Atlas of Nuclear Medicine in Musculoskeletal System

Atlas of Nuclear
Medicine in
Musculoskeletal
System
Case Oriented Approach

Seoung-Oh Yang
So Won Oh
Yun Young Choi
Jin-Sook Ryu
Editors
123
Atlas of Nuclear Medicine
in Musculoskeletal System
Seoung-Oh Yang • So Won Oh
Yun Young Choi • Jin-Sook Ryu
Editors
Atlas of Nuclear
Medicine in
Musculoskeletal System
Case-Oriented Approach
Editors
Seoung-Oh Yang So Won Oh
Department of Nuclear Medicine Department of Nuclear Medicine
Dongnam Institute of Radiological Seoul National University
and Medical Sciences Boramae Medical Center
Busan, Republic of Korea Seoul, Republic of Korea
Yun Young Choi Jin-Sook Ryu

Department of Nuclear Medicine Department of Nuclear Medicine
Hanyang University College of Asan Medical Center, University
Medicine of Ulsan College of Medicine
Seoul, Republic of Korea Seoul, Republic of Korea
ISBN 978-981-19-2676-1 ISBN 978-981-19-2677-8 (eBook)

https://doi.org/10.1007/978-981-19-2677-8
© The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature
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To the patients of all cases presented in this atlas textbook
Preface
Many nuclear medicine textbooks and case studies in forms of atlas have
been published so far, but there seems to be no in-depth nuclear medicine
imaging atlas focused on diseases of the musculoskeletal system. Since an
independent volume focusing on nuclear imaging of musculoskeletal disease
has been rare, publication of this book has its significance. In the attempt to
cover a specified area of musculoskeletal nuclear medicine, this book includes
a large number of correlative clinical images in musculoskeletal disorders.
Therefore, the authors wish to write about common cases as well as rare mus-
culoskeletal disorders in which various imaging techniques of nuclear medi-
cine (bone scan, SPECT, SPECT/CT, PET/CT, etc.) are useful based on the
author’s clinical experience in many different hospitals.
Nuclear medicine imaging in the musculoskeletal system with its ability to
assess disease activities has contributed to accurate diagnosis and improved
medical and surgical treatment. This book is intended to share the reading
experiences of the authors with nuclear medicine and radiology residents and
board specialists, and to help other clinicians who manage musculoskeletal
disorders such as orthopedic and rheumatology, through various cases of
musculoskeletal disorders to support their patient care. We aim to publish an
easy-to-read clinical atlas by organizing the proper roles and features of vari-
ous nuclear medicine imaging technics in musculoskeletal disorders by case-
oriented approach.
Please consider that the format of each chapter varies according to the
characteristics of each chapter title, and it is challenging to achieve complete
integrity by respecting the opinions of the authors of each chapter. The editors
wish to thank all contributors who spent much time and efforts in the prepara-
tion of their chapters. All the authors who participated in this issue are experts
in their field. We are indebted to them for their time and effort.
It is our expectation that the original purpose of publishing cases of mus-
culoskeletal disease including various nuclear medicine images experienced
in hospitals in Republic of Korea as a case-oriented textbook has been ful-
filled to a certain extent and becomes a helpful book to readers.
Busan, Republic of Korea Seoung-Oh Yang

Seoul, Republic of Korea So Won Oh
Seoul, Republic of Korea Yun Young Choi
Seoul, Republic of Korea Jin-Sook Ryu
vii
Contents
Part I Inflammatory and Infectious Disorders
1 Musculoskeletal Infections�� 3

Jung Mi Park, Jae Pil Hwang, Joon Ho Choi, Jang Gyu Cha,
and Yu Sung Yoon
2 Septic Arthritis �� 17
You Mie Han
3 Inflammatory Arthritis�� 29
Ju Won Seok
4 Non-inflammatory Arthritis: Osteoarthritis �� 41
Young-Sil An
5 Hypertrophic Osteoarthropathy�� 49
Young Seok Cho
Part II Traumatic and Circulatory Disorders
6
Fracture, Non-union, and Bone Graft�� 63
Soon-Ah Park, Su Jin Lee, Hye Joo Son, and Jung Mi Park
7
Stress Fractures and Sports Injury�� 73
Su Jin Lee
8 Osteonecrosis�� 83
So Won Oh, Jee Won Chai, and Jung Mi Park
9
Complex Regional Pain Syndrome�� 93
Joon-Kee Yoon, Soon-Ah Park, Young Seok Cho,
Jung Mi Park, and Jang Gyu Cha
Part III Spine and Joint Disorders
10 Spine�� 105
Tae Joo Jeon
11 Hip �� 115
Sun Jung Kim and So Won Oh
ix
x Contents
12 Knee Prostheses�� 131

Yoo Sung Song
13 Ankle and Shoulder �� 141
So Won Oh and Jee Won Chai
Part IV Metabolic and Endocrine Osseous Disorders
14 Metabolic Bone Disease �� 157

Jin-Sook Ryu and Hye Won Chung
15 Osteoporosis�� 179
Seoung-Oh Yang, Jung Mi Park, Hye Joo Son, Jang Gyu Cha,
Jee Won Chai, and So Won Oh
16 Fibrous Dysplasia�� 195
Yong-il Kim and Jin-Sook Ryu
Part V Musculoskeletal Neoplastic Disorders
17 Primary
Bone and Soft Tissue Tumors�� 205
Jin Chul Paeng and Seoung-Oh Yang
18 Metastatic Musculoskeletal Tumors �� 217
Young-Sil An and Seoung-Oh Yang
19 Marrow Replacement Disorders�� 227
Joo Hyun O and Ie Ryung Yoo
Part VI Miscellaneous Features in Musculoskeletal

Nuclear Imaging
20 Soft
Tissue Uptake of Bone Scan Agents�� 239
Yun Young Choi and Soo Jin Lee
21 Musculoskeletal
Nuclear Imaging Pitfalls �� 257
Yun Young Choi, Ji Young Kim, and Seoung-Oh Yang
Index�� 269
Contributors
Young-Sil An Department of Nuclear Medicine and Molecular Imaging,

Ajou University School of Medicine, Suwon, Republic of Korea
Jang Gyu Cha Department of Radiology, Soonchunhyang University
Hospital, Bucheon, Republic of Korea
Jee Won Chai Department of Radiology, Seoul National University
Boramae Medical Center, Seoul, Republic of Korea
Young Seok Cho Department of Nuclear Medicine, Samsung Medical
Center, Sungkyunkwan University School of Medicine, Seoul, Republic of
Korea
Joon Ho Choi Department of Nuclear Medicine, Soonchunhyang University
Yun Young Choi Department of Nuclear Medicine, Hanyang University
College of Medicine, Seoul, Republic of Korea
Hye Won Chung Department of Radiology, Asan Medical Center, University
of Ulsan College of Medicine, Seoul, Republic of Korea
You Mie Han Department of Nuclear Medicine, Dongtan Sacred Heart
Hospital, Hwaseong-si, Gyeonggi-do, Republic of Korea
Jae Pil Hwang Department of Nuclear Medicine, Soonchunhyang University
Tae Joo Jeon Department of Nuclear Medicine, Gangnam Severance
Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
Ji Young Kim Department of Nuclear Medicine, Hanyang University
Sun Jung Kim Department of Nuclear Medicine, National Health Insurance
Service Ilsan Hospital, Goyang, Republic of Korea
Yong-il Kim Department of Nuclear Medicine, Asan Medical Center,
University of Ulsan College of Medicine, Seoul, Republic of Korea
Soo Jin Lee Department of Nuclear Medicine, Hanyang University College
of Medicine, Seoul, Republic of Korea
xi
xii Contributors
Su Jin Lee Department of Nuclear Medicine, Ajou University School of

Medicine, Suwon, Republic of Korea
Joo Hyun O Department of Nuclear Medicine, Seoul St. Mary’s Hospital,
The Catholic University of Korea, College of Medicine, Seoul, Republic of
Korea
So Won Oh Department of Nuclear Medicine, Seoul National University
Boramae Medical Center, Seoul, Republic of Korea
Jin Chul Paeng Department of Nuclear Medicine, Seoul National University
Jung Mi Park Department of Nuclear Medicine, Soonchunhyang University
Soon-Ah Park Department of Nuclear Medicine, Wonkwang University
School of Medicine, Iksan, Republic of Korea
Jin-Sook Ryu Department of Nuclear Medicine, Asan Medical Center,
University of Ulsan College of Medicine, Seoul, Republic of Korea
Ju Won Seok Department of Nuclear Medicine, Chung-Ang University,
Hye Joo Son Department of Nuclear Medicine, Dankook University College
of Medicine, Cheonan, Republic of Korea
Yoo Sung Song Department of Nuclear Medicine, Seoul National University
Bundang Hospital, Seongnam-si, Gyeonggi-do, Republic of Korea
Seoung-Oh Yang Department of Nuclear Medicine, Dongnam Institute of
Radiological and Medical Sciences, Busan, Republic of Korea
Ie Ryung Yoo Department of Nuclear Medicine, Seoul St. Mary’s Hospital,
The Catholic University of Korea, College of Medicine, Seoul, Republic of
Korea
Joon-Kee Yoon Department of Nuclear Medicine, Ajou University Medical
Center, Suwon, Republic of Korea
Yu Sung Yoon Department of Radiology, Soonchunhyang University
Part I
Inflammatory and Infectious Disorders
Musculoskeletal Infections
1
Jung Mi Park , Jae Pil Hwang , Joon Ho Choi ,
Jang Gyu Cha, and Yu Sung Yoon
Abstract Keywords
Pedal ulcer occurs in approximately 25% of the Diabetic foot infection · Chronic prosthetic
diabetics. Three-phase bone scan plays a role in joint infection · Charcot foot · Pyogenic
the assessment of vascular supply including spondylitis
small arteries and capillary vessels in diabetic
foot ulcer. Peri-prosthetic joint infection occurs
in 1%–2% of primary and in 4% of revision 1.1 Diabetic Foot Infection
arthroplasties. Serum CRP may be less specific
after post-operative infection and antibiotics 1.1.1 Clinical Course, Assessment,
therapy; however, combined WBC scan with and Treatment
three-phase bone scan can detect peri-prosthetic
infection accurately. Charcot neuropathic osteo- Development of pedal ulcer can be estimated to
arthropathy is a non-inflammatory and progres- occur in 25% of the diabetics. Diabetic foot dis-
sive destruction of the bone and joint. Bone order is the most common cause of lower extrem-
single-photon emission computed tomography/ ity amputations [1]. Hyperglycemia can cause
computed tomography (SPECT/CT) provides an direct damage to the nerves and blood vessels.
additional anatomical information to distinguish Diabetic vascular disease has three components:
from bone and soft tissue inflammation or infec- arteritis and small vessel thrombosis, neuropathy,
tion in evaluating Charcot foot. Typical pyogenic and large vessel atherosclerosis. Once tissue
spondylitis affects two adjacent vertebrae and damage has occurred in ulcer or gangrene, the
the intervening disc. Differential diagnosis for two main threats are infection and ischemia.
tuberculous spondylitis could be performed with Various foot ulcer classifications have been pro-
clinical symptom and imaging findings. posed to organize the appropriate treatment plan:
the University of Texas diabetic foot ulcer clas-
sification is based on ulcer depth and is graded
J. M. Park (*) · J. P. Hwang · J. H. Choi according to the presence or absence of infection
Department of Nuclear Medicine, Soonchunhyang and ischemia. Many ulcers where critical isch-
University Hospital, Bucheon, Republic of Korea
e-mail: jmipark@schmc.ac.kr;
emia exists fail to heal and lead to irreparable tis-
zandazanda@schmc.ac.kr; 114780@schmc.ac.kr sue damage and amputation [2].
J. G. Cha (*) · Y. S. Yoon
The 5-year mortality in patients with diabetes
Department of Radiology, Soonchunhyang University and critical limb ischemia is 30%, and the 5-year
Hospital, Bucheon, Republic of Korea mortality in patients with diabetic foot infections
e-mail: mj4907@schmc.ac.kr; yusungy@schcmc.ac.kr
© The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2022 3
S.-O. Yang et al. (eds.), Atlas of Nuclear Medicine in Musculoskeletal System,
https://doi.org/10.1007/978-981-19-2677-8_1
4 J. M. Park et al.
who have foot amputations is about 50% [3]. While transluminal angioplasty in the case of bedridden
the neuropathic foot is characterized by warm, dry, patients and patients with life-threatening sepsis
bounding pulses as a result of peripheral vasodila- and extensive muscle necrosis.
tion, callosities, painless penetrating ulcers at pres-
sure points, painless necrosis of toes, spreading Case 1.1
infection along plantar spaces, and loss of pain and A 58-year-old man was referred from an outside
thermal sensation, the ischemic foot is character- hospital; he was treated for necrosis of the left
ized by cold, absent pulses, trophic changes, pain- first toe for 3 months. He had a history of having
ful ulcers around heels and toes, and claudication his entire right toes amputated 3 years ago for
and rest pain. Although these factors may co-exist, atherosclerosis obliterans. His left first to third
it is important to early detect ischemia in the dia- toes were discolored black, and gangrene was
betic foot ulcer. Diabetes itself shows a 25% progressing. Enterobacter cloacae was cultured
increased risk for peripheral arterial disease [4]. from his wound; he was treated with antibiotics.
Bone scan can provide a useful assessment of vas- His angiography showed multifocal stenosis in
cular supply including small arteries and capillary both superficial femoral arteries. His plain radi-
vessels [5]. Proper vascular assessment in small ography could not depict any significant bone
vessel disease with associated gangrenous toes can abnormality on his left toes. However his three-
be help to provide a successful treatment with phase bone scan showed perfusion defect in the
debridement and minor amputation instead of wide left first to third toes with complete absence of
amputation. In chronic and progressive diabetes, a bone uptake (Fig. 1.1). WBC SPECT/CT demon-
conservative surgical approach such as revascular- strated the strong WBC uptake in the left fourth
ization can be considered. But primary amputation and fifth toe soft tissue, as well as a cold defect in
is better than revascularization or percutaneous the left first to third toe gangrene (Fig. 1.2).
a b c
Fig. 1.1 There is no significant abnormal bone lesion in observed on the blood pool image and bone phase image
the left foot plain radiography (a). Perfusion defects and of the three-phase bone scan (b, c)
loss of bone uptake in the left 1st–3rd toes are clearly
a b
Fig. 1.2 WBC scan and SPECT/CT show cold defects in all of the left toes as well as increased uptake in the soft tissue
overlying the 3rd–5th toes (a, b)
1 Musculoskeletal Infections 5
1.2 Chronic Prosthetic Joint (PMMA) beads can become colonized by bacte-
Infection ria due to rapid decrease of local antibiotic con-
centration, resulting in new biofilm formation
1.2.1 Clinical Course, Assessment, [6]. In patients with numerous previous revi-
and Treatment sions, or when local conditions require time,
two-stage exchange with 4- to 6-week antibiot-
Peri-prosthetic joint infection (PJI) occurs in ics treatment can be applied. Longer intervals
1%–2% of primary and in 4% of revision arthro- (>8 weeks) of persistent sign of infection,
plasties. Management of PJI requires multiple debridement, and antibiotic-loaded spacer
surgical revisions and long-term antimicrobial cement are used for dead space management
treatment. About two thirds of PJI results from with two-stage revision surgery for treatment of
intra-operative inoculation of microorganisms golden standard.
[6]. However, all prosthetic joints have hematog-
enous seeding from a distant primary focus, Case 1.2
where highly vascular peri-prosthetic tissue is A 78-year-old woman with diabetes visited the
exposed to the highest risk of hematogenous hospital for discharge from the right pre-tibial
infection in the first years after implantation. The area, which had undergone knee arthroplasty at
most common primary foci are skin and soft tis- an outside hospital 7 months ago. She underwent
sue infection, respiratory tract infections, gastro- prostheis removal due to septic arthritis and anti-
intestinal infections, or urinary tract infections. biotic bead insertion, and baseline three-phase
According to the definition criteria for PJI by the bone scan showed increased perfusion and joint
European Bone and Joint Infection Society uptake in the right knee joint and pre-tibial space
2018 in Helsinki, if there is one more criteria, PJI (arrow) suggesting septic arthritis (Fig. 1.3). Her
including chronic infection can be diagnosed. serum CRP level decreased from 5.2 mg/L to
It shows better sensitivity for diagnosing PJI [7]. 0.13 mg/L after 2 months of antibiotic IV therapy
The sensitivity of synovial fluid culture is and antibiotic bead insertion. She underwent a
45% to 75% with a specificity of 95% [7]. The baseline three-phase bone scan (Fig. 1.3) and 2
sensitivity of intra-operative swab is low, and the months later follow up scan (Fig. 1.4). It was to
swab should be avoided. This is because a swab determine an optimal timing of revision of arthro-
from the wound or sinus tract can mislead by plasty; contrary to expectations, the scan showed
detecting colonizing microorganisms. Generally severely increased perfusion and bone uptake in
three to five intra-operative tissue samples the right tibia shaft (Fig. 1.4). WBC scan also
should be obtained for the culture. Histopathology showed diffuse WBC uptake along the previously
of peri-prosthetic tissue should be considered a inserted antibiotic beads in the tibia (Fig. 1.4).
standard procedure in the diagnosis of PJI. Rapid decrease of local antibiotic concentration
In PJI caused by low-virulence pathogens, in the inserted antibiotic-coated beads resulted in
blood tests such as WBC, ESR, and CRP are new biofilm formation. She underwent surgery to
often normal [8]. CRP can be increased after sur- remove infectious granulation tissues meticu-
gery, due to post-operative inflammation. Serial lously in the bone marrow with massive irrigation
measurements of CRP are more important for and new cement insertion with VPMMA for
accurate interpretation. In acute post-operative removal of dead space in the tibia. A few months
infections (<4 weeks) or acute hematogenous later, she underwent joint replacement sur-
infections, debridement, antibiotics, and implant gery. Three-phase bone scan and WBC scan
retention are the best treatment. Local antibiotics may be useful for accurate diagnosis of infection
can be additionally used during revision surgery. even when serum CRP returns to normal range
Antibiotic-loaded polymethylmethacrylate after antibiotic treatment.
6 J. M. Park et al.
Fig. 1.3 Pretibial soft tissue a b c

