neoplasms
Skin lesions on face and upper trunk
Birt-Hogg-Dub Syndrome ing architecture is obscured. CT typically cannot estab-

lish the cause of lung consolidation but common causes
This autosomal dominant disease is characterized by the include infection, hemorrhage, neoplasm, edema, and
development of soft-tissue lesions on the face and upper noninfectious inflammation such as organizing or
trunk (primarily fibrofolliculomas), lung cysts, and renal eosinophilic pneumonia. Typically, obtaining additional
neoplasms. Many patients report a personal or family his- clinical information is sufficient to establish a cause for
tory of spontaneous pneumothorax. The lung cysts in Birt- the consolidation.
Hogg-Dub syndrome have a characteristic bilenticular
shape and a predilection for the lower lobes, along the pul- Lung Carcinoma Presenting as Consolidation
monary fissures, pulmonary veins, and septopleural junc-
tion. These cysts may be encountered in patients undergo- Non-resolving, slowly progressive lung consolidation is
ing hybrid imaging for renal cell carcinoma, and the di- an uncommon manifestation of lung carcinoma. Many of
agnosis should be suggested given the implications for these neoplasms are mucinous adenocarcinomas and can
nephron-sparing therapy and the screening of family grow slowly over several years. It is often the case that
members. patients are initially diagnosed as having recurrent infec-
tion. Documenting slow progression across serial exami-
Lung Consolidation nations usually suggests the diagnosis. Percutaneous or
transbronchial biopsy usually confirms the diagnosis.
Lung consolidation (Table 2) is defined as increased at- Clues to the diagnosis on CT include lucencies within ar-
tenuation of the lung parenchyma such that the underly- eas of consolidation (pseudocavitation), small solid and
subsolid nodules adjacent to larger areas of consolida-
Table 2. Causes of lung consolidation tion, and distortion (stretching) of the involved bronchi.
Cause Other clues
Lymphoma Presenting as Lung Consolidation
Hemorrhage Acute hypoxia and dyspnea
Hemoptysis (~50%)
Whether primary or secondary, lymphoma can present as
Infection Fever single or multiple mass-like areas of consolidation on CT.
Leukocytosis
Purulent sputum Distinguishing lymphoma from other causes of consoli-
Edema Other signs of heart or kidney failure
dation can be extremely difficult without previous imag-
Pleural effusion ing or tissue confirmation.
Cardiomegaly
Neoplasm (lung Slowly progressive Organizing Pneumonia
adenocarcinoma Pseudocavitation (adenocarcinoma)
or lymphoma) Bronchial stretching (adenocarcinoma) Organizing pneumonia (OP) is defined as the accumula-
Organizing pneumonia Peripheral and peribronchial distribution tion of newly synthesized collagen in the airspaces (alve-
(OP) and eosinophilic Reversed halo sign (OP) oli and alveolar ducts) of the lung. OP is a normal healing
pneumonia Drug reaction (antibiotics and
chemotherapeutic agents) mechanism of the lung and typically occurs in conjunction
Large opacities Background of small pneumoconiotic
with other processes, such as infection or hemorrhage. It
of pneumoconiosis nodules can also be an immunologic response to an extrinsic (drug,
Upper lung predominant inhaled antigen) or intrinsic (autoimmune) stimulus. In the
Coalescence of small nodules setting of oncologic imaging, OP most commonly results
Lateral margins typically smooth from drug reaction, as many antibiotics and chemothera-
Volume loss in affected lobe(s)
peutic agents can trigger an OP response in the lung. On
CT, OP manifests as peripheral and peribronchial foci of ic bronchial obstruction, bronchial wall damage, or
consolidation. Air bronchograms are usually visible within parenchymal fibrosis. With parenchymal fibrosis, the di-
the foci of consolidation. In approximately 20% of pa- lation of bronchi, termed traction bronchiectasis, occurs
tients, the reversed halo or atoll sign is present, de- by the maturation and retraction of fibrous tissue formed
fined as a focus of peripheral consolidation with central adjacent to an airway. The CT findings of bronchial dila-
ground-glass opacity. In a small number of patients under- tion include lack of tapering of bronchial lumena (the pri-
going chest wall radiation for breast carcinoma, OP can de- mary sign of bronchiectasis), internal diameter of bronchi
velop outside the small portion of irradiated lung, even af- greater than that of the adjacent pulmonary artery (signet
fecting the contralateral lung. The CT appearance of OP in ring sign), bronchi visible within 1 cm of the costal pleu-
this setting is similar to that of other causes. ra or abutting the mediastinal pleura, and mucus-filled di-
lated bronchi. Bronchiectasis can be described as cylin-
Eosinophilic Pneumonia drical, varicose, or cystic, depending on the morphology.
This inflammatory condition of the lung is associated

with tissue (and sometimes peripheral) eosinophilia. The Pleura
CT findings of eosinophilic pneumonia (EP) are very
similar to those of OP and the two entities should be con- Aside from the pulmonary fissures and an occasional thin
sidered in the differential diagnosis of multifocal lung pleural stripe along the chest wall, the normal pleura is
consolidation. However, the reversed halo sign is not a not visible on CT, particularly on the thicker section im-
feature of EP. The most common cause of EP encountered ages that are typically used with PET/CT. For many on-
in hybrid imaging is drug reaction. cology patients, the presence of pleural effusion or soft
tissue involvement will be part of the malignant process.
Large Opacities of Pneumoconiosis However, some pleural findings may be benign.
Silicosis and coal workers pneumoconiosis (CWP) are Pleural Effusion

associated with lung carcinoma and may be encountered
on PET/CT studies of patients undergoing staging. Sim- Pleural effusions are classified as transudative or exuda-
ple pneumoconiosis is characterized by the formation of tive depending on their content. Malignant pleural effu-
small nodules (10 mm) in the lungs in response to in- sions are almost always exudative and can even be
halation of silica or coal dusts. Simple silicosis and CWP bloody. By contrast, pleural effusions associated with
are readily diagnosed by a combination of occupational heart failure are typically transudative. Malignant pleural
exposure and findings on chest radiography and/or chest effusion often shows 18F-fluorodeoxyglucose (FDG)
CT. Complicated pneumoconiosis (progressive massive avidity on PET/CT, and occasionally tumor deposits are
fibrosis, PMF) is defined by the formation of large opac- apparent in the pleural space. Small, layering pleural ef-
ities (10 mm in diameter) in the lungs, resulting from fusions that are not hypermetabolic, especially when bi-
the coalescence of small pneumoconiotic nodules into lateral, may reflect congestive heart failure or fluid over-
mass-like areas of consolidation. These large opacities load from treatment-related renal toxicity.
can be misinterpreted as lung carcinoma if the typical ap-
pearance and background of small nodules are over- Pleural Plaque
looked. Large opacities usually have lateral margins that
parallel the chest wall and are associated with significant Pleural plaques appear as focal thickening of the pleura,
volume loss (recognized by displacement of the pul- usually the parietal surface, and are almost always the re-
monary fissure(s) and hilar distortion). Large pneumoco- sult of asbestos exposure. Pleural plaques are acellular
niotic opacities are often bilateral, especially as PMF be- and contain hyaline. They typically form along the
comes more advanced. hemidiaphragms, costal pleura anterolaterally and pos-
teromedially, and occasionally along the mediastinal
Airways pleura. Pleural plaques have no malignant potential and
are usually not associated with altered respiratory physio-
Evaluation of the airways is usually the purview of volu- logy.
metric thin-section CT. However, abnormalities of larger
airways, especially the bronchi, can be encountered on Diffuse Pleural Thickening
hybrid imaging.
There is no specific definition of diffuse pleural thicken-
Bronchiectasis ing as seen on CT. The causes of diffuse pleural thicken-
ing vary but commonly include instrumentation (e.g.,
Bronchiectasis is a chronic condition characterized by lo- pleural drainage, thoracic or cardiac surgery), healed
cal, irreversible dilation of the bronchi, usually associat- empyema, pleural hemorrhage (hemothorax), and as-
ed with inflammation. Bronchiectasis results from chron- bestos exposure.
194 J.P. Kanne
Fibrothorax Thymic Hyperplasia

Extensive pleural thickening can result in a restrictive The thymus can increase in size and weight after an im-
physiology in the affected lung, a condition termed fi- munologic insult to the body. This may occur following a
brothorax. Thickened pleura can also calcify as well, ei- severe illness, chemotherapy, or other injury. Cross-
ther in focal areas or diffusely. Densely calcified pleura sectional imaging will show enlargement of the thymus.
is usually the result of previous hemithorax or empyema. This may be seen on PET/CT performed for restaging of
malignancy.
Rounded Atelectasis
Lymphoid Thymic Hyperplasia
Rounded atelectasis develops when there is progressive
infolding of lung adjacent to thickened visceral pleura. Lymphoid thymic hyperplasia occurs when lymphoid fol-
Over time, the infolded lung becomes mass like. The licles with germinal centers develop in the thymus. Lym-
characteristic feature of rounded atelectasis on cross- phoid hyperplasia is often associated with autoimmune
sectional imaging is a soft-tissue nodule or mass located disease such as myasthenia gravis. Distinguishing true
immediately adjacent to thickened visceral pleura. Ves- hyperplasia from lymphoid hyperplasia on CT is typical-
sels and bronchi can be seen swirling into the focus of ly not possible.
rounded atelectasis, giving the comet tail sign. Other
signs of volume loss include displacement of the nearby Foregut Duplication Cysts
fissure and decreased volume in the affected lobe.
Foregut duplication cysts are congenital remnants of
Talc Pleurodesis foregut tissue and are usually lined with either bronchial or
esophageal mucosa. Over time they can enlarge, producing
Pleurodesis is often used to palliate malignant pleural ef- mass effect, resulting in symptoms such as pain. Usually
fusion by inducing fusion of the pleural layers and sub- the diagnosis is readily apparent on CT, but dedicated MRI
sequently obliterating the pleural space. Pleurodesis can can be used in cases in which there is diagnostic uncer-
be performed through mechanical or chemical means, but tainty. Symptomatic cysts are usually resected.
for malignant effusions, instillation of talc slurry into the
pleural space is the most commonly used method. Talc Bronchogenic Cysts
pleurodesis has a characteristic appearance on CT, mani-
festing as nodular high-attenuation pleural thickening, Bronchogenic cysts most commonly occur in the subcari-
similar to faint calcification. Importantly, the pleura can nal space and less commonly in the paratracheal spaces
remain hypermetabolic for many years following talc and inferior pulmonary ligaments. On CT, bronchogenic
pleurodesis and should not be mistaken for malignant cysts are typically spheroid and have homogeneous atten-
pleural disease. uation. Attenuation may exceed that of water secondary to
accumulation of proteinaceous fluid. FDG activity is typ-
Pleural Lipoma ically nil unless there is active inflammation.
Pleural lipomas are benign neoplasms containing fat and Esophageal Duplication Cysts
a thin capsule. Occasionally, they are large enough to be
visible on chest radiographs, and most are easily de- Esophageal duplication cysts usually occur in the lower
tectable on cross-sectional imaging. On CT, pleural lipo- mediastinum adjacent to the esophagus. Esophageal du-
mas have fat attenuation and lie in contact with the chest plication cysts can also be lined with pancreatic or gas-
wall. A thin capsule may be visible. tric mucosa, and intracystic hemorrhage can occur.
Esophageal Diverticula
Mediastinum
Esophageal diverticula are described as either pulsion or
Normal Thymus traction, depending on the underlying cause. Pulsion di-
verticula usually occur in the superior or inferior medi-
The normal thymus is large at birth and gradually atro- astinum whereas traction diverticula typically form in the
phies, usually replaced primarily with fat in early adult- central mediastinum, usually from adjacent inflammation
hood. However, normal thymic tissue may be apparent in such as tuberculous lymphadenitis.
middle-age adults as well. On CT, the normal thymus con-
sists of two triangular or ellipsoid lobes, one typically Neurogenic Neoplasm
larger than the other. A trapezoidal configuration can also
occur, particularly in young women. Strands of fat cours- Neurogenic neoplasms are the most common posterior me-
ing through normal thymic tissue are often apparent. diastinal masses. The vast majority of mediastinal neuro-
genic neoplasms are benign and include schwannoma and MAC can be exuberant, with milk of calcium deposition
neurofibromas. Neurofibromas commonly course along and a tumefactive appearance. MAC is typically an inci-
the intercostal nerves and can lead to bone remodeling. dental finding and is only rarely associated with dys-
Schwannomas may be seen extending into and widening rhythmias. However, studies have correlated the presence
the neural foramen, taking on a dumbbell appearance. of MAC with an increased risk of atherosclerotic disease
These lesions are best characterized with dedicated MRI. of the coronary arteries.
Aortic Valve Leaflet Calcification

Heart, Pericardium, and Aorta
Aortic valve leaflet calcification usually indicates aortic
The heart is frequently overlooked on hybrid nuclear valvular stenosis. While it is commonly present in pa-
imaging for a variety of reasons. First, cardiac metabolic tients older than 70 years of age, its presence in young in-
activity is quite variable and detecting malignant disease dividuals is an important finding that may suggest ab-
can be challenging. Second, because attenuation correc- normal valve structure, particularly a bicuspid aortic
tion CT is performed during free breathing and at slower valve, which leads to premature stenosis. Long-standing
acquisitions, cardiac motion can be extensive. Neverthe- aortic stenosis can lead to both left ventricular hypertro-
less, several important findings may still be apparent on phy and ascending aortic aneurysm.
CT, especially if a higher quality CT is performed in con-
junction with PET. Pericardium
Coronary Arteries The normal pericardium is visible as a thin (4 mm)

structure surrounding the heart, separating mediastinal
Coronary artery disease remains the number one cause of fat (superficial to pericardium) from epicardial fat (deep
death, both for men and for women, in the developed to pericardial fat). A small amount of liquid (usually 50
world. CT has been shown to be effective in detecting the mL) distributes throughout the pericardium, most com-
presence of coronary calcification, a marker of coronary monly seen on cross-sectional imaging along the right
artery atherosclerosis. Extensive research has confirmed heart border, anterior pericardium, base of the heart, and
that quantifying coronary calcification on CT can be used in the superior pericardial recesses.
to risk-stratify patients for subsequent major adverse car-
diac events. While most CT performed for attenuation Pericardial Effusion
correction and anatomic localization may be insufficient
to accurately quantify coronary calcium, the images typ- As with pleural effusions, pericardial effusions can be
ically show the presence of moderate or severe coronary transudative or exudative. Pericardial effusions can be a
calcium and its distribution. In patients with a known di- sign of pericarditis or pericardial malignancy. Effusions
agnosis of coronary artery disease, reporting the presence associated with nodular pericardial thickening are usual-
of coronary calcium is probably not necessary on hybrid ly malignant. High-attenuation pleural effusions usually
nuclear imaging. However, it may be an unexpected find- reflect the presence of blood.
ing in other, particularly younger patients, and should be
commented on in the body of the report and in the con- Pericardial Thickening
clusions.
Pericardial thickness 4 mm is considered to be abnor-
Cardiac Valves mal. Pericardial thickening is the sequela of pericarditis
and can either cause no physiologic impact or result in
Calcification of the cardiac valve leaflets and annuli may constrictive pericarditis. CT findings of constrictive peri-
be apparent on hybrid nuclear imaging. In most patients, carditis include pericardial thickening with large atria and
the clinical significance is little or none, but leaflet cal- small ventricles, the latter reflecting the inability of the
cification in particular can reflect valvular stenosis. ventricles to relax during diastole. Pericardial calcifica-
tion may present in addition to thickening and indicates
Mitral Annular Calcification remote pericarditis. Constrictive physiology may or may
not be present in patients with pericardial calcification.
This is an extremely common incidental finding on CT
of the chest, and its prevalence increases with age. Pericardial Cyst
Women are affected more than men. The characteristic
appearance of mitral annular calcification (MAC) on CT Pericardial cysts form from a pinched off portion of peri-
is a crescent- or C-shape band of calcium outlining the cardium during embryogenesis. Approximately 90% oc-
lateral and inferior margins of the mitral valve annulus. cur in the right cardiophrenic space, with the remainder
More extensive MAC can involve the septal and anterior occurring anywhere adjacent to the pericardium. On CT
portions of the mitral annulus. In a minority of patients, they have homogeneous water attenuation (10 HU).
196 J.P. Kanne
Pericardial cysts can change shape depending on the pa- Ribs

tient position during imaging and rarely result in symp-
toms. Treatment is rarely indicated. The normal thorax contains twelve paired ribs. Incidental
findings may include healed fractures, hypoplastic ribs
Aorta (usually one or both of the first ribs), or fused ribs. In pa-
tients who have had thoracotomy, portions of one or more
The aorta can be readily assessed on hybrid nuclear imag- ribs may have been resected. Cervical ribs, either single
ing studies involving CT or MRI. The thoracic aorta is di- or bilateral, may be present, arising from the C7 vertebral
vided into root (valve plane, sinuses of Valsalva), as- body. These ribs can be fused to the first ribs, either
cending aorta (sinotubular junction until the first arch through an osseous or fibrous bridge. In some patients,
vessel), arch, and descending (just distal to the last arch cervical ribs can cause thoracic outlet syndrome, in
vessel until the diaphragmatic hiatus). The normal adult which there is neural (most common), venous, or arterial
aorta measures up to 40 mm in transverse diameter, typ- (least common) compression. Dense sclerotic lesions
ically largest in the ascending segment and gradually ta- (bone islands or enostoses) are commonly found in the
pering toward the diaphragm. ribs and should not be mistaken for metastases.
Atherosclerosis Thoracic Vertebrae

Aortic atherosclerosis is apparent on hybrid imaging by Degenerative findings such as disc-space narrowing, os-
the presence of mural calcification. Similar to coronary teophytes, and endplate sclerosis are commonly encoun-
calcification, it should be reported on if it has not been tered on cross-sectional imaging of the chest. Endplate
previously documented or if the patient is younger, typi- sclerosis can be mistaken for osteoblastic metastases;
cally 55 years of age for men and 67 years of age for however, recognizing the associated findings of disc-
women. space narrowing and osteophytes should help in distin-
guishing degenerative sclerosis from metastases. Sagittal
Aortic Aneurysm reformations are especially useful for depicting lesions of
the spine. Bone islands are commonly encountered on
When the aortic diameter is between 40 and 50 mm, it is cross-sectional imaging of the thoracic spine. As in other
termed ectatic (dilated). A diameter 50 mm is consid- bones, they present as dense sclerotic foci with irregular,
ered to be an aneurysm. Aneurysms are classified as ei- often spiculated margins. Osteoblastic metastases are
ther fusiform or saccular. Fusiform aneurysms are char- usually less dense, with smoother margins.
acterized by diffuse dilation of the affected segment
whereas saccular aneurysms are characterized by an ec- Other Bones
centric outpouching. Fusiform aneurysms usually result
from atherosclerosis and less commonly aortitis whereas Bone islands may be seen in the sternum, clavicle, and
saccular aneurysms, which are often pseudoaneurysms, scapula. Additionally, subchondral cysts may be apparent
can result from infection (mycotic aneurysm), trauma, or in the humeral head. In the latter, they appear as well-
subsequent to the rupture of an ulcerative atherosclerot- corticated lucencies located just below its articulating sur-
ic plaque. FDG uptake may be apparent if an aortic face. Osteophytes may be present along the corresponding
aneurysm is associated with infection or inflammation scapular glenoid. With severe osteoarthritis of the gleno-
(aortitis). humeral joint, intra-articular loose bodies (joint mice)
may be seen, and fluid may be seen accumulating in the
bursae of the shoulder joints. Increased FDG activity may
Chest Wall be apparent depending on the degree of inflammation.
The chest wall consists of the bones of the thorax, the Soft Tissues
supporting and surrounding musculature, subcutaneous
fat, and the skin. Incidental findings, particularly those of Lipoma
the skeleton, are common and the majority of these find-
ings require neither mentioning nor further workup. Chest wall lipomas are commonly identified on cross-
sectional CT. Most are small and are clinically silent.
Bones They are commonly seen within a chest wall muscle as
an encapsulated, homogeneous fat-attenuation mass.
The ribs, thoracic vertebrae, clavicles, sternum (includ-
ing manubrium and xyphoid) constitute the bones of Sebaceous Cyst
the chest wall. The bones of the shoulder girdle (scapu-
la and proximal humerus) are typically included, as Sebaceous cysts are occasionally seen on cross-sectional
well. imaging of the chest. They may result from inflammation
or infection of a sebaceous gland, resulting in obstructing Einstein AJ, Johnson LL, Bokhari S et al (2010) Agreement of vi-
of the normal drainage route. On CT, they have a defined sual estimation of coronary artery calcium from low-dose CT
attenuation correction scans in hybrid PET/CT and SPECT/CT
capsule, central low attenuation, and occur immediately with standard Agatston score. Journal of the American College
deep to the skin. They can become infected or inflamed of Cardiology 56:1914-1921.
and may have increased FDG uptake. Targeted ultrasound Elicker B, Pereira CA, Webb R, Leslie KO (2008) High-resolution
can be used if the diagnosis is uncertain. computed tomography patterns of diffuse interstitial lung dis-
ease with clinical and pathological correlation. Jornal
brasileiro de pneumologia: publicacao oficial da Sociedade
Breast Tissue Brasileira de Pneumologia e Tisilogia 34:715-744.
Holloway BJ, Rosewarne D, Jones RG (2011) Imaging of thoracic
CT does not perform well in evaluating breast tissue. aortic disease. Br J Radiol 84 Spec No 3:S338-354.
Abnormalities encountered on CT are best evaluated Jeong YJ, Kim KI, Seo IJ et al (2007) Eosinophilic lung diseases:
with mammography with or without additional imaging a clinical, radiologic, and pathologic overview. Radiographics
27:617-637; discussion 637-619.
with breast ultrasound or MRI. Patients with abnormal MacMahon H, Austin JH, Gamsu G et al (2005) Guidelines for
hybrid imaging findings in the breast, such as soft-tis- management of small pulmonary nodules detected on CT
sue nodules or fluid collections, should be referred for scans: a statement from the Fleischner Society. Radiology
dedicated breast imaging if it has not been recently per- 237:395-400.
formed. Naidich DP, Bankier AA, MacMahon H et al (2013) Recommen-
dations for the management of subsolid pulmonary nodules
detected at CT: a statement from the Fleischner Society. Radio-
logy 266:304-317.
Suggested Reading Roberton BJ, Hansell DM (2011) Organizing pneumonia: a kalei-
doscope of concepts and morphologies. European Radiology
Andreu J, Mauleon S, Pallisa E et al (2002) Miliary lung disease 21:2244-2254.
revisited. Current problems in diagnostic radiology 31:189- Sayyouh M, Vummidi DR, Kazerooni EA (2013) Evaluation and
197. management of pulmonary nodules: state-of-the-art and future
Bogaert J, Francone M (2013) Pericardial disease: value of CT and perspectives. Expert Opin Med Diagn 7:629-644.
MR imaging. Radiology 267:340-356. Seaman DM, Meyer CA, Gilman MD, McCormack FX (2011) Dif-
Cox CW, Rose CS, Lynch DA (2014) State of the art: Imaging of fuse cystic lung disease at high-resolution CT. AJR Am J
occupational lung disease. Radiology 270:681-696. Roentgenol 196:1305-1311.
Date H (2009) Diagnostic strategies for mediastinal tumors and Shahrzad M, Le TS, Silva M (2014) Anterior mediastinal masses.
cysts. Thoracic surgery clinics 19:29-35, vi. AJR Am J Roentgenol 203:W128-138.
IDKD 2015-2018
Integrated Cardiac Imaging

Philipp A. Kaufmann, Tobias A. Fuchs
Nuclear Medicine, University Hospital Zurich, Switzerland
Introduction for diagnosing coronary stenosis. However, its accuracy

is severely hampered by a large intra- and interobserver
Noninvasive cardiac imaging has evolved substantially variability (up to 50%) in defining the anatomic rele-
over the past few years. New reconstruction algorithms vance of the stenosis [6]. Furthermore, the poor agree-
and a new generation of y-cameras with cadmium-zinc ment between the severity of coronary artery stenosis
telluride (CZT) semiconductor detectors have shortened (morphological assessment) and the hemodynamic rele-
scan time and improved image quality in myocardial per- vance of the stenosis (functional assessment) has been
fusion imaging (MPI) by single photon emission comput- shown [7]. Thus, invasive coronary angiography not on-
ed tomography (SPECT). In addition, technical refine- ly is affected by limitations regarding anatomical evalu-
ments in coronary computed tomography angiography ation but the anatomic findings of angiographically doc-
(CCTA) have led to a substantial dose reduction while im- umented coronary artery stenosis are known to be poor
age quality has improved. However, invasive coronary an- predictors of a lesions physiologic relevance [6]. The
giography has remained the anatomic standard of refer- low yield of invasive coronary angiography (approxi-
ence even though it is associated with a nonnegligible peri- mately 38%) [8] has stimulated the search for strategies
operative morbidity and mortality that suggests confining of noninvasive coronary angiography, of which CCTA
its use to patients who will benefit from a subsequent has emerged as the most promising and well established
revascularization procedure. The poor agreement between in large series of patients such as the COronary CT an-
the severity of coronary artery stenosis (morphological as- giography evaluatioN For clinical outcomes InteRnation-
sessment) and the hemodynamical relevance of the steno- al Multicentre (CONFRIM) registry [9]. However, in in-
sis (functional assessment) has been shown; thus, the termediate lesions, many factors influence the relation-
coronary anatomy rarely allows estimation of the patho- ship between anatomic findings and hemodynamic con-
physiologic relevance of a coronary lesion. sequence in ways that cannot be fully elucidated by
The potential of cardiac hybrid imaging, which offers anatomic evaluation alone, not even with the use of
a comprehensive evaluation of coronary artery disease quantitative coronary angiography [10]. Accordingly, the
(CAD) by combining both morphological and functional actual guidelines on myocardial revascularization recom-
information after fusion of SPECT with CCTA, is well mend the documentation of ischemia using functional
established, as documented in the emerging guidelines for testing in patients with suspected stable CAD before
cardiac hybrid imaging presented by several societies elective invasive procedures [11]. The large gap between
[1, 2]. Hybrid imaging with SPECT-CT can provide en- these evidence-based guidelines and the above-men-
tirely noninvasively, unique information that helps to im- tioned reality in daily clinical routine emphasizes the
prove diagnostic assessment and risk stratification in ad- need to increase both awareness of the importance and
dition to impacting decision-making with regard to revas- availability of noninvasive testing by SPECT for CAD.
cularization in patients with CAD [3]. Fusion of SPECT-MPI and CCTA for cardiac hybrid
imaging is a unique technique combining both function-
al and morphological assessment of CAD.
Functional Versus Morphological Assessment of CAD
Morphological Assessment: CCTA
Despite its considerable morbidity (1.5%) [4] and mor-
tality (0.3%) rates [5], invasive coronary angiography CCTA is an important non-invasive tool for the evaluation
has remained the most widely used method for visualiz- of CAD. Technical refinements in CCTA have led to the
ing the coronary arteries and is the standard of reference rapid implementation of CCTA in daily clinical routine