hyperperfusion (arrow) and
diffuse hyperperfusion
surrounding the right knee
joint are seen on the
three-phase bone scan (a, b).
Soft tissue swelling and fluid
collection are seen in the
patellofemoral compartment
of the knee on the plain
radiography (c)
a b c d
Fig. 1.4 Prosthetic removal and antibiotic bead insertion tion widely extends to the tibial shaft (b, c). WBC SPECT/
in the right tibia are seen on the plain radiography (a). CT shows strong WBC accumulation in the tibia, consis-
After 2 months, serum CRP has returned to the normal tent with bone marrow infection (d)
range. Followed up three-phase bone scan finds the infec-
1.3 Charcot Foot progress without proper treatment, and may result
in Lisfranc’s joint destruction and callopse of the
1.3.1 Etiology and Clinical longitudinal arch of the foot. The typical end-stage
Significance appearance of a Charcot foot is the rocker bottom
deformity. Calcaneal insufficiency fracture is an
Charcot neuropathic osteoarthropathy is a dis- uncommon, which can be associated with neuroar-
ease spectrum of the bone, joint, and soft tissue thropathy or severe osteoporosis, and may be
and is non-inflammatory and progressive caused by spontaneous condition or repeated
destruction of the bone and joints. Charcot the- microtrauma of the pull of the calcaneal tendon.
ory is not yet clear for its pathogenesis or mecha-
nism; there is consensus that the cause is
multifactorial including polyneuropathy (loss of 1.3.2 Radiographic Imaging
sensation and proprioception), neurotraumatic,
and neurovascular conditions with combined The Charcot foot can be classified using various
osteoarthropathy [9]. systems according to anatomical landmarks and
From a clinical perspective, its early phase is clinical symptoms. The most common one is the
characterized by a hot or warm, red, and swelling Sanders and Frykberg classification; this classifi-
of foot, often without pain due to polyneuropathy, cation identified five zones of disease distribution
and by osteopenia with fractures. The disease will according to the anatomical location. The most
a b
Fig. 1.5 Plain radiography and sagittal image of 3D foot CT show fracture in the calcaneal tuberosity and fluid collec-
tions at the posterior aspect of the calcaneus and tibiotalar joints (a, b)
a b
Fig. 1.6 Three-phase bone scan shows decreased radioactivity in the calcaneal fracture site and diffusely and mildly
increased perfusion and bone uptake in the talocalcaneal joints (a, b)
commonly involved areas are about 45% in zone Bone SPECT/CT provides an additional anatom-
II in about 35% in zone III of cases. ical information to distinguish bone and soft tis-
Conventional radiographs of the Charcot foot sue inflammation or infection. Bone scintigraphy
are traditionally the standard imaging technique with radiolabeled leukocytes is more specific for
to establish the diagnosis, to stage, and to monitor osteomyelitis [11].
the disease. MRI is a well-known imaging modal-
ity to diagnose a suspected early active Charcot Case 1.3
disease. Early signs of a Charcot foot in MRI are An 82-year-old woman presented to the outpa-
bone marrow edema, soft tissue edema, joint effu- tient clinic due to left heel pain developed 2 days
sion, and subchondral microfractures. MRI of ago. She sprained her foot from walking 3 days
late-stage Charcot foot shows joint destruction, ago and had a long time of diabetes history for
cortical fractures, joint dislocations, bone marrow 25 years. Plain radiography and foot 3D CT
edema, superior and lateral dislocation of revealed right calcaneal tuberosity fracture and
Lisfranc’s joint, prominent well-marginated sub- fluid collections at posterior aspect of calcaneal
chondral cysts, bone proliferation, sclerosis, fracture site and anterior aspect of tibiotalar
debris, intraarticular bodies, and dislocation of joints (Fig. 1.5). 99mTc-DPD three-phase bone
talus and navicular bones [10]. scan and bone SPECT/CT also showed diffusely
Three-phase bone scintigraphy is gener- increased perfusion and bone uptake along the
ally used to exclude osteomyelitis in diabetic anterior and posterior talocalcaneal joints
patients. Increased perfusion and bone uptake (Figs. 1.6 and 1.7). These additionally showed
are not specific to diagnose osteomyelitis, decreased perfusion and bone uptake from bony
because they may also occur in chronic soft tis- fragmentation at calcaneal avulsion fracture site.
sue infections, fractures, and neuropathic joints. Based on the clinical exam including a long his-
8 J. M. Park et al.
a b c
d e f
Fig. 1.7 Bone SPECT/CT shows diffuse osteopenia and head in b) on its fusion axial, sagittal, and coronal images
small bony fragment in the talocalcaneal joint area as well (a–c), axial, sagittal, and coronal CT images (d–f)
as the avulsion fracture in the calcaneal tuberosity (arrow-
tory of diabetes mellitus, no evidence of tender- decreasing friction between skeletal and soft tissue
ness, and imaging work-ups including avulsion structures, including bone-tendon, bone-skin, and
fracture and joint activity of common location, tendon-ligament interfaces. The bursa can be
early Charcot arthropathy was suggested. divided into anatomical and adventitious bursae;
lateral malleolar bursa is adventitious type. Lateral
malleolar bursitis is a rare cause of ankle pain and
1.4 Malleolar Bursitis swelling characterized by bursa wall thickening
and excess bursal fluid accumulation. This disease
1.4.1 Etiology and Clinical is caused by the inflammation or infection, repeti-
Significance tive irritation, constant pressure, swelling, compli-
cation from arthritis, and repeated stress or injury
The bursa is fluid-containing, extra-articular of the lateral malleolar area of the ankle. Treatment
closed sacs that provide cushioning and assist in includes a lifestyle modification, combination of
oral or parenteral antibiotics, and needle aspiration lateral malleolar area on blood pool phase image
or incisional drainage, and surgical intervention and mildly increased uptake in the distal fibular
may be necessary in some cases. area suggesting reactive change on delay bone
phase image (Fig. 1.10). Blood pool phase
SPECT/CT showed localized increased uptake
1.4.2 Radiographic Imaging with diffuse soft tissue swelling centering
around the lateral malleolar bursa of right ankle.
Typical ultrasonographic finding is a fluid- Otherwise, delay bone phase SPECT/CT
filled anechoic structure with a thickened showed increased bone uptake suggesting reac-
hyperechoic wall. On MRI, the bursa is seen as tive change in the right distal fibula (Fig. 1.11).
a high T2 fluid-filled structure, and CT shows
the inflamed bursa as hypodense with an
enhancing wall [12]. Three-phase bone
scan and perfusion SPECT/CT show hyper-
emia and focal increased bone uptake. In addi-
tion, SPECT/CT can provide higher diagnostic
accuracy and anatomical information distin-
guished bone and soft tissue inflammation or
infection due to additional CT imaging tech-
nique [11].
Case 1.4
A 52-year-old man presented to the outpatient
clinic due to right ankle pain with ulceration
(Fig. 1.8). He has had diabetes mellitus for a
long time. Radiographs showed no bony abnor-
mality except for soft tissue shadow correspond-
Fig. 1.9 Plain radiography of both feet and ankles
ing the lesion in the right lateral malleolar area
(Fig. 1.9). 99mTc-DPD three-phase bone scan
showed increased soft tissue uptake in the right
a b
Fig. 1.10 Three-phase bone scan shows increased perfu-

Fig. 1.8 Photograph of lateral malleolar lesion of right sion in the swelling area of the right lateral malleolus and
ankle at the time of admission mildly increased bone uptake in the lateral malleolus (a, b)
10 J. M. Park et al.
a b c
d e f
Fig. 1.11 Blood pool and bone SPECT/CT; blood pool anatomical differentiation between soft tissue and bone,
phase axial, bone phase axial, bone axial CT images (a– while in a planar three-phase bone scan increased uptake
c), blood pool phase coronal, bone phase coronal, and area can be obscure for an exact localization
bone coronal CT (d–f). SPECT/CT can provide accurate
1.5 Pyogenic Spondylitis bral osteomyelitis, septic discitis, and epidural