Integrated Cardiac Imaging 199
and its high accuracy compared to invasive coronary an- individual myocardial-wall territories with impaired myo-
giography has been demonstrated [12]. With the increas- cardial perfusion by the subtending coronary artery was
ing acceptance of CCTA, the associated radiation expo- initially described by Namdar and colleagues [22]. The
sure has been the focus of growing attention. However, added diagnostic clinical value beyond that of either tech-
the introduction of prospective ECG-triggering, including nique alone or that of side-by-side analysis has been
high-pitch spiral acquisition, has led to a substantial dose demonstrated [23, 24]. In low-risk populations, hybrid
reduction [13, 14]. Recently, iterative reconstruction al- imaging may increase the confidence to rule out CAD; for
gorithms for CCTA have demonstrated significant noise example, in the stepwise evaluation of CAD, when equiv-
reduction, allowing tube current and tube voltage reduc- ocal results were obtained with the first study and a sec-
tion without degradation of image quality such that in ond modality is needed to finally rule out disease. Many
some settings CCTA can be performed using a radiation of these patients would end up having invasive coronary
exposure similar to a chest X-ray [15]. angiography, whereas hybrid imaging increases diagnostic
confidence by avoiding equivocal findings, which helps to
Functional Assessment: MPI with SPECT reduce the number of patients unnecessarily exposed to
the risk associated with invasive coronary procedures. It
MPI with SPECT represents the most widely available, was recently shown that cardiac hybrid imaging (by
robust, and by far best established noninvasive method SPECT and CCTA) in CAD evaluation has a profound
for the evaluation of ischemic heart disease [16]. A per- impact on patient management and may contribute to op-
fect agreement of MPI SPECT and coronary angiogra- timal downstream resource utilization [25]. At the other
phy, however, is inherently precluded because the main end of the spectrum, i.e., in older patients, who often suf-
role of SPECT is not to correctly predict or exclude epi- fer from multivessel disease with more jeopardized myo-
cardial coronary lesions but rather to evaluate the physio- cardium, hybrid imaging provides important comprehen-
logical relevance of a given lesion. In fact, only 40% of sive information to allow timely and appropriate treat-
coronary lesions with a luminal narrowing of 5070% in- ment. In these settings, the value of hybrid imaging lies
duce ischemia, as documented in the FAME sub study by far beyond the simple addition of a further diagnostic test,
Tonino et al. [17]. Despite this wisdom, SPECT MPI has as it allows the accurate spatial association of perfusion
often been compared with findings of coronary angio- defects with their subtending coronary stenosis (Fig. 1).
graphy, as this is the generally accepted standard of refer- The CT part of hybrid imaging has an excellent abili-
ence for coronary lesions. One of the largest reports, the ty to rule out anatomic CAD, but an abnormal CCTA
British Royal Brompton and UCL study of Thallium (or an abnormal conventional angiography) is a poor pre-
and Technetium (ROBUST), assessed 2,560 patients who dictor of ischemia. Therefore, MPI testing is recom-
were randomized to one of the commonly used tracers mended to identify patients who might benefit from a
(thallium, sestamibi, or tetrofosmin) during stress, main- revascularization procedure, i.e., those with an ischemic
ly adenosine-induced. This study documented a sensitiv-
ity of 91% and a specificity of 87% without differences
among the tracers [18].
Several attempts to improve MPI by using iterative re-
construction algorithms, early-imaging protocols, or dif-
ferent tracers have provided valuable benefits. However,
the novel CZT detector systems have the potential to rep-
resent the much awaited milestone in the technical im-
provement of MPI. The CZT technique has enabled a
substantial miniaturization of the detectors, a develop-
ment exploited by new cameras in that a stationary posi-
tioning of numerous CZT detectors can be chosen, with
pinhole geometry around the heart. As a result, the scan
on the CZT camera covers the entire heart, allowing very
fast acquisition times, comparable to those of cardiac
PET imaging. The first clinical studies reported very en-
couraging results [19], a high accuracy for the detection
of angiographically documented CAD [20], and the fea-
sibility of fast acquisition protocols [21].
Integrated Cardiac Imaging

The feasibility of cardiac hybrid imaging with the use of Fig. 1. Cardiac hybrid imaging of a patient with bypass grafts re-
PET and CT for noninvasive simultaneous visualization of vealed a perfusion defect in the territory of the diagonal branch
200 P.A. Kaufmann, T.A. Fuchs
burden 10% [26, 27]. The technologic refinements im- significant coronary artery disease in patients undergoing
plemented in the latest generation of CT scanners have coronary computed tomographic angiography: results from the
multinational coronary CT angiography evaluation for clinical
reduced the number of non-evaluable coronary segments, outcomes: an international multicenter registry (CONFIRM).
and further improvements may be expected. However, the Circulation 124:2423-2432, 2421-2428.
two pieces of information obtained with perfusion imag- 10. Bartunek J, Sys SU, Heyndrickx GR et al (1995) Quantitative
ing versus morphology are difficult to compare and will coronary angiography in predicting functional significance of
likely remain complementary. By contrast, the receiver stenoses in an unselected patient cohort. J Am Coll Cardiol
26:328-334.
operator characteristic analysis for detecting perfusion 11. Windecker S, Kolh P, Alfonso F et al (2014) 2014 ESC/EACTS
defects (by SPECT) has been shown to result in a similar Guidelines on myocardial revascularization: The Task Force on
area under the curve for the reference standard (conven- Myocardial Revascularization of the European Society of Car-
tional angiography) as for CCTA, documenting the com- diology (ESC) and the European Association for Cardio-Tho-
racic Surgery (EACTS) Developed with the special contribution
parable performance and limitations of both anatomic of the European Association of Percutaneous Cardiovascular In-
and morphologic techniques [28]. terventions (EAPCI). EuroIntervention [Epub ahead of print].
Results from a multicenter study emphasize the value 12. Budoff MJ, Dowe D, Jollis JG et al (2008) Diagnostic perfor-
of a combined functional and anatomical approach even mance of 64-multidetector row coronary computed tomo-
without image fusion, i.e., without creating a hybrid im- graphic angiography for evaluation of coronary artery stenosis
in individuals without known coronary artery disease: results
age, showing that this combination allows improved risk from the prospective multicenter ACCURACY (Assessment
stratification [29]. The added value of hybrid imaging by Coronary Computed Tomographic Angiography of Individ-
seems most pronounced for functionally relevant lesions uals Undergoing Invasive Coronary Angiography) trial. J Am
in distal segments and diagonal branches and in vessels Coll Cardiol 52:1724-1732.
with extensive coronary lesions of heavy calcification on 13. Buechel RR, Husmann L, Herzog BA et al (2011) Low-dose
computed tomography coronary angiography with prospective
CCTA. The prognostic value of cardiac hybrid imaging electrocardiogram triggering: feasibility in a large population.
has been confirmed, and matched defects on hybrid J Am Coll Cardiol 57:332-336.
imaging have been shown to be a strong predictor of ma- 14. Achenbach S, Marwan M, Ropers D et al (2010) Coronary
jor adverse cardiovascular events [30]. Cardiac hybrid computed tomography angiography with a consistent dose be-
imaging in CAD evaluation may have the potential to op- low 1 mSv using prospectively electrocardiogram-triggered
high-pitch spiral acquisition. Eur Heart J 31:340-346.
timize the downstream resource utilization [25]. 15. Fuchs TA, Stehli J, Bull S et al (2014) Coronary computed to-
mography angiography with model-based iterative reconstruc-
tion using a radiation exposure similar to chest X-ray exami-
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by the European Association of Nuclear Medicine (EANM), 17. Tonino PA, Fearon WF, De Bruyne B et al (2010) Angio-
the European Society of Cardiac Radiology (ESCR) and the graphic versus functional severity of coronary artery stenoses
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NC/SCCT guideline for cardiac SPECT/CT and PET/CT 1.0. three radionuclide myocardial perfusion tracers in clinical
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4. Achenbach S, Daniel WG (2001) Noninvasive coronary an- with a novel cadmium-zinc-telluride detector gamma camera.
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tween myocardial blood flow and the severity of coronary- sibility study. J Nucl Med 46:930-935.
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IDKD 2015-2018
FDG PET/CT in the Imaging of Mediastinal Masses

Pek-Lan Khong
Department of Diagnostic Radiology, The University of Hong Kong, Queen Mary Hospital, Hong Kong, China
Anterior mediastinal tumors that may be encountered on thymoma, and thymic carcinoma. Of these, lymphomas that
18F-fluorodeoxyglucose-positron emission tomography/ involve the mediastinum are the most common.
computed tomography (FDG-PET/CT) scans include ma- Lymphomas that involve the anterior mediastinum
lignant lymphoma, benign and malignant germ cell tumors, may be Hodgkin lymphoma (HL) (Figs. 1, 2) or non-
a b c d
e f g
h i Fig. 1 a-i. A 27-year-old male who underwent

staging PET-CT for nodular sclerosing
Hodgkin lymphoma. a A 3D-maximum inten-
sity projection (MIP) image shows a bulky,
markedly hypermetabolic mediastinal mass
(SUVmax9.4) and matted mediastinal lymph
nodes. b Contrast-enhanced CT performed at
the same setting shows a heterogeneously en-
hancing mass. c Fused axial PET-CT shows the
hypermetabolic mass with central area of re-
duced uptake. d-f End-chemotherapy PET-CT
scans of the MIP image (d), and fused PET-CT of two axial sections (e, f) show a residual anterior mediastinal mass with minimal residual
uptake (Deauville 5-point score3). The patient underwent radiation therapy (RT) of the mediastinal mass. A post-RT treatment scan 3
months after the end of RT was performed. MIP image (g) and fused axial PET-CT image (h) show a reduction in the size of the mass and
a complete metabolic response (CMR). Routine surveillance PET-CT scan was obtained 5 years later. Fused axial PET-CT image (i) shows
a persistent residual mediastinal mass that has further reduced in size and CMR
FDG PET/CT in the Imaging of Mediastinal Masses 203
a b c
Fig. 2 a-c. A 31-year-old male with nodular sclerosing Hodgkin lymphoma. a Staging PET-CT was performed. MIP image (b) shows a hy-
permetabolic mediastinal mass with lower cervical, mediastinal, and diaphragmatic lymphadenopathy (SUVmax11.7). He was treated
with ABVD (adriamycin, bleomycin, vinblastine and darcarbacine) 8 and radiotherapy. Subsequent recurrent disease in the left lower
chest wall was treated with DHAP (dexamethasone, cytarabine, cisplatin) and autologous bone marrow transplantation (BMT). PET-CT
was performed post-BMT. MIP image (b) and fused axial PET-CT image (c) show a residual mediastinal mass with minimal residual up-
take (Deauville 5-point score2). Punch biopsy showed fibrofatty tissue only, with no malignancy
a b c
d e
Fig. 3 a-e. A 37-year-old female with primary mediastinal B-cell lymphoma. Staging PET/CT was performed. MIP image (a), contrast-en-
hanced CT (b) and fused axial PET-CT image (c) show a heterogeneously contrast-enhancing mass in the anterior and middle mediastinum
that extends from the thoracic inlet to the lower end of the sternum. The lesion shows central necrosis and peripheral contrast enhancement
(SUVmax10.6). The end-chemotherapy PET scan shows a complete metabolic response with residual mass. The mediastinal mass was
treated with radiotherapy (RT). PET-CT was performed 3 months after end of RT. MIP image (d) and fused axial PET-CT image (e) show
suspicious focal uptake in the mass. Follow-up PET-CT 3 months later shows resolution of the focal uptake suggesting false positive find-
ings in the previous scan (d, e)
Hodgkin lymphoma subtypes, with the latter including zone lymphoma (B-cell lymphoma, unclassifiable, with
diffuse large B-cell lymphoma (DLBCL), primary me- features intermediate between DLBCL and classical
diastinal B-cell lymphoma (PMBCL) (Fig. 3), gray- HL), and T-cell lymphoblastic lymphoma [1] (Fig. 4).
204 P.L. Khong
a b
b
Fig. 4 a-c. A 10-year-old male with T-lymphoblastic lymphoma. Staging PET/CT scan was performed. MIP image (a), fused axial PET-CT
image of 2 sections (b, c) show a hypermetabolic anterior mediastinal mass (SUVmax6.4). The patient responded poorly to chemother-
apy and died from progressive disease 2 years later
In about 5% of these cases, the anterior mediastinum is before consideration of radiotherapy (RT), because the
the only site of disease and may manifest as isolated PET/CT findings may have an impact on RT planning
thymic involvement, as isolated nodal involvement, or and design of the RT field. A single nodal mass/medi-
as a combination of both [2]. HL accounts for the ma- astinal mass should be measured on the CT scan across
jority of mediastinal lymphomas. Lymphoblastic lym- the longest measurement. In HL, tumor bulk 10 cm is
phomas mainly occur in children and adolescents, while defined as bulky disease and has prognostic and thera-
DLBCL is usually seen in young to middle-aged adults. peutic implications. Moreover, contrast-enhanced CT, if
Diagnosis is made based on the pathological examina- not already performed, should ideally be done as part of
tion, with mandatory immunohistochemical staining, a one-stop approach during a single imaging session
and a typical clinical presentation. PMBCL belongs to combined with PET/CT [6]. Baseline findings should be
the group of aggressive DLBCLs but was distinguished used to determine whether contrast-enhanced CT or low-
as a separate entity in the WHO 2008 classification due er dose and non-enhanced PET/CT will suffice for addi-
to its specific clinical and pathological features, name- tional imaging examinations. A bone marrow biopsy is
ly, gene expression profile studies showing common no longer indicated for routine staging of HL or most
features with classical HL and thus having an impact on DLBCLs [7].
the choice of therapy [1]. Since all the above-mentioned For response assessment, conventional morphologic
lymphomas that involve the mediastinum fall into the imaging using CT or magnetic resonance imaging was
subtypes are FDG-avid [3], FDG-PET/CT is the imag- shown to lack specificity in the characterization of resid-
ing modality of choice for staging and treatment re- ual masses that often remain after treatment. However,
sponse assessment. FDG-PET allows better discrimination between viable
For disease staging, compared to conventional CT, tissue and fibrotic residual masses, by showing the al-
FDG-PET/CT may lead to a change in disease stage, tered metabolism of the former (Figs. 13). Thus, FDG-
more often upstaging [4, 5]. This is particularly important PET/CT was incorporated into the 2007 International
Working Group guidelines for response assessment of Early treatment assessment is potentially of impor-
these malignant lymphomas [8]. In the previous guide- tance for response-adapted treatment, both to optimize
lines, visual interpretation of positive or negative treatment and to avoid unnecessary toxicity. For HL, it
PET/CT scans was based on comparison with the medi- has been found that early metabolic changes are highly
astinal blood pool for end-of-treatment response assess- predictive of final treatment response and progression-
ment [8]. For HL, end-of-treatment scans were shown to free survival [9]. Currently, based on interim PET find-
carry a high negative predictive value (80100%), al- ings after two courses of ABVD (adriamycin, bleomycin,
though the positive predictive value is more variable vinblastine, and darcarbacine) chemotherapy, early treat-
(25100%). In the recent updated recommendation, a 5- ment intensification with BEACOPPesc (bleomycin,
point scale (5-PS) based on visual assessment is used to etoposide, adriamycin, cyclophosphamide, vincristine,
assess response to PET/CT [7]. The 5-PS score assess- procarbazine, and prednisone escalated regimen) should
es uptake at the site of initial disease as follows: 1, no be instituted in patients with a positive PET scan. Multi-
uptake; 2, uptake mediastinum, 3, uptake medi- ple clinical trials are on-going to determine the value of
astinum but liver; 4, uptake moderately higher than early PET in response-adapted therapy for the identifica-
liver; 5, uptake markedly higher than liver (2-to 3-fold tion of patients with poor treatment response who may
higher than a large region of normal liver) and/or new benefit from escalation to more aggressive therapy, and
lesions. In the recommendation, a score of 1 or 2 repre- for patients with good treatment response who can be
sents a complete metabolic response (CMR); a score 3 cured with less than standard therapy, including omission
of represents a probable CMR in patients receiving stan- of RT to the mediastinum.
dard treatment (Fig. 1); and a score of 4 or 5 with re- In children, FDG accumulation in the thymus is a com-
duced uptake from baseline is considered a partial meta- mon, normal finding and thymic rebound hyperplasia can
bolic response, but if the assessment is at the end of be observed after chemotherapy (Fig. 5), which may be a
treatment it represents residual metabolic disease. An potential pitfall in the interpretation of FDG-PET/CT in
increase in FDG uptake to a score of 5, or a score of 5 pediatric patients. Thymic rebound may reflect a hemato-
with no decrease in uptake, and new FDG-avid foci con- logical rebound phenomenon, characterized by lymph
sistent with lymphoma represent treatment failure follicles with large nuclear centers and plasma cell infil-
and/or progression. tration. Although thymic rebound usually appears within
For interim assessment, patients should undergo scan- 612 months after cessation of chemotherapy, it can
ning as long after the previous chemotherapy administra- develop over a period as short as 1 week. The time course
tion as possible, since non-specific FDG uptake may oc- of FDG uptake in the thymus is such that it is usually not
cur with treatment-related inflammation. A minimum of apparent at cessation of therapy, with uptake reaching a
3 weeks but preferably 68 weeks after the completion of peak within 12 months after treatment (10 months in a
the last chemotherapy cycle, 2 weeks after granulocyte few reported series), with a slow decline thereafter [10,
colony-stimulating factor treatment, or 3 months after RT 11]. Moreover, there is often a concurrent increase in
is recommended (Fig. 3). bone marrow uptake due to increased bone marrow
a c
b Fig. 5 a-c. A 10-year-old boy

with rebound thymic hyper-
plasia after chemotherapy.
a Mid-treatment PET-CT
scan, b fused axial PET-CT
image, c MIP image. a, b
show that the thymus gland
is enlarged, with a convex
border, and low-grade dif-
fuse uptake, increased
compared to the mid-treat-
ment PET-CT scan (a)
206 P.L. Khong
stimulation from cytokine therapy [11]. Generally, it is of a

diffuse low metabolic activity compared to malignant
mediastinal soft tissue. Although there is considerable
overlap in SUV values, thymic rebound is of homogenous
soft-tissue density, with a typical shape and convex mar-
gins [12] (Fig. 5). It is important to also be aware of nor-
mal-variant, whereby thymic tissue extends superiorly
and thus appears as a superior mediastinal nodule, in
which case it may be confused with superior mediastinal
adenopathy (Fig. 6).
Other potential pitfalls are inflammatory or infective
lesions in the form of mediastinal lymphadenopathy,
b
which occur more frequently after chemotherapy, and
brown fat activity in the anterior mediastinum.
The differential diagnosis of mediastinal lymphoma
includes thymic epithelial tumors, i.e., thymoma, thymic
carcinoma, and thymic carcinoid, and benign and malig-
nant germ-cell tumors. Differentiation of these tumors
based solely on imaging can be challenging. Findings of
associated thoracic nodal disease are rare in thymomas
and instead usually suggest lymphoma. Thymomas are
soft-tissue-density tumors although they may have areas
of cysts, hemorrhage, necrosis, and calcification (Fig. 7).
They are classified as high-risk (WHO type B2 and B3) Fig. 6 a, b. A 17-year-old female with Hodgkin lymphoma who com-
or low-risk (WHO type A, AB, B1) and non-invasive or pleted treatment 2 years earlier. Surveillance PET/CT shows superi-
invasive depending on whether the capsule of the gland or extension of the thymus between the left brachiocephalic vein and
the left common carotid artery in the superior mediastinum (a), with
has been transgressed. Thymomas typically spread along low-grade FDG uptake (b). No interval change was noted in the sub-
pleural and pericardial surfaces, and may spread into sequent follow-up scans. The findings are in keeping with rebound
regional lymph nodes, but hematogenous metastasis thymic hyperplasia with extension into the superior mediastinum
a b c
d e f
Fig. 7 a-f. PET-CT scans from patients with thymoma. a A 61-year-old female with a history of ovarian cancer. Fused axial PET-CT image
shows an anterior mediastinal nodule with low grade uptake (SUVmax1.6) which was detected as an incidental finding. Biopsy showed
a type AB thymoma with microscopic foci of capsular invasion. b A 51-year-old female with an incidental finding of an anterior medi-
astinal mass (SUVmax2.0). Biopsy showed a type AB thymoma. c-f A 45-year-old female with invasive thymoma type B2. MIP image
(c) and fused axial PET-CT images at 3 sections of the mediastinum (d-f) show a moderately hypermetabolic anterior mediastinal mass
with mediastinal invasion (d) and extension to the left posterior pleura and hemidiaphragm (e, f) (SUVmax5.2)
a b
c
Fig. 8 a-c. PET-CT scan of a 46-
year-old male with metastatic
thymic carcinoma who presented
with hoarseness and dyspnea. MIP
image (a), contrast-enhanced CT
image (b) and fused axial PET-CT
image (c) show the invasive tumor
has a necrotic center (SUVmax
12.7). Additional nodules were
detected in the lower anterior me-
diastinum; skeletal metastases
were also present (a)
a b
Fig. 9 a-c. A 48-year-old male with

a mediastinal germ cell tumor
(seminoma). Staging PET/CT was
performed. MIP image (a), con-
trast-enhanced CT image (b) and
fused axial PET-CT image (c)
show an invasive mediastinal
mass with a necrotic component
(SUVmax7.7)
is very rare. Thymic carcinomas are aggressive in ap- for up front surgery, and those with high-risk tumors,
pearance, can be associated with vessel invasion and/or who will need to have an open biopsy for histological
the invasion of mediastinal fat, and may present with diagnosis before surgery and for neoadjuvant therapy, if
nodal and distant metastases [13] (Fig. 8). FDG uptake appropriate. Cystic changes may be found in thymomas,
is significantly higher in thymic carcinoma than in thy- thymic carcinoma, and germ-cell tumors (Fig. 9) and
moma and can be used to differentiate between high- rarely in lymphoma before treatment. Calcifications are
grade and low-grade thymomas [14, 15]. This can aid in sometimes seen in lymphoma post-therapy and in ter-
selecting patients with low-risk tumors, who are eligible atomas, which may also contain fat. Clinical history,
208 P.L. Khong
e.g., B-cell symptoms in malignant lymphoma, the as- 7. Cheson BD, Fisher RL, Barrington SF et al (2014) Recommen-
sociation of myasthenia gravis in thymic epithelial tu- dations for initial evaluation, staging and response assessment
of Hodgkin and Non-Hodgkin lymphoma: The Lugano Classi-
mors, and biochemical tests are helpful, e.g., elevated fication. J Clin Oncol 32:3059-3067.
serum -fetoprotein levels in patients with malignant 8. Cheson BD, Pfistner B, Juweid ME et al (2007) Revised re-
germ-cell tumors. sponse criteria for malignant lymphoma. J Clin Oncol 25:579-
586.
9. Biggi A, Gallamini A, Chauvie S et al (2013) International val-
idation study for interim PET in ABVD-treated advanced-
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IDKD 2015-2018
Integrated Cardiovascular PET/MR: Lessons Learned

Christoph Rischpler, Stephan G. Nekolla, Markus Schwaiger
Nuklearmedizinische Klinik und Poliklinik, Klinikum rechts der Isar, Technische Universitt Mnchen, Munich, Germany
Introduction TF PET/MR) [2]. In the second approach, which com-

prises a truly integrated system, simultaneous PET and
Before the wide distribution of positron emission tomo- MRI scans are feasible (Siemens Biograph mMR) [3]. As
graphy/computed tomography (PET/CT) systems, nuclear part of a major instrumentation initiative of the German
cardiology was mainly restricted to single-photon emis- Research Foundation, the latter was installed in our insti-
sion computed tomography (SPECT) scanners. With the tution by the end of 2010. Photodetectors that are insen-
broader availability of PET/CT systems which was main- sitive to the magnetic field had to be designed for this ar-
ly caused by their tremendous success in oncology, a va- chitecture and the feasibility of avalanche photodiodes
riety of imaging strategies, using different PET tracers (APDs) for this purpose, even at high field strengths,
such as 18F-fluorodeoxyglucose (FDG) for viability imag- were proven [4]. Eventually APD-lutetium oxyorthosili-
ing or 13N-ammonia for perfusion imaging, became feasi- cate crystal PET detectors were used for the construction
ble. Furthermore, PET/CT systems with multislice CT of the Siemens Biograph mMR.
components increased the interest in hybrid imaging The newest system on the market is the SIGNA
strategies, since combined metabolic imaging with as- PET/MRI, constructed by General Electric Healthcare.
sessment of the coronary anatomy finally became feasible This scanner also operates in a fully integrated fashion
[1]. Another advantage of the CT component is the fast but instead uses silicon photomultiplier detectors. An ad-
and simple determination of the attenuation correction vantage of this system is the capability of time-of-flight
map, which is an important prerequisite for (quantitative) PET imaging [5].
myocardial perfusion imaging. A disadvantage of hybrid
imaging systems, however, is the increased complexity of
the workflow, which may result in a higher susceptibility Approaches to and Issues with Attenuation Correction
to errors. Given the markedly higher complexity of mag- Using MRI
netic resonance imaging MRI compared to CT, this might
particularly hold true for integrated PET/MRI systems. Generation of a -Map
Nonetheless, with the advantages of MRI, such as higher
soft-tissue spatial resolution, the lack of ionizing radia- One of the major hurdles using this novel scanner tech-
tion, and the better tolerated contrast agents, it was gener- nology was the requirement to assess a -map for 511-
ally expected that the positive aspects would outweigh the keV photons. The generation of an appropriate -map is
constraints. In this review we provide an overview of the of great importance as it is essential for quantitative PET
technical and workflow peculiarities and describe initial imaging (such as the absolute quantification of myocar-
experiences with common imaging strategies, especially dial blood flow) [6]. Inaccuracies in the -map may re-
in patients with particular cardiac diseases, using inte- sult in significant errors in the resulting PET images [7,
grated simultaneous PET/MRI systems. 8]. In stand-alone PET systems which are no longer avail-
able commercially, the -map was generated by a rotat-
ing rod source, while in state-of-the-art PET/CT systems
Commercially Available PET/MRI Systems the -map is derived from X-rays emitted by the CT tube.
A disadvantage of the latter approach is an additional ra-
Currently, three different architectures of PET/MRI sys- diation dose of about 0.8 mSV to the patient per
tems are commercially available. In the first, the PET and stress/rest scan [9].
MRI components are arranged in direct proximity and There is no direct connection between MRI or MRI-
connected via a common rail system (Philips Ingenuity based parameters and tissue density. Therefore, novel