abscess. Pyogenic spondylitis usually develops
1.5.1 Etiology and Clinical from bacterial origin. The arterial route is more
Significance widespread than the venous route, usually from the
skin, oral cavity, respiratory tract, and genitouri-
The term “pyogenic spondylitis” is a broad term nary tract [13]. The vertebral segmental artery pro-
which includes pyogenic spondylodiscitis, verte- vides an intervening disc as well as the upper and
lower portion of vertebrae. Thus, typical pyogenic The most characteristic features of tubercu-
spondylitis affects two adjacent vertebrae and the losis spondylitis are (a) predominantly pattern
intervening disc. The spines infections could of bone destruction, (b) relatively preserved disc
involve all levels of the spines. The result shows the due to a lack of proteolytic enzymes in myco-
lumbar spine (45–50%) is the most common site, bacteria [17], (c) enhanced focal and heteroge-
and the rest of the level is the thoracic (35%), cervi- neous contrast of vertebral bodies, (d)
cal (3–20%), and sacral regions [14]. well-defined perivertebral regions of abnormal
signal intensity, and (e) rim enhancement of ver-
tebral intraosseous lesion in the sagittal plane.
1.5.2 Radiographic Imaging On the other hand, the common findings of pyo-
genic spondylitis are (a) mainly the appearance
Radionuclide studies showed more sensitive of intervertebral disc disease, (b) mild to moder-
results than radiograph images in early stages. ately peridiscal bone involvement, (c) relatively
Bone scans reveal little anatomical details and diffuse and homogeneous enhancement of the
can be positive in osteoporotic fractures and neo- vertebral body, (d) ill-defined abnormal signal
plastic disease. Magnetic resonance imaging intensity paraspinal region, and (e) interverte-
(MRI) is known as the gold standard for detect- bral rim enhancement findings. If three or more
ing pyogenic spondylitis. The infection com- of the five criteria are found, it is strongly sug-
monly begins at the anterolateral vertebral body gestive of tuberculosis or pyogenic spondylitis
near the endplate [15]. Associated edema is [17].
declared and includes much of the vertebral body
and intervertebral disc. MRI is also a dependable Case 1.5
method for evaluating and assessing the spinal An 87-year-old woman visited an outpatient
canal, especially the epidural space and spinal clinic with her back pain for 4 months, and ten-
cord. Epidural abscess with neurological deficit derness was elicited at left lower back area. The
is a surgical emergency [13]. laboratory findings showed elevated ESR and
CRP. MR showed enhancement of bone marrow
and disc in L4–L5 with bilateral paravertebral
1.5.3 Differential Diagnosis abscess and phlegmon (Fig. 1.12a). Three-phase
with Pyogenic Spondylitis bone scan with bone SPECT/CT showed diffuse
Versus Tuberculous increased perfusion and bone uptake in the L4
Spondylitis and L5 vertebare (Fig. 1.12c–f). Pyogenic spon-
dylitis was diagnosed by bone biopsy.
Infective spondylitis may result from hematoge-
nous spread, direct external inoculation, or con- Case 1.6
tiguous tissues. The hematogenous arterial route A 64-year-old man visited an outpatient clinic for
is predominant in pyogenic spondylitis, starting back pain and left leg numbness sensation with
infection from various sites to the vertebral col- fever. Laboratory results showed positive for the
umn. Contrary to pyogenic infections, tubercu- blood TB-specific antigen. MR revealed well-
lous infection usually spread from the venous defined paravertebral soft tissue abscess forma-
system such as Batson’s venous plexus. In the tion (Fig. 1.13), combined with edematous bone
case of tuberculous spondylitis, there are few change and heterogenous cortical loss but rela-
clinical symptoms such as fever, pain, and swell- tively preserved disc. Three- phase bone scan
ing due to infection, and the disease progresses and following SPECT/CT showed increased per-
gradually. However, infective spondylitis is fusion and bone uptake in the L3–L4 bodies with
highly likely to be accompanied by severe pain increased perfusion in the paravertebral soft tis-
and high fever [16]. sues at the L3–L5 level (Fig. 1.13c).
a b
c d
L-spines
e f
Fig. 1.12 Contrast-enhanced MR images of L-spines vening disc (arrows in b). Three-phase bone scan (c, d)
show enhancement of the bilateral paravertebral abscesses and bone SPECT/CT (e, f) show increased perfusion and
(arrows in a) and two adjacent vertebrae with the inter- bone uptake in the L4 and L5 spines
Fig. 1.13 Contrast-

enhanced MR images of a b
L-spines show multiple
paravertebral abscesses
(arrowheads in a, b) and
bone loss in the L3
(arrow in b). Posterior
view of three phase bone
scan shows subtle
increased soft tissue
perfusion in the left
paravertebral area
(arrowhead in c), mildly
increased perfusion in
the L3 and L4 (arrows in
c), and relatively subtle
increased bone uptake in c d
the L3 and L4 (c, d).
Bone SPECT/CT shows
bone defect with mildly
increased bone uptake in
the L4 body (e, f)
e f
Case 1.7 in the left side of screw of L3 body (Fig. 1.14c,

A 58-year-old man visited an outpatient clinic d). White blood cell scan with SPECT/CT dem-
due to back pain after receiving interbody fusion onstrated cold defect in L2 and L3 spines
4 months ago. He was treated with antibiotics (Fig. 1.14e, f) suggesting osteomyelitis. In
intensively, however his clinical symtpoms were chronic sponydlitis, the presence of necrotic
not improved. MR showed hyperenhancement bones can reduce the effectiveness of antibiotic
on L2 and L3 bodies and paravertebral soft tissue treatment by preventing the antibiotics
(Fig. 1.14a, b). Prosthetic loosening and associ- from entering the tissue, which in turn may pro-
ated edema were also revealed. Three-phase bone duce a new inflammation or thrombosis and
scan showed increased perfusion and bone uptake result in more severe necrosis.
a b c
d e f
Fig. 1.14 Contrast-enhanced MR images of L-spines (c, d). WBC scan and SPECT/CT show cold defects in the
show enhancement of paravertebral soft tissue at the level L2 and L3 bodies in comparison to the uptake in other
of L2–L3 (a, b). Bone scan and SPECT/CT show lumbar spines suggesting osteomyelitis (e, f)
increased perfusion and bone uptake in the level of L2-L3
Case 1.8
A 78-year-old man presented to the outpatient Teaching Points
clinic with neck pain and fever. Laboratory study • Bone scan can provide a useful assess-
showed elevation of ESR and CRP. MR demon- ment of vascular supply including small
strated decreased intervertebral space and paraver- arteries and capillary vessels in diabetic
tebral abscess at C6–C7 level with anterior foot.
epidural abscess formation (Fig. 1.15a). Three- • Even CRP can be less specific after
phase bone scan revealed mildly increased perfu- post-operative infection and antibiotics
sion and bone uptake in the lower C spines at therapy, combining WBC scan with
anterior and oblique views (Fig. 1.15c–e). three-phase bone scan can be useful for
Empirical antibiotic treatment was applied for detecting peri-prosthetic infection
pyogenic spondylitis. Bone scan for cervical spon- accurately.
dylitis should be carefully reviewed, because it has • Early detection and proper treatment of
a relatively low incidence and bone uptake of C Charcot foot are important for preven-
spine lesion is easily obscured in comparison tion of disease progression and predic-
to the thoraco-lumbar spines. tion of disease prognosis.
a b
c d e
Fig. 1.15 Contrast-enhanced MR images of C-spines increased perfusion in the lower C spine area and increased
show paravertebral abscess at the level of C4–C7 (arrow, bone uptake in the lower C spines on the three-phase bone
double arrows in a, b) and anterior epidural abscess at the scan (arrowheads in c–e)
C6–C7 level (arrowheads in a). Suspicious mildly
• SPECT/CT allows accurate anatomical involvement of bony inflammation or

correlation with CT to functional infor- infection.
mation with SPECT; it can improve the • Pyogenic spondylitis involves various
diagnostic accuracy for inflammation or clinical entities such as pyogenic spon-
infection, traumatic injury, and degen- dylodiscitis, septic discitis, vertebral
erative change of the foot and ankle. osteomyelitis, and epidural abscess.
• WBC SPECT/CT can help increase • Pyogenic spondylitis affects two adja-
diagnostic accuracy for infections in vio- cent vertebrae and intervening disc and
lated bone lesions compared to relatively infectious spondylitis can show cold
low sensitivity of three-phase bone scan. defect in WBC scan.
• Malleolar bursitis is a rare inflammatory • Differential diagnosis between pyo-
disease involving the soft tissue of the genic spondylitis and tuberculous spon-
ankle and foot. dylitis can be made by clinical symptom
• Blood pool and delay bone phase and imaging findings.
SPECT/CT can help discriminate the
References infections, particularly chronic and low-grade infec-

tions. Int Orthop. 2017;41:1315–9.
9. Jones E, Manaster B, May D, Disler D. Neuropathic
1. P alestro CJ, Love C. Nuclear medicine and diabetic
osteoarthropathy: diagnostic dilemmas and differ-
foot infections. Semin Nucl Med. 2009;39:52–65.
ential diagnosis. Radiographics. 2000; https://doi.
2. Lipsky BA, Berendt AR, Deery HG, Embil JM,
org/10.1148/radiographics.20.suppl1.g00oc22s279.
Joseph WS, Karchmer AW, LeFrock JL, Lew DP,
10. Rosskipf A, Loupatatzis C, Pfirrmann C, Boni T,

Mader JT, Norden C, Tan JS. Diagnosis and treat-
Berli M. The Charcot foot: a pictorial review. Insight
ment of diabetic foot infections. Clin Infect Dis.
Imaging. 2019;10:77.
2004;39:885–910.
11. Yoo IR. Bone SPECT/CT of the foot and ankle:

3. Lipsky BA, Berendt AR, Cornia PB, Pile JC,
potential clinical application for chronic foot pain.
Peters EJ, Armstrong DG, Deery HG, Embil JM,
Nucl Med Mol Imaging. 2020;54:1–8.
Joseph WS, Karchmer AW, Pinzur MS, Senneville
12. Hirji Z, Hunjun J, Choudur H. Imaging of the

E. Infectious diseases society of America. Clinical
Bursae. J Clin Imaging Sci. 2011; https://doi.
practice guidelines for the diagnosis and treat-
org/10.4103/2156-7514.80374.
ment of diabetic foot infections. Clin Infect Dis.
13. Cheung WY, Luk KD. Pyogenic spondylitis. Int

2012;54:132–73.
Orthop. 2012;36(2):397–404.
4. Selvin E, Marinopoulos S, Berkenblit G, et al. Meta-
14. Jaramillo-de la Torre JJ, Bohinski RJ, Kuntz

analysis: glycosylated hemoglobin and cardiovas-
C. Vertebral osteomyelitis. Neurosurg Clin N Am.
cular disease in diabetes mellitus. Ann Intern Med.
2006;17(3):339–51. vii
2004;141:421–31.
15. Modic MT, Feiglin DH, Piraino DW, Boumphrey

5. Masaoka S. Evaluation of arterial obstructive leg and
F, Weinstein MA, Duchesneau PM, et al. Vertebral
foot disease by three-phase bone scintigraphy. Ann
osteomyelitis: assessment using MR. Radiology.
Nucl Med. 2001;15:281–9.
1985;157(1):157–66.
6. Zimmerli W, Trampuz A, Ochsner PE. Prosthetic-
16. Tsiodras S, Falagas ME. Clinical assessment and

joint infections. N Engl J Med. 2004;351:1645–54.
medical treatment of spine infections. Clin Orthop
7. Izakovicova P, Borens O, Trampuz A. Periprosthetic
Relat Res. 2006;444:38–50.
joint infection: current concepts and outlook. Efort
17. Chang MC, Wu HT, Lee CH, Liu CL, Chen

Open Rev. 2019;4:482–94.
TH. Tuberculous spondylitis and pyogenic spondy-
8. Perez-Prieto D, Portillo ME, Puig-Verdie L, et al.
litis: comparative magnetic resonance imaging fea-
C-reactive protein may misdiagnose prosthetic joint
tures. Spine (Phila Pa 1976). 2006;31(7):782–8.
Septic Arthritis
2
You Mie Han
Abstract Keywords
Septic arthritis is a painful infection in a joint Septic · Infectious · Arthritis · Tuberculous

induced by an infectious agent. Release of Bone · Scintigraphy
proteolytic enzyme from bacteria and inflam-
matory cells may cause articular cartilage
damage within hours. So, prompt diagnosis 2.1 Etiology
and treatment are essential to prevent signifi- and Pathophysiology
cant morbidity and mortality. Although arthro-
centesis is commonly used to make an accurate Septic arthritis is also known as infectious arthri-
diagnosis of septic arthritis, imaging modali- tis or pyogenic arthritis, a painful infection in a
ties are helpful to evaluate the disease. Whole- joint induced by an infectious agent. It can be
body or three-phase bone scintigraphy has caused by bacterial, viral, mycobacteria, or fun-
been widely used in diagnosis of septic arthri- gal infections. The most common causative
tis. Although its findings are nonspecific, it is organism is S. aureus (Staphylococcus aureus).
a sensitive study to diagnose septic arthritis An organism can enter the joint by the blood
and detect associated bone erosion or osteo- stream from another infected body focus, by con-
myelitis under suspicion of infectious condi- tiguous spread from infected periarticular tissue,
tion. A total of six cases of septic arthritis are or by direct inoculation via penetrating injury,
presented in this chapter: four bacteria- surgery, or injection. Knees and hips are com-
confirmed and one bacteria-suspected infec- monly affected joints, but septic arthritis can
tions and one tuberculous infection. Each case affect other joints including both large and small
contains a closely correlated combination of joints. Symptoms and signs of septic arthritis are
images of three-phase bone scintigraphy, sim- acute pain, swelling, redness, and heating sensa-
ple radiography, MRI, and/or PET/CT. tion on the affected joint with discomfort and
limited range of motion. Active bacterial prolif-
eration resulted from invasion of the highly vas-
cular synovium. Release of proteolytic enzyme
from bacteria and inflammatory cells may cause
Y. M. Han (*) articular cartilage damage within hours.
Department of Nuclear Medicine, Dongtan Sacred
Heart Hospital,
Furthermore, increased intra-articular pressure
Hwaseong-si, Gyeonggi-do, Republic of Korea from accumulation of the purulent fluid results in
e-mail: youme@hallym.or.kr
https://doi.org/10.1007/978-981-19-2677-8_2
18 Y. M. Han
necrosis of the synovium, cartilage, and bone. Septic arthritis is potentially serious, because it
Revascularization, synovial proliferation, granu- can cause rapid joint destruction leading to per-
lation tissue, and finally bony ankylosis can also manent deformities and irreversible loss of joint
develop according to progression of arthritis. function in 25–50% [1].
a b c
Bone
Joint
capsule
Synovial
membrane
Cartilage
Synovial
cavity
containing
synovial fluid
Septic arthritis – pathophysiology Normal (a). In the acute stage (b), there is an acute synovial inflammation
with a purulent joint effusion. Soon articular cartilage is damaged by proteolytic enzyme secreted from bacteria
and cells. If the infection is not controlled, the cartilage may be completely destroyed and subcortical bone is
eroded. Healing may occur with irregular joint space narrowing and bony ankylosis (c)
2.2 Diagnosis Scintigraphy with 99mTc-labeled phosphonates

is helpful for a supportive study in the septic
Diagnosis of septic arthritis is generally based on arthritis and is sensitive, though not specific, to
the patient’s history, clinical examination, and lab- detect destructive bone change or associated
oratory and imaging findings. Imaging modalities osteomyelitis which shows increased bone turn-
such as radiography, CT (computed tomography), over. In three-phase bone scintigraphy, because
MRI (magnetic resonance image), ultrasound, or of hyperemia in synovial vessels to the affected
bone scintigraphy can help determine areas of joint, all three phases (flow, blood pool, delayed)
inflammation but cannot confirm the infection. show increased radionuclide uptake [2, 3]. Flow
Arthrocentesis is used to make an accurate diagno- and blood pool images show diffusely increased
sis of septic arthritis. However, false-negative activity at the suspected periarticular area.
gram stains and cultures of synovial fluid can Delayed bone images obtained at 2–4 h after
occur. The infection can damage rapidly and injection of radiopharmaceuticals may demon-
severely the cartilage and bone within the joints, strate diffuse mild bone marrow uptake in the
so urgent treatment is needed. Prompt diagnosis is articular confinement and continued intense bone
essential for the better outcome, and MRI is the uptake with process of destructive cortical bone
initial imaging study of choice for the septic arthri- change. Periarticular bone marrow uptakes also
tis. Septic arthritis should be differentiated from possibly represent so-called reactive bone mar-
acute osteomyelitis because the treatment strate- row edema on MRI [4, 5]. In addition, other fac-
gies are not identical. Sometimes, septic arthritis tors (e.g., trauma, osteoarthritis) could also cause
and acute osteomyelitis can co-exist. a false-positive scan.
2 Septic Arthritis 19
F-FDG PET (fluorine-18 fluorodeoxyglucose

18
thick synovial membrane and grafted tissue (*),
positron emission tomography)/CT has an incre- a large joint effusion, and mildly enhanced bone
mental value in detection of infectious disease due marrow in the periarticular bones. 99mTc-HDP
to its excellent sensitivity and specificity. In pyo- (hydroxymethylene diphosphonate) three-phase
genic arthritis, FDG uptake is increased at synovium bone scintigraphy was performed on the third
which has abundant neutrophils. However, day after the MRI. Images of flow and blood
increased FDG uptake is a usual feature in various pool phases showed diffusely increased soft tis-
types of arthritis, because of the increased cellular- sue uptake about right knee joint, suggesting
ity of the synovial membrane in synovitis and syno- synovial hyperemia and inflammation. Delayed
vial hypertrophy. Therefore, it is difficult to bone phase image showed asymmetric diffuse
distinguish the septic arthritis from other types of and mildly increased periarticular bone uptake at
arthritis with PET/CT images only. The advantages the right knee probably due to regional hyper-
of PET/CT are high spatial resolution and the abil- emia (Fig. 2.1).
ity of detecting tissue metabolic state, which reflect
well the extent and severity of the disease [6]. Case 2.2
A 56-year-old woman presented with continuous
pain in the right shoulder. She had a history of
2.3 Tuberculous Arthritis surgical drainage of pus (S. aureus) and antibiotic
therapy for the right shoulder joint and muscle
Tuberculous arthritis is a slowly progressive, infection, which had been developed after injec-
chronic monoarticular infection and is almost tions at a local clinic, 2 months ago.
always combined with tuberculous osteomyelitis. Three-phase bone scintigraphy showed no sig-
Joint invasion may be a result from hematoge- nificantly increased blood flow activity at the right
nous synovial infection or, more commonly, from shoulder. Asymmetric, uneven hot uptake was
epiphyseal or metaphyseal bone infection that noted at the right shoulder on blood pool image.
erodes into the joint space. Hip is the second There was diffuse mild periarticular increased bone
most common site followed by vertebra; it uptake with two focal areas of intense hot uptake at
accounts for about 15% of all cases of musculo- the right humerus head on delayed bone image.
skeletal tuberculosis [7]. As synovial inflamma- There were intra-articular erosive bone changes at
tion is started, granulomatous tissue develops and the right humeral head. Plain radiography showed
expands over the bone at the synovial reflections, focal radiolucencies at the anatomical neck of the
with subsequent cartilage destruction and bone right humerus. These areas were corresponding to
erosions. However, joint destruction occurs in the the areas with focal hot uptake on the delayed bone
late phases of disease, because the lack of proteo- image of three- phase bone scintigraphy.
lytic enzymes in tuberculosis preserves the carti- Postcontrast FS T1W coronal MRI showed focal
lage for a considerable length of time [8, 9]. cortical defects at the same areas of the humerus as
shown on plain radiography and bone scintigraphy.
Case 2.1 There was thick synovial enhancement with small
A 46-year-old man was admitted to the hospital joint effusion, enhancement of surrounding mus-
under suspicion of acute osteomyelitis. He com- cles and tendons, and reactive bone marrow edema
plained of pain and swelling of the right knee in the humerus head. During arthroscopic surgery,
with heating sensation that had been developed pus from the scapular area and synovial prolifera-
on the same day after a slip down. He had a his- tion were noted. Pathologic report was chronic
tory of debridement and skin grafting over the active inflammation, revealing chronic infectious
right knee due to the burn injury 5 months ago. arthritis (Figs. 2.2 and 2.3).
Purulent discharge (S. aureus) was coming from
a small external wound on the right knee. Case 2.3
Postcontrast FS (fat-saturated) T1-weighted A 47-year-old woman was hospitalized under the
(W) sagittal and axial MRI showed enhanced impression of septic arthritis of the right hip. She
20 Y. M. Han
Fig. 2.1 (a, b)

Postcontrast FS T1W a b
MRI: synovial
inflammation and
reactive bone marrow
edema in the
periarticular bones,
grafted tissue (asterisk).
Three-phase bone
scintigraphy 3 days
later: (c, d) periarticular
hot uptake at right knee
on flow and blood pool
phases, associated with
septic arthritis. (e)
Asymmetric diffuse
mild periarticular
increased bone uptake at
right knee, suggestive of c
periarticular bone edema
complained right hip pain, which had developed No microorganisms were found in the bacterial
2 months ago and aggravated recently, extending culture.
to inguinal and buttock areas. The result of aspi- Precontrast T1W and postcontrast FS T1W
ration biopsy was chronic active inflammation. axial MRI showed right hip joint inflammation
a b
8 sec
32 sec
56 sec
Fig. 2.2 Three-phase bone scintigraphy: (a) no signifi- blood pool image. (c) Diffuse mild periarticular increased
cant hyperemia at the right shoulder on flow image. (b) bone uptake with two focal areas of intense hot uptake at
Asymmetric uneven hot uptake at the right shoulder on the right humerus head on delayed image
with enhanced thick synovial membrane and erosions and sclerosis in the femoral head and the
enhanced periarticular soft tissue. Heterogeneous acetabulum (Fig. 2.4).
T1 low signal intensities and contrast enhance-
ments were in the right femoral head and neck Case 2.4
and in the acetabulum. Non-enhanced T1 low A 67-year-old woman was admitted due to spon-
signal intensity area was at the posterior aspect of taneous painful swelling in the left wrist for
the right femoral head, suggesting osteonecrosis. 2 weeks. There was purulent discharge
99m
Tc-HDP three-phase bone scintigraphy (Streptococcus agalactiae) from the left wrist.
showed asymmetric hot uptake at the right hip on Plain radiography of the left wrist showed
flow and blood pool images. Delayed image soft tissue swelling, uneven joint space narrow-
showed asymmetric increased bone uptake in the ing, and periarticular bone erosion and sclero-
right hip joint. There was no significant bony sis. FS T2W coronal MRI showed high signal
lesion on the initial plain radiography. Plain radi- intensity of synovial and parasynovial inflam-
ography taken 7 months later showed uneven nar- mation in the left wrist joint with uneven joint
rowing of the right hip joint space with bone space narrowing, subchondral bone erosions,
22 Y. M. Han
Fig. 2.3 (a) Plain

radiography: focal bone a
erosions (arrows) at the
anatomical neck of the
right humerus. (b) Bone
scintigraphy: focal hot
uptakes at right humerus
head corresponding to
bone erosions. (c)
Postcontrast FS T1W
MRI: bone erosions with
reactive bone marrow
edema in the humerus
head and synovial and
adjacent soft tissue
inflammation
b c
and patchy bone marrow edema. Mid-carpal Case 2.5

joint space was relatively preserved. 99mTc- A 64-year-old man was admitted to the hospital
HDP three-phase bone scintigraphy showed due to incidentally detected gastric cancer during
diffuse hot uptake throughout the left wrist on health screening. He complained pain and swell-
both perfusion and blood pool images, indicating on both knees. He had a clinical history of
ing articular hyperemia and inflammation. intra-articular injection at a local clinic 5 days
Delayed scan shows diffuse periarticular ago. He underwent arthroscopic pus (S. aureus)
increased bone uptake with intense radiotracer drainage and irrigation.
uptakes at proximal and distal carpal (espe- Initial plain radiography of the right knee shows
cially second to fourth carpometacarpal) joint distension of suprapatellar bursa without evidence
areas (Fig. 2.5). of bone lesion. 18F-FDG PET/CT was taken 1 day
a f g
c d
24 sec
48 sec
Fig. 2.4 (a) Precontrast T1W and (b) postcontrast FS uptake in right femoral head and neck and in acetabulum.
T1W MRI: right hip joint and adjacent soft tissue inflam- (f) Initial plain radiography: no significant bone lesion. (g)
mation with bone marrow change in femoral head and Plain radiography taken 7 months later: uneven joint
neck and in acetabulum. Three-phase bone scintigraphy: space narrowing with bone erosions and sclerosis in fem-
(c) asymmetric mild hyperemia, (d) hot uptake at right hip oral head and acetabulum
on blood pool image, (e) periarticular increased bone
after surgical pus drainage and irrigation. Maximum PET/CT images showed intense FDG uptake in the
intensity projection (MIP) image shows intense right knee joint along the synovial lining without
FDG uptake at the right knee. Coronal and sagittal evidence of bone involvement (Fig. 2.6).
24 Y. M. Han
a b
c d
Fr:1-2
Ant Post
e
Fr:11-12
Fr:21-22
Fig. 2.5 (a) Plain radiography: soft tissue swelling, patchy bone marrow edema. Three-phase bone scintigra-
uneven joint space narrowing, and periarticular bone ero- phy: (c, d) diffuse hot uptake throughout left wrist on both
sion and sclerosis. (b) FS T2W MRI: high signal intensity perfusion and blood pool images and (e) periarticular hot
of synovial and parasynovial inflammation with uneven uptakes at carpal bones on delayed scan
joint space narrowing, subchondral bone erosions, and
a b
Fig. 2.6 (a) Plain radiography: distended suprapatellar uptake at right knee on MIP image. (c) Intense FDG
bursa without evidence of bone lesion. FDG PET/CT after uptake in right knee joint along synovial lining without
surgical pus drainage and irrigation: (b) intense FDG evidence of bone involvement on CT and PET/CT images
Case 2.6 ral head and the greater trochanter of the left
A 79-year-old woman spontaneously developed femur. 99mTc-HDP bone scintigraphy showed
left hip pain a week ago. Operative findings were periarticular increased bone uptakes in the left
necrosis of the greater trochanter of the left acetabulum, left femoral head, and trochanteric
femur, multiple abscess pockets around the area. A round photopenia was in the intertrochan-
greater trochanter, and granuloma and inflamma- teric area, which is corresponding to intramedul-
tory tissue around abscess. The pathologic report lary abscess in the femur on MRI (Fig. 2.7).
of hip joint biopsy was active granulomatous
inflammation with caseous necrosis. MTB-PCR Teaching Points
result was positive. • Three-phase bone scintigraphy is a good
Plain radiography of the left hip showed peri- modality showing active tissue inflam-
articular radiolucencies in the acetabulum, the mation and bone change. However, it is
femoral head, and the proximal femur. Mixed nonspecific to detect a infection and is
erosive and sclerotic bone lesions were in the only representing tissue hyperemia and
greater trochanter. FS T2W coronal MRI showed bone turnover. So, similar findings can
heterogeneous intermediate to high signal inten- be demonstrated in aseptic other joint
sity of bone marrow changes in the acetabulum disease.
and in the head and intertrochanteric area of the • Mild periarticular increased bone uptake
left femur. Fluid accumulation (cold abscesses) may be a finding of reactive bone change
of mixed high and low signal intensity was in the resulted from synovial hyperemia or
left hip joint space and in the femur, suggesting reactive bone marrow edema.
tuberculous arthritis combined with tuberculous • Associated cortical bone destructions in
osteomyelitis. Fluid accumulations were also the course of the disease can be repre-
noted in para-articular soft tissues and in the tro- sented as focal intense bone uptakes.
chanteric bursa. Bone erosions were at the femo-
26 Y. M. Han
a b
Fig. 2.7 (a) Plain radiography: periarticular radiolucen- space, proximal femur, trochanteric bursa, and para-
cies (arrows) in acetabulum, femoral head, and proximal articular soft tissues. (c) Bone scintigraphy: periarticular
femur. Mixed erosive and sclerotic bone lesions (arrow- increased bone uptake at left hip with small round photo-
heads) in greater trochanter. (b) FS T2W MRI: bone mar- penia in proximal femur, corresponding to intramedullary
row changes in acetabulum and proximal femur with bone abscess
erosions. High signal intensities of cold abscesses in joint
References 5. Eriksen EF, Ringe JD. Bone marrow lesions: a uni-

versal bone response to injury? Rheumatol Int.
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H. Fluorodeoxyglucose PET/CT of arthritis in rheu-
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2020;40:223–40.
myelitis in children by combined blood pool and bone
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imaging. Radiology. 1975;117:331–5.
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Delhi: Jaypee Brothers Medical Publishers Pvt, Ltd;
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4. Starr AM, Wessely MA, Albastaki U, Pierre-Jerome
etal tuberculosis. Eur Radiol. 2003;13:1809–19.
C, Kettner NW. Bone marrow edema: pathophysiol-
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ogy, differential diagnosis, and imaging. Acta Radiol.
review with patient presentations and discussion. Am
2008;49:771–86.
J Med. 1970;48:77–84.
Inflammatory Arthritis
3
Ju Won Seok
Abstract Keywords
Inflammatory arthritis is a joint inflammation Rheumatoid arthritis · Ankylosing spondylitis