210 C. Rischpler, S.G. Nekolla, M. Schwaiger
Fig. 1. Attenuation correction in PET/MRI. The attenuation map is generated using fat and water images from a DIXON magnetic reso-
nance sequence. The -map only differentiates between air, lung, fat, and soft tissue. Using this -map NAC (non-attenuation-corrected)
PET images are then corrected according to the respective tissue-specific attenuation coefficients
ways to generate a -map had to be found [6], resulting The first application of this approach was in imaging
in the development of different approaches. of the head, where a rigid model is sufficient [17, 18].
1. The segmentation-based approach using individual For whole-body imaging, however, an elastic model is
attenuation coefficients for specific tissue classes; necessary, which remains a problem regarding the
this approach was already described in 1981 [10]. It translation into clinical use. The combined use of a
was adopted by our group, who proposed using it for template- and segmentation-based approach has been
the generation of a -map for whole-body PET/MRI described [19].
[11]. By making use of water- and fat-weighted im- 3. It is also possible to generate -maps using PET
ages from a Dixon magnetic resonance sequence, emission data [20, 21]. The underlying principle of
each voxel can be assigned to one of the following tis- this approach is that any voxel exhibiting at least some
sue classes: air, lung, fat, or soft tissue [12] (Fig. 1). tracer uptake has to be part of the body and must thus
Cortical bone is ignored because it is virtually impos- add to the attenuation. An undesirable property of
sible to segment this tissue class from these data. Da- many tracers, namely, their unspecific uptake in non-
ta acquisition usually requires about 18 s per bed po- targeted tissues, is thus a prerequisite for this tech-
sition during one breath-hold. The obvious major dis- nique. This approach is particularly useful in combi-
advantage of this approach is the limited number of nation with the segmentation-based approach, to ad-
tissue classes with fixed attenuation coefficients. This dress motion and truncation problems when body
is particularly relevant in cardiac imaging, as there is parts are outside the field of view (FOV) [7, 22]. Ac-
significant inter-patient variability in lung structure tually, this combined approach is used in the Siemens
and location. The neglecting of bone may result in dif- Biograph mMR, where the FOV of the magnetic res-
ferences in tumor uptake between PET/CT and onance device is only 45 cm [22, 23]. The extension
PET/MRI that can be as high as 23% [11, 13, 14]. of the field of view is the most obvious solution to
Other disadvantages of this approach are that contrast this problem [24].
agents may cause inaccuracies due to reduced T1 val- Another source of photon scatter and attenuation in
ues, and metal implants do not contribute to the at- PET/MRI are artificial components outside the body but
tenuation map [15]. This segmentation-based ap- within the FOV, such as coils, patient monitoring devices,
proach is used in currently commercially available positioning aids, earphones, cables, and the patient bed it-
PET/MRI scanners, such as the Biograph mMR [11] self. For the MRI system these objects are invisible and
or the Ingenuity TF [13]. Our group demonstrated a thus do not contribute to the -map. Only the patient bed
good correlation between PET/MRI and PET/CT da- and the fixed coils are implanted in the precalculated at-
ta in oncologic studies [16]. tenuation models [25]. Consequently, vendors have re-
2. The second route to -map generation is the template- designed their hardware, although the effects are still de-
(or atlas-) based approach. Here, the model-based tectable. Whether there is a relevant impact on diagnostic
known -map is adjusted to the patients real anatomy. scans is not yet known [26].
Integrated Cardiovascular PET/MR: Lessons Learned 211
Cardiac Devices volume data have to be coregistered with the MRI data in
various (partially overlapping) slices of various positions
Cardiac devices, such as pacemakers, implantable car- (e.g., short axes; two-, three-, and four-chamber view).
dioverter defibrillators (ICDs), or cardiac resynchroniza- However, researchers are aware of this problem and tech-
tion therapy (CRT), cause artifacts on CT that result in an niques such as motion-triggered acquisition [32] and
overestimation of the attenuation. The effect on the quan- software corrections [33] are being developed that allow
tification of tracer uptake seems to be negligible in free-breathing during imaging.
PET/CT [27]. Analogously, non-magnetic metals cause a Still, parallel PET/MRI is much more favorable than
signal void in MRI that exceeds the actual size of the ob- sequential PET/MRI. The sequential approach (either on
ject, possibly resulting in an underestimation of the at- separate scanners or on scanners connected via a com-
tenuation. More importantly, these devices may interact mon rail system) is not only inconvenient for the patient
with the radiofrequency, which may result in their mal- and personnel; it is also logistically demanding. Parallel
function or heating. Therefore, many subjects cannot be PET/MRI, on the other hand, can not only improve pa-
examined using MRI (and thus by PET/MRI); this is a tient compliance and comfort, it can also increase patient
growing problem because the number of patients with throughput and thus cost-efficiency. Two potential work
diseases qualifying for the implantation of such cardiac flows are depicted in Fig. 2.
devices is increasing [28, 29]. Phase analysis using nu- An application that might benefit from the truly si-
clear medicine studies (such as PET or SPECT) has been multaneous acquisition of PET and MRI data is myocar-
proposed to better identify patients who might respond to dial perfusion imaging (MPI). The initial benefit would
CRT implantation [30, 31]; however, larger clinical trials be the capability to cross-validate one modality with the
are still warranted. other (which is of research interest). Taking into consider-
ation PET, with its vast variety of specific tracers and its
good volume-coverage, and MRI, with its high in-plane
Workflows for Cardiac PET/MRI resolution, a synergistic effect would, for example, be the
separate investigation of epicardial and endocardial perfu-
As mentioned above, attenuation correction is a crucial sion. However, some hurdles still need to be overcome:
aspect of imaging and so is the exact alignment of the - (1) MRI usually only acquires a few slices of the heart,
map and the acquired PET data. One major advantage of (2) Gd-chelate based contrast medium, used in most ap-
MRI over CT is that the attenuation correction scan may plications, has properties that are unfavorable for truly
be repeated as often as necessary without any radiation. quantitative perfusion assessment, such as a low extrac-
Unfortunately, the subsequent necessary choice of the tion fraction and a non-specific (only partially perfusion-
ideal -map is a time-consuming, inconvenient matter. dependent) uptake by the myocardium. The major advan-
According to our experience, however, in the vast major- tage is, however, that PET and MRI data can be acquired
ity of cases there is satisfactory alignment between PET under truly identical conditions, even though the injection
data and the -map. speed of the imaging agent (PET: 30 s, MRI: 5 s) as
Another important consideration regarding PET/MRI well as the acquisition time (MRI: 1 min, PET: 10
is that most data are acquired in parallel and not truly min) differ significantly.
simultaneously. PET acquires a volume with frame
lengths ranging from a few seconds up to 2030 min (or
more) depending on the chosen protocol (tracer, half-life, Cardiovascular Applications Using Hybrid PET/MRI
injected activity, endurance of the patient, etc.). Conse-
quently, the acquired PET data comprise motion that took Myocardial Perfusion Imaging
place during the scan (e.g., heart beat, ventilation and
true patient motion) whereas in MR data are usually ac- The diagnosis of flow-limiting coronary artery disease
quired sequentially (even in 3D acquisitions), with acqui- (CAD) and the investigation of the hemodynamic signif-
sition times ranging from about 50 ms for dynamic scans icance of known CAD are the most regularly conducted
to several breath-holds for high-resolution images. A ma- studies in nuclear cardiology, due to its high sensitivity
jor problem with sequential imaging is that the data are and specificity [34] and its high value in patient man-
acquired over several breath-holds; since the repro- agement [35-37]. PET MPI helps in clinical decision-
ducibility of breath-holding is limited, this results in par- making as the extent of ischemic tissue determined by
tially overlapping (or partially lacking) data. However, this imaging modality allows patients to be assigned to
the imaging of moving objects with MRI would result in optimal therapy, either revascularization or medical ther-
enormous, unacceptable artifacts. With cardiac apy [38]. Furthermore, there is increasing evidence that
PET/MRI, this raises the issue, that ungated (cardiac cy- PET MPI offers advantages over SPECT MPI due to the
cle and ventilation) PET images are compared to or fused absolute quantification of myocardial blood flow (MBF),
with, for example, end-diastolic magnetic resonance im- attenuation correction, and superior image quality, espe-
ages that are acquired during breath-hold. Another in- cially in obese patients [39]. So far, several PET perfu-
convenient and time-consuming matter is that the PET sion tracers have been established: N-13 ammonia, O-15
Fig. 2. Two potential workflows

(stress/rest perfusion, viability in-
cluding perfusion) for simultaneous
PET/MRI
water, rubidium-82 (Rb-82), and F-18 flurpiridaz. The mentioned advantages of PET MPI and its use in many
relatively short half-lives of N-13 ammonia (10 min), centers, MRI has also been evaluated recently for the pur-
O-15 water (122 s) and Rb-82 (76 s) allow rapid PET pose of MPI. The underlying principle that first-pass
MPI with only short lag times between the stress and the MRI with gadolinium-based contrast agents (e.g., Gd-
at-rest studies. The disadvantages of these tracers are, DTPA) can be used to detect CAD was shown about 20
however, the high positron energies, resulting in de- years ago [42]; since then, a multitude of studies have in-
creased image quality (Rb-82), the need of an on-site cy- vestigated its value in flow-limiting CAD [43, 44]. While
clotron (N-13 ammonia, O-15 water) or of a generator, these studies consisted almost exclusively of visual
which is only cost-effective when a certain patient- analysis, the absolute quantification of MBF is known to
throughput can be guaranteed (Rb-82), or the fact that be of great value in patients suffering from extensive
stress imaging is only feasible when the patient is ad- CAD and balanced ischemia [45, 46]. The feasibility of
ministered the pharmacological agent and the tracer quantifying MBF using MRI has been investigated. One
while inside the scanner (N-13 ammonia, O-15 water, study evaluated a rather simple approach, namely, the up-
Rb-82). F-18 flurpiridaz offers some advantages, e.g. a slope ratio as an index of coronary flow reserve [47].
low positron energy, a half-life that is long enough to en- However, in a subsequent study, this approach was defin-
able tracer distribution even to hospitals and clinics in itively shown to result in an underestimation of the flow
rural areas, the option of ergometer exercise with tracer reserve when compared to N-13 ammonia PET MPI [48].
injection outside the scanner, and possibly a simplified Subsequently, a more complex model, using the central
MBF estimation approach [40, 41]. Despite the above- volume principle, was investigated for absolute MBF
a b c
Fig. 3 a-c. FDG PET/MRI viability imaging shortly after acute myocardial infarction (MI). Example from a patient who was imaged a few
days after acute MI by FDG PET/MRI (hyperinsulinemic/euglycemic clamp). Four-chamber views of late gadolinium enhancement (LGE)
MRI (a), FDG PET (c), and fusion of LGE MRI and FDG PET (b) are depicted. Early after acute MI, different patterns of FDG uptake
and LGE transmurality can be observed: (1) normal FDG uptake and no LGE (white arrows), (2) reduced/absent FDG uptake and trans-
mural LGE (black arrows), and (3) reduced FDG uptake and non-transmural LGE (red arrows)
quantification [49]. This approach was recently studied in alternative. Notably, however, unlike FDG PET, this ap-
41 patients who underwent PET and MRI MPI separate- proach images non-viable, scarred myocardium, informa-
ly [50]. Good agreement for the coronary flow reserve tion used to draw conclusions regarding the potential of
between these two modalities was obtained; the correla- non-scarred myocardium to recover. The enrichment of
tion was weak for absolute MBF values, though. It should Gd-chelates in increased extracellular space (such as
be noted, however, that a rare quantification method for scarred myocardium) results in a reduced wash-out of the
N-13 ammonia was applied [51] and that differences in contrast agent compared to remote myocardium which
absolute MBF may also be due to the fact that Gd- may be visualized in cardiac MRI using inversion recov-
chelates do not enter the cells and thus show a distribu- ery sequences, in which the signal of the remote my-
tion only in the interstitial space (also in increased inter- ocardium is nulled [57]. Despite the fundamental differ-
stitial spaces such as scarred myocardium) [52]. ence in these approaches (imaging viable vs. non-viable
There are patients in whom even extremely well-toler- tissue) there is good agreement between the two modali-
ated MRI contrast agents cannot be used and alternative ties [58]. One essential property of MRI is its high in-
approaches, without the use of any contrast medium, are plane resolution (13 mm), which enables the differenti-
being developed. For example, arterial spin labeling ation between transmural (50%) and non-transmural
(ASL), which originates from techniques to determine (50%) scarred myocardium [59]. Another interesting
cerebral blood flow, has been investigated in a preclinical finding is that in patients with suspected CAD but with-
study, where it demonstrated a good correlation with the out known myocardial infarction, even small areas of
results of O-15 water PET [53]. In patients, ASL was able scarred myocardium carry prognostic significance [60].
to measure the increase in blood flow induced by adeno- A similar observation was described in a study compar-
sine [54]. The obvious advantages of ASL are the possi- ing areas of non-transmural LGE with SPECT MPI [61].
bility of repetitive and continuous measurements of MBF Since small areas of infarction may be overlooked by
without need for any contrast agents PET because of partial volume effects, this fact is rele-
In summary, cardiac MPI using simultaneous vant in hybrid PET/MRI, as an improved tissue classifi-
PET/MRI might be valuable to detect subendocardial is- cation can be expected. Our group made similar observa-
chemia by MRI and to quantify absolute MBF using PET. tions in patients shortly after myocardial infarction, in
whom severely reduced FDG uptake was accompanied by
Myocardial Viability Imaging non-transmural LGE signal only (Fig. 3). Accordingly,
hybrid PET/MRI might ultimately result in an improved
Another potential application of PET/MR in cardiology is prediction of wall motion recovery after revasculariza-
myocardial viability imaging. Hypoperfused myocardium tion, when information such as wall motion and thicken-
exhibits a shift of its metabolism from fatty acids towards ing, FDG uptake, perfusion, and LGE transmurality are
glucose, a state called hibernation [55]. Several studies integrated.
have shown that myocardium in this state is prone to re- As mentioned above, the assessment of global and re-
cover after revascularization [56]. Usually, FDG PET is gional wall motion is a relevant surrogate marker for myo-
the method of choice for non-invasive viability imaging cardial vitality and therapy response after revasculariza-
[55]. Recently, cardiac MRI using the late gadolinium en- tion. Several studies have shown that left ventricular pa-
hancement (LGE) technique has emerged as a possible rameters, such as ejection fraction, end-systolic volume,
and end-diastolic volume carry prognostic significance. Conclusion

MRI is the gold standard for the assessment of these pa-
rameters and it has been extensively validated [62]. The For a long time, the integration of PET and MRI seemed
disadvantages of MRI regarding the assessment of left practically impossible. Accordingly, following the recent
ventricular function are, however, that data are acquired introduction of hybrid PET/MRI systems, expectations
in multiple slices in short- and long axis orientations were high. Yet, almost 4 years after the introduction of the
(usually in 2030 phases) and thus do not provide fully first clinically available hybrid PET/MRI scanner, studies
volumetric data. Gated PET, however, is fully volumetric with a cardiovascular focus are scarce. The main advan-
and acquired at typically 812 phases; it has been vali- tages of this novel technique are the reduction of the ra-
dated in patients with and without cardiac diseases [63, diation dose to the patient, increased patient comfort and
64]. Furthermore, gated PET can be performed in pa- throughput compared to sequential imaging, and the ca-
tients regardless of implanted cardiac devices. Another pability to simultaneously investigate biological process-
fact worth noting is that gated PET data are analyzed uses under the same physiological conditions. The major
ing highly automated software, which results in high in- downside is a complex workflow requiring additional
tra- and interobserver reproducibility, whereas MRI usu- personnel and training, which results in extra costs. In
ally requires at least some manual interaction for seg- summary, PET/MRI systems represent a superb research
mentation of the myocardium. tool, and first studies demonstrating their additional val-
ue in clinical routine are being conducted.
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PEDIATRIC RADIOLOGY SATELLITE COURSE
KANGAROO
IDKD 2015-2018
Pediatric Chest Tumors Including Lymphoma

Alexander Oshmyansky, Thierry A.G.M. Huisman
Division of Pediatric Radiology and Pediatric Neuroradiology, Russell H. Morgan Department of Radiology and Radiological Science,
Baltimore, MD, USA
Introduction Ultrasound
Pediatric chest neoplasms are heterogeneous in etiology Ultrasound can often be of great utility in evaluating neo-
and presentation and their diagnosis is often challenging. plasms that arise from or abut the chest wall. It is rela-
Radiography, ultrasonography, computed tomography tively inexpensive, widely available, and does not require
(CT), and magnetic resonance imaging (MRI) are all of the use of ionizing radiation. It allows for the assessment
utility in the diagnosis of pediatric chest neoplasms. In of tissue characteristics and vascularity in many superfi-
this chapter we review the imaging appearance of various cial chest lesions. However, evaluating the mediastinal
common and rare pediatric chest neoplasms. structures through a trans-thoracic approach, especially
In the following, chest neoplasms are categorized as structures in the middle and posterior mediastinum, is of-
chest wall malignancies, mediastinal masses, metastatic ten difficult because of difficulties in finding acoustic
disease, and primary lung parenchymal neoplasms. We windows between ribs and issues with depth of penetra-
emphasize the imaging features of neoplasms, which can tion [2]. Ultrasound is also often problematic for intra-
be used to obtain an accurate diagnosis of visualized pulmonary lesions. Lung parenchymal processes can be
masses prior to pathologic evaluation. difficult to evaluation due to acoustic reflections from the
We also discuss the distinguishing characteristics that air-containing lungs. Also, any process that does not
differentiate neoplastic processes from congenital mal- abut/reach the chest wall is usually difficult to evaluate.
formation or other non-neoplastic mass lesions that occur
in the chest. Differentiation between these categories is Computed Tomography
often challenging, but a consideration of clinical infor-
mation may facilitate this process. The mainstay of imaging lesions originating from or
We begin with a discussion of the various methods of within the lung parenchyma is chest CT. CT offers a high
imaging pediatric chest neoplasms. spatial resolution, excellent contrast to noise ratio, and a
high speed of acquisition such that imaging can usually
be done within a single, short, patient breath hold. It per-
mits a higher level of anatomic resolution and tissue char-
Imaging of Chest Neoplasms acterization than radiography and, unlike MRI, is not im-
peded by respiratory motion. However, CT necessitates
the use of ionizing radiation, and radiation dose issues of-
Radiography ten arise in pediatric patients who require serial follow-
up evaluations. New, low dose CT dose techniques have
Radiography is a common initial method for imaging the reduced the radiation dose required for diagnostic imag-
pediatric chest and for evaluating pediatric chest neo- ing, but concerns remain regarding repeated radiation ex-
plasms. It is widely available in a variety of settings and posure in diagnostic imaging [1].
inexpensive. However, it is limited in its inherent contrast
resolution between different soft-tissue structures and for Magnetic Resonance Imaging
precise anatomic localization of the extent of a patholog-
ic process. Nonetheless, radiography remains useful in MRI allows high levels of contrast and anatomic resolu-
both the initial evaluation and follow-up of pediatric tion in the pediatric chest without the use of ionizing ra-
chest neoplasms [1]. diation. By applying various magnetic resonance pulse

220 A. Oshmyansky, T.A.G.M. Huisman
sequences and imaging techniques, a broad spectrum of On radiography, lymphoma frequently presents as a
tissue characteristics can be visualized. In particular, large anterior mediastinal mass. CT is critical in the ini-
hypercellularity in malignant neoplastic structures often tial diagnosis, to evaluate for potential tracheobronchial
manifests as restricted diffusion on diffusion-weighted compromise. Life threatening airway obstruction is seen
imaging (DWI). Thus, DWI can be useful in the initial in up to 10% of patients with mediastinal lymphoma. En-
evaluation and staging of pediatric malignancies. Howev- dotracheal anesthesia is reported to be safe in patients
er, even though DWI sequences are typically relatively with lymphoma in the anterior mediastinum when the ex-
rapid, issues with motion artifacts during respiration and pected cross-sectional area of the trachea is reduced by
susceptibility artifact from air in the lungs remain [3]. no more than 50% [7].
Another matter of concern is that MRI in the pediatric The role of MRI in the initial diagnosis of lymphoma
population often requires the use of general anesthesia in is generally considered to be limited. However, some re-
order to prevent patient motion during longer imaging se- ports indicate that whole body DWI may be useful in the
quences. In these instances, MRI thus brings with it the staging of lymphoma. MRI may also be of value in de-
inherent risks of general anesthesia. This is countered, termining the amount of fibrous stroma in a lymphoma-
however, by the lack of ionizing radiation in MRI, an ad- tous mass, which can indicate the expected residual mass
vantage over CT. after treatment [6].
Germ-Cell Tumors
Neoplasms of the Pediatric Mediastinum
Germ cell tumors are less common masses of the anterior
Anterior Mediastinum mediastinum, accounting for 618% of all mediastinal
masses [6]. The majority are benign teratomas (80% of all
Hodgkins and Non-Hodgkins Lymphoma mediastinal germ cell tumors) [4, 5]. Malignant germ cell
tumors in the pediatric population include both semino-
Hodgkins lymphoma is the most common mediastinal
matous and non-seminomatous lesions. Seminomatous le-
mass in the pediatric population. Malignant lymphoma
sions typically lack serologic markers and usually do not
overall accounts for 23% of all mediastinal masses in
contain internal calcifications. For this reason, seminomas
children [4, 5]. Presentation with an anterior mediasti-
typically require histologic diagnosis. Non-seminomatous
nal mass occurs with lymphomatous infiltration of the
germ cell tumors can usually be identified through a com-
thymus and lymph nodes (Fig. 1). Hodgkins disease is
bination of imaging appearance, serum markers such as
typically nodal and spreads in direct continuity, where-
-human chorionic gonadotropin and -fetoprotein, and
as non-Hodgkins lymphoma tends to be extranodal and
clinical symptoms such as precocious puberty [8].
to spread hematogenously. A mediastinal mass occurs
in 50% of patients with non-Hodgkins lymphoma
[4-6]. In both processes, invasion of the pericardium Thymic Neoplasms
can result in pericardial effusion. Pleural effusion, on Primary thymic neoplasms are typically benign in the pe-
the other hand, can result from venous or lymphatic diatric population, with thymolipomas as the most com-
compromise and does not necessarily indicate direct mon lesions. Thymolipomas usually present as fat- and
tumor extension [4]. soft-tissue-containing lesions of the anterior medi-
astinum. They typically do not have internal calcifica-
tions [9, 10].
Most of the other mass-type lesions arising from the
thymus are non neoplastic. Of these, perhaps the most
important to consider is benign thymic hyperplasia. In in-
fants, the mean thickness of the thymus is 1.50 cm, with
a standard deviation of 0.46 cm. In children over the age
of 10 years, the mean thickness of the thymus is 1.05 cm,
with a standard deviation of 0.36. An abnormal process
should be considered when thymic thickness on cross-
sectional imaging is over two standard deviations above
normal (upper limits of normal thymic thickness are 2.42
cm from ages 010 and 1.77 cm respectively) [4, 11].
The thymus normally atrophies as a result of cytotox-
ic injury, but may undergo secondary, benign hyperplasia
thereafter. This period is referred to as thymic rebound.
Fig. 1. An 18-year-old-female presenting with Hodgkins lym-
phoma as a mediastinal mass. The mass is irregular in shape, hav- The smooth contours of the hypertrophied thymus and a
ing lost the normal morphology of the thymus, and is heteroge- homogeneous soft-tissue density distinguish thymic re-
neous in appearance bound from tumor recurrence [6] (Fig. 2).
Pediatric Chest Tumors Including Lymphoma 221
which may be bronchogenic, enteric, or neurenteric. As a

group, foregut cysts comprise 11% of mediastinal masses
in children [4, 5]. It can be difficult to precisely determine
the structure of origin associated with a foregut cyst, but
it is often the structure that the cyst is most closely asso-
ciated with anatomically. The CT appearance of foregut
cysts is typically diagnostic. Most foregut cysts are well-
defined, well-circumscribed, homogeneous, fluid-density
structures, although internal proteinacious debris can con-
fer them with a hyperdense CT appearance [4, 5].
Lymphadenopathy
Lymphadenopathy, either in association with lymphoma
or with an infectious or inflammatory process, is often
encountered in the middle mediastinum. Identifiable me-
diastinal lymph nodes in infants are typically abnormal.
Fig. 2. A 16-year-old female with thymic rebound after undergoing
In adolescents, lymph nodes 1 cm in their short axis are
chemotherapy for a sarcoma of the lower extremity. The margins of the typically considered abnormal [4, 15].
thymus are preserved and the thymus is homogenous in appearance
Posterior Mediastinal Neoplasms
Thymic cysts are another potential non-neoplastic le- Neurogenic Tumors
sion that involve the anterior mediastinum. These are flu-
id density, smooth, well-demarcated lesions found within Neurogenic tumors make up approximately 90% of pos-
otherwise normal thymic tissue [6, 12]. terior mediastinal masses in the pediatric population [6].
Tumors of ganglion-cell origin include neuroblastoma,
Middle Mediastinal Neoplasms ganglioneuroblastoma, and ganglioneuroma. Neuroblas-
toma is most common amongst infants and young chil-
The most common primary pediatric middle mediastinal dren with a median patient age at presentation of 2 years
neoplasms are lymphomatous or leukemic [4, 5]. Other- (Figs. 3, 4). Ganglioneuroma, typically a benign lesion,
wise, primary middle mediastinal neoplasms are unusual occurs in older children with a median age at presenta-
in the pediatric population. Other neoplasms of the mid- tion of 10 years. For ganglioneuroblastoma, the median
dle mediastinum include cardiac tumors, which are rare, age at presentation is 5.5 years [6, 16].
and metastatic disease, which is more common. The ma- All three tumors of ganglion cell origin typically ap-
jority of middle mediastinal masses in the pediatric pop- pear as a vertically elongated mass with tapered superior
ulation are either infectious, inflammatory, or congenital and inferior margins. Internal calcifications are seen in
(such as bronchopulmonary foregut cysts; discussed be- 30% of ganglion cell origin tumors and adjacent bony
low) in origin. changes are common [17].
Cardiac Tumors
Cardiac tumors are rare in the pediatric population. The
most common pediatric tumor is a cardiac rhabdomyoma
which is usually seen in association with tuberous scle-
rosis. In one series, 91% of cardiac rhabdomyomas were
found in association with tuberous sclerosis. In general,
any intracavitary mass found in infants should be consid-
ered a rhabomyoma until proven otherwise [13, 14].
Other tumors include cardiac fibroma, which is
thought to be a hamartomatous lesion, and cardiac myx-
oma. The latter are typically found in association with
myxoma syndrome, a familial disorder [13, 14].
Foregut Cysts
Fig. 3. A 3-month-old male with a partially calcified posterior me-
The most frequently encountered developmental anomaly diastinal mass found to be a neuroblastoma. Normal thymic tissue
of the pediatric middle mediastinum is the foregut cyst, is seen anteriorly
Fig. 5. Multiple osteosarcoma metastatic lesions seen on axial CT

scan through the chest without contrast
Fig. 4. Bilateral apical masses in a 2-year-old male with neurofi-