caused by an overactive immune system. It Gout · Synovial hyperplasia · Joint effusion
usually affects many joints throughout the Bone erosions · Tenosynovitis
body at the same time. Inflammatory arthritis
is much less common than osteoarthritis,
which affects most people in their later stages 3.1 Ankylosing Spondylitis
of life. The major types of inflammatory
arthritis including rheumatoid arthritis, sero- 3.1.1 Etiology and Clinical
negative spondyloarthropathies (ankylosing Significance
spondylitis), and crystal-induced arthritis
(gout and pseudogout) will be presented in Ankylosing spondylitis (AS) is a chronic inflam-
this chapter. matory disease that affects the sacroiliac (SI)
Clinical symptoms, physical examination, joints and/or spine in particular. AS is often more
blood tests, and imaging techniques, including common in men and becomes symptomatic in the
plain radiography, ultrasonography of joints, second or third decades as lower back pain and
CT, and MRI, are essential to make an accu- spinal immobility [1]. In addition, approximately
rate diagnosis. Bone scintigraphy is frequently 90% of AS patients are HLA-B27 positive.
used in the workup of patients with inflamma- Though the pathogenesis of AS has not yet
tory arthritis, because it is not specific, but been fully understood, it is now clear that spinal
sensitive in the detection of inflammatory bone formation in AS is a post-inflammatory tis-
joint diseases. sue remodeling reaction. Enthesitis is an impor-
tant pathologic feature of AS and believed to
represent the primary pathogenic process in such
a group of disease [2]. Studies have shown pre-
disposing factors such as genetic background,
microbial infection, endocrine abnormalities, and
immune responses associated with the occur-
J. W. Seok (*) rence of AS [3–5].
Department of Nuclear Medicine, Chung-Ang
University, College of Medicine,
Seoul, Republic of Korea
e-mail: joneseok@cau.ac.kr
https://doi.org/10.1007/978-981-19-2677-8_3
30 J. W. Seok
3.1.2 Radiographic Imaging

Teaching Points
Symmetrical and bilateral sacroiliitis is usually • Bone scan may be helpful with ambigu-
the first manifestation. The sacroiliac joints were ous findings on SI joint in conventional
first widened, and subchondral erosions, sclero- imaging methods.
sis, and proliferation on the iliac side of the SI • Qualitative evaluation of radionuclide
joints were detected. Early spondylitis, along accumulation in SI joints can be difficult
with reactive sclerosis, is characterized by small due to normal uptake at this location.
erosions at the corners of vertebral bodies. AS is Therefore, quantitative analysis may be
the most common cause of vertebral body squar- more useful.
ing. It usually includes several steps and gener-
ally begins in the lumbar spines and precedes the
bamboo spine. Case 3.1
Chronic structural changes such as erosions, A 16-year-old man with left wrist and right hip
subchondral sclerosis, and bony ankylosis are pain that started several months ago. Bone scan
better observed in CT. MRI may play a role in shows markedly increased uptake in the left wrist
early diagnosis of sacroiliitis. MRI is more sensi- and right sacroiliac joint. MRI shows bone mar-
tive in detecting inflammatory changes such as row edema around the right sacroiliac joint, rep-
bone marrow edema, synovitis, and capsulitis. resenting osteitis with erosions, synovitis, and
Bone scan may be helpful in selected patients capsulitis, suggesting right active sacroiliitis. He
with normal or equivocal findings on sacroiliac was clinically diagnosed with ankylosing spon-
joint, and quantitative analysis by uptake ratio of dylitis (Fig. 3.1).
SI joint to sacrum may be useful.
Fig. 3.1 Bone scan images show increased uptake of left wrist and right sacroiliac joint, and MRI also shows findings
suggesting sacroiliitis
3 Inflammatory Arthritis 31
Case 3.2 3.2 Rheumatoid Arthritis

A 17-year-old man with persistent bilateral hip
and back pain. Radiologic imaging shows bilat- 3.2.1 Etiology and Clinical
eral sacroiliitis. Bone scan shows increased Significance
uptake in both SI joints. The uptake ratio of sac-
roiliac joint to sacrum was measured high 2.46 Rheumatoid arthritis (RA) is a systemic autoim-
on the right and 2.86 on the left (normal value, mune disease characterized by inflammatory
within 1.2), meaning that uptake of SI joints arthritis and extra-articular involvement [6].
increased due to sacroiliitis (Fig. 3.2). Although the cause of RA is unknown, a genetic
predisposition and an environmental trigger were
Case 3.3 generally considered to have led autoimmune
A 35-year-old man with ankylosing spondylitis resactions [7]. Activation and accumulation of
has had stiffness and pain in his back since he CD4 T cells in the synovium cause a continuation
was 20 years old. He had never been treated, and of inflammatory reactions [8]. An inflammatory
the pain has worsened recently. Radiographic reaction induces pannus formation. Pannus grad-
imaging shows bilateral sacroiliitis. Bone scan ually erodes at the bare area at first, followed by
shows increased uptake in both sternoclavicular the articular cartilage, and it causes fibrous anky-
junctions and both SI joints. He was clinically losis which becomes an ossfication [9].
diagnosed with SAPHO syndrome accompanied The most common clinical manifestation of
by ankylosing spondylitis (Fig. 3.3). RA is the polyarthritis of the small joints of the
Fig. 3.2 Sacroiliitis is observed in both sacroiliac joints on X-ray images, and increased uptake of both sacroiliac joints
is also observed on bone scan images
32 J. W. Seok
Fig. 3.3 Bone scan images show increased uptake in both sacroiliac joints. Characteristically, increased uptake in both
sternoclavicular junctions is observed in bone scan images
hands: proximal interphalangeal (PIP), metacar- proximal joints in a bilaterally symmetrical dis-
pophalangeal (MCP) joints, and wrist. Other tribution. The acquired changes of RA are sub-
joints that are generally affected include wrists, chondral cyst formation, hitchhiker’s thumb
elbows, shoulders, hips, knees, ankles, and meta- deformity, scapholunate dissociation, and anky-
tarsophalangeal (MTP) joints. The arthropathy losis. The feet are the same as the hands, and PIP
has a typical inflammatory phenotype with joint and MTP joints are preferred.
stiffness, reduced range of motion, and decreased Ultrasonography can evaluate soft tissue man-
function. ifestations such as synovial proliferation and
inflammation of the superficial joints, tenosyno-
vitis, and bursitis [10]. MRI is particularly sensi-
3.2.2 Radiographic Imaging tive to the initial and subtle characteristics of
RA. Characteristics of RA, which are best dem-
Radiographic features of RA are marginal ero- onstrated by MRI, include synovial hyperemia,
sions, soft tissue swelling, osteoporosis, and nar- synovial hyperplasia, pannus formation, reduc-
rowing of joint space. Diagnosis and follow-up of tion in the thickness of cartilage, subchondral
patients with RA generally include images of cysts and erosion, juxta-articular bone marrow
hands and wrist. The disease tends to affect the edema, and joint effusions [11].
phalangeal joints of both hands. Bone scan shows

Teaching Points increased uptake in both hands, wrists, elbows,
• Bone scan appeared to be a more sensi- both knees, ankles, and both feet, suggestive of
tive method for detecting inflammatory polyarthritis (Fig. 3.4).
joint disease than conventional imaging
methods and more sensitive than clini- Case 3.5
cal evaluation in diagnosis of joint A 50-year-old woman presented with pain in the
inflammation. wrist and knee joints. Radiologic imaging of
• The occurrence of erosion of RA can be both feet showed bone erosions at left first inter-
predicted through bone scan. phalangeal joint, both third and fourth metatar-
• When the high activity persists, erosions sophalangeal joint, and left fifth
were most likely to occur in joints show- metatarsophalangeal joint, subluxation of right
ing high radionuclide uptake. third and left fourth metatarsophalangeal joint,
and soft tissue swelling around left fifth metatar-
sophalangeal joint. It suggested rheumatoid
Case 3.4 arthritis. There was no significant bony abnor-
A 52-year-old woman presented with pain in all mality on both knees and both hands, except for
finger joints and wrists lasting more than 10 years. joint effusion of the left knee. Bone scan shows
She had pain, swelling, and stiffness in the increased uptake in both wrists; both knees; right
knuckles in the morning, which lasted for more first, second, and third metatarsophalangeal
than 1 h. Plain radiograph of both hands shows joints; and left third, fourth, and fifth metatarso-
degenerative change and erosions on metacarpophalangeal joints (Fig. 3.5).
Fig. 3.4 Increased uptake of both wrists; the second and third, and fourth proximal interphalangeal joints of the left
fifth metacarpophalangeal joints; the third, fourth, and fifth hand; both ankles; the first, second, third, fourth, and fifth
proximal interphalangeal joints; and the second and third metatarsophalangeal joints of the right foot; and the first,
distal interphalangeal joints of the right hand; the first, sec- second, third, and fifth metatarsophalangeal joints of the
ond, and third metacarpophalangeal joints and the second, left foot are observed in bone scan images
34 J. W. Seok
Fig. 3.5 Bone scan images show increased uptake of multiple metatarsophalangeal joints of both feet, and X-ray
images also show bone erosion of multiple metatarsophalangeal joints of both feet
Fig. 3.6 Severe deformity is also observed in X-ray imaging in both wrist joints where increased uptake is observed in
bone scan imaging
Case 3.6 increased uptake in both wrists, left first metacar-

A 61-year-old woman was diagnosed with rheu- pophalangeal joint, and fourth proximal interpha-
matoid arthritis 10 years ago due to multiple joint langeal joint of the left hand (Fig. 3.6).
pains and was treated at another hospital, but did
not improve, and was admitted to the outpatient Case 3.7
hospital. Radiologic imaging shows severe defor- A 47-year-old woman was admitted with wrist
mity on both wrist joints. Bone scan shows pain lasting more than 1 year. Radiologic imag-
Fig. 3.7 In both wrist joints, bone scan images show increased uptake, and severe deformity was observed in X-ray
images
ing suggested advanced rheumatoid arthritis on tion, and swollen joints, typically in the lower
both wrists. Bone scan shows markedly increased limb, and classically affects the first metatarso-
uptake in both wrist joints (Fig. 3.7). phalangeal joint. Gout accumulated monoso-
dium crystals in tissues; it causes arthritis, soft
tissue mass, nephrolithiasis, and urate nephrop-
3.3 Gout athy [14].
The main risk factor is hyperuricemia, which
3.3.1 Etiology and Clinical can leave uric acid crystals such as needles inside
Significance joints [15]. The main symptom is joint pain that
appears often first on the big toe. Other joints that
Gout is a metabolic disorder [12]. However, may be affected include ankles, feet, knees, and,
since clinical presentations are very similar to in severe cases, wrists, elbows, and fingers [16].
arthritis, gout is also classified as a form of crys- A similar condition, known as pseudogout, has
tal-induced arthritis [13]. Acute gout arthritis similar symptoms. In both conditions, white
represents a monoarticular redness, inflamma- blood cells surround chemical crystals that cause
36 J. W. Seok
inflammation. In pseudogout, the associated Case 3.8

crystals are formed from calcium pyrophosphate A 34-year-old man was admitted with a 1-month
dihydrate, rather than uric acid as in gout, and history of pain in the ankle joints followed by
knee joints are primarily affected. involvement of both first metatarsophalangeal
joints. Radiographs show erosive changes on the
right medial hallux sesamoid bone and small ero-
3.3.2 Radiographic Imaging sion on the left first proximal phalangeal base.
Bone scan shows increased uptake in both first
Although not all patients progress to this stage, metatarsophalangeal joints. Ultrasound image
characteristic radiologic changes occur in the shows synovial thickening and joint effusion
chronic stage. Small joints of the hands and feet with echogenic nodular lesions of medial capsule
are preferred. The earliest change is the swelling of bilateral metatarsophalangeal joints. It sug-
of soft tissue. At a later stage, erosions occur gested gout arthritis (Fig. 3.8).
that may be far from the articular cortex. These
erosions are well defined, often sclerotic and Case 3.9
with edges, often protruding edges. It is because A 48-year-old man presented with sudden right
there are urate sediments in the bone. These foot pain. Radiographic imaging shows degenera-
sediments are so large that they can cause exten- tive change and soft tissue swelling on the right
sive bone destruction. Usually, there is no osteo- first metatarsophalangeal joint. Bone scan shows
porosis. Due to the collection of sodium urate increased uptake in the right first metatarsophalan-
known as tophi, localized soft tissue lumps may geal joint. Ultrasound image shows echogenic foci
occur in the periarticular tissues. The swellings and capsular thickening on right first metatarsopha-
may be large and sometimes calcification may langeal joint; it suggested gout arthritis (Fig. 3.9).
be shown [17].
Although there may be changes in appear- Case 3.10
ance, the tophi are hyperechoic and heteroge- A 41-year-old man was diagnosed with gout at an
neous and tend to be poorly defined contours in outside hospital and was admitted. He complained
ultrasound. CT and MRI can distinguish between of pain in both knee and ankle joints. Radiographic
urate mineralization and calcification and can be imaging shows moderate osteoarthritis on both
useful if clinical and biochemical presentations knee joints, but no abnormal findings were found
are atypical. in both ankles. Bone scan shows increased uptake
in the right knee and right ankle joints. Ultrasound
image shows echogenic tophi on medial aspect of
Teaching Points both ankles and right knee (Fig. 3.10).
• Bone scan has high sensitivity to osse-
ous abnormality detection, but the scin- Case 3.11
tigraphic findings in gout are often A 47-year-old woman was admitted with pain in
non-specific. both feet lasting for 1 year. Radiographic imag-
• Asymmetrical, bilateral, and multifocal ing showed diffuse osteopenia and osteoarthritis
joint involvement tends to be associated on both feet. Bone scan shows increased bone
with severe abnormal uptake area. uptake in both cuboid bones of both feet and joint
• The intense uptake usually extends uptake in the first metatarsophalangeal joint and
beyond the associated joints, because of proximal interphalangeal joints of the right foot.
the swelling of soft tissue. Ultrasound image shows mild synovitis and
echogenic change on both first metatarsophalan-
Fig. 3.8 In both first metatarsophalangeal joints, increased uptake is observed in bone scan images, bone erosion is
observed in X-ray images, and synovial thickening was observed in ultrasound images
geal joints and synovial thickening and erosive showed no abnormality on both feet. Bone scan
change with joint effusion on tarsometatarsal shows increased uptake in the right first metatar-
joints of both feet. The patient was clinically sophalangeal joint, both knee joints, and both
diagnosed with gout (Fig. 3.11). ankle joints. Ultrasound image shows large echo-
genic foci with bony erosion and synovial thick-
Case 3.12 ening and small joint effusion. CT image with
A 42-year-old man presented with unbearable uric acid spectral CT shows gout tophi on the
pain in the right first toe. Radiographic imaging right first toe (Fig. 3.12).
38 J. W. Seok
Fig. 3.9 Increased uptake is observed in the first metatarsophalangeal joint on the right foot, and echogenic foci is
observed in ultrasound images
Fig. 3.10 Increased uptake is observed in the right knee and right ankle joints in bone scan images, and tophi is
observed in the ultrasound images of the same area
Fig. 3.11 Bone scan images shows increased uptake in the first metatarsophalangeal joint and the first proximal inter-
phalangeal joint of the right foot
Fig. 3.12 In the bone scan images, the increased uptake of the first metatarsophalangeal joint of the right foot is
observed, and the tophi is observed in the uric acid spectral CT image in the same area
40 J. W. Seok
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Non-inflammatory Arthritis:
Osteoarthritis 4
Young-Sil An
Abstract 4.1 Etiology