bromatosis type I. Post-contrast coronal MRI shows prominent pe-
ripheral enhancement in both lesions. Carcinoid Tumor
The vast majority (8085%) of primary malignant lung
tumors in children are carcinoid tumors, with approxi-
Peripheral nerve sheath tumors, schwannomas, and mately 85%, of them occurring within the tracheo-
neurofibromas, are generally indistinguishable by imag- bronchial tree [20, 21]. These are endoluminal lesions
ing criteria alone. Schwannomas are encapsulated tumors that are often associated with internal calcifications, and
that lack nerve fibers. Neurofibromas are non-encapsu- therefore with post-obstructive atelectasis or pneumonia.
lated and contain nerve fibers. Both masses are general- Presenting symptoms typically include cough, hemopty-
ly well-demarcated and spherical/lobulated in appear- sis, or recurrent pneumonia. Carcinoid tumors are often
ance. Both are associated with a target-sign appearance spherical, lobulated, or elongated along the axis of the
on T2 weighted MRI sequences, consisting of peripheral associated bronchi. Their typically prominent internal
T2 bright sequences and internal T2 dark signal. Schwan- contrast enhancement is helpful in distinguishing these
nomas and neurofibromas are usually associated with the tumors from mucus plugs [20, 22].
diagnosis of neurofibromatosis [4, 6, 18].
Approximately 5% of peripheral nerve sheath tumors Metastatic Pulmonary Neoplasms
undergo malignant degeneration, characterized by large
size, central necrosis, and restricted diffusion on DWI se- The most common pediatric pulmonary neoplasm is
quences [6]. metastatic disease (Fig. 5). Metastatic disease can involve
the pulmonary structures through hematogenous spread,
lymphatic spread, or direct extension. Renal malignancies
Primary Pulmonary Neoplasms in particular, such as Wilms tumor, can invade the chest
by direct extension in the renal veins and inferior vena ca-
Pleuropulmonary Blastoma va [15].
Distinguishing infectious or inflammatory pul-
Pleuropulmonary blastoma (PPB) is a rare entity that has monary nodules from metastatic disease in the pedi-
recently been separated from the adult pulmonary blas- atric chest is often a challenging proposition. Inflam-
toma. It is considered to be a dysontogenetic tumor, such matory and neoplastic pulmonary nodules are often in-
as Wilms tumor of the kidney, neuroblastoma, or hepa- distinguishable on both CT and MRI. Reports in the lit-
toblastoma [19]. The imaging appearance of PPB has erature suggest that in a patient with a known primary
been described primarily in a series of case reports. PPB malignancy a nodule with a sharp contour is more like-
is typically quite large on presentation, probably because ly to represent a metastatic lesion than is a nodule with
of the late diagnosis. These tumors can be a solid lesion, a less well-defined, hazy border. However, this distinc-
mixed solid and cystic, or predominantly cystic. Most are tion is somewhat controversial [23]. Other potentially
heterogeneous in appearance and pleural-based. For rea- distinguishing characteristics, such as anatomic loca-
sons that are unclear, PBB most frequently occurs in the tion and distribution, have not been demonstrated to be
right hemithorax, with 70% of reported cases being right- useful in the differentiating benign from malignant
sided [19]. nodules.
Chest Wall Neoplasms Vascular malformations of the chest wall are a het-
erogeneous group of congenital lesions that include ve-
Benign Soft-Tissue Lesions nous sascular malformations, hemangiomas, arteriove-
nous malformations/fistula, and lymphatic malforma-
Lipomas are benign masses consisting of adipose tissue tions (Fig. 7). A complete discussion of vascular malfor-
that commonly occurs in the chest wall. Lipoblastoma is mations is beyond the scope of this review. However,
a tumor of fetal embryonic fat; despite its rapid growth it vascular malformations can typically be diagnosed based
is typically benign. After resection, a lipoblastoma can re- on their avidly bright signal on T2 weighted MRI se-
cur years later as a mature lipoma. The two lesions are quences as well as their prominent vascular flow.
typically differentiated histologically and are usually eas- Pheloboliths can often be seen with venous malforma-
ily identified on CT or MRI by the presence of macro- tions. In most cases, the dynamic contrast enhancement
scopic fat within the lesion [24, 25]. features of vascular malformations readily allow their
Other benign neoplastic lesions include neurofibro- differentiation [28].
mas, discussed above, and fibromas. Fibromas associated
with Gardners syndrome are nodular subcutaneous le- Malignant Soft-Tissue Lesions
sions that contain hyaline or collagen. They are soft-
tissue-density structures on CT and slightly T1 and T2 Rhabdomyosarcoma is the most common pediatric sarco-
bright on MRI. However, histologic diagnosis is normal- ma, although it is generally uncommon in the chest wall
ly required [24, 26]. (Fig. 8). Rhabdomyosarcoma accounts for 24% of pedi-
Mesenchymal hamartomas are benign lesions resulting atric malignancies. On imaging, it presents as an enhanc-
from the overgrowth of normal skeletal elements of the ing, aggressive mass with imaging characteristics similar
rib (Fig. 6). They are well defined, extra-pleural, and often to that of skeletal muscle [24, 28].
cystic. Hemorrhagic and cystic findings with associated Neuroblastoma can also occur in the chest wall in ad-
fluid-fluid levels and partial calcification are said to be dition to the posterior mediastinum and has similar imag-
diagnostic [24, 27]. ing characteristics.
a b c
Fig. 6 a-c. A 16-year-old male with a chest wall hamartoma of the right lower chest. a Axial T2 fat-saturated image shows a heterogeneous,
partially cystic mass, initially mistaken for a neuroblastoma; b axial post-contrast MRI; c axial post-contrast CT through the lesion
a b
Fig. 7 a, b. A large lymphangioma extending from the mediastinum into the left chest on axial T2 fat-saturated sequence (a) and axial post-
contrast MRI sequence (b)
a b
Fig. 8 a, b. A 16-year-old male with an alveolar rhabdomyosarcoma of the left posterior chest wall. a Axial CT scan through the chest shows
a soft-tissue mass arising from the soft tissues of the right back. b Axial post-contrast MRI of the lesion shows avid contrast enhancement
a b c
Fig. 9 a-c. A 15-year old female with a mass arising from right first rib, found to be Ewings sarcoma. Axial CT (a), axial post-contrast MRI
(b), and focused ultrasound (c) examinations
Small Round Blue Cell Tumors Langerhans cell histiocytosis is a multisystem disease
characterized by the proliferation of bone-marrow-
Small round blue cell tumors, including Ewings sarcoma derived Langerhans cells and eosinophils. Imaging features
and primitive neuroectodermal tumors (PNETs), can oc- include lytic, expansive bone lesions that are typically T2
cur in the chest wall in both osseous and extraosseous lo- bright and T1 dark [30].
cations (Fig. 9). These are collectively referred to as
Askin tumors of the chest wall [24]. One-third of extra-
osseous Ewings tumors and half of PNETs present in the Conclusions
chest wall. Both lesions are typically heterogeneous, en-
hancing lesions on CT and MRI [28]. However, the imag- Pediatric chest neoplasms are a heterogeneous group of
ing appearance of either lesion is non-specific and histo- diseases. They can arise from any structure within the pe-
logic correlation is required for a definitive diagnosis. diatric chest. Differentiation between malignant and be-
Cross-sectional imaging is useful for demarcating the ex- nign processes such as congenital abnormalities is of es-
tent of disease [29]. sential importance. Overall, primary pediatric pulmonary
malignancies are uncommon. However, mediastinal
Osseous Neoplasms masses and chest wall masses are not and should prompt
a thorough investigation.
Osseous malignancies such as osteosarcoma can occur in
the chest wall and the spine, just as they do in other por-
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IDKD 2015-2018
Pediatric Cardiovascular Diseases

Edward Y. Lee
Department of Radiology, Boston Childrens Hospital and Harvard Medical School, Boston, MA, USA
Introduction fants, in whom the lateral chest radiograph cannot be eas-

ily obtained, an anteroposterior view chest radiograph may
Cardiovascular diseases are important causes of morbid- suffice. Although the radiographic findings of cardiovas-
ity and mortality in the pediatric population. Affected in- cular diseases, particularly in cases of complex congenital
fants and children usually present with various clinical heart diseases, may be varied and non-specific, some con-
manifestations and imaging evaluation is often essential genital cardiovascular conditions, such as transposition of
for early and accurate diagnosis. However, due to the in- the great arteries (TGA), Ebsteins anomaly, tetralogy of
herent complexity of cardiovascular disease particularly Fallot (TOF), and scimitar syndrome, have a classic radio-
in pediatric patients, imaging assessment continues to be graphic appearance, as described later in this chapter [2].
a challenge for many radiologists. Therefore, the overar-
ching goal of this chapter is to review the current imag- Computed Tomography
ing algorithm and techniques as well as the characteristic
imaging appearance of some of the more commonly en- In recent years, technical advances and the wide avail-
countered congenital cardiovascular diseases in the pedi- ability of CT angiography (CTA) have had a substantial
atric population. Clear knowledge of underlying etiolo- impact on imaging evaluation of cardiovascular diseases
gies and their characteristic imaging appearances of pe- in the pediatric population. In fact, CTA has largely re-
diatric cardiovascular diseases can help radiologists avoid placed conventional diagnostic catheter-based angiogra-
potential pitfalls and render a more timely and accurate phy in this setting. Although CT is associated with poten-
diagnosis. tially harmful ionizing radiation and nephrotoxic iodinat-
ed contrast media, careful attention to the proper selection
of technical factors and optimal use of currently available
Imaging Algorithm and Imaging Techniques dose reduction techniques can enable successful pediatric
CTA with low radiation doses in the range of 13 mSv or
Three main radiological imaging modalities currently less [3]. Common clinical indications of pediatric CTA in-
used in the evaluation of infants and children with conclude imaging evaluation of congenital mediastinal vascu-
genital cardiovascular diseases are chest radiograph, lar anomalies (i.e., vascular rings and sling) and anom-
computed tomography (CT), and magnetic resonance alous pulmonary veins [4]. In addition, CT can be used as
imaging (MRI) [1]. Echocardiography, which is helpful an ancillary study to echocardiography or MRI in pedi-
for real-time assessment of the intracardiac structures, atric patients with limited acoustic window or indwelling
with excellent temporal and spatial resolution, is typical- MRI-incompatible metals. Specific CT technical factors
ly within the domain of cardiologists rather than radiolo- depend on the type of CT scanners; however, in general,
gists. Therefore, the following sections focus on radio- thin collimation (1 mm), the lowest possible kilovoltage,
graphs, CT, and MRI. weight- or age-based low-dose milliamperage, and pitch
1.5 can be used to evaluate most congenital (extra-car-
Chest Radiographs diac and non-coronary) cardiovascular diseases [3, 4]. For
the evaluation of intracardiac structures or anomalies of
Chest radiograph is currently the initial imaging modality the coronary arteries, electrocardiographic gating is usu-
of choice for the infant or child with clinically suspected ally needed. Once an axial CT dataset is obtained, 2D and
cardiovascular diseases. Standard chest posteroanterior 3D reformatted CT images, which increase both diagnos-
and lateral views are useful for the optimal evaluation of tic accuracy and the confidence level of detecting cardio-
cardiovascular diseases in children. For neonates and in- vascular anomalies, can be generated.

Pediatric Cardiovascular Diseases 227
Magnetic Resonance Imaging cular imaging. These diseases include coarctation of the
aorta, cardiac septal defects, TGA, Ebsteins anomaly,
Both anatomic and functional information on cardiovas- TOF, vascular rings and sling, and partial anomalous pul-
cular diseases can be obtained with MRI. It is a particu- monary venous return.
larly useful imaging technique due to the lack of ionizing
radiation exposure, unlike CT. Static spin echo black Coarctation of the Aorta
blood sequences (T1/T2) or cine gradient echo bright
blood sequences (2D steady state free precession) are Coarctation of the aorta is the most common congenital
useful for evaluating cardiovascular morphology [1, 5]. anomaly of the thoracic aorta, occurring in 0.04% of
Extracardiac thoracic vasculature can be assessed with newborns [57]. It is characterized by the presence of
spin echo black blood techniques. If there is a need for a congenital narrowing of the aorta near the region where
dynamic assessment of the thoracic vessels, cine gradient the ductus or ligamentum (after regression) arteriosus in-
echo imaging can be acquired throughout the cardiac cy- serts (Fig. 1). Coarctation of the aorta is seen in approx-
cle [1, 5]. Contrast-enhanced 3D magnetic resonance an- imately 7% of patients with congenital heart disease and
giography (MRA), which can provide superb morpholog- has a strong male predominance (male-to-female ratio of
ical evaluation of the thoracic vasculature with time re- 4:1) [57]. Although it has been historically categorized
solved techniques, is useful in pediatric patients with un- into two types: infantile (i.e., preductal) and adult (i.e.,
derlying cardiovascular diseases [1, 5]. In fact, compared postductal) [57], this categorization is currently not fa-
to CTA, MRA has the advantage of superior tissue char- vored because all aortic coarctations are juxtaductal in
acterization and direct multiplanar imaging. Furthermore, location, with various degrees and extension of aortic
newer 3T MRA scanners can deliver improved signal-to- narrowing. Affected neonates typically present with con-
noise ratio, which can be traded for higher resolution and gestive heart failure whereas affected older children usu-
for decreased overall scanning times when a parallel ally come to medical attention during the evaluation of
imaging technique is employed. Once the MRA dataset is arterial hypertension in the upper extremities and nor-
obtained, maximum intensity projection and 3D magnet- mal-to-decreased blood pressure in the lower extremities
ic resonance images can enhance the visualization of car- [57].
diovascular anomalies and abnormalities. In neonates with coarctation of the aorta, increased pul-
monary vascularity with cardiomegaly is often seen on
chest radiographs. In older children with delayed diagno-
Spectrum of Imaging Findings sis of aortic coarctation, the figure of 3 sign, which re-
flects pre-stenotic dilatation of the aortic arch and left sub-
This review focuses on congenital cardiovascular dis- clavian artery, indentation at the coarctation site, and post-
eases that are considered to be of widespread clinical rel- stenotic dilatation of the descending aorta, may be present
evance and of current importance in pediatric cardiovas- [5-7]. Other typical concomitant findings are collateral
a b
Fig. 1 a, b. Coarctation of the aorta in an 11-year-old male who pre-

sented with upper extremity hypertension. a Axial MRI shows a
normal sized ascending aorta (AA) and a markedly small descend-
ing aorta (arrow) in the region of the aortic coarctation. PA, pul-
monary artery. b 3D volume rendered image demonstrates marked
focal narrowing (arrow) of the descending aorta, consistent with
aortic coarctation. Enlarged collateral vessels, including those of
the internal mammary artery and intercostal arteries, are also seen
228 E.Y. Lee
vessel formations, including those of the internal mamma-

ry, intercostal, and superior epigastric arteries (Fig. 1b). In
particular, enlarged intercostal arteries can result in the de-
velopment of rib-notching under the posterolateral aspects
of the fourth to eighth ribs [57]. Additionally, the bicus-
pid valve can be seen in 2550% of patients with aortic
coarctation [57]. In the evaluation of coarctation of the
aorta using cross-sectional imaging studies such as multi-
detector CT, multiplanar (2D) and 3D images performed
better than axial CT images alone [8].
Three currently used management options for aortic
coarctation include surgical resection of the narrowed
segment followed by primary end-to-end anastomosis,
balloon angioplasty, and placement of a vascular stent.
Imaging evaluation also plays an important role in the
evaluation of residual or recurrent aortic coarctation as
well as complications such as aortic dissection or
pseudoaneurysm formation [57].
Fig. 2. Ventricular septal defect in a 13-month-old male. Chest ra-
diograph shows increased pulmonary vascularity and cardiomegaly
Cardiac Septal Defect
Cardiac septal defect refers to a hole or discontinuation While small VSDs (also called restrictive VSDs) often
in either the atrial or the ventricular septum, or both. Af- close spontaneously or can be managed with a percuta-
fected pediatric patients with small septal defects come to neous septal occlusion device, hemodynamically signifi-
attention because of murmur on physical examination. cant moderate to large VSD are usually treated surgical-
By contrast, affected pediatric patients with moderate to ly with a patch graft. Infectious endocarditis is a poten-
large septal defects typically present early in life (13 tial complication of untreated VSD.
months) with congestive heart failure due to pulmonary
arterial overcirculation, which results from left-to-right Atrial Septal Defect
shunt via the septal defect.
Atrial septal defect (ASD) is the most common shunt le-
Ventricular Septal Defect sion detected in adults, accounting for approximately
10% of congenital heart anomalies [13].
Ventricular septal defect (VSD) is the second most com- On physical examination, diastolic murmur is present
mon congenital cardiac malformation, accounting for ap- because blood flow across the VSD is primarily during
proximately 20% of all congenital cardiac anomalies diastole. Based on the location of the defect, there are
[13]. On physical examination, systolic murmur is pre- three subtypes of ASD: (1) ostium primum, in which the
sent because blood flow across the VSD is primarily dur- defect is located in the anteroinferior portion of the sep-
ing systole. Based on the location of the defect, VSD is tum; (2) ostium secundum, in which it is located in the
classified into four different types: (1) subpulmonary type, midportion of the atrial septum; and (3) sinus venous
caused by a deficiency of the conal septum; (2) membra- defect, in which the defect is located at the superior por-
nous type, in which the defect is located posterior to the tion of the interatrial septum, near the superior vena ca-
septal leaflet of the tricuspid valve; (3) atrioventricular va (SVC).
canal, which is caused by a deficiency of the endocardial Although chest radiographs can be normal in affected
cushion component of the interventricular septum; and (4) pediatric patients with small ASDs, increased pulmonary
muscular, which is the most common type of VSD and can vascularity due to underlying left-to-right shunt, an en-
occur in any portion of the muscular septum. larged main pulmonary artery, right heart enlargement,
Although chest radiographs may be normal in affected and a normal size left atrium and aorta are typically seen
pediatric patients with small VSDs, increased pulmonary in patients with moderate to large ASDs (Fig. 3a). CT and
vascularity due to an underlying left-to-right shunt (i.e., MRI can directly show the exact location and extent of an
shunt vascularity), an enlarged main pulmonary artery, ASD as well as associated anomalies, such as anomalous
biventricular enlargement, and left atrial enlargement are drainage of the right superior pulmonary vein, which is
present on chest radiographs in pediatric patients with highly associated with ASD of the sinus venous defect
moderate to large VSDs (Fig. 2). Shunt vascularity refers type (Fig. 3b).
to an increase in the number and caliber of pulmonary Small ASDs often close on their own during infancy or
vessels resulting from the increased arterial flow. CT and early childhood or they can be managed with a septal oc-
MRI can directly show the discontinuation of the ven- clusion device [9]. Surgical repair is typically necessary
tricular septum in affected patients. for managing large or multiple ASDs.
a b
Fig. 3 a, b. Atrial septal defect in a 14-year-old female. a Chest ra-

diograph shows increased pulmonary vascularity, a dilated main
pulmonary artery, and cardiomegaly. b Axial MRI demonstrates an
atrial septal defect (asterisk) along with enlargement of the right
atrium (RA). LA, left atrium; DA, descending aorta
Transposition of the Great Arteries in series rather than in parallel as in D-TGA. Systemic ve-
nous return flows to the right atrium, enters the morpho-
TGA refers to a congenital malformation of the great ar- logic left ventricle, and is eventually delivered to the pul-
teries in which they are reversed in their origins from the monary circulation via the main pulmonary artery. Pul-
heart (Fig. 4). There are two different types of TGA: monary venous return subsequently flows to the left atri-
D-transposition of the great arteries (D-TGA) and L-trans- um, enters the morphologic right ventricle, and is delivered
position of the great arteries (L-TGA) [13]. In D-TGA, to the systemic circulation via the aorta. While patients
the aorta arises from the morphologic systemic right ven- with D-TGA usually present with cyanosis during the first
tricle and the pulmonary artery arises from the morpho- day of life, those with L-TGA are typically asymptomatic.
logic systemic right ventricle, resulting in ventricular arte- On chest radiographs, increased pulmonary vasculari-
rial discordance. The pulmonary and systemic circulations ty and mild to moderate cardiomegaly are usually seen in
exist in parallel, requiring bidirectional shunting between patients with D-TGA [13]. Additionally, the superior
the two sides of the heart via an ASD, VSD, patent ductus mediastinum is narrowed because of the abnormal posi-
arteriosus (PDA), or patent foramen ovale for survival. By tion of the great vessels and a concave main pulmonary
contrast, congenitally corrected TGA, or L-TGA, is char- artery. The constellation of these findings results in the
acterized by both ventriculoarterial and atrioventricular radiographic appearance of the cardiomediastinal silhou-
discordance. The pulmonary and systemic circulations are ette, referred to as the egg-on-a-string sign [2]. CTA or
MRA is useful for the assessment of postoperative com-
plications including narrowing of the anastomosis of the
aorta or pulmonary artery in addition to branch pul-
monary artery stenosis and coronary artery narrowing.
Corrective surgery via a Jatene arterial switch pro-
cedure is required for managing patients with D-TGA in
the first few days of life [13] (Fig. 5). By contrast, pa-
tients with congenitally corrected L-TGA may require
pacemaker placement for progressive right ventricular
dysfunction and conduction abnormalities in later life.
Ebsteins Anomaly
Ebsteins anomaly is the most common cause of marked
cardiomegaly in the newborn period. It is characterized by
the displacement of the septal and posterior leaflets of the
tricuspid valve towards the apex of the right ventricle of
Fig. 4. D-transposition of the great vessels (D-TGA). Axial CT the heart [10]. This results in atrialization of a portion
shows the aorta (A) located anterior to the pulmonary artery (PA) of the morphologic right ventricle and subsequent
230 E.Y. Lee
in visualizing the morphology of the anterior leaflet of

the tricuspid valve and right ventricular free wall.
Tricuspid annulopasty and plication of the atrialized
portion of the right ventricle are the current management
procedures of choice for symptomatic pediatric patients
with severe Ebsteins anomaly.
Tetralogy of Fallot
Four anomalies of the cardiac structures comprise TOF:
VSD, infundibular pulmonary stenosis, an overriding aor-
ta, and right ventricular hypertrophy. It is the most com-
mon congenital heart defect resulting in cyanosis. A right
aortic arch with a mirror-image branching, peripheral
pulmonary arterial stenosis, and an anomalous anterior
Fig. 5. Jatene procedure. Axial CT after an arterial switch proce- descending coronary artery that courses over the right
dure for TGA shows characteristic draping of the main pulmonary ventricular outflow tract are also often associated with
artery (MP) around the aorta (A) TOF. Affected pediatric patients typically present with
cyanosis in the first 6 months of life.
The radiographic findings of TOF vary according to
enlargement of the right atrium and a reduction in the size the severity of the obstruction of the pulmonary outflow
of the anatomic right ventricle [10]. This condition may be tract. The classic appearance of TOF is a boot-shaped
an isolated finding or associated with other congenital heart due to an underlying right-sided aortic arch, a small
heart defects, such as a patent foramen ovale or an atrial or concave main pulmonary artery, and right ventricular
septal defect, allow the passage of a right-to-left shunt. Al- hypertrophy [2] (Fig. 7). Pulmonary vascularity can be
though patients with mild Ebsteins anomaly may be either normal or diminished. The heart size is usually
asymptomatic, in those with severer forms of the disease normal. However, increased pulmonary vascularity and
cyanosis and systolic murmur are often present [10]. cardiomegaly similar to that in patients with VSD can be
On radiographs, decreased pulmonary vascularity, a seen in affected patients with very mild pulmonary steno-
concave pulmonary artery segment, and marked car- sis, which is sometimes referred to as a pink tetralogy.
diomegaly due to underlying right atrial enlargement are MRI can be useful for evaluating the morphology and
characteristically seen [2, 10] (Fig. 6a). In affected pa- function of the cardiac chambers, calculating blood flow
tients with concomitant PDA, the pulmonary vasculari- and velocities through the vessels to determine the pres-
ty may be increased. CT and MRI can better demon- ence of regurgitation, stenoses, and relative flow, and
strate a small right ventricle and atrialized right ventri- mapping collateral vessels in affected patients with pul-
cle (Fig. 6b), and MRI is better than echocardiography monary atresia [1, 2].
a b
Fig. 6 a, b. Ebsteins anomaly in a 4-year-old female. a Chest radiograph shows decreased pulmonary vascularity and cardiomegaly with a
prominent right heart (arrows). b Axial MRI demonstrates a large atrialized superior right ventricle (ARV). RA, right atrium
of all congenital heart disease [46, 8, 11, 12]. Although

relatively rare, they are important causes of respiratory
and swallowing symptoms due to compression of the tra-
chea and/or esophagus in infants and young children.
Chest radiograph and esophagram may be used for the
initial evaluation. More detailed preoperative assessment
of vascular anomalies and associated large-airway mal-
formation can be achieved with CT or MRI [46, 8, 12].
The three main types of vascular rings and sling are: dou-
ble aortic arch, right aortic arch with an aberrant left sub-
clavian artery, and pulmonary artery sling, which are dis-
cussed in the following sections.
Double Aortic Arch

The double aortic arch results from persistence of the
right dorsal aorta and is the most common symptomatic
Fig. 7. Tetralogy of Fallot in a 3-day-old male. Chest radiograph
vascular ring. In this aortic vascular anomaly, the as-
shows uplifting of the cardiac apex and decreased underlying pul- cending aorta bifurcates into the right and left aortic
monary vascularity. Concavity (arrow) is also seen in the region arches which encircle the trachea and esophagus and join
where the main pulmonary artery should be. Also note that the tra- together posteriorly to form a single descending aorta
chea is displaced toward the left side by the right aortic arch (RA) [46, 8, 12] (Fig. 8a). Each aortic arch gives rise to its
own common ceratoid and subclavian arteries. The right
aortic arch is usually larger in size and higher in position
After initial palliative surgery using a Blalock-Taussig than the left aortic arch. Sometimes, an atretic segment
anastomosis via the subclavian artery to the pulmonary of either right or left aortic arch is present. The double
artery, definitive surgical repair focuses on relieving the aortic arch is rarely associated with other congenital
right ventricular outflow obstruction and closing the sep- heart anomalies, which include TOF, VSD, and TGA. Af-
tal defect. During surgery, it is important to carefully as- fected patients typically present in the first 3 months
sess the coronary arteries because an anomalous anterior of life.
descending coronary artery that courses over the right On chest radiographs, bilateral paratracheal opacities
ventricular outflow tract can be present in pediatric pa- representing two aortic arches and narrowing of the mid-
tients with TOF and mistakenly incised at surgery. line positioned trachea are typically seen. Bilateral in-
dentations are seen on frontal esophagogram, and poste-
Vascular Rings and Sling rior compression of the esophagus on lateral esopha-
gogram. CT and MRI with multiplanar and 3D recon-
Vascular rings and sling are congenital anomalies of the struction of the mediastinal vessels and large airway are
aortic arch and pulmonary artery. They account for 13% useful for preoperative and postoperative assessments
a b
Fig. 8 a, b. Double aortic arch in a 4-month old male who presented with stridor and repeated apnea. a Axial maximum intensity projection
image shows a double aortic arch (R, right arch; L, left arch; S, superior vena cava). b 3D volume-rendered image demonstrates a double
aortic arch (R, right arch; L, left arch) surrounding the trachea (T)
232 E.Y. Lee
[46, 8, 12, 13] (Fig. 8b). In particular, paired inspirato- tion of the esophagus is seen on frontal esophagogram,
ry and expiratory multi-detector CT should be considered and oblique compression of the posterior esophagus on
as part of the routine preoperative evaluation of tracheo- lateral esophagogram. The entire course of the right aor-
malacia (TM) in pediatric patients with double aortic tic arch, the aberrant left subclavian artery, and tracheal
arch because 33.3% of these patients have underlying compression are best evaluated with CT and MRI with
concomitant TM [14]. multiplanar and 3D reconstruction [46, 12, 15] (Fig.
The double aortic arch in symptomatic pediatric pa- 9b). Surgical division of underlying vascular ring is the
tients is currently treated with surgical division of the current management procedure of choice in symptomatic
smaller of the two aortic arches. When concomitant TM pediatric patients with right aortic arch with an aberrant
is present, surgical repair of the trachea is also required left subclavian artery [46, 12].
[12, 13, 15].
Pulmonary Artery Sling
Right Aortic Arch with an Aberrant Left Subclavian Artery
In pulmonary artery sling, also known as anomalous left
The right aortic arch with an aberrant subclavian artery pulmonary artery, the left pulmonary artery arises from
is the second most common vascular ring in the pedi- the right pulmonary artery [16, 17] (Fig. 10). Embryo-
atric population. Embryologically, it is due to persis- logically, it is due to the regression or failure of devel-
tence of the right dorsal aorta, regression of the left dor-
sal aorta, and regression at the left fourth aortic arch
[46, 8, 12]. In this condition, the aorta is located on the
right side of the spine and the left subclavian artery
comes off the descending aorta, crosses the midline, and
enters the left hemithorax (Fig. 9a). The ligamentum ar-
teriosum (i.e., the remnant of the ductus arteriosus),
which originates from a bulbous dilatation at the base of
the left subclavian artery (the diverticulum of Kom-
merell) and attaches to the left pulmonary artery, is al-
so present. The trachea and esophagus are encircled by
the aortic arch on the right, the ligamentum arteriosum
and the left pulmonary artery on the left, the ascending
aorta anteriorly, and the descending aorta posteriorly
[46, 12].
On the frontal chest radiograph, a right paratracheal
opacity representing the right-sided aortic arch and an ab-
sent left-sided aortic arch shadow are characteristic. The
Fig. 10. Pulmonary artery sling in a 2-day-old female who present-
right-sided compression or left-sided deviation of the tra- ed with severe respiratory distress. Axial CT shows an anomalous
chea at the level of the right aortic arch and an aberrant left pulmonary artery (arrow) arising from the right main pul-
left subclavian artery are also seen. Right-sided indenta- monary artery (RP). T, Trachea
a b
Fig. 9 a, b. Right aortic arch with an aberrant left subclavian artery in a 2-year-old female who presented with respiratory distress. a Axial
CT shows a right aortic arch (RA) with an aberrant left subclavian artery (arrow). Note the nasogastric tube in the esophagus. T, trachea.
b 3D volume rendered image demonstrates the exact location, degree, and extent of the tracheal compression (arrow) caused by a right
aortic arch and an aberrant left subclavian artery
opment of the left pulmonary artery [4, 16, 17]. The vein drains into the left brachiocephalic or innominate
anomalous left pulmonary artery courses between the tra- vein, creating a vertical vein positioned lateral to the left
chea and esophagus on its way to the left side after aris- superior mediastinum (Fig. 11). On chest radiographs,
ing from the right pulmonary artery. This can lead to ex- left superior mediastinal widening is seen. In case of the
trinsic compression of the distal trachea and/or right main scimitar, or hypogenetic lung syndrome, which is a spe-
stem bronchus, and thus in respiratory distress. Intrinsic cial form of anomalous pulmonary venous return from
large airway anomalies such as TM and tracheal stenosis the lung that is associated with a hypoplastic lung, a ver-
as well as right lung agenesis may also be present con- tically oriented, curvilinear opacity representing the
comitantly [16, 17]. scimitar vein, projecting over the lower hemithorax and
On frontal chest radiograph, either a hyperinflated or ipsilateral hypoplastic lung, is seen on chest radiographs
atelectatic right lung, depending on the degree of right [6, 16] (Figs. 12, 13). In case of right superior PAPVR,
main stem bronchial narrowing, is seen. On lateral chest CT and MRI can show an anomalous vein that usually
radiograph or esophagogram, anterior displacement of drains into the SVC and an associated sinus venosus
the trachea and posterior displacement of the esophagus
due to an anomalous left pulmonary artery are character- a
istically seen. CT and MRI with multiplanar and 3D re-
construction of the mediastinal vessels and large airway
can demonstrate the entire course of an anomalous left
pulmonary artery and an associated large airway narrow-
ing or stenosis [4, 13, 1517].
Surgical reimplantation of the left pulmonary artery
and tracheal reconstruction in case of tracheal stenosis or
TM are current treatment options in symptomatic patients
[12, 15, 17].
Partial Anomalous Pulmonary Venous Return