and Pathophysiology
Osteoarthritis is the most common form of
non-inflammatory arthritis. Osteoarthritis
Non-inflammatory arthritis is so named because
mainly involves the knee, hip, and hand joints,
it does not show inflammatory features such as
and obesity or repetitive joint damage is
warmth or swelling in the joint area and is mostly
known risk factors. Diagnosis of osteoarthritis
known to be associated with osteoarthritis (OA)
is based on clinical and/or radiological fea-
[1, 2]. Therefore, this chapter will mainly focus
tures; nuclear medicine imaging studies can
on OA.
be helpful when the diagnosis is ambiguous or
OA usually occurs frequently in people over
when evaluating disease severity. Bone scans
the age of 50, and aging and being overweight are
are traditional imaging studies used in the
known risk factors. In addition, OA can occur
field of nuclear medicine for evaluating osteo-
due to joint injury and repetitive joint damage
arthritis, and bone single-photon emission
due to daily activities, such as occupation-related
computed tomography (SPECT) or SPECT/
activities or hobbies. OA commonly involves
computed tomography is also clinically used
weight-bearing large joints (such as the knee and
to compensate for the limitations of bone
hip joints) and small joints (such as the hands) [2,
scans. Here, we will elucidate cases where
3]. Patients with OA usually complain of joint
nuclear medicine imaging studies has pro-
pain, stiffness, and restriction without systemic
vided valuable information in diagnosing and
involvement of other organs [1].
evaluating osteoarthritis.
OA can cause breakdown of cartilage and
periarticular bones [3]. This leads to alteration of
Keywords
osteoclast and osteoblast activity and changes in
Non-inflammatory arthritis · Osteoarthritis bone material properties and architecture, lead-
Bone scan · Bone SPECT · Bone SPECT/CT ing to the formation of osteophytes [4]. In addi-
tion, hyperplasia of the joint synovium may
appear in OA, which can be observed in imaging
findings such as magnetic resonance imaging
(MRI) and ultrasonography, and could be corre-
Y.-S. An (*) lated with joint symptoms of OA [3, 5].
Department of Nuclear Medicine and Molecular
Imaging, Ajou University School of Medicine,
Suwon, Republic of Korea
https://doi.org/10.1007/978-981-19-2677-8_4
42 Y.-S. An
4.2 Diagnosis Case 4.1

A 69-year-old man presented with bilateral knee
Most patients with OA visit the hospital mainly pain that began 3 years prior. The patient mani-
because of symptoms such as joint pain or dis- fested with a bilateral sore pain in his knees,
comfort. Diagnosis of OA is mainly conducted necessitating him to rest after a 20-min walk due
by evaluating patients’ symptoms; however, the to pain. In the simple radiograph performed at
primary aim is to differentiate OA from other our hospital, joint space narrowing was observed
arthritis such as rheumatoid arthritis, ankylosing in both knees, suggesting arthritis (Fig. 4.1a).
spondylitis, gouty arthritis, septic arthritis, and The patient underwent a bone scan in our depart-
psoriatic arthritis. This can help rule out other ment for further evaluation of OA in both knees.
diseases by assessing the rheumatoid factor, On the anterior and posterior view images of
erythrocyte sedimentation rate, and C-reactive the bone scan, hot uptakes were observed in the
protein levels through blood tests. medial compartments and patellar region of both
Imaging studies can assist when the clinical knees (Fig. 4.1b). However, localization of the
diagnosis of OA is unclear or when evaluating lesion is limited due to the nature of the views;
disease severity. Typical findings of simple X-ray therefore, medial and lateral images were addi-
imaging in OA include joint space narrowing, tionally obtained after flexion of the patient’s
osteophyte formation, and subchondral sclerosis. knee using a staircase tool. During the evaluation
However, in early OA, these findings may not be of the additional images, the hot uptakes were
clear, and MRI may be useful in these cases. A located in the right medial tibial condyle, the pos-
bone scan is the most commonly used nuclear terior portion of the medial femoral condyle, and
medicine imaging study to evaluate OA. This patella, and the patellofemoral joint was also
imaging tool can be used to deposit bone-seeking accompanied by a hot uptake in the right knee
radiopharmaceuticals in areas where osteoblastic (Fig. 4.1c). Additional regional view images of
activity and perfusion are increased in OA lesions the left knee showed a hot uptake in the medial
[6]. However, bone scan has a limitation in evalu- tibial condyle and patellofemoral joint (Fig. 4.1d).
ation of OA, because a bone scan can provide According to this case, it is clearly shown that a
only planar images and it can be supplemented more detailed lesion location that was not known
by using bone single-photon emission computed in simple anterior and posterior view images can
tomography (SPECT) or SPECT/CT. Because be confirmed in an additional view obtained by
SPECT can provide a three-dimensional image flexing the joint.
of the joint area, the localization of the lesion can
be more clearly evaluated. In particular, it is pos- Case 4.2
sible to obtain a fusion image of SPECT and CT A 77-year-old woman visited our hospital com-
images from SPECT/CT; therefore, its clinical plaining of pain in the right knee, which started
utility in arthritis is expected to increase [7, 8]. 5 months prior. The patient’s pain worsened
during a squatting position and when she stands
up from a sitting position. The patient underwent
Teaching Points a simple radiograph to evaluate pain in both
• When a bone scan is performed to eval- knees, and the findings showed joint space nar-
uate OA, a regional view can be helpful rowing in both knees, which was suggestive of
in finding more detailed lesions. arthritis (Fig. 4.2a). The patient further under-
• SPECT/CT may be more useful than went a bone scan and bone SPECT/CT of both
planar bone scan in evaluating OA. knees in our department for further evaluation.
• In a bone scan, the whole body can be On planar bone scan, intense hot uptakes were
covered with a single examination, so it observed in the medial, lateral, and patellar
is possible to detect OA in areas the regions of the right knee (Fig. 4.2b). Although
patient is not aware of. there was no pain in the patient’s left knee joint,
mild radiopharmaceutical deposition was also
4 Non-inflammatory Arthritis: Osteoarthritis 43
a c
b d
Fig. 4.1 (a) A simple radiograph showed narrowing of femoral condyle, and patella in the flexion view of the
the bilateral knee joint spaces. (b) Hot uptakes were right knee (red arrowheads), which was also accompanied
observed in the medial compartments and patellar region by hot uptakes in the patellofemoral joint (green arrow-
of both knees on bone scan (red arrowheads for the right head). (d) In the regional view of the left knee, hot uptakes
knee and blue arrowheads for the left knee). (c) were noted in the medial tibial condyle and patellofemoral
Additionally, hot uptakes were confirmed in the right joint (blue arrowheads)
medial tibial condyle, the posterior portion of the medial
observed in the medial compartment and patellar Case 4.3

region of the left knee (Fig. 4.2b). However, there A 49-year-old man visited our hospital complain-
is a limit to clearly distinguishing anatomical ing of persistent pain in both ankles for 8 months.
regions of hot uptake in knees with only a planar Pain is mainly evident during a squatting posi-
bone scan image. On additional bone SPECT/CT, tion. A simple radiograph showed arthritis in
intense hot uptake lesions were observed in the both ankle joints (Fig. 4.3a). The patient was
medial and lateral femoral condylar region, referred to our department for a bone scan and
patella, and patellofemoral joint of the right knee. bone SPECT/CT examination for a more detailed
It was confirmed that mild hot uptakes of the left evaluation of arthritis.
knee were lesions of the left medial femoral con- Hot uptake was observed in both ankle joints
dylar area and left patellofemoral joint (Fig. 4.2c, on a bone scan (Fig. 4.3b). These hot uptake
d, f and g). In the CT image, it was additionally lesions were more clearly confirmed to be lesions
observed that the space of the bilateral patello- of both tibiotalar and fibulotalar joints on SPECT/
femoral joints was narrowed (Fig. 4.2e). The CT images (Fig. 4.3c–f). The patient was finally
patient was diagnosed with bilateral knee joint diagnosed with OA of both ankle joints. As seen
OA (more active on the right side). In this case, it in this case, the hot uptake seen in the bone scan
shows that bone SPECT/CT provides a clearer shows a clearer localization through bone
anatomical information about OA lesions than SPECT/CT.
bone scan.
44 Y.-S. An
a c e
b
d
Fig. 4.2 (a) On a simple radiograph, joint space narrow- intensity projection (MIP) image], d [MIP image of fusion
ing was observed in both knees. (b) Intense hot uptakes with CT], f [SPECT image], and g [SPECT fusion with
were noted in the medial, lateral, and patellar regions of CT]) and mild hot uptakes in the left medial femoral con-
the right knee (red arrowheads), and mild hot uptakes dyle and patellofemoral joint (blue arrowheads in c, d, f,
were also noted in the medial region of the left knee on and g) were confirmed by SPECT/CT. Also, it was found
bone scan (blue arrowheads). (c–g) Intense hot uptakes in that both patellofemoral joint spaces were narrowed on
the right medial, lateral femoral condyle, patella, and CT image (arrows in e)
patellofemoral joints (red arrowheads in c [maximum
a c e
b
d f
Fig. 4.3 (a) A simple radiograph showed that the spaces lesions in both tibiotalar and fibulotalar joints (arrow-
between the ankle joints were narrowed. (b) Hot uptakes heads in c [MIP image], d [MIP image of fusion with CT],
were observed in both ankle joints on a bone scan (arrow- e [coronal SPECT image], and f [coronal SPECT fusion
heads). (c–f) SPECT/CT images showed hot uptake with CT])
Case 4.4 (Fig. 4.4c, d, f and g). Moreover, a possible

A 34-year-old man presented with left foot pain. arthritic change in this area was considered. In
The patient had a fracture of the left calcaneus this case, bone SPECT/CT was advantageous,
due to a fall 2 years prior and underwent surgery. detecting lesions that were not visible on bone
Subsequently, pain in the left foot area persisted scans in posttraumatic OA.
during the recovery process. X-ray of his left foot
region was performed and showed no specific Case 4.5
findings other than a metallic prosthesis from the A 55-year-old woman who was diagnosed with
left calcaneus surgery (Fig. 4.4a). Bone scan and left breast cancer 4 years previously underwent a
bone SPECT/CT were performed in our depart- bone scan and 18F-fluorodeoxyglucose (18F-FDG)
ment for further evaluation of foot pain. positron emission tomography (PET)/CT for fol-
In the bone scan, hot uptake with a diffuse low-up examination. The patient’s bone scan
mild pattern was observed in the left foot region showed no suspicious hot uptake indicative of a
(Fig. 4.4b). Bone SPECT/CT showed a mildly metastasis, and a mild radiopharmaceutical accu-
hot uptake with a postoperative change pattern in mulation at the right shoulder joint was observed
the left calcaneus area (Fig. 4.4c, d, f and g), and (Fig. 4.5a). 18F-FDG PET/CT showed no recur-
the inserted pins were also confirmed on the CT rent malignancy or metastasis, but hot uptake was
image (Fig. 4.4e). Another hot uptake lesion was observed in the right shoulder joint, which was
observed in the left talocalcaneal joint above the more active than that in the bone scan (Fig. 4.5b–
surgical site (Fig. 4.4c, d, h and i), and this area d). The patient mainly used her right arm due to
coincided with the patient’s main pain area; surgery on the left breast and was diagnosed with
therefore, OA was confirmed. There were no spe- OA of the right shoulder joint. In this case, we
cific symptoms in the patient’s right foot, but a show an OA caused by the excessive use of the
hot uptake was incidentally observed in the right contralateral joint due to the deterioration of the
intercuneiform joint on bone SPECT/CT unilateral joint due to surgery or trauma.
e h
a c
b d
i
Fig. 4.4 (a) On a simple radiograph of the patient’s left [SPECT fusion with CT]). In the CT image, the pins
foot, there were no specific findings except for the metal- inserted into the left calcaneus can also be confirmed
lic prosthesis from surgery. (b) Hot uptake with mild dif- (arrow in e). Another hot uptake lesion was seen in the left
fuse pattern is shown in the left foot area on the bone scan. talocalcaneal joint, which coincided with the patient’s
(c–i) On SPECT/CT images, there was mildly hot uptake pain area (red arrowheads in c, d, h [SPECT image], and i
lesion in the left calcaneus area with a postoperative [SPECT fusion with CT]). Also, hot uptake in the right
change pattern (green arrowheads in c [MIP image], d intercuneiform joint is an incidental lesion found only in
[MIP image of fusion with CT], f [SPECT image], and g SPECT/CT (blue arrowheads in c, d, f, and g)
46 Y.-S. An
a b c
Fig. 4.5 (a) Mildly hot uptake lesion was noted in right observed on 18F-FDG PET/CT (arrowheads in b [MIP]
shoulder joint on bone scan (arrowhead). (b–d) More image], c [PET image], and d [PET fusion with CT])
active hot uptake lesion of right shoulder joint was
Case 4.6 The patient had no specific past history other than
A 55-year-old man visited our hospital complain- a history of lumbar disc surgery 3 years previ-
ing of bilateral knee and elbow pain. The patient ously. A simple X-ray was performed to evaluate
has been working on a construction site for 15 years the presence of arthritis. As a result, severe joint
and has had persistent pain in the knee and elbow space narrowing was observed in the left hip joint
since about 8 years prior, and the pain worsened (Fig. 4.7a), which was highly suggestive of
while working. A simple radiograph of both knees OA. The patient underwent a bone scan in our
was performed, and both knee joint spaces were department for a more detailed evaluation.
narrowed, suggesting arthritis (Fig. 4.6a). He per- On bone scan, a significantly large intense hot
formed a bone scan in our department for a more uptake lesion was observed in the left hip joint,
detailed evaluation of pain in the joints. suggesting severe advanced OA (Fig. 4.7b). In
In the bone scan, hot uptake was observed in addition, hot uptakes of both shoulder joints and
both elbows and bilateral knee joints (Fig. 4.6b), small joints of both hands were also seen in the
which were associated with OA. As in this case, bone scan, confirming OA in this area as well
a patient may complain of joint pain in several (Fig. 4.7b). As seen in this case, the hip and hand
areas instead of one location, and this case joints are areas where OA can easily occur, and
showed that a bone scan encompassing the whole bone scans show that the uptake level of radio-
body with one examination can be useful for pharmaceuticals can reflect the severity of the
evaluating multiple OA. disease.
Case 4.7
A 73-year-old man visited our hospital with left
hip joint pain that had begun 2 years previously.
Fig. 4.6 (a) On a simple radiograph, joint space narrowing of both knees was observed. (b) Hot uptakes in both elbows
(red arrowheads) and bilateral knee joints (blue arrowheads) were noted on bone scan
Fig. 4.7 (a) A simple radiograph showed the left hip joint (red arrowheads). Additionally, hot uptakes in both shoul-
space was severely narrowed (arrow). (b) Intense hot ders (blue arrowheads) and small joints of both hands
uptake lesion was observed in left hip joint on bone scan (arrows) were noted in the bone scan
48 Y.-S. An
References toms and cartilage volume loss in knee osteoarthritis

patients using MRI. Osteoarthr Cartil. 2008;16(Suppl
3):S8–13. https://doi.org/10.1016/j.joca.2008.06.007.
1. Pujalte GG, Albano-Aluquin SA. Differential diag-
6. Park DY, Jin LH, Min BH, Kwack KS, An YS, Kim
nosis of polyarticular arthritis. Am Fam Physician.
YJ. Subchondral bone scan uptake correlates with
2015;92(1):35–41.
articular cartilage degeneration in osteoarthritic knees.
2. Mies Richie A, Francis ML. Diagnostic approach
Int J Rheum Dis. 2017;20(10):1393–402. https://doi.
to polyarticular joint pain. Am Fam Physician.
org/10.1111/1756-185X.12909.
2003;68(6):1151–60.
7. An YS, Park DY, Min BH, Lee SJ, Yoon JK. Comparison
3. Martel-Pelletier J, Barr AJ, Cicuttini FM, Conaghan
of bone single-photon emission computed tomography
PG, Cooper C, Goldring MB, et al. Osteoarthritis.
(SPECT)/CT and bone scintigraphy in assessing knee
Nat Rev Dis Primers. 2016;2:16072. https://doi.
joints. BMC Med Imaging. 2021;21(1):60. https://doi.
org/10.1038/nrdp.2016.72.
org/10.1186/s12880-021-00590-8.
4. Burr DB, Gallant MA. Bone remodelling in osteo-
8. Kim J, Lee HH, Kang Y, Kim TK, Lee SW, So Y, et al.
arthritis. Nat Rev Rheumatol. 2012;8(11):665–73.
Maximum standardised uptake value of quantitative
https://doi.org/10.1038/nrrheum.2012.130.
bone SPECT/CT in patients with medial compartment
5. Pelletier JP, Raynauld JP, Abram F, Haraoui B,
osteoarthritis of the knee. Clin Radiol. 2017;72(7):580–
Choquette D, Martel-Pelletier J. A new non-invasive
9. https://doi.org/10.1016/j.crad.2017.03.009.
method to assess synovitis severity in relation to symp-
Hypertrophic Osteoarthropathy
5
Young Seok Cho
Abstract 5.1 Etiology and Clinical

Significance
Hypertrophic osteoarthropathy (HOA) is a
syndrome characterized by abnormal skin
Hypertrophic osteoarthropathy (HOA) is a syn-
proliferation at the distal parts of the extremi-
drome defined by abnormal skin proliferation at
ties as well as periosteal proliferation of the
the distal parts of the extremities as well as peri-
long bones. Bone scintigraphy, usually with
osteal generation of the long bones. HOA can be
99m
Tc methylene diphosphonate (MDP), is
a primary disease entity, known as pachydermo-
usually more sensitive for the detection and
periostosis, or can be secondary to extraskeletal
characterization of the extent of HOA than
conditions, with different prognoses and manage-
radiography alone. Typically, there is sym-
ment implications for each. There is a high asso-
metrically increased tracer uptake at the peri-
ciation between secondary HOA and thoracic
osteum in a linear fashion along the cortical
malignancy, especially non-small cell lung can-
margins of the diaphysis and metaphysis of
cer. In such cases, it can be considered a form of
the long tubular bones, termed “the tram line”
paraneoplastic syndrome. The most prevalent
or “double stripe sign.”
secondary causes of HOA are pulmonary in ori-
gin, which is why this condition was formerly
Keywords
referred to as hypertrophic pulmonary osteoar-
Hypertrophic osteoarthropathy · HOA thropathy (HPO). HOA can also be associated
Hypertrophic pulmonary osteoarthropathy with pleural, mediastinal, and cardiovascular
HPO · Clubbing · Periosteal reaction causes, as well as extrathoracic conditions such
as gastrointestinal tumors and infections, cirrho-
sis, and inflammatory bowel disease [1]. The
main clinical features are a peculiar bulbous
deformity of the tips of the fingers conventionally
described as clubbing, periosteal reaction of the
tubular bones, and synovial effusions. In HOA,
there is a spectrum of symptoms. At one extreme,
Y. S. Cho (*) patients may be asymptomatic and unaware of
Department of Nuclear Medicine, Samsung Medical the deformity of their fingers and toes. Other
Center, Sungkyunkwan University School of patients, in particular those with lung cancers,
Medicine, Seoul, Republic of Korea may notice a burning sensation of the fingertips
e-mail: ysnm.cho@samsung.com
https://doi.org/10.1007/978-981-19-2677-8_5
50 Y. S. Cho
and may also experience incapacitating bone and right lung lower lobe with ipsilateral hilar lymph
joint pain. Characteristically, this pain is deep- node metastasis had a 99mTc-MDP whole body
seated, more prominent in the lower extremities, bone scan to check for bone metastasis.
and aggravated by dependency of the limbs [2]. Heterogeneous cortical uptakes with relatively
symmetrical distribution can be seen in the cortex
of the metaphysis and diaphysis of both femurs
5.2 Imaging (Fig. 5.1).
Plain X-ray images of the extremities are often Case 5.2

the first imaging modality used to evaluate the A 63-year-old man who underwent right lung
pain and may demonstrate abnormalities even in upper lobectomy and mediastinal lymph node
asymptomatic patients. Periosteal reaction is the dissection for adenocarcinoma of the right lung
imaging hallmark of HOA and manifests along upper lobe 7 years prior had periodic 99mTc-MDP
the shafts of tubular bones and usually spares the whole-body bone scan to screen bone metastasis.
epiphyses in the earliest phases. Symmetric and At the time of bone scan, multiple pulmonary
widely distributed bone involvement is a typical nodules suggesting lung-to-lung metastasis were
finding in primary and generalized secondary seen on chest CT. Symmetric cortical uptakes
HOA. The tibia, fibula, radius, and ulna are the with diffuse pattern are seen in the whole appen-
most commonly affected bones, followed by the dicular skeletons (Fig. 5.2a). Periosteal reactions
phalanges of the fingers. The patterns of perios- were observed on X-ray images of bilateral
teal reaction may be solid, linear, dense, or lay- humeri (Fig. 5.2b) and CT images of bilateral
ered [1, 3]. femurs (Fig. 5.2c).
Periosteal reaction at MR imaging typically
exhibits low-to-intermediate signal intensity on Case 5.3
T1-weighted images and low signal intensity on A 35-year-old man was hospitalized for hemop-
T2-weighted images. Its appearance at MR imag- tysis as chief compliant. His chest CT showed
ing usually correlates with the radiographic find- multiple thin-walled cystic lesions containing
ings and can manifest as simple periosteal soft tissue with nodular growth pattern in both
elevation or laminated or onion-skin periosteal lungs suggesting benign lung disease such as
reaction [1, 4]. tuberculosis or aspergillosis. Bronchoscopy with
Bone scintigraphy, usually with 99mTc methy- transbronchial lung biopsy was performed for
lene diphosphonate (MDP), is usually more sen- differential diagnosis. The biopsy specimen
sitive for the detection and characterization of the showed acute inflammation with many eosino-
extent of HOA than radiography alone [5]. phils suggesting pulmonary aspergillosis. In
Typically, there is symmetrically increased tracer 99m
Tc-MDP whole-body bone scan, the cortical
uptake at the periosteum in a linear fashion along bone uptakes of bilateral upper and lower extrem-
the cortical margins of the diaphysis and metaph- ities were diffusely increased (Fig. 5.3a, b). X-ray
ysis of the long tubular bones, termed the tram showed periosteal thickening along the outer cor-
line or double stripe sign [6, 7]. Prominent tracer tices (Fig. 5.3c, d).
uptake in the digits is reflective of digital club-
bing [8]. Case reports of PET/CT with Case 5.4
18
F-fluorodeoxyglucose (FDG) and sodium fluo- A 67-year-old man who was recently diagnosed
ride ([18F]NaF) have reported uptakes corre- with poorly differentiated adenocarcinoma of
sponding to the periosteal thickening seen on the right lung upper lobe performed a whole-body
corresponding CT image [9, 10]. bone scan for staging. His clinical stage was
T2aN0M0. The patient had complained arthral-
Case 5.1 gia of both hands and knees and clubbing of fin-
A 59-year-old man who was diagnosed with a gers for 3 years. On 99mTc-MDP bone scintigraphy,
4-cm-sized pulmonary adenocarcinoma of the heterogeneous patterns of uptakes were observed
5 Hypertrophic Osteoarthropathy 51
a b
Fig. 5.1 Symmetrical cortical uptakes with heteroge- obtained by continuous acquisition (a) and additional pla-
neous pattern were observed in the cortex of the metaphy- nar spot view images (b)
sis and diaphysis of both femurs on whole-body images
along the appendicular skeleton of the whole body bone scan taken at the time of initial diag-
body (Fig. 5.4a). In particular, increases in nosis showed only mild degenerative changes,
radiouptake were prominent in the bilateral distal and there was no demonstrable abnormal
femurs and the bones of both hands, but the peri- radiouptake suggesting bone metastasis or hyper-
osteal reactions in these areas were not clearly trophic osteoarthropathy (Fig. 5.5a). But, in
seen on X-rays of both hands and both knees whole-body bone scan taken 9 months later,
(Fig. 5.4b, c). On 18F-FDG PET/CT scan, mild newly developed bone metastasis was shown,
periosteal reactions and faint FDG uptake were and the cortical uptakes of both tibiae were
seen along the medial aspect of the proximal increased in diffuse manner (Fig. 5.5b).
femurs (Fig. 5.4d). Comparing CT images, the subcarinal lymphade-
nopathy worsened in the intervening period
Case 5.5 (Fig. 5.5c, d).
A 66-year-old man with a neuroendocrine tumor
located in the central portion of the right lung Case 5.6
with extensive malignant lymphadenopathy in A 57-year-old man with a 7-cm-sized adenocar-
right pulmonary hilum and subcarinal area and cinoma in the upper lobe of the left lung and ipsi-
hepatic metastasis performed a 99mTc-MDP lateral mediastinal lymph node metastasis
whole-body bone scan for staging. The whole- underwent a 99mTc-MDP whole-body bone scan
52 Y. S. Cho
a b
Fig. 5.2 Symmetric cortical radiouptakes with diffuse were observed in the cortex of bilateral distal humeri on
pattern were observed in the cortex of both humeri, both shoulder X-ray images (b) and the cortex of bilateral
radii, both ulnae, both femurs, and both tibiae on whole- proximal femurs on abdomen and pelvis CT images (c)
body bone scan images (a). Periosteal reactions (arrows)
for screening of bone metastasis. The cortical the intense uptakes of multiple bone metastases
uptake of the whole appendicular skeletons was were newly observed (Fig. 5.7b). During the
increased in a diffuse manner, which is typical of interval period, the sizes of mediastinal meta-
hypertrophic osteopathy. But, the X-ray images static lymph nodes and pulmonary metastatic
of both wrists and both ankles did not show a nodules were significantly decreased on chest CT
clear sign of periosteal reaction (Fig. 5.6). images (images not shown).
Case 5.7 Case 5.8