In partial anomalous pulmonary venous return (PAPVR),
some, but not all of the pulmonary veins have aberrant
drainage into systemic veins or the right atrium [6, 16].
This condition results in a left-to-right cardiac shunt and
the admixture of deoxygenated and oxygenated blood.
PAPVR may be an isolated finding but it is often asso-
ciated with other congenital cardiac or lung anomalies. b
Affected pediatric patients often present with respirato-
ry distress, tachypnea, feeding intolerance, and failure to
thrive. Depending on the degree of underlying shunting,
the patient may also present with cyanosis. In addition,
patients with associated lung anomalies may clinically
present with recurrent lung infections.
PAPVR commonly involves the left superior, right in-
ferior, and right superior pulmonary veins [6, 16]. In left
superior PAPVR, the anomalous left superior pulmonary
Fig. 11. Left upper lobe partial anomalous pulmonary venous return Fig. 12 a, b. Scimitar syndrome in a 3-year-old female. a Chest ra-
in a 17-year-old male. Axial (right) and coronal (left) CT show an diograph shows a curvilinear opacity (arrow) in the right lower
anomalous left upper lobe partial anomalous pulmonary vein (ar- lobe, representing the anomalous draining vein. b Angiography
rows). A, aorta; S, superior vena cava demonstrates an anomalous draining vein (arrow)
234 E.Y. Lee
Conclusion
A variety of congenital cardiovascular diseases can occur
in the pediatric population. Clear knowledge of the un-
derlying etiologies and their characteristic imaging ap-
pearances can help radiologists avoid potential pitfalls
and render a more timely and accurate diagnosis in pedi-
atric patients with cardiovascular diseases. This, in turn,
will contribute to optimal pediatric patient care.
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of breath and mild hypoxia. Bright-blood MRA shows right upper tive evaluation of thoracic vascular and tracheobronchial
lobe anomalous pulmonary venous return (arrow) into the superi- anomalies and abnormalities in pediatric patients. J Pediatr
or vena cava (SVC) Surg 45:811-821.
13. Lee EY, Siegel MJ (2007) MDCT of tracheobronchial nar-
rowing in pediatric patients. J Thorac Imaging 22:300-309.
14. Lee EY, Zurakowski D, Waltz DA et al (2008) MDCT evalua-
ASD, which is often associated with right superior tion of the prevalence of tracheomalacia in children with medi-
PAPVR [6] (Fig. 14). astinal aortic vascular anomalies. J Thorac Imaging 23:258-265.
15. Lee EY, Greenberg SB, Boiselle PM (2011) Multidetector
The current management procedure of choice of computed tomography of pediatric large airway diseases: state-
PAPVR in symptomatic pediatric patients is surgical of-the-art. Radiol Clin North Am 49:869-893.
reconnection of the anomalous pulmonary vein with the 16. Lee EY, Boiselle PM, Cleveland RH (2008) Multidetector CT
atrium. Imaging plays an important role in the assess- evaluation of congenital lung anomalies. Radiology 247:632-648.
ment of postoperative complications, including throm- 17. Lee EY (2007) MDCT and 3D evaluation of type 2 hypoplas-
tic pulmonary artery sling associated with right lung agenesis,
bosis or stenosis of the reimplanted anomalous vein hypoplastic aortic arch, and long segment tracheal stenosis. J
[6, 15, 16]. Thorac Imaging 22:346-350.
IDKD 2015-2018
The Radiology of Diffuse Interstitial Pulmonary Disease in Children:

Pearls, Pitfalls and Newly Recognised Disorders
Catherine M. Owens
Cardiothoracic Imaging Department, Great Ormond Street Hospital for Children NHS Trust, London, UK
Introduction slow in the neonate and suppressor K cell activity higher

[11]. The pattern of cytokine secretion is variable: levels
Diffuse interstitial lung disease (ILD) represents a het- of production of IL-2 (interleukin 2) are controversial
erogeneous group of disorders characterised by restrictive [12], but secretion of IL-4 and interferon-gamma is
lung function and impaired gas exchange. As these dis- markedly reduced [13].
eases occur against a background of the developing lungs B-cell function is reduced, but whether this is intrinsic
and immune system, the clinical presentation and disease or secondary to reduced T-cell function is unclear. Pe-
progression are modified compared to their adult equiva- ripheral blood monocyte function, by contrast, seems rel-
lents [1]. Thus, diffuse ILD often differs markedly in pre- atively mature, although alveolar macrophages may be
sentation, clinical features, and progress from ILD in functionally deficient [14].
adults, and it is not safe to extrapolate from adults to chil- Morbidity and mortality associated with paediatric
dren. Rather, it is important to understand the normal ILDs are high (range 1439%), with a higher mortality in
growth and development of the lungs in children so as to younger infants.
understand the development of ILD [2]. The diagnosis may be delayed, but once suspected the
aim is to confirm the presence and severity of ILD, to un-
cover any predisposing factors, and to identify the domi-
Normal Growth and Development of the Lung and nant pathology. Although a diagnosis without biopsy is
Immune System sometimes possible, the majority of patients will require
histological studies using either open lung biopsy, video-
ILD may present soon after birth, which suggests an ante- assisted thoracoscopic biopsy, or high-resolution com-
natal onset in some cases. Thus, an understanding of the puted tomography (HRCT)-guided percutaneous biopsy.
early changes in the morphology and biology of the prim- The general classification includes disorders of known
itive lung is important. The mature airway pattern is deter- aetiology (aspiration, chronic infection, hyper-sensitivity
mined by week 16 of gestation [3] and is driven by growth pneumonitis, lipid storage diseases), un-known primary
factors produced by mesenchyme and extracellular ma- pulmonary disorders with lung involvement or systemic
trix (including fibronectin, tenascin, the integrins, synde- disorders with pulmonary involvement, and finally those
cans, and cadherins), and epimorphin and epidermal diseases unique to childhood.
platelet-derived and insulin-like growth factors [4, 5]. Ma-
ture alveoli begin to develop late in foetal life, but most ap-
pear in the first 2 years of life [6]. Numbers increase more HRCT Technique
slowly in later childhood, and adult levels are attained by
about 8 years of age [7, 8]. Treatment with steroids and Because the chest radiograph is often non-specific,
oxygen in early life has been shown to interfere with alve- HRCT has been shown in adults and children to increase
olar development in the rat model [9]. Data from humans the accuracy at diagnosis of diffuse lung disease. The
suggest that only limited catch-up growth may occur in lat- trade-off in sensitivity and specificity of HRCT over
er childhood following neonatal interference with lung chest radiography is related to radiation dose, which is
growth [10]. Thus, ILD and its treatment, particularly ear- significantly higher with conventional spiral or volumet-
ly in life, may profoundly affect long-term function. ric CT. However, the use of low-dose (50 mA, 0.75 s)
The immune system is immature at birth and the im- limited (1-mm slices every 1520 mm) HRCT in inspira-
mune-pathogenesis of ILD therefore is different in chil- tion, with three expiratory supplementary scans allows
dren than in adults. Briefly, T-cell receptor activation is accurate assessment of the presence and extent of diffuse

236 C.M. Owens
lung disease at a dose equivalent to approximately ten the most frequent feature of interstitial pneumonitis/fibro-
chest radiographs. Images are reconstructed based on a sis [20]. There are no discriminating features for the radio-
high spatial resolution algorithm and displayed with a logical appearance of DIP, which includes widespread
wide window setting, at a width of 1,500 Hounsfield ground glass opacification; thus, it has a wide differential
units (HU) and at a level of 500 HU. diagnosis, including subacute extrinsic allergic alveolitis,
If a child is unable to breath-hold, the scans can be per- opportunistic infections such as Pneumocystis jirovecii
formed during quiet breathing, and decubitus scans can pneumonia and, although it is rare in children, sarcoido-
replace expiratory scans (the dependent lung behaving as sis. On HRCT, ground glass opacification is the dominant
the expiratory lung). pattern and often has a lower zone predominance; long-
The role of HRCT in paediatric ILD is evolving. In term follow-up usually shows complete resolution
adults, the diagnostic accuracy of HRCT has led to a de- Based on the few reported cases of childhood NSIP,
crease in the number of lung biopsies. The histospecific there is a distinct pattern of involvement. In a review of
accuracy of HRCT compared with chest radiographs in CTs of six cases of biopsy-proven NSIP [21], a distinct
making a correct first-choice diagnosis in an adult popu- upper zone predominance of honeycomb pattern and
lation with diffuse lung disease ranges from 46% to 75% parenchymal distortion on a background of diffuse
for HRCT and from 38% to 63% for chest radiography ground glass opacification was seen in three children.
[1517]. HRCT had a diagnostic accuracy of 56% for a The honeycomb pattern resembled emphysematous de-
confident first-choice diagnosis in one series of 20 chil- struction with some cystic change.
dren with ILD [18]. This is comparable to a more recent Seely et al. described a similar HRCT appearance in
series of 20 children with biopsy-proven ILD from a sin- their review of paediatric idiopathic interstitial fibrosis [20],
gle institution [19]. A correct first-choice diagnosis was but did not provide pathological correlation. Ground glass
made in 61% of the cases on HRCT compared with 34% opacification, honeycombing and peripheral consolidation
on chest radiographs. were features seen in three other cases of childhood NSIP.
The diseases that were correctly diagnosed on HRCT In the study by Copley et al. [19], one case of DIP resem-
with a high degree of confidence were alveolar pro- bled NSIP with predominant upper lobe involvement.
teinosis, pulmonary lymphangiectasia and idiopathic pul- The existence of UIP (usual interstitial pneumonitis) in
monary haemosiderosis. Differentiation between non- childhood is controversial and said to be exceedingly
specific interstitial pneumonitis (NSIP), desquamative in- rare. The adult form of UIP has a poor prognosis. The
terstitial pneumonitis (DIP) and lymphocytic interstitial HRCT findings of adult UIP include a subpleural reticu-
pneumonitis (LIP) was, however, less reliable. lar pattern of honeycombing that may result eventually in
There are several pitfalls in the interpretation of HRCT thick-walled cystic spaces and irregularity of the pleural
in children. One of the most important is in distinguish- surface with underlying traction bronchiectasis and bron-
ing diffuse ground glass infiltration from increased lung chiolectasis.
attenuation resulting from a suboptimal inspiration. In the LIP is characterised histologically by a diffuse inter-
upper zones, the position of the posterior tracheal mem- stitial infiltrate of polyclonal lymphocytes, plasma cells
brane is helpful in distinguishing between the two. The and histocytes. LIP is associated with viral infections in-
posterior tracheal membrane is convex outwards in inspi- cluding Ebstein Barr virus (EBV) and the acquired im-
ration, and appears horizontal or slightly concave on ex- munodeficiency syndrome. LIP is present in up to 30%
piration. The other difficulty that may be encountered is of children with human immunodeficiency virus (HIV)
in determining which areas of the lung are abnormal disease, especially those from the sub-Saharan African
when an investigation reveals a widespread mosaic pat- continent, where EBV is endemic. This is unlike the sit-
tern of lung attenuation. Deciding on whether the areas uation in adult HIV disease, in which LIP is rare. Other
of diminished attenuation represent, for example, small associations include autoimmune diseases and lympho-
airways disease or whether areas of increased attenuation proliferative disease secondary to underlying congenital
(ground glass opacity) represent diffuse infiltration can immunodeficiency.
be challenging. Although expiratory images may be help- Chest radiographs show reticulonodular change with
ful, obtaining images at known phases of respiration is or without areas of consolidation. HRCT shows intersti-
usually not achievable in children. Thus, the above-men- tial reticulonodular change of varying degrees There is
tioned use of lateral decubitus imaging CT, with the de- usually marked resolution of the striking radiological ap-
pendent lung simulating expiration, is an important tool. pearances with therapy for HIV disease; however, if there
has been chronic interstitial disease, fibrosis and ensuing
traction bronchiectasis may result.
HRCT Features of Diffuse Interstitial Lung Disease Follicular bronchiolitis is a term coined to described a
form of LIP in which the lymphoid aggregates congre-
Idiopathic Interstitial Pneumonitis gate around the small airways.
Chronic pneumonitis of infancy is a recently described
NSIP, DIP and LIP in childhood appear to share common pathological entity. Its HRCT appearance was reported
CT appearances. Widespread ground glass attenuation is based on a single biopsy-proven case, in which wide-
The Radiology of Diffuse Interstitial Pulmonary Disease in Children: Pearls, Pitfalls and Newly Recognised Disorders 237
spread ground glass opacification without focal areas of fat with bilateral pleural effusions and pleural thickening
consolidation or cystic change was seen. [23] is highly suggestive of the diagnosis. The condition
is related to congenital lymphangiectasia, in which there
is abnormal dilatation of the lymphatics. The CT findings
Connective Tissue Disorders of these two conditions are indistinguishable.
The prevalence of lung disease in paediatric patients

with connective tissue disorders is high. In a study by Idiopathic Pulmonary Haemosiderosis
Seely et al. [20], 10 of 11 children with systemic sclero-
sis who underwent HRCT had evidence of ILD. HRCT Idiopathic pulmonary haemosiderosis (IPH) is a rare dis-
features included ground glass opacification, subpleural ease occurring in children and adults. It is characterised
micronodules, linear opacities and honeycomb lung by recurrent episodes of pulmonary haemorrhage with
(consistent with UIP histologically). Aspiration pneu- haemoptysis. The aetiology is unknown. The childhood
monitis secondary to abnormal oesophageal peristalsis form of IPH usually presents before the age of 3 years,
may result in acute and chronic parenchymal change with no specific gender prevalence [24].
with bronchiectasis. On HRCT, acute haemorrhage is characterised by
Systemic-lupus-erythematosus-induced vasculitis ma- ground glass opacification or consolidation. In the suba-
nifests as patchy areas of ground glass attenuation. Crypto- cute/chronic phase, discrete pulmonary nodules of uni-
genic organising pneumonia with subsequent pulmonary form size can be seen throughout the lung and are a char-
fibrosis has been described. acteristic feature. Interlobular septal thickening can also
occur.
Pulmonary Alveolar Proteinosis

Sarcoidosis
Congenital pulmonary alveolar proteinosis (PAP) is an
inherited autosomal recessive disorder caused by surfac- Childhood sarcoidosis is rare. There appear to be two dis-
tant protein B deficiency. This condition presents early tinct types of sarcoidosis in children [25, 26]. The major-
in a full-term neonate with clinical and radiological ity of these patients present at 1315 years of age with a
features indistinguishable from hyaline membrane dis- multisystem disease inseparable from the adult type.
ease. The differential diagnosis includes congenital viral Lymphadenopathy and pulmonary involvement are com-
infection and neonatal fibrosing alveolitis. The recently mon, with systemic symptoms of fever and malaise. The
described chronic pneumonitis of infancy, characterised HRCT appearance of this form of childhod sarcoidosis is
by alveolar septal thickening, alveolar pneumocyte hy- identical to that of the adult disease.
poplasia and an alveolar exudate containing By contrast, children under 4 years of age [25, 26] pre-
macrophages and cellular debris, has a similar appear- sent with a distinct form of the disease, characterised by
ance. rash, uveitis and arthritis/tenosynovitis. Although pul-
A later form of PAP usually occurs at between a few monary involvement has been reported, it is rare in young
months to several years of age [22]. Chest X-rays show patients.
bilateral air space disease with ground glass opacifica-
tion. Air space filling with low-attenuation proteinacious
material and a superimposed crazy/paving pattern, Extrinsic Allergic Alveolitis
which represents thickened interlobular septa, are char-
acteristic HRCT features enabling a confident diagnosis Extrinsic allergic alveolitis (hypersensitivity pneumoni-
to be made in most cases. tis) is uncommon in children and is due to an immuno-
logical response to a variety of allergens. HRCT features
are identical to those seen in adults. In the acute/subacute
Congenital Lymphangiectasia/Diffuse Pulmonary phase, diffuse ground glass shadowing is seen in the
Lymphangiomatosis lungs, with small, poorly defined centrilobular nodules)
[27, 28]. Patchy air trapping may also occur because of
Congenital lymphangiectasia and diffuse pulmonary lym- small airway inflammation [29]. In chronic phases, inter-
phangiomatosis represent a minority of chronic ILDs in stitial fibrosis develops [30].
childhood and result from the abnormal proliferation and
dilatation of lymphatic channels. The CT appearances of
lymphangiomatosis can be easily predicted by knowing Langerhans Cell Histiocytosis
the distribution of the lymphatic system within the lungs.
The constellation of smooth thickening of the interlobular Pulmonary involvement in children with LCH is usually
septa, peribronchial thickening, patchy ground glass part of a disseminated disease. Approximately 50% of
opacification and increased attenuation of the mediastinal children with multisystemic LCH will have pulmonary
238 C.M. Owens
involvement, but this is not always associated with an Newer Disorders and Mimics of ILDs of Childhood
adverse outcome [29, 30]. Isolated pulmonary LCH is ex-
tremely rare in children. Pulmonary Veno-occlusive Disease
In children under 10 years of age, pulmonary involve-
ment tends to regress spontaneously (V. Nandhuri, person- Patients with this rare disorder present with the clinical
al communication), but in older children the acute features picture of pulmonary hypertension. Chest X-ray shows
resemble those seen in adults. HRCT shows multiple thin- enlarged pulmonary arteries, Kerley B lines, pleural effu-
walled cysts usually less than 1 cm in size and predomi- sions and mediastinal adenopathy. CT demonstrates pul-
nantly within the upper and mid-zones of the lungs. monary arterial enlargement, mediastinal lymphadenopa-
Nodules show diffuse distribution throughout the lung, thy and normal main pulmonary veins but shows smooth
with relative sparing of the costophrenic angles. Multiple interlobular septal thickening due to peripheral pul-
nodules measuring 13 mm in size occur and may be monary venous congestion. There is a mosaic pattern of
peribronchial in distribution. Nodules may cavitate and lung attenuation.
are the precursors of thin-walled cystic lesions. The dis- Aetiological factors include the idiopathic type, inher-
tribution and profusion of the nodules correlates with dis- ited factors, post viral infections, autoimmune disorders
ease activity [31]. and post bone marrow transplantation [32].
Pleuroparenchymal Fibroelastosis
Depositional Lung Diseases
Pleuroparenchymal fibroelastosis is a rare disorder, ob-
Lipid Storage Diseases served most often after allogenetic bone marrow trans-
plantation, although it has previously been reported as an
Niemann-Pick disease is an inherited defect in sphin- idiopathic, and related to dyskeratosis congenita. Fibrosis
gomyelinase production and has five clinical variants re- of the peripheral lung parenchyma with pleural thicken-
sulting in sphingomyelin deposition within the lung, liv- ing occurs often with pneumothorax. The lung apices are
er, bone marrow and brain. HRCT shows a diffuse retic- often more severely affected [33].
ulonodular pattern with nodules 12 mm in size due to
the accumulation of aggregates of large multi-vaculolated Filamin A Protein Deficiency Related Progressive Multilobar
foam cells deposited in the lungs. Emphysema
Gauchers disease is due to a deficiency of beta-glu-
cosidase (the enzyme catabolizer of glucosylceramide), The role of the filamin proteins in lung growth was not
resulting in the accumulation of the latter in reticulo- previously recognized, but their importance for normal
endothelial cells of the liver, spleen, lymph nodes, bones lung development and growth is crucial. Filamin protein
and the brain (especially in the infantile form of the dis- A (FLNA) encodes actin-binding cytoskeletal scaffold-
ease). The Gaucher cells then accumulate in the alveolar ing protein, which is involved in neuronal migration,
interstitial and adjacent air spaces, leading to diffuse mil- cardiovascular development and connective tissue in-
iary or reticulo-nodular patterns that may be associated tegrity.
with lytic rib lesions. Mutations of FLNA are associated with multisystemic
disorders, including periventricular cerebral nodular het-
Aspiration Pneumonitis erotopia, cardiac valve dysplasia, aneurysms and Ehlers-
Danlos variants. Infants normally present with progres-
Children with chronic gastro-oesophageal reflux with sive respiratory deterioration, sometimes complicated by
silent or clinically overt aspiration of gastric contents pulmonary hypertension.
can develop very severe pulmonary dysfunction with as- Chest X-ray and CT demonstrate hyperlucent lung
sociated radiological changes. Chest X-ray initially parenchyma with peripheral pulmonary vascular attenua-
shows air space disease, with subsequent interstitial fi- tion, especially in the upper and middle lobes [34].
brosis. In the infant, recurrent episodes of unexplained
respiratory distress related to feeding, together with peri-
hilar consolidations especially in the dependent right up- Conclusion
per and superior segments lower lobe should suggest as-
piration pneumonitis. Diffuse ILD in children comprises a rare but heteroge-
In the more chronic untreated forms, diffuse airway neous group of conditions, many of which have no known
and interstitial changes with peripheral pulmonary fibro- cause. There is a clear need for definitive histological
sis ensue. In these more advanced cases lung biopsy classification, which, along with the increasing experi-
shows numerous fat-laden macrophages, confirming the ence in HRCT, will aid us in our ability to diagnose and
diagnosis of aspiration-induced pulmonary fibrosis. follow these unusual, fascinating conditions.
The Radiology of Diffuse Interstitial Pulmonary Disease in Children: Pearls, Pitfalls and Newly Recognised Disorders 239
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IDKD 2015-2018
Neonatal Medical and Surgical Lung Diseases

George A. Taylor
Department of Radiology, Boston Childrens Hospital, Boston, MA, USA
Introduction
Respiratory distress is a common problem in the neonate,
and imaging plays an important part in the initial diag-
nosis and management of these infants. This chapter dis-
cusses the most common medical and surgical conditions
of the lung encountered in the newborn, with emphasis
on the role of a multi-modal evaluation for surgical
planning.
Medical Diseases
Approximately half of all premature infants suffer from
some form of respiratory distress. The most common
causes include surfactant deficiency (50%), transient
tachypnea (4%), and sepsis (2%). In the full-term infant,
transient tachypnea, meconium aspiration syndrome, and
persistent pulmonary hypertension are the most frequent-
ly encountered etiologies of acute respiratory failure. Be-
cause there is a great deal of overlap in the radiographic Fig. 1. Surfactant deficiency. A 27-week-gestation infant on the first
appearance of several conditions, knowledge of the pa- day of life. Portable chest radiograph shows hypoinflated lungs
with scattered air-bronchograms
tients gestational age and post-partum age, the clinical
setting, and the degree of respiratory support is crucial in
accurately assessing the underlying pathological process
and its progression or resolution. Standard treatment regimens include positive pressure
ventilation and endotracheal administration of exoge-
Surfactant Deficiency (Hyaline Membrane Disease) nous surfactant. Treatment with surfactant typically re-
sults in symmetric central clearing of the lungs. Howev-
Alveoli that are deficient in surfactant tend to collapse, er, the uneven distribution of surfactant may result in
resulting in generalized hypoinflation of the lungs, venti- over-aeration of one lung or lung segment (Fig. 2). Un-
lation-perfusion mismatch, and poor gas exchange. complicated surfactant deficiency typically resolves
Breathing causes overdistention of open alveoli and shear within the first week of life. However, high levels of in-
stresses on the fragile lung. As a result, there is leakage spired oxygen and inspiratory pressures may lead to pro-
of proteinaceous fluid into the alveolar lumen (hyaline longed respiratory difficulties, with eventual fibrosis
membranes), which further impairs gas exchange and and emphysema [1].
worsens the respiratory distress.
The typical radiographic findings are hypoinflated Pneumonia
lungs with a diffuse, reticulo-nodular appearance to the
lungs and air bronchograms, caused by fluid-filled alve- The incidence of pneumonia in the newborn appears to be
oli interspersed with air-filled sections of lung (Fig. 1). inversely proportional to gestational age, occurring in up

Neonatal Medical and Surgical Lung Diseases 241
Fig. 4. Transient tachypnea of the newborn. A 36-week-gestation in-

fant, born by cesarean section, on the first day of life. Chest radio-
graph shows increased central bronchovascular markings and a
Fig. 2. Asymmetric surfactant administration. A 28-week-gestation mild interstitial prominence
infant on the first day of life. Chest radiograph obtained after in-
tratracheal surfactant administration shows asymmetric central in-
flation of the right mid-lung due to asymmetric surfactant admin-
istration to the right lung Transient Tachypnea of the Newborn
Transient tachypnea of the newborn is one of the most
to 4% of premature infants 1000 g. The most common common causes of respiratory distress in the older pre-
pathogens in this age group currently include Escherichia mature and full-term infant. The basic underlying patho-
coli, group B streptococcus, and staphylococcus species. physiology is one of delayed clearing of fetal lung fluid.
Although alveolar infiltrates may be seen in the prema- Risk factors include prematurity and birth by cesarean
ture infant with pulmonary infection (Fig. 3), both the section, usually without preceding labor. Respiratory dif-
clinical signs and the radiographic features of pneumonia ficulties begin within a few hours of birth, lasting be-
may be indistinguishable from those of hyaline mem- tween a few hours up to 2 days in uncomplicated cases.
brane disease. Chest radiographs typically show increased perihilar
bronchovascular markings and fluid in the pulmonary fis-
sures (Fig. 4). The lungs may vary in their degree of in-
flation, from normal to hyperinflated.
Meconium Aspiration
Meconium aspiration syndrome consists of fetal acidosis
and subsequent hyperperistalsis, passage of meconium,
fetal gasping, and aspiration of meconium into the tra-
chea and lungs [2]. Thick meconium may cause physical
obstruction of the distal airways, resulting in patchy, al-
ternating areas of pulmonary overinflation and atelecta-
sis. Meconium also inactivates surfactant and causes sec-
ondary surfactant deficiency and poor lung compliance.
The clinical course of many patients with meconium as-
piration syndrome is complicated by pulmonary hyper-
tension, which increases illness severity and worsens
clinical outcomes. The radiographic features of meconi-
um aspiration vary widely, depending on the severity of
aspiration. The mildest cases manifest as pulmonary
hyperinflation with scattered interstitial pulmonary
opacities, while in more severe cases patchy alveolar and
Fig. 3. Neonatal pneumonia. A 26-week-gestation infant at 2 weeks
of life. Portable chest radiograph shows a focal right upper lobe
interstitial infiltrates and more pronounced hyperinflation
pneumonia with air bronchograms superimposed on early chronic are seen, often together with pneumothorax and pneumo-
lung disease mediastinum as complications (Fig. 5).
242 G.A. Taylor
Fig. 5. Meconium aspiration. A 39-week-gestation infant on the Fig. 6. Pulmonary air leak. A 27-week-gestation infant with surfac-
first day of life. Heavy meconium staining and low APGAR scores tant deficiency requiring positive pressure ventilation. Chest X-ray
at birth were recorded. Portable chest X-ray shows hyperinflated shows tubular and flame-shaped lucencies throughout the left lung
lungs with coarse bilateral interstitial opacities and focal right up- due to pulmonary interstitial emphysema. A large left pneumotho-
per lobe atelectasis rax is also present
Complications of Respiratory Support day management of these infants, cross-sectional imag-

ing is the key to the accurate characterization of these le-
Pulmonary air leaks are complications of greatest con- sions and to surgical planning [5]. Important goals for
cern in newborns receiving positive pressure ventila- imaging evaluation include identifying the location of a
tion. They can manifest as pulmonary interstitial em- lesion as well as its arterial and venous supply and the
physema, pneumomediastinum, pneumothorax, and in- assessment of internal components and associated
travascular gas. As alveoli become overdistended and anomalies.
rupture, gas is forced into the connective tissues of the
lung and can dissect along the interlobular septae to- Bronchial Atresia
ward the hilum of the lung. This pattern is of flame-
shaped lucencies that may be bilateral or unilateral and Bronchial atresia refers to complete atretic occlusion of a
is characteristic of pulmonary interstitial emphysema lobar or segmental bronchus close to its origin. The
(PIE). Increasing distention can progress to plural or pathogenesis of bronchial atresia appears to be related to
mediastinal air collections with or without PIE. In rare vascular accidents during organogenesis. While bronchial
cases, gas is forced through lymphatic channels into atresia may occur as a separate entity, it is often seen as
the vascular tree, resulting in cardiovascular collapse a component of pulmonary sequestration and CPAMs.
(Fig. 6). The upper lobes are most commonly affected, appearing
hyperexpanded on prenatal sonography, radiography, and
computed tomography (CT). A bronchocele with tubular
Surgical Diseases or finger-like impacted mucus may also be present on
imaging studies (Fig. 7).
Congenital anomalies of the lung that have surgical im-
plications include a heterogeneous set of disorders of the Congenital Pulmonary Airway Malformation
lung parenchyma and of the vascular supply of the lung.
They can occur alone or in various combinations that re- These lesions reflect the overgrowth of lung parenchyma
sult in a wide range of clinical symptoms and outcomes. into micro- or macrocystic malformations. They may
The most commonly occurring lesions, based on the arise from acinar tissue (microcystic lesions), bronchi-
Langston pathological classification system, include oles (mixed types), or more proximal airways (macro-
bronchial atresia, congenital pulmonary airway malfor- cystic lesions). Most are unilateral, but multiple or bilat-
mation (CPAM), bronchopulmonary sequestration, and eral lesions have been reported. While many communi-
congenital lobar hyperinflation, which together account cate with the central airway, the communication is often
for up to 90% of the congenital lesions encountered in abnormal, resulting in an initially fluid-filled pulmonary
the newborn [3, 4]. The majority of these lesions are now mass that gradually becomes air-filled and cystic (Fig. 8).
detected prenatally during routine screening, and while Macrocystic (type I) CPAMs are the most frequently oc-
radiography still plays an important role in the day-to- curring. They are seen in approximately 65% of postnatal
Neonatal Medical and Surgical Lung Diseases 243
a b
Fig. 7 a, b. Bronchial atresia and congenital pulmonary airway malformation. A 36-week-gestation infant at 2 weeks of life. Prenatal sonography
had depicted a focal right lower lobe lesions (not shown). Chest radiograph (a) shows an ill-defined opacity in the right lower lobe (arrows). Coro-
nal reconstruction of a contrast-enhanced chest CT (b) shows a hyperlucent segment of the right lower lobe with a lobulated, mucus-filled bron-
chocele (arrow) due to segmental bronchial atresia
Fig. 9. Congenital lobar hyperinflation. A full-term newborn with a

prenatally diagnosed hyperexpanded lung. Chest X-ray shows an
overinflated, hyperlucent left lung with a centrally-placed atelecta-
sis (arrows) and a contralateral mediastinal shift due to congenital
lobar hyperinflation of the upper lobe
Fig. 8. Extralobar pulmonary sequestration. A full-term infant with a
prenatally diagnosed lung mass. Coronal reconstruction of the con-
trast-enhanced CT shows a heterogeneous mass at the base of the Bronchopulmonary Sequestration
left lung with a systemic arterial supply arising from the descending
aorta (arrow) Sequestrations are characterized by a lack of communica-
tion between the central airway and a systemic arterial sup-
ply, commonly arising from the descending thoracic aorta.
cases, are typically located in the lower lobes, and in- There are two basic types of sequestration: intralobar se-
volve a single lobe in over 95% of cases. Microcystic questrations are part of the normal pulmonary lobe, are
(type II) lesions comprise 1520% of CPAMs and have located within the visceral pleura, and their venous
a higher association with other congenital chest anom- drainage is via the pulmonary artery. They are typically lo-
alies, such as sequestration, diaphragmatic hernia, and cated in the lower lobes. Extralobar sequestrations are ac-
congenital heart disease. Mixed cystic and solid (type cessory lung tissue outside of the visceral pleura, drained
III) lesions account for about 10% of CPAMs and can in- by systemic or portal veins. They may be located within or
volve an entire lobe or lung. CPAM lesions, even large below the diaphragm. Ultrasound can be used to identify
ones associated with hydrops, regress prenatally in 50% the systemic arterial blood supply in solid or fluid-filled
of the cases. masses in the early postnatal period. CT arteriography is
244 G.A. Taylor
very useful in fully characterizing the vascular connections References

prior to thoracoscopic removal of the lesion (Fig. 9).
1. Jackson CJ (2012) Respiratory distress in the preterm infant.
In: Gleason CA, Devaskar SU (2012) Averys Diseases of the
Congenital Lobar Hyperinflation Newborn, 9th Ed. Elsevier, pp 633-646.
2. Parker TA, Kinsella JP (2012) Respiratory failure in the term
Congenital lobar hyperinflation is primarily seen in the infant. In: Gleason CA, Devaskar SU (2012) Averys Diseases
upper lobes and is caused by obstruction of the lobar of the Newborn, 9th Ed. Elsevier, pp 647-657.
bronchus. The obstruction may be intrinsic, due to mala- 3. Langston C (2003) New concepts in the pathology of congen-
cia, stenosis, or atresia, or caused by extrinsic compres- ital lung malformations. Semin Pediatr Surg 12:17-37.
sion from mediastinal cysts or abnormal pulmonary ves- 4. Epelman M, Daltro P, Soto G et al (2013) Congenital lung
anomalies. In: Coley BD (2013) Caffeys Pediatric Diagnostic
sels. On prenatal imaging, the affected lobe is typically Imaging, 12th Ed, vol 1. Elsevier, pp 550-556.
overdistended. However, a specific prenatal diagnosis 5. Lee EY, Dorkin H, Vargas SO (2011) Congenital pulmonary
may be difficult because of the overlapping appearances malformations in pediatric patients: review and update on etio-
of CPAM and bronchial atresia. On postnatal imaging, logy, classification and imaging findings. Radiol Clin North
Am 49:921-948.
the affected lobe is distended and may exert a mediasti-
nal shift. The cyst transitions from fluid-filled to air-
filled over the first few days of life.
BREAST IMAGING SATELLITE COURSE
PEARL
IDKD 2015-2018
Scintimammography
Einat Even-Sapir
Sourasky Medical Center, Tel Aviv, Israel
Nuclear medicine has been i nvolved in the field of func- and the breast hangs freely through a small ring of de-
tional tumor imaging for decades. Its hallmark is the detectors. The first system to become commercially avail-
tection of viable tumor tissue based on functional and bi- able was a stationary flat detector-based PEM scanner
ological characteristics rather than on an altered tumor that used limited-angle tomosynthetic reconstruction
morphology. Scintigraphy has an important role in mon- with a spatial resolution of 2.4 mm [5]. A newer design
itoring the response to therapy, by distinguishing active is mammography with molecular imaging (MAMMI), a
tumor mass, where the tumor-seeking tracer still accu- dedicated breast PET system that uses a complete ring of
mulates, from residual mass composed of necrosis or detectors for full tomographic image reconstruction with
scar, where tracer no longer accumulates. The use of a spatial resolution of 1.6 mm [6]. Dedicated breast PET
scintigraphy in tumor detection depends on the mecha- systems were shown to be significantly more sensitive for
nism of tracer uptake in the tumor, the pharmacokinetic the detection of breast cancer than either whole-body
and normal biodistribution of the tracer, and on the tech- PET or PET-CT [7].
nology of the detecting system. The tracer used for breast imaging with a gamma-cam-
The detection of breast cancer using single-photon- era is 99mtechnetium (Tc)-sestaMIBI. The mechanisms of
emitting tracers with a gamma camera and positron-emit- the enhanced cellular uptake of 99mTc-sestaMIBI in can-
ting tracers with PET technology has been an ongoing cer cells is the subject of ongoing investigation. 99mTc-
challenge of nuclear medicine [1]. The whole-body sys- sestaMIBI is a small lipophilic cation whose uptake is
tems used originally in scintimammography were sub- nine times higher in tumor tissue than in normal tissue,
optimal for the detection of small lesions in the breast, as reflecting the high vascularity and mitochondrial activity
the distance from the collimator to the breast is approxi- of the former [8, 9]. The major advantage of 99mTc-
mately 15 cm and to the region of interest up to 25 cm. sestaMIBI in breast cancer imaging is its wide availabil-
Instead, dedicated systems for breast imaging were need- ity in the routine practice of nuclear medicine depart-
ed, which are now commercially available. ments, as it is also used in cardiac perfusion studies.
Gamma-cameras dedicated to breast imaging may be Moreover, unlike PET tracers, it does not require cy-
single- or dual-headed cameras; in the latter, each breast clotron facilities for its production.
is positioned between the two detectors in two views sim- The most commonly used tracer for scintimammogra-
ilar to the acquisition mode on mammography, with no phy with positron-emission technology is 18F-fludeoxyglu-
pressure. Detectors can be the NaI (Tl) detectors rou- cose (FDG). As a rule of thumb, 18F-FDG uptake is high-
tinely used in nuclear medicine, a technology referred to er in breast tumors with prognostically unfavorable char-
as breast-specific gamma imaging (BSGI), or the new acteristics [10]. Primary tumor 18F-FDG uptake was found
generation of pixilated semiconductor [cadmium zinc tel- to correlate with tumor size, histological type and grade,
luride (CZT)] detectors with improved spatial resolution. pleomorphism, lymphatic invasion, high Ki-67 level, and
A dual-headed system composed of CZT detectors, the triple negativity (i.e., negative for the estrogen receptor, the
molecular breast imaging system (MBI), was reported to progesterone receptor, and the human epidermal growth
have a high sensitivity in the detection of clinically rele- factor receptor 2) [11]. Yet, it should be borne in mind that
vant breast lesions as small as 3 mm [2-4]. 18F-FDG avidity is a characteristic of the individual tumor
Several dedicated breast imaging systems for positron- and some tumor types, such as ductal carcinoma in situ and
emitting tracers have been designed. The earliest one, lobular carcinoma, may show only low-intensity uptake [7,
positron emission mammography (PEM), uses two oppo- 12]. Moreover, when dedicated PET systems are used for
sitely placed detectors, as in mammography. With anoth- breast imaging, heterogeneous uptake in a large tumor
er prototype, dedicated breast PET, the patient is prone probably reflects tumor heterogeneity within the mass [13].

248 E. Even-Sapir
Publications on the clinical use of scintimammography patients response to therapy, and to the antiangiogenic ef-
have explored its role in tumor detection in patients with fects of the chemotherapeutic agent, which can alter the
no known malignancies and as a diagnostic tool in pa- contrast kinetics thus leading to an overestimate of the re-
tients with diagnosed breast cancer. The reported sensi- sponse [1]. Assessing response to therapy by means of
tivity of BSGI for the detection of breast cancer is functional rather than anatomic changes is another indi-
78100% for all tumor types, including lobular carcino- cation for scintimammography. 99mTc-sestaMIBI is a sub-
ma [2, 14]. Using the MBI system, researchers at the strate of the transmembrane P-glycoprotein (Pgp-170)
Mayo Clinic were able to detect small malignant lesions present in cells overexpressing the multidrug resistance
of 3 mm and calculated a sensitivity of 90% for abnor- gene (MDR1). Pgp acts as a protective pump by extrud-
malities 520 mm in size. Scintigraphy was found to be ing out of the tumor cells a wide range of molecules, in-
a valuable procedure when routinely used screening cluding 99mTc-sestaMIBI. Studies performed in humans
modalities, mainly mammography, were suboptimal, such demonstrated that in tumors with high levels of Pgp,
as in the case of patients with dense breasts. Based on the 99mTc-sestaMIBI efflux was significantly faster than in
screening of 936 at-risk women, Rhodes et al., of the the control group or in tumors with no Pgp, suggesting a
Mayo Clinic, reported a sensitivity of 27% for mammo- role for 99mTc-sestaMIBI scintigraphy in monitoring the
graphy alone and 91% for combined mammography and response to chemotherapy [8, 9]. Serial 99mTc-sestaMIBI
MBI [15]. This group reported the good performance of scintimammography was shown to accurately predict tu-
MBI with a low-dose of 8 mCi 99mTc-sestaMIBI, with mor response in patients with locally advanced breast car-
ongoing efforts aimed at dose-reduction to perform MBI cinoma undergoing neoadjuvant chemotherapy. Patients
with 4 mCi, with an effective dose twice that of a screen- with residual high uptake had poorer disease-free survival
ing mammogram. and overall survival, and uptake at completion of treat-
A recently published meta-analysis evaluated eight stud- ment was found to be an independent prognostic factor
ies on the use of 18F-FDG-PEM, comprising 873 women [18]. In a recent study, changes in the tumor to back-
with breast lesions. The pooled sensitivity and specificity ground ratio on MBI images performed at 35 weeks
values of PEM were 85% and 79%, respectively, accord- following the initiation of neoadjuvant chemotherapy
ing to a per-lesion-based analysis [16]. Currently, however, were found to accurately predict the presence or absence
scintigraphy is not recommended as a routine screening of residual disease at the completion of treatment [19].
tool because of the higher total body radiation compared to An MBI system was installed at our center in 2009. We
routinely used breast imaging modalities. approached our clinicians, breast surgeons, oncologists,
Accurate assessment of disease extent in the breast is and breast radiologists in conducting a registry research
essential to optimize the treatment approach in patients aimed at understanding the potential complementary role
with newly diagnosed breast cancer. As in the case of MRI, of MBI in the imaging algorithm of breast imaging. In
scintimammography can identify additional, unexpected patients with unknown cancer, indications for MBI in-
sites of disease, resulting in a change in diagnosis from lo- cluded genetic and familial high-risk; equivocal findings
calized to multifocal, multicentric, or even bilateral dis- on mammography, ultrasound (US), and/or MRI; nipple
ease. In a retrospective study of 159 women with one sus- discharge with no suggested breast abnormality; con-
picious breast lesion on physical exam and/or mammogra- traindication for MRI or claustrophobia in patients with
phy, BSGI detected additional suspicious lesions in 29% equivocal mammography and US assessment; and further
and occult cancer in 9%, both in the same breast as the in- assessment of the contralateral breast. In patients with di-
dex lesion (6%) and in the contralateral breast (3%) [12]. agnosed breast cancer, the indications for MBI were: as-
PEM and MRI were performed and compared in 388 sessment of the disease extent in the breasts of patients
patients with diagnosed cancer who were scheduled for with newly diagnosed solitary breast cancer planned for
surgery. Additional cancers were found in 21% of the lumpectomy, in which the surgeon was uncertain that dis-
women. PEM and MRI had comparable breast-level sen- ease was localized; in patients with locally advanced dis-
sitivity, although MRI had greater lesion-level sensitivity ease before and after neoadjuvant therapy; in assessing
and more accurately depicted the need for mastectomy. the presence of residual disease after surgery or of sus-
PEM had greater specificity at the breast and lesion lev- pected recurrence; to search for a primary occult tumor
els. In 3.6% of the women, tumors were seen only on in patients with metastatic axillary lymph nodes of breast
PEM [16]. In another study of 367 patients, 4% had con- cancer; and in follow-up.
tralateral cancer. The sensitivity and specificity of MRI in Scintimammography technology and clinical cases re-
detecting these lesions was 93% and 89.5% respectively, flecting the complementary role of scintimammography
compared to 73% and 95%, respectively, for PEM [17]. are discussed in the workshop for this chapter.
In patients with locally advanced disease receiving
neoadjuvant therapy, monitoring response to therapy by
morphologic imaging modalities reduces potential errors References
in interpretation due to findings of fibrosis or scar for-
mation and tumor fragmentation rather than concentric 1. Fowler AM (2014) A molecular approach to breast imaging. J
shrinkage, which can lead to an underestimation of the Nucl Med 55:177-180.
Scintimammography 249
2. Sun Y, Wei W, Yang HW, Liu JL (2013) Specific gamma imag- prognostic factors in breast carcinoma. Nucl Med Commun
ing as an adjunct modality to mammography for diagnosis of 34:1055-1067.
breast cancer: a systemic review and meta-analysis. Eur J Nu- 12. Buck A, Schirrmeister H, Khn T et al (2002) FDG uptake in
cl Med Mol Imaging 40:450-463. breast cancer: correlation with biological and clinical prog-
3. Brem RF, Shahan C, Rapleyea JA et al (2010) Detection of oc- nostic parameters. Eur J Nucl Med Mol Imaging 29:1317-
cult foci of breast cancer using breast-specific gamma imag- 1323.
ing in women with one mammographic or clinically suspicious 13. Koolen BB, Vidal-Sicart S, Benlloch Baviera JM, Valds Ol-
breast lesion. Acad Radiol 17:735-743. mos RA (2014) Evaluating heterogeneity of primary tumor
4. Hruska CB, Phillips SW, Whaley DH et al (2008) Molecular (18)F-FDG uptake in breast cancer with a dedicated breast
breast imaging: use of a dual-head dedicated gamma camera PET (MAMMI): a feasibility study based on correlation with
to detect small breast tumors. AJR Am J Roentgenol PET/CT. Nucl Med Commun 35:446-452.
191:1805-1815. 14. Brem RF, Ioffe M, Rapelyea JA et al (2009) Invasive lobular
5. MacDonald L, Edwards J, Lewellen T et al (2009) Clinical carcinoma: detection with mammography sonography MRI,
imaging characteristics of the positron emission mammogra- and breast-specific gamma imaging. AJR Am J Roentgenol
phy camera: PEM Flex Solo II. J Nucl Med 50:1666-1675. 192:379-383.
6. Moliner L, Gonzalez AJ, Soriano A et al (2012) Design and 15. Rhodes DJ, Hruska CB, Phillips SW et al (2011) Dedicated
evaluation of the MAMMI dedicated breast PET. Med Phys dual-head gamma imaging for breast cancer screening in
39:5393-5404. women with mammographically dense breasts. Radiology
7. Kalinya JE, Berg WA, Schilling K et al (2014) Breast cancer 258:106-118.
detection using high-resolution breast PET compared to whole- 16. Berg WA, Madsen KS, Schilling K et al (2011) Breast cancer:
body PET or PET/CT. Eur J Nucl Med Mol Imaging 41:260-275. comparative effectiveness of positron emission mammography
8. van Leeuwen FW, Buckle T, Kersbergen A et al (2009) Nonin- and MR imaging in presurgical planning for the ipsilateral
vasive functional imaging of P-glycoprotein-mediated doxoru- breast. Radiology 258:59-72.
bicin resistance in a mouse model of hereditary breast cancer 17. Berg WA1, Madsen KS, Schilling K et al (2012) Comparative
to predict response, and assign P-gp inhibitor sensitivity. Eur J effectiveness of positron emission mammography and MRI in
Nucl Med Mol Imaging 36:406-412 the contralateral breast of women with newly diagnosed breast
9. Vecchio SD, Zannetti A, Salvatore B et al (2006) Functional cancer. AJR Am J Roentgenol 198:219-232.
imaging of multidrug resistance in breast cancer. Phys Med 18. Dunnwald LK, Gralow JR, Ellis GK et al (2005) Residual tu-
21(Suppl 1):24-27. mor uptake of [99mTc]-sestaMIBI after neoadjuvant chemo-
10. Koolen BB, Vrancken Peeters MJ, Wesseling J et al (2012) As- therapy for locally advanced breast carcinoma predicts sur-
sociation of primary tumour FDG uptake with clinical, vival. Cancer 103:680-688.
histopathological and molecular characteristics in breast can- 19. Mitchell D1, Hruska CB, Boughey JC et al (2013) 99mTc-
cer patients scheduled for neoadjuvant chemotherapy. Eur J sestaMIBI using a direct conversion molecular breast imaging
Nucl Med Mol Imaging 39:1830-1838. system to assess tumor response to neoadjuvant chemotherapy
11. Ekmekcioglu O, Aliyev A, Yilmaz S et al (2013) Correlation in women with locally advanced breast cancer. Clin Nucl Med
of 18F-fluorodeoxyglucose uptake with histopathological 38:949-956.
IDKD 2015-2018
Breast MRI BI-RADS: Second Edition Highlights

Elizabeth A. Morris
Department of Radiology, Breast Imaging Center, Memorial Sloan-Kettering Cancer Center, New York, NY, USA
Since the first edition of the magnetic resonance imaging geneous enhancement, and not very high in signal on
(MRI) section of the illustrated BI-RADS lexicon, the bright fluid imaging.
field of breast MRI has grown enormously. Understand-
ably, certain terms have been added or deleted as better
terms have been identified. Additionally, concepts such Mass
as background parenchymal enhancement (BPE) have
been proposed and included. A section on nonenhancing A mass is an area of enhancement with an epicenter and
findings has been added. A section devoted to implant convex borders, existing as a three-dimensional (3D)
description and assessment is new. structure. The committee decided not to assign a size re-
quirement, recognizing that suspicious masses can be of
all sizes. In general, as the mass size increases so does the
Focus likelihood of malignancy.
Mass descriptors for shape and margins have been
An enhancing focus is a tiny round pin-point dot of en- adopted from the mammography BI-RADS lexicon. In
hancement that is seen only on the postcontrast images. general, as with mammography, circumscribed oval or
It is a round, homogeneously enhancing area with cir- round masses are seen more with benign lesions, where-
cumscribed margin. In general, foci are too small to ex- as irregular, spiculated masses are more likely to be ma-
hibit internal enhancement characteristics. Foci can be lignant. Care should be taken with respect to morpholo-
found in women of any age and menopausal status. A fo- gy, as round circumscribed masses on MRI represent can-
cus can be benign or malignant. cer more frequently than at mammography. There are sev-
In general, foci are a few millimeters in size; however, eral possible explanations for the presence of morpho-
applying strict size criteria is not favored. It must be not- logically benign lesions representing cancer on MRI.
ed that cancers 5 mm can be identified in the breast on First of all, MRI does not have the spatial resolution of
MRI. If margins and internal enhancement can be as- mammography with current techniques and field strength
sessed, then the lesion would be considered a mass. As so that margin analysis internal enhancement may suffer.
techniques improve, with higher resolution capabilities, Second, the cancers with benign morphology on MRI are
fewer lesions will be described as a focus and more will usually small, and smaller than we might be used to de-
be classified as a mass. tecting on mammography. As with most imaging tech-
If a focus is not unique, it is likely to represent a com- niques, the ability to resolve margins depends on the size
ponent of the patients background parenchymal en- of the lesion. Kinetic evaluation is important when con-
hancement (BPE). If it is unique and separate from the sidering these morphologically benign appearing lesions.
BPE, it may warrant evaluation. Margin analysis, kinetic As with other imaging techniques, the worst feature of
analysis, internal enhancement and T2-weighted charac- the lesion under evaluation should be used to determine
teristics can be evaluated to determine whether a focus is the need for biopsy.
likely to be benign or suspicious. Imaging features that A mass has internal enhancement that can be charac-
favor benign etiology are circumscribed, persistent, ho- terized. In general, homogeneous enhancement and
mogeneous and very high signal intensity on bright fluid nonenhancing internal septations indicate a possible be-
imaging. Imaging characteristics that favor malignancy nign process. While it is certainly possible to see classic
are irregular, spiculated, wash out kinetics, rim or hetero- appearances of certain lesions, morphologic overlap can
occur between benign and malignant lesions; if there is
This chapter was previously published in: Hodler J, von Schulthess any doubt, biopsy should be performed. The committee
GK, Zollikofer ChL (eds) Musculoskeletal Diseases 2013-2016. recognizes that when masses become large and ill-de-
Springer-Verlag Italia, Milano 2013, pp. 275-281. fined they might be described as regional enhancement.
Breast MRI BI-RADS: Second Edition Highlights 251
Mass analysis can benefit from bright fluid sequences As in the fifth edition of BI-RADS Mammography,
[i.e., T2 weighted or short-tau inversion recovery (STIR)] in the amount of fibroglandular parenchyma is not de-
addition to the postcontrast sequences obtained. In general, scribed using percentages. Unlike mammography, where
benign mass lesions can be increased in signal relative to fi- noncalcified breast lesions can be obscured by dense tis-
broglandular parenchyma on bright fluid imaging, particu- sue, breast MRI is able to easily reveal an enhancing sus-
larly cysts, lymph nodes and fibroadenomas. Cancers may picious lesion independent of breast composition. There-
or may not exhibit increased signal on bright fluid imaging. fore, the amount of fibroglandular parenchyma does not
Cancer can be heterogeneously high in signal on bright flu- adversely impact lesion detectability.
id imaging if the tumors are necrotic, cellular or mucinous.
Mucinous carcinoma and liposarcoma classically demon- Background Parenchymal Enhancement
strate very high signal on bright fluid sequences; however,
there are usually other suspicious features, such as irregu- As MRI is performed with intravenous contrast, the fi-
lar shape or noncircumscribed margins, that warrant biopsy. broglandular breast parenchyma can demonstrate contrast
enhancement. BPE refers to the normal enhancement of
the patients fibroglandular tissue on the first postcontrast
Non-Mass Enhancement image. BPE refers to both the volume of enhancement as
well as the intensity of enhancement, and an evaluation
In the first edition of the MRI section of the illustrated of background enhancement should take both into con-
BI-RADS lexicon, non-mass enhancement (NME) was sideration.
used to describe BPE as well as areas that are still con- The background enhancement is described as one of
sidered to be NME. With greater experience and under- the following:
standing of BPE, some terms have been removed and the Minimal
NME descriptors have been refined. NME describes en- Mild
hancement in a pattern that does not have convex borders Moderate
and may have intervening fat or normal fibroglandular Marked
tissue contained within the extent of the enhancement. Although these categories are roughly quartiles, as-
Clumped enhancement refers to enhancement that has signing strict percentages to indicate the degree of en-
the appearance of cobble-stones where there are small hancement is likely artificial, difficult to assess without
aggregates of enhancement that are variable in size and automation, and should be avoided. In general, BPE might
morphology. The term clumped refers to enhancement in not be evenly distributed throughout the entire breast. Due
a focal, linear or linear-branching, segmental or regional to preferential blood supply, there is the probability of
distribution. The term clumped on MRI is similar to the greater enhancement in the upper outer quadrant of the
term pleomorphic on mammography, as it indicates en- breast and along the inferior aspect of the breast (former-
hancement in varying shapes and sizes. As ductal carci- ly described as sheet-like enhancement). BPE might be
noma in situ (DCIS) can present with this morphologic more prominent in the luteal phase of the cycle if the pa-
pattern, a description of clumped usually indicates a need tient is premenopausal. Therefore, for elective examina-
for biopsy. The diagnosis of DCIS is usually made solely tions (e.g., high-risk screening), effort should be made to
on lesion morphology, as many times the kinetic appear- schedule the patient in the second week of her cycle (days
ance does not meet minimal threshold and the time in- 7-14) to minimize the issue of background enhancement.
tensity curves are not typical for malignancy. Despite scheduling the patient at the optimal time of her
cycle, BPE will still occur and the BPE terms should be
applied. Women in whom cancer has been diagnosed and
Report Organization MRI is performed for staging (i.e., diagnostic) should be
imaged with MRI regardless of the timing of the men-
Amount of Fibroglandular Tissue strual cycle or menstrual status.
The pattern of BPE can be variable from patient to pa-
MRI is unique in that 3D volumetric data can be acquired tient, though in general the pattern of BPE for an individ-
from the image, and separation of fat and fibroglandular ual is fairly constant. It is uncertain what the patterns of en-
parenchyma is performed relatively easily. There are no hancement mean, therefore description beyond the recom-
data comparing mammographic density (breast composi- mended descriptors is optional. There is some evidence that
tion) with MRI assessment of amount of fibroglandular BPE might indicate a level of risk for the development of
tissue. Density is a term that should be applied only to breast cancer, as therapeutic measures such as anti-estrogen
mammography. The amount of fibroglandular tissue therapy can decrease the level of BPE. However, BPE does
should be described as one of the following: not appear to affect the ability to detect breast cancer.
Almost entirely fatty BPE can occur regardless of the menstrual cycle or
Scattered fibroglandular tissue menopausal status of the patient. BPE might not be di-
Heterogeneous fibroglandular tissue rectly related to the amount of fibroglandular parenchy-
Extreme fibroglandular tissue ma present. Patients with extremely dense breasts at
252 E.A. Morris
mammography might demonstrate little or no BPE, examination is technically unacceptable (e.g., poor fat
whereas patients with mildly dense breasts might demon- suppression, poor positioning) and would not be suffi-
strate marked BPE. Nevertheless, most of the time, cient for interpretation, a meaningful report could not be
younger patients with dense breasts are more likely to issued and a category 0 may be issued. The MRI exami-
demonstrate BPE. nation has characteristics that make it unique in compar-
In general, BPE is progressive over time; however, sig- ison to mammography and ultrasound. The first and most
nificant and fast enhancement can occur on the first post- obvious difference is the use of a contrast agent. This
contrast image despite fast imaging techniques. BPE on adds the parameter of blood flow to morphology with the
MRI is unique to a patient as is breast density at mam- associated flow metrics that may be calculated. The sec-
mography. A description of background enhancement ond is the acquisition of the exact same number and se-
should be included in the breast MRI report. quences whether the examination is for screening or di-
Patterns of BPE are under investigation, as there is wide agnostic. As with mammography, BI-RADS 0 should be
variation in the appearance from woman to woman. BPE used in the screening setting only. In interpreting breast
may present as multiple foci either uniformly scattered or MRI, there is enough information on the properly per-
more focal in one area, described previously as stippled formed examination to decide to biopsy or recommend
enhancement. Stippled enhancement is a pattern of BPE; it short-term follow-up of a specific finding. MRI, like
is usually diffuse and symmetric, however it can present as mammography, can give a category 0 for prior MRIs be-
a focal finding (particularly in an area where cysts are fore a report is issued that for auditing purposes will be
found) suggesting focal fibrocystic disease. replaced by the final assessment rendered in the addend-
ed report once prior examinations do become available
Non-Enhancing Findings similar to a category 0 for technical reasons. This recom-
mendation may change in the future when MRI screening
Non-enhancing findings seen on the precontrast or bright becomes more commonplace.
fluid images are benign. Examples include cysts, duct ec- A final assessment of 0 is helpful when a finding on
tasia and some fibroadenomas and postoperative collec- MRI is suspicious but a benign corresponding finding
tions. Assessment of the absence of enhancement is best on an additional study would prevent a biopsy. If a cat-
made on the subtraction image. Follow-up or biopsy of egory 0 is given on MRI, then an explanatory note in the
areas of non-enhancement is not necessary unless there MRI report clarifying why this suspicious morpholo-
are suspicious findings on another imaging modality, gy is not immediately given a 4 or 5 is called for. For
such as mammography or ultrasound. example, if a mass is suspicious on MRI but there is a
possibility that it might represent a benign finding such
as a lymph node, a targeted ultrasound that would prove
Assessment Categories that the lesion is benign would prevent a biopsy. In the
case of an ultrasound recommendation following the
The final assessment should be based on the most suspi- MRI examination, the terms MRI directed or MRI
cious finding present in each breast. A separate BI- targeted ultrasound are preferable to second look ul-
RADS assessment for each breast should be stated after trasound, as it is not always certain that a first look ul-
the impression text. If the interpretation is straightfor- trasound has been performed. Another example where
ward and the same for both breasts, an overall impression category 0 would be useful is for a finding on MRI that
that includes both breasts may be used. The overall as- is most likely fat necrosis, but the reader would like to
sessment should be based on the most worrisome find- confirm and correlate the findings to a mammogram
ings present in each breast. For example, if benign find- that is not available.
ings, such as lymph nodes or cysts, are noted along with When additional studies are compared or completed, a
a more suspicious finding, such as a spiculated mass, the final assessment category attached to those additional
final assessment code should be reported category 4 or 5. studies would close out the MRI 0. When interpreting
Similarly, if immediate additional evaluation is needed MRI it is extremely helpful to have all available imaging
for one breast for a suspicious finding (with targeted ul- studies in order to give a complete report. If the addi-
trasound, for example), and there is a probably benign tional studies can be reported in the same report, separate
finding in the breast as well, the final assessment code paragraphs indicating the pertinent findings from each
for that breast would be category 4. If a breast with a imaging study can contribute to the final integrated as-
known cancer has an additional suspicious finding war- sessment that takes into consideration the findings of all
ranting biopsy, then the final assessment code for that imaging studies.
breast is category 4, not category 6.
Category 1
Category 0
This is a normal examination. A description of the fi-
Every effort should be made not to use category 0 in broglandular tissue and background parenchymal en-
reading breast MRI. However, in the event that the hancement should be included.
Breast MRI BI-RADS: Second Edition Highlights 253
Category 2 nonspecific benign pathology to ensure adequate sam-

pling of the lesion. Some authors have suggested a single
Benign findings are described in the report. Benign find- non-contrast T1-weighted image following ultrasound-
ings include intramammary lymph nodes, cysts, duct ec- guided biopsy for a suspicious lesion to ensure adequate
tasia, postoperative collections, fat necrosis, scar, and and accurate sampling.
masses, such as fibroadenomas, assessed as benign by
morphology/kinetics or prior biopsy. Category 5
Category 3 Category 5, highly suggestive of malignancy, was estab-

lished at a time when most nonpalpable breast lesions un-
We recognize that there are few data in defining types of derwent preoperative wire localization prior to surgical
lesions that can be followed. There are reports that sup- excision. Category 5 assessments were used for those le-
port short-term follow-up of (1) a new unique focus that sions that had such characteristic features of cancer that
is separate from the BPE but has benign morphologic and one-stage surgical treatment might be performed imme-
kinetic features, and (2) a mass on an initial examination diately following frozen-section histological confirma-
with benign morphologic and kinetic features. There are tion of malignancy. Today breast cancer diagnosis for
data to suggest that BPE should not be followed, there- imaging-detected lesions almost always involves percuta-
fore BPE is inappropriate for follow-up. Similarly, non- neous tissue sampling, so the current rationale for using
mass enhancement should be characterized as either be- category 5 assessment is to identify lesions for which any
nign or malignant and given a final assessment; it should nonmalignant percutaneous tissue diagnosis is consid-
not be recommended for surveillance imaging. ered discordant, resulting in the recommendation for re-
peat (usually surgical) biopsy.
Category 4 The likelihood of malignancy for category 5 assess-
ments is 95%, so use of this assessment category is re-
Category 4 is used for the vast majority of findings served for classic examples of malignancy. Note that
prompting breast interventional procedures, ranging from there is no single MRI feature that is associated with a
diagnostic aspiration of complicated cysts to biopsy of likelihood of malignancy of 95%. Just as it is found for
fine linear and branching calcifications. According to BI- mammography and breast ultrasound examinations, it
RADS definitions expressed in terms of likelihood of takes a combination of suspicious MRI findings to justi-
malignancy, the cut points between category 3 versus cat- fy a category 5 assessment.
egory 4 assessments, and category 4 versus category 5 as-
sessments, are 2% and 95%, respectively. Many institu- Category 6
tions have, on an individual basis, subdivided category 4
to account for the vast range of lesions subjected to in- This assessment category was added to the fourth edition
terventional procedures and corresponding broad range of BI-RADS Mammography for use in the special cir-
of likelihood of malignancy. This allows a more mean- cumstance when breast imaging is performed after a tis-
ingful practice audit, is useful in research involving re- sue diagnosis of malignancy but prior to complete surgi-
ceiver-operating characteristic curve analysis, and is an cal excision. Unlike the more common situations when
aid for clinicians and pathologists. BI-RADS categories 4 and 5 are used, a category 6 as-
Lesions that are appropriate to place in this category sessment will not usually be associated with recommen-
are: (1) suspicious non-mass enhancement such as dation for tissue diagnosis of the target lesion because
clumped, linear, linear branching or segmental; (2) irreg- biopsy has already established the presence of malignan-
ular, heterogeneous or rim enhancing masses; (3) foci cy. Category 6 is the appropriate assessment, prior to
with any suspicious morphology or kinetics. Specifically, complete surgical excision, for staging examinations of
a new focus with any suspicious feature warrants further previously biopsied findings already shown to be malig-
evaluation by biopsy. nant, after attempted complete removal of the target le-
Suspicious findings on MRI warranting biopsy can be sion by percutaneous core biopsy, and for the monitoring
evaluated by targeted ultrasound. In general, masses are of response to neoadjuvant chemotherapy.
more likely to be seen on ultrasound than non-mass le- However, there are other scenarios in which patients
sions. Biopsy of the finding should be performed with with known biopsy-proven malignancy have breast imag-
the modality that best illustrates the finding. If a corre- ing examinations. For example, the use of category 6 is
late to the MRI finding can be reliably found on ultra- not appropriate for breast imaging examinations per-
sound, ultrasound biopsy might be preferable as it is usu- formed following surgical excision of a malignancy
ally more ubiquitous and cheaper than MR biopsy. Fol- (lumpectomy). In this clinical setting, tissue diagnosis
low-up after both ultrasound and MRI biopsy is recom- will not be performed unless breast imaging demon-
mended, as missed lesions have been reported. Regarding strates residual or new suspicious findings. Therefore, if
the timing of follow-up, it has been recommended that a a postlumpectomy examination demonstrates surgical
6-month follow-up MRI is performed for all concordant scarring but no visible residual malignancy, the appropriate
254 E.A. Morris
assessment is benign (BI-RADS category 2). On the mined that tissue diagnosis is not appropriate, then a cat-
other hand, if there are, for example, residual suspi- egory 6 assessment should be rendered accompanied by
cious lesions, the appropriate assessment is category 4 the recommendation that subsequent management now
or 5. should be directed to the cancer. As for any examination
There is one other potentially confusing situation in- in which there is more than one finding, the management
volving the use of assessment category 6. This occurs section of the report might include a second sentence that
when, prior to complete surgical excision of a biopsy- describes the appropriate management for the finding(s)
proven malignancy, breast imaging demonstrates one or not covered by the overall assessment.
more possibly suspicious findings other than the known
cancer. Because subsequent management should first
evaluate them as yet undetermined finding(s), involving Suggested Reading
additional imaging, imaging-guided tissue diagnosis or
American College of Radiology (ACR) (2013) ACR BI-RADS,
both, it must be made clear that in addition to the known 5th Ed.
malignancy there is at least one more finding requiring DOrsi CJ, Mendelson EB, Morris EA et al (2012) Breast imaging
specific prompt action. The single overall assessment reporting and data system: ACR BI-RADS. American College
should be based on the most immediate action needed. If of Radiology, Reston, VA.
a finding or findings are identified for which tissue di- American College of Radiology (ACR) (2013) ACR BI-RADS
Magnetic Resonance Imaging, 2nd Ed.
agnosis is recommended, then a category 4 or 5 assess- Morris EA, Ikeda DM, Lehman C et al (2012) Breast Imaging Re-
ment should be rendered. If at additional imaging for porting and Data System. American College of Radiology, Re-
finding(s) other than the known malignancy, it is deter- ston, VA.
IDKD 2015-2018
Recent Developments in Breast Ultrasound with a Special Focus on

Shear-Wave Elastography
Claudia Kurtz
Institute of Radiology, Cantonal Hospital Lucerne, Switzerland
Introduction Tissue Harmonic Imaging

Since the first use of breast ultrasound by Wild and Reid [1] Despite technical advances, b-mode images with funda-
in 1953, it has taken half a century to achieve a level mental frequency contain artifacts that degrade image
of ultrasound technology that allows it to be considered quality [7]. High-frequency imaging in particular is often
as a multimodality imaging tool for use at the highest lev- responsible for the internal echo artifacts of otherwise
el in breast diagnostics. Ultrasound has been described to simple cysts. By filtering (away) the fundamental fre-
detect mammographically occult breast cancer [2]. In- quency responsible for reverberations and speckle arti-
deed, mammography and ultrasound are complementary facts, artifact-reduced higher frequencies, so-called har-
imaging tools for breast examination in everyday prac- monics, are generated. In addition, tissue harmonic imag-
tice. The main indications for breast ultrasound are mam- ing (THI) helps to increase lesion conspicuity by im-
mographically dense breasts, unclear or suspicious find- proving image contrast and lateral resolution [8, 9], re-
ings on mammography, patients with breast complaints, sulting in the following advantages :
preoperative localization of breast cancer, aftercare of 1. Isoechoic lesions within fatty breast tissue on b-mode
breast cancer patients, evaluation of high risk patients (fa- can be visualized with better contrast if THI is used
milial history of BRCA 1 and 2 mutation), and second- (Fig. 1a, b)
look sonography after magnetic resonance imaging 2. Complicated cysts with internal echoes on b-mode
(MRI) [3]. appear anechoic on THI (Fig. 1c, d)
Originally, in the early Breast Imaging Reporting and 3. Echogenic parts (e.g., septal structures) are accentuat-
Data System version (BIRADS, 4th edition) of the Amer- ed (Fig. 1c, d).
ican College of Radiology (ACR), mainly b-mode fea- As a shortcoming, THI is not applicable to deeper re-
tures of mass lesions were used to describe and classify gions and macromastia, since due to their physical prop-
the risk of a lesions malignancy [4]. Masses were char- erties harmonics can only be generated in more superfi-
acterized according to their shape, orientation, margin, cial layers.
boundary, echo pattern, posterior acoustic features, sur-
rounding tissue features, presence of calcifications, and
the presence of vascularity. Over the last decade, howev- Color Doppler
er, improved spatial resolution with higher-frequency
transducers and further technical developments, such as The development and growth of tumors is predominantly
compound imaging, tissue harmonic imaging, color based upon neovascularization as a result of angiogenin
Doppler, 3D imaging, and elastography, have largely con- production by the tumor cells [10]. This feature is used to
tributed to an increase in sonographic sensitivity and visualize malignant lesions on MRI and color Doppler ul-
specificity [5]. These newer technical components play a trasound. Numerous qualitative (morphological) and
vital role in lesion interpretation and have been integrat- quantitative criteria, such as the resistance index (RI), the
ed in the latest (5th) edition of BIRADS [6]. pulsatility index (PI), and systolic peak flow velocity
This chapter focuses on harmonic imaging, color (Vmax) have been described with varying diagnostic sig-
Doppler, and elastography, describing the particular ben- nificance [11-13]. A larger number of penetrating vessels
efits and limitations of each approach. Elastography, a and higher values of RI, PI, and Vmax were considered as
more recent method, is discussed in detail, including the indicators of malignancy [14]. However, these flow-para-
possibilities to reduce false-positive and false-negative meters are of less significance because of a large overlap
findings. between slowl-growing cancers with low vascularity and

256 C. Kurtz
a b
c d
Fig. 1 a-d. Advantages of tissue harmonic imaging (THI) (a,

c) compared to normal b-mode (b, d). Isoechoic fibroade-
noma with lower visibility on normal b-mode (b) and bet-
ter conspicuity on THI (a). Complicated cyst with internal
echoes and less clearly visible septal structures (d); on
THI, the internal part becomes anechoic and the septal
structures more accentuated (c)
fast-growing cancers with higher vascularity. Moreover, larity, higher vascularity in the periphery, and peripheral,
they are not reproducible when the examination condi- marginal vessels connecting with internal vessels, signif-
tions differ (device, choice of flow parameter, location of icantly differed from malignant patterns. Typical of ma-
measurement). Additionally, flow measurements are lignant lesions were radially aligned external vessels, ra-
time-consuming and require vast experience. By contrast, dial internal vessels connected with radial external ves-
morphological parameters are easier to assess, more re- sels, and a higher degree of internal than external vessels.
producible, and of a higher diagnostic yield [15]. Thus, It is worth mentioning that when using the Doppler func-
Madjar recommended simply observing the presence and tion, it is essential to apply only a slight pressure on the
number of vessels. Setting the cut-off for the depiction of probe and to keep the field of view (FOV) very small,
vessels at 2, he was able to reach a sensitivity and thus obtaining better Doppler signals (Fig. 3).
specificity for the detection of malignancy of 90% and To summarize, the essential features to be applied
93%, respectively [15]. Moreover, vascular pattern helps when evaluating a lesion with color Doppler are the pres-
to predict the probability of a lesions malignancy if used ence of vascularity, the number of vessels, and the vessel
together with other criteria [14]. In this context, it can be pattern. However, vascular categorization is not always
helpful to consider the exact course of the vessels adja- applicable due to poor vessel visualization and, even
cent to the lesion, as performed by Svennson [16] more importantly, vascular characterization can only be
(Fig. 2). Thus, benign vascular patterns, such as avascu- regarded as an adjunct to other b-mode features.
a b
Benign Malignant
radial extern radial intern radial externintern

Fig. 2 a, b. Vascular pattern with color Doppler to estimate the risk of malignancy, according to Svennson: vessels in benign lesions tend to
be more in the periphery, partially connecting with internal vessels (a), whereas vessels in malignant lesions have a radial pattern either in
the outer or the inner part and a higher degree of internal than external vessels (b).
Recent Developments in Breast Ultrasound with a Special Focus on Shear-Wave Elastography 257
a b
Fig. 3 a, b. Demonstration of the use of the color Doppler function in a strongly vascularized cancer lesion. A small region of interest, just
around the lesions, should be chosen to achieve better Doppler signals. Only very slight pressure should be applied on the probe (a). If
higher pressure is applied the Doppler signals, and thus vascularization, cannot be depicted (b)
Elastography Free-Hand Strain Elastography
Ultrasound elastography is a recently introduced exami- The manual compression applied on the probe can be de-
nation technique. In response to an external force, breast scribed as rapid and sinusoidal movements of the hand.
tissue is displaced, with stiff tissue being less displaced The induced tissue movements between the frames are
than soft tissue. Carcinomas exhibit an increased stiffness calculated by a dedicated software, and the resulting sig-
and thus less tissue displacement than normal breast tis- nals registered before and after tissue displacement are
sue, and this mechanical characteristic is used to differ- transformed into b-modes images. Strain data are dis-
entiate benign from malignant lesions. Thus, elastogra- played as either a black/white elastogram, with black rep-
phy is primarily a characterization rather than a detection resenting a stiff area and white a soft area, or a color map
tool, due to following physical properties: elasticity can [19]. Color-coding is not uniform among the manufac-
generally be seen as the relation of necessary stress (pres- turers, thus partially aggravating the interpretation. The
sure) to the relative change in length obtained (strain). It most commonly applied color map, primarily used by the
describes how much pressure has to be applied to elasti- Hitachi ultrasound device, is the one developed by Itoh et
cally deform a tissue, which is dependent on its intrinsic al. [20]. This elasticity score (the Tsukuba score, named
elasticity (Young`s modulus of elasticity) [17]. Young`s after the clinic where the work was conducted) has been
modulus of elasticity can therefore be considered as a de- validated in large series of histologically proven breast le-
scription of tissue elasticity according to the formula: sions and is based upon a 5-point scale (Fig. 4), with the
E / (elasticitypressure applied to the breast/ breast risk of malignancy increasing from a score of 1 (be-
tissue deformation under pressure). nign) to a score of 5 (malignant). Numerous studies
This differentiation criterion of absent strain (in- have shown that the additional use of an elasticity score
creased stiffness) has been evaluated in terms of its addi- increases specificity from 5683% to 6887% compared
tional benefit to normal b-mode features in a series of to normal b-mode images [21-23]. Another helpful tool is
studies, which demonstrated a general increase in speci- to compare the b-mode image with the elastographic im-
ficity [18]. Nevertheless, the conditions of application age: benign lesions on the elastographic display are typi-
and interpretation considerably vary between the differ- cally identical in size or smaller than on b-mode display,
ent elastography software and devices. Essentially, two whereas malignant lesions appear to be larger on elastog-
main elastography techniques can be distinguished: free- raphy than on b-mode display.
hand strain elastography and shear-wave elastography. Nevertheless, the main disadvantage of strain elastog-
Strain elastography can be further subdivided into real- raphy is that it is strongly operator-dependent such that
time-elastography (e.g., Hitachi) and tissue-Doppler/ tis- large images may vary widely [23, 24]. Attempts have
sue strain imaging (e.g., Toshiba), whereas shear-wave been made to reduce the interobserver variability by im-
elastography can be subdivided into genuine shear-wave plementing semi-quantitative region of interest (ROI)
elastography (e.g., Supersonic) and acoustic radiation measurements, such as the strain-ratio (strain of sur-
force impulse (AFRI) technology (e.g., Siemens). In the rounding fat tissue/ strain of the lesion to be investigat-
following, only real-time elastography, as the most com- ed). Lesion assessment was further improved by the ad-
monly applied form of strain elastography, and genuine ditional use of a cut-off value, which can vary between
shear-wave elastography are discussed in detail. 2.27 and 4.3 [21, 25, 26]. Values below the cut-off value
258 C. Kurtz
Tsukuba Score
1
benign
Tsukuba Score
2
benign
Tsukuba Score
3
probably benign
Fig. 4. Tsukuba elasticity score to es-

timate the risk of a lesion of being
Tsukuba Score malignant. 1: lesion entirely green
4 (same elasticity throughout the le-
suspicious sion). 2: blue and green mosaic (most
of the lesion deformable). 3: de-
formability only in the periphery of
the lesion. 4: blue lesion (no de-
Tsukuba Score formability throughout the entire le-
5 sion). 5: lesion and adjacent tissue are
highly suspicious blue (no deformation of the lesion or
the adjacent tissue).
indicate a benign lesion whereas values above the cut-off pression/decompression, and angulation of the probe.
indicate a suspicious lesion. Although a certain improve- Hence, misinterpretations are possible by improper com-
ment in interobserver agreement [21] and accuracy [25] pression, deeply located lesions (3 cm), large lesions
has been obtained by the strain-ratio compared to the ba- (especially lesions larger than the FOV), non-perpendic-
sic Tsukuba-elastography scoring, the difficulty in accu- ular orientation of the probe, and if the lesions slides out
rately assigning a lesion to a certain category remains, of the FOV. When drawing the FOV, it is essential that the
since strain-ratio measurements are based upon the indi- lesion is surrounded by sufficient adjacent tissue to avoid
vidually generated elastography image. images of poor quality and misleading color coding; thus,
Moreover, free-hand elastography requires a certain it is advisable to draw the FOV as large as possible (from
training phase to learn the adequate manual skills to be the subcutaneous fat layer to the superficial fascia of pec-
applied [19]: pressure on the probe, frequency of com- toral muscle) (Fig. 5).
a b
Fig. 5 a, b. Demonstration of improper field of view (FOV) placement for strain elasticity measurements (a, b) of a hypoechoic lesion with
posterior shadowing on b-mode (a). The originally placed FOV covers only the lesion; thus, its estimation using the obtained color map re-
mains difficult (b). For correct calculations, the lesion has to be surrounded by enough adjacent tissue. Therefore, the size of the FOV
should reach from the subcutaneous fat layer to the superficial fascia of pectoral muscle (red rectangle in b)
Shear-Wave Elastography shear-wave speed can be located either in the center or

at the margin of the lesion. There are two theories ex-
In shear-wave elastography, unlike the method described plaining the absence of shear waves in the lesion`s cen-
above, mechanical vibrations are generated by an ter: (1) the shear-wave speed is too high to be captured
acoustic radiation impulse induced by the ultrasound by the probe and (2) the ultrasound beam to capture the
probe itself. This push impulse generates slowly propa- shear waves cannot penetrate the deeper parts of scir-
gating shear waves at a low-frequency (50 Hz) and at rhous cancer [28]. It is worth mentioning that there are
different depths. The ultrasound probe is equipped with different modes of lesion visualization (Fig. 6b, c). Thus,
an ultrafast acquisition frequency (5000 frames/s) and in penetration rather than standard mode, the amplitude
captures the propagation of shear waves. The propagation of the signal and the signal-to-noise ratio (SNR) are in-
speed is used to calculate Young`s modulus of elasticity creased based upon constructive interfaces and color-
according to the formula: Eacoustic radiation impulse/ coding of the lesion can thus be modified, e.g., from no
strain3 3 p v2 (m/s) where is the shear wave, p is shear waves in the center of the lesion with standard
a constant and v the shear wave speed. mode to a certain color-coding assigned with penetration
Stiffness information can be displayed in kPa based mode.
upon ROI measurements (e.g., maximum elasticity, Emax,
in kPa). Additionally, images can be evaluated on a real- Interpretation
time color map linked to the value in kPa, ranging from
0 to 249 kPa (Ecol ) (Fig. 6). Benign lesions (viscous cysts, fibroadenomas) and nor-
Given that the probe is constantly held using only a mal soft tissue are generally displayed in blue, but inter-
light pressure, interobserver agreement is good, or at pretation difficulties may occur, as non-viscous cysts do
least much better than strain imaging [27]. As shear not support shear waves (Fig. 7a, b). Thus, absent shear
waves propagate quickly in stiff tissue and slowly in soft waves in the center of a lesion have to be carefully as-
tissue, higher shear-wave speeds are typical of cancer sessed, as both malignancy and benign findings are pos-
(red colorhighly suspicious). The color indicating sible (Figs. 6, 7).
a b
Fig. 6 a-c. Color spectrum of shear waves with quantitative parame-

ters of maximum elasticity Emax (kPa) and qualitative parameters
of elasticity color Ecol (a) to characterize the depicted cancer
lesion. The red color at the margin of the cancer lesion along with
the measured Emax of 156 kPa (region of interest within the red
area) indicates increased stiffness. With standard mode (b) no
shear waves are visible in the center of the lesion, which suggests
that their shear wave speed is extremely high. When penetration
mode (c) is used, shear-wave signals are increased and shear waves
become visible even in the center of the lesion, even though the
stiffest part is still at the margin of the lesion
260 C. Kurtz
a b
Fig. 7 a, b. Visualization of shear waves in cystic lesions. Viscous cysts (a) support shear waves, thus demonstrating a blue color. Non-
viscous cysts (b) do not support shear waves, resulting in a black/absent shear-wave signal. As no increased stiffness is observed at the
margin of the lesion, it can still be classified as benign
Although shear-wave images can be interpreted more Stronger (pre-)compression: Overly strong pressure
reliably than strain elastography, difficulties remain in applied on the probe will cause the peak in the generated
image generation and assessment. shear waves to occur at an earlier time, thus simulating a
higher shear-wave speed, as observed in cancers (Fig. 8).
False-Positives and Strategies to Avoid Them Therefore, it is crucial to use only slight pressure, except
the lesion is small (5 mm ), since small lesions might
False positives can be generated by: (1) poorly de- be missed if insufficient pressure is used.
formable lesions (e.g. scar, larger calcifications, fibrous Insufficient FOV: As with strain imaging, the FOV
fibroadenoma, focal strong fibrosis); (2) too-strong com- should be as large as possible, with sufficient adjacent
pression; and (3) insufficient normal tissue surround- normal tissue surrounding the lesion. This is important
ing the lesion (too-small FOV). because the propagation of shear waves in the surround-
Poorly deformable lesions: This feature is peculiar to ing tissue is more visible such that misinterpretation will
the lesion and thus other imaging modalities, including be unlikely. In particular, artifacts (from too-strong pre-
mammography, b-mode, Doppler function, and compar- compression) arising between the subcutaneous fat layer
isons to a preceding imaging study of the same lesion and the lesion are easier to perceive (vertical-cord arti-
have to be taken into account. fact). The 4-pattern visual evaluation system described by
a b c d
Fig. 8 a-d. False positive findings by applying high pressure on the probe. Left picture (a) indicates correct pressure, since no vertical-cord
artifacts within the subcutaneous fat layer are seen. The subcutaneous fat layer is blue (white arrow). b-d With increasing pressure on the
probe, higher shear wave speed is simulated thus producing a color coding typical of cancer. The green-yellow background noise within
the subcutaneous fat layer indicates the artifact induced by too strong (pre-)compression (white arrow)
a Pattern 1: homogeneously blue (no findings)
b Pattern 2: color, that differs from the color

around the lesion, observed at the margin or
the interior of the lesion and extends in
vertical cords beyond the lesion (artifact)
c Pattern 3: localized colored area at the margin

of the lesion (positive finding)
Fig. 9 a-d. Four-pattern visual evaluation of

shear waves according to Tozaki as a method
to avoid misinterpretations. a Pattern 1: ho-
mogeneously blue (no findings). b Pattern 2:
d Pattern 4: colored areas in the interior of the color that differs from the color around the
lesion and heterogeneous (positive finding) lesion observed at the margin or interior of
the lesion and extending in vertical cords be-
yond the lesion (artifact). c Pattern 3: local-
ized, colored area at the margin of the lesion
(positive finding). d Pattern 4: colored areas
in the interior of the lesion and heteroge-
neous (positive finding)
Tozaki [29] is very helpful in better differentiating be- Lesions larger than the FOV: Although the reasons are
tween real positive findings and artifacts (Fig. 9). still unclear, it seems to be related to the fact that the le-
If a pattern-2 vertical- cord artifact (Fig. 8 b-d) is sion is not surrounded by sufficient normal tissue such
observed during real-time elastography, then less pressure that only differences in the elasticity the lesion and the
should be applied until the artifact disappears (Fig. 8a). surroundings are too small [18].
Only if a colored area at the lesion`s margin persists can Small lesions: Normal (pre-)compression can be insuf-
the lesion be assumed to have increased stiffness. ficient to generate abnormal shear waves, given that the
area of stiffness is too small. Applying a higher (pre-)com-
False-Negatives and Strategies to Avoid Them pression on the probe often allows the visualization of
shear waves [19], even if the degree of stiffness is subtle.
False negatives occur due to the following: (1) deeply lo-
cated lesions (2.53 cm); (2) as a reflection of the can- Diagnostic Value of Shear-Wave Elastography
cer type (high stiffness in scirrhous cancer, less stiffness
in mucinous cancer or ductal carcinoma in situ); (3) le- A previous large multicenter trial [30] evaluated diverse
sions larger than the FOV (large single lesion, diffusely parameters of shear-wave elastography in terms of highest
infiltrating cancer); (4) small lesions (5 mm) diagnostic value if used in addition to the normal
Deep lesions: At a depth of approximately 2.53 cm, BIRADS classification. The results showed that the quali-
shear waves are hardly visible. Better visibility can some- tative parameter Ecol (observed color in or around the le-
times be gained by rotating the patient, so that the lesion sion) had the highest accuracy (AUCBIRADSEcol
under investigation is possibly displaced to a more su- 0.971), followed by the quantitative parameter of maxi-
perficial layer. mum elasticity Emax (kPa) (AUCBIRADSEcol 0.962).
Cancer type: If shear waves are absent on the standard For this reason, only the observation of the displayed col-
mode, they are more likely to be visualized using the pen- or is of major significance and might be sufficient for le-
etration mode (increased amplitude of the shear waves) sion assessment. The same study found that masses with
(Fig. 6). Nevertheless, in certain cancer types abnormal Emax3080 kPa had a malignancy rate of 8.9% and those
shear waves cannot be depicted; in such cases, other with Emax80 to 160 had a malignancy rate of 39.9%.
imaging modalities or further ultrasound techniques/fea- At an Emax 60 kPa, 74.1% of the masses were malignant.
tures have to be considered. In a preceding multinational study, shear-wave elastography
262 C. Kurtz
Table 1. Shear wave parameters for upgrading BIRADS 3 respectively downgrading BIRADS 4 a lesions whith an increase in specificity
and no change in sensitivity according to Berg [30]
BIRADS 3 parameters for BIRADS 4 parameters for Increase in
BIRADS upgrading BIRADS downgrading specificity
Ecol red Ecol black to light blue 61.178.5
Irregular shape on SW elastography oval shape on SW elastography 61.169.4
Emax160 kPa Emax 80 kPa 61.177.4
was shown to be particularly helpful in borderline lesions lesion (THI, compound imaging, color Doppler, 3D imag-
(between benign and malignant) according to b-mode cri- ing, elastography). But depending on the chosen ultra-
teria. By using these elastographic features as an adjunct to sound device, only a certain number of technical features
b-mode features, these lesions could be more accurately will be available with different diagnostic value. Irrespec-
assigned to either BIRADS 3 or 4 [30]. Initially classified tive of the technical component is utilized, ultrasound al-
BIRADS 4a lesions with a lack of stiffness were more fre- ways has to be considered in the context of further imag-
quently benign, and initially classified BIRADS 3 lesions ing modalities or technical components. This chapter has
with increased stiffness were more often malignant. With focused on THI, color Doppler, and elastography, as fast
the use of certain parameters for upgrading BIRADS 3 le- and easy methods that are also very helpful in lesion de-
sions and downgrading BIRADS 4a lesions, specificity tection and differentiation. In particular, shear-wave elas-
could be increased while maintaining sensitivity (Table 1). tography is considered a promising method because it is
The conclusion would be that unclear findings, e.g., a less operator-dependent than strain elastography and has a
complicated cysts planned for biopsy, could be more fre- significant increase in specificity. The major benefit is
quently sent to follow-up, and initially classified BIRADS seen in lesions primarily categorized as BIRADS 3 or 4a,
3 lesions with an increased stiffness but in fact malignant which can be more accurately assessed based on their
could be sent earlier to biopsy. However, shear-wave elas- elastographic features. In this regard, patients with suspi-
tography should not be used to change the strategy in typ- cious lesions (BIRADS 4a characterization without shear-
ical BIRADS 2 , BIRADS 4c and BIRADS 5 lesions, as it wave elastography) with benign features on elastography
might lead to misguided decisions. (dark blue color within the lesion and its surroundings)
Another study [31] was performed to exactly deter- could be spared from biopsy and instead be sent to follow-
mine the benefit of shear-wave elastography in ultra- up. Conversely, unclear lesions (BIRADS 3 characteriza-
sound-characterized BIRADS 3 lesions (primarily char- tion without shear-wave elastography) with suspicious
acterized without elastographic features). The aim was to elastographic features could be sent for biopsy with high-
search for features that would help to not send the patient er confidence. To reduce misinterpretations and avoid
to follow-up but rather to reclassify the lesion to a new misguided decisions, it is essential to be familiar with the
BIRADS 2 without downgrading a malignant lesion to reasons for false-positives and false-negatives. It is also
new BIRADS 2. Only the color (black to dark blue) and important that every imaging finding be evaluated in a
Emax 20 kPa were sufficiently safe and helpful criteria larger context, such as clinical complaints, findings in
to downgrade a benign-appearing BIRADS 3 lesions to a previous examinations, age of the patient, individual risk
new BIRADS 2, thus sparing patients from short-term situation, and comparison with other imaging methods.
follow-up.
Further advantages of shear-wave elastography cur-
rently being investigated or still to be evaluated are its ap- References
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IDKD 2015-2018
Magnetic Resonance Imaging of Breast Implants and the Reconstructed

Breast
Isabelle Thomassin-Naggara1, Michael Atlan2, Jocelyne Chopier1, Emile Darai3
1 Department of Radiology, Hopital Tenon - APHP, Paris, France
2 Plastic Reconstructive and Aesthetic Surgery Unit, Hopital Tenon - APHP, Paris, France
3 Department of Gynecology and Obstetrics, Hopital Tenon - APHP, Paris, France
Introduction shells (textured or smooth). The silicone used is cohesive,

to maintain the shape of the implant in the body and to
For many years, breast augmentation was exclusively ob- avoid silicone migration in case of rupture.
tained by the use of breast implants. However, during the Saline- or silicone-containing gel breast prostheses are
last 20 years, the multiplication of plastic surgical treat- still the two main types of implants, although there are
ments has been such that several different methods of other, albeit rarely used, implant materials, such as hy-
breast augmentation are now available. In asymptomatic drogel. The silicone used to fill the envelope comes main-
women with breast implant abnormalities detected with ly from two manufacturers. More than 25% of poly-im-
conventional imaging, as well as in symptomatic women plant prostheses (PIP) are filled with non-medical-grade
with breast implants or a reconstructed breast, magnetic silicone, which is less cohesive at body temperature
resonance imaging (MRI) may be the best imaging tech- and do not include an anti perspiration barrier; thus in
nique in the absence of a consensus on imaging follow-up. case of rupture they have a higher risk of an uncontrolled
dispersion [2-4].
Different surgical approaches are used to place the im-
Breast Implants plant in the breast (hemi-areolar, sub-mammary, or axil-
lary incisions), with three possible locations, or pockets,
General Considerations relative to the position of the pectoralis major muscle:
pre, retro-pectoral, or dual plane (the upper half of the
There are two main types of breast implants: saline im- implant under the muscle and the lower half under the
plants and silicone implants, which are used in similar gland). When the implants are positioned in the breast, a
proportions according the U.S. Food and Drug Adminis- foreign-body reaction is induced and a fibrous capsule
tration (FDA) (FDA Update on the Safety of Silicone corresponding to a second, frequently very soft, envelope
Gel-Filled Breast Implants. http://www.fda.gov/). Most is created. However, this capsule may undergo capsular
breast implants have a single compartment that is filled contracture, thereby becoming rigid and sometimes
with a saline solution or with silicone, or two such com- painful and causing a deformation of breast shape. For re-
partments. During the last 50 years, the breast implant in- construction, surgeons typically use the previous scar of
dustry has evolved. Silicone of the first generation was the mastectomy, placing the implant under the pectoralis
dense and viscous, with a very thick shell, and did not ac- major or, in some cases, under the pectoralis minor or
curately mimic breast tissue. In the second generation of serratus anterior muscle. New devices such as biologic
implants, the filler material was a less viscous gel (with matrix are used to cover the implant in the lower aspect
less cross-linking) and the shell was thinner. However, that is not covered by muscle [5].
because of a high rate of rupture and leakage, the need Patients with breast implants are vulnerable to a vast
for a third generation implant soon became obvious. In array of complications that should be familiar to the ra-
this attempt, the gel was more viscous and the envelope diologist, including hematoma, infection, implant rota-
was thicker (textured or smooth), with a barrier within tion, pain, change of breast size or shape, capsular contrac-
the shell to avoid perspiration of the gel [1]. The last gen- ture, implant rupture, and the extrusion of soft-tissue sili-
eration of implants, still in use today, is a stable implant, cone. The two most frequent complications are capsular
with a variety of shapes (anatomic or round implant) and contracture and implant rupture. The physiopathology of

Magnetic Resonance Imaging of Breast Implants and the Reconstructed Breast 265
capsular contracture is unclear but probably involves sub- Acquisition Technique

clinical infections with, e.g., Staphyloccus epidermidis or
Pseudomonas acnei [3, 6], silicone fluid bleed, hema- Using MRI, both the axial and the sagittal planes should
toma, glove-talc reaction, implant rupture, and foreign be imaged because every rupture suspected in one plane
body reaction to the silicone elastomer shell. Capsular must be confirmed in its perpendicular plane [10]. Spe-
contracture may occur within the first month after cial attention must be paid to ensure that the field of
surgery or several years later. Its occurrence usually cor- view includes the axillary regions. The imaging protocol
relates with the age of the implant and it is most fre- must include sequences that suppress or emphasize the
quently observed after 10 years. In 2011, the FDA re- signal from water, fat, or, especially, silicone, i.e. T2-
ported a possible association of breast implants with weighted fast spin-echo, T1-weighted sequences, and, if
anaplastic large cell lymphoma [7], but the relationship the implant contains silicone, a water-fat suppression se-
has yet to be confirmed in a prospective study. quence (silicone only), to differentiate water from sili-
To enhance the cosmetic results of implant-based re- cone since both appear bright on T2-weighted sequences
constructions, a fat graft procedure can be performed in (Fig. 1).
the subcutaneous plane above the gland, to avoid ripples
and implant visibility. MR Analysis
MR Findings In the Breast Imaging-Reporting and Data System (BI-

RADS) lexicon published in 2013, Chapter IV is devoted
MRI of breast implants has the highest sensitivity and to describing breast implants, in the section on MRI. The
specificity for the detection of silicone implant rupture MRI report should include implant type (silicone or
and is thus considered the gold standard in this specific saline content), location (pre or retropectoralis), contour
setting. MRI is not performed systematically in the fol- (regular, focal budge, ruptured), and the location of the
low-up of patients with breast implants. Rather, it is in- silicone. Intra-capsular rupture is observed in 80% and
dicated if the patient is symptomatic (including pain, extra-capsular rupture in 20% of patients with silicone
burning, or a mass in the implant-bearing breast or the gel implants The combination of five different features
surrounding tissue). The patient may note hardening or needs to be analyzed to diagnose a rupture: (a) the fi-
softening of the implant [8] with the degree of hardness brous capsule, (b) the implant envelope, (c) the signal of
defined according to the Baker classification [9]. MRI is the periprosthetic fluid, (d) the location of the detected
also usually a second-line technique after ultrasonogra- silicone, and (e) the overall implant shape (Table 1).
phy, as recommended by the FDA, because of its high The radial folds are illustrated in Fig. 2. Water droplets
sensitivity (7397%) and specificity (7397%) in diag- inside breast implants are seen on water-specific images;
nosing implant rupture. In patients with silicone breast they may be normal (due to the injection of silicone gel
implants, an implant rupture should be diagnosed as during surgery, for example) or associated with implant
soon as possible so as to limit the risk of capsular con- rupture. The presence of silicone within axillary lymph
tracture. nodes does not necessarily imply implant rupture.
Water Silicone Fat Tissue
T2-weighted sequence
(water-specific images)
T1-weighted sequence
(fat-specific images)
Silicone only (turbo inversion

recovery magnitude, TIRM;
silicone-specific images)
Optional: T1 fast-spin
gadolinium-weighted sequence
Fig. 1. MRI standard proto-
col and findings according
to tissue characteristics
266 I. Thomassin-Naggara, M. Atlan, J. Chopier, E. Darai
a b
Fig. 2 a-d. Radial folds. a, b T2-weighted sequence showing dark

lines with different signal intensities inside and outside the implants.
Periprosthetic fluid displays a high T2-weighted signal intensity.
c, d Silicone-only sequence shows the absence of silicone outside
the prosthesis
Table 1. Implant analysis using magnetic resonance imaging

Intact implant Rupture
Normal Capsule contraction Intracapsular Extracapsular rupture
Fibrous capsule Not seen Focal bulge Undisrupted Seen
Disrupted
Implant envelope Smooth, or radial fold Smooth, or radial folds Key-hole, tear drop, noose Linguine sign
(with dark ball end) (with dark ball end) (with white ball end)
Linguine sign
Periprosthetic fluid Signal Thin Thin or thick Thick Absent
Water Water Silicone* Silicone*
Silicone location* Only inside the implant Only inside the implant Outside the implant Outside the implant
envelope envelope envelope envelope and fibrous
Inside fibrous capsule capsule
Overall implant shape Normal Abnormal Normal Abnormal (extruded
silicon globe separated
by a dark line)
*In the case of silicone breast implants
Autologous Reconstruction skin-and nipple-sparing mastectomies that can be com-

pleted with silicone-filled implants, an autologous flap
During the last 20 years, oncological, reconstructive, and (pedicled or free flaps), or by autologous fat grafting. In
cosmetic surgery techniques have evolved considerably, certain oncological or prophylactic cases, a skin-sparing
with the development of novel surgical approaches and or nipple-areola-complex-sparing mastectomy may allow
enhanced cosmetic results by conserving most of the skin The potential complications of autologous reconstruc-
envelope. The need for systematic imaging follow-up of tion include partial or total necrosis, pulmonary em-
these patients is unclear, including for patients with on- bolism, edema, hematoma, and seroma. After 12 years,
cological indications [11, 12]. Normal mammary gland is steatonecrosis (including potential sclerosing retraction
found in about 60% of patients after a skin-sparing mas- and calcification) may occur, with the risk depending on
tectomy, according to Tokin et al. [13]. In skin- and nip- the quality of the anastomosing pedicle. According to
ple-sparing mastectomy performed in oncology patients, Garvey et al., the rates of fat necrosis are higher for the
it should be noted that the risk of local recurrence corre- TRAM flap (58.5%) than for the DIEP flap (17.7%) [16].
lates with the margin status and the type of mastectomy. Moreover, abdominal hernias occur more frequently in
According to Kroll et al. [14], regardless of the recon- patients receiving a TRAM flap (16%) than a DIEP flap
struction technique, this risk is 46% at 5 years, similar (1%). Together, these considerations account for the pref-
to that in the group of patients not undergoing recon- erence for and further refinement of DIEP rather than
struction. Depending on the location of the recurrence, TRAM reconstructions [18, 19].
the patient may or may not be symptomatic. In 5070%
of cases, the recurrence develops in the anterolateral part MR Findings
of the reconstructed breast and is easily detected by the
clinician, but in 30% of cases the recurrence may be in In the follow-up of patients with a reconstructed
the axillary region or within the thoracic wall, which in breast(s), MRI is not systematically performed except in
either case is very difficult to diagnose clinically. When patients who are at high risk of breast and ovarian cancer.
the patient is symptomatic, the radiologist must be able to The radiologist may have to analyze the autologous re-
distinguish normal imaging features from features of ma- construction if the patient undergoes MRI for the con-
lignancy, which as a prerequisite requires an awareness of tralateral breast or if there is a suspicion of recurrence in
the different types of breast reconstruction options. the reconstructed breast. At MRI, the volume of the flap
decreases over time such that eventually it is composed
Autologous Flaps only of fat or muscle or of a fatty component, depending
on the type of autologous reconstruction. The radiologist
General Considerations should examine the remaining mammary gland and its lo-
cation to help the clinician to orient the sites of normal
The two most common types of conventional pedicled tissue and/or correlate normal tissue with a potential ab-
flaps are the latissimus dorsi myocutaneous (LDM) flap normality at clinical examination.
and the transverse rectus abdominis myocutaneous
(TRAM) flap; the latter is harvested from excess abdom- Autologous Fat Grafting
inal tissue. These autologous breast reconstruction meth-
ods allow the insertion of a muscle with a skin island and This technique of breast augmentation consists of har-
are mainly indicated when there is a lack of skin after vesting the fat by classic liposuction followed by treat-
conservative mastectomy. The LDM flap is vascularized ment of the harvested tissue (centrifugation, washing,
by the thoracodorsal pedicle whereas the epigastric supe- and/or filtration) to enhance the viability of the
rior vessels supply the TRAM flap. These flaps include adipocytes and mesenchymal stem cells, before their in-
the muscle to insure good vascularization of the skin and jection into the breast. Autologous fat grafting can be
fat. By contrast, free flaps, such as the deep inferior epi- used as the sole technique in a reconstruction or it may
gastric perforator (DIEP) flap, are becoming increasing- be combined with autologous-tissue- or implant-based
ly popular because they are muscle-sparing. Autologous breast reconstructions. If the autologous fat graft tech-
tissue transfer involves complete separation of the donor nique is used by itself, e.g., in breast augmentation, all
tissue. In the case of the abdominal excess transferred in the layers of the breast can be injected: pectoralis major
the DIEP flap, a pedicle is dissected in the muscle, and muscle, the retropectoral space, above the gland, and
there is absolutely no muscle within the flap (hence the within the gland. When it is combined with another tech-
name perforator flap). The harvested tissue is then con- nique of breast augmentation, the lipoaspirate is mainly
nected to the recipient site by an anastomosis, with mi- injected into the subcutaneous space above the gland.
crosurgical sutures performed under the microscope: the
deep inferior vessels are ligated to the internal mammary Imaging Features
vessels lying under the cartilage of the third or fourth rib
[15]. The techniques required for perforator flaps are The classic MRI findings of a fat-injection site include
more complex, with a significantly longer operating time, hyperintensity on non-fat-saturated T1-weighted images,
than those involved in the placement of a conventional hypointensity on fat-saturated images, and hypointensity
pedicled flap [16, 17]. Other flaps that may be used are on T2-weighted images [15]. Three types of abnormali-
the superior inferior epigastric perforator (SIEP) flap, the ties as seen on MRI have been described:
superior gluteal artery perforator (SGAP) flap, and the 1. Oil cyst without any enhancement after gadolinium in-
inferior gluteal artery perforator (IGAP) flap. jection (BI-RADS 2) (Fig. 3)
268 I. Thomassin-Naggara, M. Atlan, J. Chopier, E. Darai
a b e
c d f
Fig. 3 a-f. Autologous fat grafting, oil cyst. Primary breast augmentation by transverse rectus abdominis myocutaneous (TRAM) flap com-
bined with autologous fat grafting. a Axial TSE T2-weighted sequence. b Axial EG T1-weighted sequence. c Axial Native EG T1 DCE
MR weighted sequence after the 24 after injection. d Axial Substracted EG T1 DCE MR weighted sequence after the 24 after injection.
e, f Sagittal Native EG T1-weighted sequence (upper and lower right). Magnetic resonance imaging shows the presence of a high T1 sig-
nal intensity without any wall enhancement in the posterior part of the breast corresponding to the location of autologous fat grafting
2. Complex cyst of fat necrosis that displays rim en- 7. Adrada BE, Miranda RN, Rauch GM et al (2014) Breast im-
hancement (BI-RADS 3) plant-associated anaplastic large cell lymphoma: sensitivity,
specificity, and findings of imaging studies in 44 patients.
3. Granuloma appearing as a heterogeneous mass con- Breast Cancer Res Treat 147:1-14.
taining inflammatory and fibrous tissue (BI-RADS 4). 8. Tolhurst DE (1978) Nutcracker technique for compression
In the third case, the detection of a small fatty compo- rupture of capsules around breast implants. Plast Reconstr
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sion technique for rupturing a contracted capsule around a
Cancer Recurrence Risk breast implant. Plast Reconstr Surg 58:137-141.
10. Ikeda DM, Borofsky HB, Herfkens RJ et al (1999) Silicone
According to the Society of Plastic Surgeons, in a report breast implant rupture: pitfalls of magnetic resonance imaging
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gous fat grafting does not affect radiologic follow-up and and ultrasound. Plast Reconstr Surg 104:2054-2062.
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is not associated with an increased risk of breast cancer breast cancer in reconstructed breasts using TRAM flap after
[20]. Long-term follow-up of these patients is ongoing. skin-sparing mastectomy: clinical and imaging features. Eur
Radiol 24:2220-2226.
12. Helvie MA, Bailey JE, Roubidoux MA et al (2002) Mammo-
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IDKD and Satellite

Diagnostic Imaging and

47th International Diagnostic Course

Pediatric Radiology Satellite Course Kangaroo

Breast Imaging Satellite Course Pearl

and additional IDKD Courses 2015-2018

presented by the Foundation for the

J. HODLER R.A. KUBIK-HUCH

G.K. VON SCHULTHESS CH.L. ZOLLIKOFER

ISBN 978-88-470-5751-7 ISBN 978-88-470-5752-4 (eBook)

Springer Milan Dordrecht Heidelberg London New York

Library of Congress Control Number: 2015931953

Springer-Verlag Italia 2015

Cover design: Massimiliano Pianta, Milan, Italy

Springer-Verlag Italia S.r.l., Via Decembrio 28, 20137 Milan

Springer is a part of Springer Science+Business Media (www.springer.com)

The International Diagnostic Course in Davos (IDKD) is a unique learning

Additional information on IDKD courses can be found on the IDKD website:

Computed Tomography Diagnosis and Management of Focal Lung Disease . . . . . . . . . 17

Approach to Imaging of Mediastinal Conditions in the Adult . . . . . . . . . . . . . . . . . . . . . . . 23

Current Approaches to Chronic and Acute Airway Diseases . . . . . . . . . . . . . . . . . . . . . . . . . . 29

Investigating a Child with a Cough: A Pragmatic Approach . . . . . . . . . . . . . . . . . . . . . . . 37

Thoracic Manifestations of Pediatric Systemic Diseases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 46

Modern Diagnosis in the Evaluation of Pulmonary Vascular Disease . . . . . . . . . . . . . . . . 57

Imaging of Pulmonary Infections . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 63

Imaging of Thoracic Trauma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 71

Plain Film and HRCT Diagnosis of Interstitial Lung Disease . . . . . . . . . . . . . . . . . . . . . . . . . 88

A Systematic Approach to Chest Radiographic Diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . 94

Diseases of the Chest Wall, Pleura, and Diaphragm . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 101

Pulmonary Manifestations of Systemic Diseases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 110

Incidental Findings on Thoracic and Cardiac CT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 129

Cardiac Magnetic Resonance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 134

An Integrative Approach to the Imaging of Ischemic Heart Disease . . . . . . . . . . . . . . . . . 143

Acute Aortic Syndrome: State-of-the-Art Diagnostic Imaging . . . . . . . . . . . . . . . . . . . . . . . 149

Interventional Techniques in the Thorax of Adults . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 157

Nonvascular Interventional Radiology of the Thorax . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 165

Dose-Lowering Strategies in Computed Tomography Imaging of the Lung

Nuclear Medicine Satellite Course Diamond

Staging, Restaging and Response Evaluation of Non-Small-Cell Lung Cancer . . . . . . . 183

How To Approach Incidental Findings on Computed Tomography Images of the

Integrated Cardiac Imaging . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 198

FDG PET/CT in the Imaging of Mediastinal Masses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 202

Integrated Cardiovascular PET/MR: Lessons Learned . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 209

Pediatric Radiology Satellite Course Kangaroo

Pediatric Cardiovascular Diseases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 226

The Radiology of Diffuse Interstitial Pulmonary Disease in Children: Pearls,

Neonatal Medical and Surgical Lung Diseases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 240

Breast Imaging Satellite Course Pearl

Breast MRI BI-RADS: Second Edition Highlights . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 250

Recent Developments in Breast Ultrasound with a Special Focus on Shear-Wave

Abbott G.F., 17 Kaufmann P.A., 198

Update in the Diagnosis and Staging of Lung Cancer

Introduction Clinical Manifestations of NSCLC

Diseases of the Chest and Heart 2015-2018,

soft-tissue component on CT [14, 15]. The frequencies of