A 53-year-old man with thymic carcinoma and A 68-year-old woman who underwent mastec-
pulmonary metastasis who had extended total tomy for right breast cancer 15 years prior and
thymectomy and adjuvant chemoradiation ther- total thyroidectomy for papillary thyroid cancer
apy 2 years prior underwent a 99mTc-MDP whole- 5 years prior had a 99mTc-MDP whole-body bone
body bone scan for annual follow-up. In the bone scan for annual follow-up. On this scan, the lin-
scan images, the cortical uptakes of both femurs ear radiouptakes consistent with the typical tram
and tibiae were significantly increased in a het- line or double stripe sign were shown along the
erogeneous pattern (Fig. 5.7a). On the follow-up cortical margins of the diaphysis of both femurs
bone scan performed 4 years later, the cortical and tibiae (Fig. 5.8a). X-ray images of both knees
uptakes of both femurs and tibiae decreased, but showed no demonstrable finding of periosteal
a b
c d
Fig. 5.3 Diffuse increases of radiouptake were seen in hands and feet (b). X-ray images of both hands (c) and
the cortex of both radii, both ulnae, both femurs, both both lower legs (d) demonstrated periosteal thickening
tibiae, and small bones of both hands and feet on whole- along the outer cortices of bilateral distal ulnae, radii,
body bone scan images (a) and planar spot images of both tibiae, and fibulae (arrows)
54 Y. S. Cho
a b
Fig. 5.4 Heterogeneous cortical radiouptakes were cortical thickening suggesting periosteal reaction. The
observed in bilateral upper and lower extremities on fusion PET/CT images (right) and CT images (left) of
whole-body bone scan (a). Particularly, the uptakes were torso FDG PET/CT showed faint FDG uptakes
increased in the distal portion of both femurs and tibiae (SUVmax = 1.3) and mild irregular cortical thickenings
and the small bones of both hands. X-ray images of both (arrows) of both proximal femurs (d)
hands (b) and both knees (c) demonstrated no significant
reaction (Fig. 5.8b). Chest CT performed at that metastases and enlarged lymph nodes suggest-
time did not show any abnormal finding sugges- ing mediastinal lymph node metastasis
tive of primary lung cancer, pulmonary metasta- (Fig. 5.9b).
sis, or mediastinal malignant lymphadenopathy
(image not shown). Teaching Points
• Bone scintigraphy is more sensitive for
Case 5.9 the detection and characterization of
A 23-year-old man who had chemoradiotherapy hypertrophic osteoarthropathy than
for nasopharyngeal 4 years prior underwent a radiography alone.
99m
Tc-MDP whole-body bone scan for screening • Typical finding of hypertrophic osteoar-
of bone metastasis. The cortical bone uptakes in thropathy is symmetrical radiouptake at
bilateral upper and lower extremities were the periosteum along the cortical mar-
increased in a heterogeneous pattern (Fig. 5.9a). gins of the long tubular bones, termed
The chest CT images at the time of bone scan “the tram line” or “double stripe sign”.
showed multiple nodules due to pulmonary
a b
Fig. 5.5 The whole-body bone scan images for staging of tasis and the diffuse cortical uptakes of both tibiae sug-
initial diagnosis demonstrated the radiouptakes suggest- gesting hypertrophic osteoarthropathy were shown (b).
ing degenerative change in the L5-S1 spine and left sacro- The size of metastatic subcarinal lymph node had
iliac joint and did not show any abnormal cortical increased significantly between the chest CT initial diag-
radiouptake suggesting hypertrophic osteoarthropathy nosis (c) and the follow-up chest CT taken 9 months later
(a). On the whole-body bone scan taken 9 months later, (d)
the focal radiouptake in L3 spine suggesting bone metas-
56 Y. S. Cho
c d
Fig. 5.5 (continued)

a b
Fig. 5.6 Diffuse radiouptakes were seen on the cortices ening or cortical irregularity suggesting periosteal reac-
of long bones of bilateral upper and lower extremities. In tion on the X-ray images of both wrists and both ankles
particular, the uptakes of both tibiae were clearly increased (b)
(a). There was no demonstrable abnormal cortical thick-
58 Y. S. Cho
a b
Fig. 5.7 Symmetric radiouptakes with uneven pattern intense radiouptake of metastatic lesions, the cortical
were seen along the cortices of both femurs and both tib- radiouptakes of bilateral distal femurs and distal tibiae
iae (a). Even considering the threshold difference due to were decreased on the follow-up bone scan images (b)
a b
Fig. 5.8 Bone scan images showed the diffuse and sym- shafts (a). On the X-ray images of both knees, there was
metric radiouptakes described as “tram line” or “double no significant sign of periosteal reaction in the cortices of
stripe” along the cortices of bilateral femoral and tibial both femurs and tibiae (b)
60 Y. S. Cho
a b
Fig. 5.9 Diffuse and symmetrical cortical uptakes in a nary nodules suggesting pulmonary metastasis of naso-
heterogeneous pattern were shown in the long bones of pharyngeal cancer were shown on chest CT (b)
bilateral upper and lower extremities (a). Multiple pulmo-
demonstrated on SPECT/CT. Clin Nucl Med.

References 2009;34:628–31.
7. Santhosh S, Bhattacharya A, Bhadada S, Kaur R,
1. Yap FY, Skalski MR, Patel DB, Schein AJ, White Singh M, Mittal BR. Three-phase skeletal scintig-
EA, Tomasian A, et al. Hypertrophic osteoarthropa- raphy in pachydermoperiostosis. Clin Nucl Med.
thy: clinical and imaging features. Radiographics. 2011;36:e199–201.
2017;37:157–95. 8. Mohan HK, Groves AM, Clarke SE. Detection of fin-
2. Martinez-Lavin M. Hypertrophic osteoarthropathy. ger clubbing and primary lung tumor on Tc-99 MDP
Best Pract Res Clin Rheumatol. 2020;34:101507. bone scintigraphy in a patient with a scaphoid frac-
3. Rana RS, Wu JS, Eisenberg RL. Periosteal reaction. ture. Clin Nucl Med. 2004;29:450–1.
AJR Am J Roentgenol. 2009;193:W259–72. 9. Aparici CM, Bains S. Hypertrophic osteoarthropathy
4. Greenfield GB, Warren DL, Clark RA. MR imag- seen with NaF18 PET/CT bone imaging. Clin Nucl
ing of periosteal and cortical changes of bone. Med. 2011;36:928–9.
Radiographics. 1991;11:611–23. discussion 24 10. Makis W, Abikhzer G, Rush C. Hypertrophic pulmo-
5. Rutherford GC, Dineen RA, O'Connor A. Imaging in nary osteoarthropathy diagnosed by FDG PET-CT in
the investigation of paraneoplastic syndromes. Clin a patient with lung adenocarcinoma. Clin Nucl Med.
Radiol. 2007;62:1021–35. 2009;34:625–7.
6. Russo RR, Lee A, Mansberg R, Emmett
L. Hypertrophic pulmonary osteoarthropathy
Part II
Traumatic and Circulatory Disorders
Fracture, Non-union, and Bone
Graft 6
Soon-Ah Park , Su Jin Lee , Hye Joo Son ,
and Jung Mi Park
Abstract duce a variety of cases performed by nuclear

medicine imaging to evaluate fracture sites,
Bone fracture results from full or partial break
non-union, and bone graft. This chapter aims
in the continuity of bone in normal or patho-
to inform you what points to keep in mind
logic conditions. In most of bone fractures,
when evaluating trauma and bone graft with
healing is a natural process. However, non-
nuclear medicine imaging.
union of fracture sites can occur in the case
with problems at the facture sites. The bone
Keywords
graft is commonly used for reconstruction of
bony defect after oncology surgery. There are Bone fracture · Non-union · Bone graft ·
various nuclear medicine examinations such Bone scan · Bone SPECT/CT
as planar or three-phase bone scan, bone
SPECT, or SPECT/CT to evaluate detection of
fracture site, reactive or atrophic non-union,
6.1 Bone Fracture
and the viability of bone graft. Here, we intro-
6.1.1 Etiology and Clinical
S.-A. Park (*) Significance
Department of Nuclear Medicine, Wonkwang
University School of Medicine,
Iksan, Republic of Korea A significant percentage of bone fractures occur
e-mail: nmbach@wku.ac.kr in the normal bone due to prolonged minor stress
S. J. Lee or of a high force impact usually in the setting of
Department of Nuclear Medicine, Ajou University trauma. However, a fracture may also be a result
School of Medicine, Suwon, Republic of Korea from a variety of settings: Firstly, some medical
e-mail: suesj202@ajou.ac.kr conditions weaken the bones such as osteoporo-
H. J. Son sis and thus prone to be fractured from forces that
Department of Nuclear Medicine, Dankook would be insufficient to cause fractures in normal
University College of Medicine,
Cheonan, Republic of Korea bones. These are known as insufficiency frac-
e-mail: neuroscience@dankook.ac.kr tures. Secondly, the prolonged application of
J. M. Park abnormal forces can result in the accumulation of
Department of Nuclear Medicine, Soonchunhyang the microfractures faster than healing, eventually
University Hospital, resulting in macroscopic fracture. These are
Bucheon, Republic of Korea termed fatigue fractures. Thirdly, the bone may
e-mail: jmipark@schmc.ac.kr
https://doi.org/10.1007/978-981-19-2677-8_6
64 S.-A. Park et al.
have some types of disease that focally weakens it can be especially useful in patients who cannot
it (e.g., malignancy, bone cyst, etc.). These are accurately describe symptoms clearly with brain
known as pathological fractures. injury or child abuse [2] and in orthopedic
In most of bone fractures, healing is a natural patients with plaster casts and metal splints which
process that will generate proliferation of perios- can interfere with examination of other radio-
teal and endosteal connective tissue for the devel- graphs [3].
opment of a cartilaginous matrix, formation of Three-phase bone scanning has a narrower
islands and bands of cartilage, and, in some cases, indication than single delayed phase imaging in
an osseous matrix [1]. The healing of fracture can patients with trauma. In cases of infection and/
take several weeks to several years, depending on or inflammation, there will be asymmetric
which bone has become injured and whether blood flow and blood pool activity showing
there are any complications such as infection. preferentially to the affected region. In cases of
The pathophysiological sequence of healing that fracture, however, immediately after a fracture,
occurs following a fracture can be divided into the area shows increased regional blood flow
three main phases: Firstly, inflammatory phase which is apparent in the first phase of three-
shows local hyperemia beginning within a few phase bone scanning. This initial increase of
hours after trauma onset. At the end of this phase, blood flow to the affected regions subsides
which usually takes approximately a week, soft gradually over a few days following the trauma.
tissue callus is present which is non-mineralized In the second phase of three-phase bone scan,
and not visible on radiography. Secondly, repair an increase in the tracer activity in the soft tis-
phase over the ensuing few weeks, this soft tissue sue of affected area can be seen. In the delayed
callus is transformed into a bony callus by the phase of three-phase scanning, there is
activation of osteoprogenitor cells which stabi- increased tracer uptake in the vicinity of the
lizes the fracture site. Thirdly, remodeling phase fracture. Whereas the initially increased blood
lasts many months and even years, and the union flow gradually disappears after the fracture,
of the fracture fragment is formed by osteoblasts callus continues to be formed at the fracture
and osteoclasts. In most instances, remodeling site. There are development of new vessels
can result in almost perfect healing. In some leading to increase in the local blood volume
instances, however, particularly if the alignment and formation of fibrous bone containing
is not perfect, a residual deformity will be increased amounts of amorphous calcium phos-
remained. phate with a high binding affinity for bone-
seeking radiotracers. This increasing uptake on
bone scanning in the initial weeks after trauma
6.1.2 Imaging is a typical finding for a fracture.
Bone SPECT is useful, especially in injuries
Bone scans visualize bone metabolic changes. of the axial skeleton or base of the skull. The
Fractures are generally imaged using conven- hybrid imaging with SPECT/CT has been partic-
tional radiographs for the identification fracture; ularly helpful in the evaluation of foot and ankle
however, in some cases that normal anatomy injuries and vertebral pathology. The
makes interpretation difficult (e.g., joints, wrist, physiological information and the anatomical

feet, the base of skull, spine) and plain radio- detail allow a better understanding of injured
graphs are insensitive to fracture, bone scans or sites and have proven to be useful in planning
bone SPECT can be useful to find missed or surgical intervention.
stress fractures that don’t show up on the conven-
tional radiography. Bone scans are commonly Case 6.1
used for the examination of fracture sites to A 58-year-old woman presented to the clinic
reveal all injuries due to its high sensitivity. And due to chest pain after multiple contusions from
6 Fracture, Non-union, and Bone Graft 65
a b
Fig. 6.1 A 58-year-old woman with the microfracture of (red arrow) is observed on bone scan (b). This case is
sternum. The CT scan shows negative finding for fracture micro- or missed fracture on the CT scan
(a); however, a focal increased uptake indicating fracture
car accident. Chest CT scan showed negative underwent bone scan to rule out metastasis due to
finding regarding fracture of sternum. Bone breast malignancy recently diagnosed. Bone scan
scan showed focal increased uptake in the ster- revealed focal area of increased uptake in the
num which is missed fracture on the CT scan lower portions of bilateral femoral neck and right
(Fig. 6.1). proximal tibia. She had a history that she had
bumped her hip joint area against the table while
Case 6.2 working at a crawl space. She underwent pelvic
A 49-year-old woman presented to the clinic due CT examination to further evaluate the lesions of
to persistent pelvic pain. Two months ago, she pelvic bone on the same day. CT image revealed
underwent pelvic radiograph to evaluate fracture sclerotic change of subcortical bone of bilat-
of pelvic bone; however, it reveled negative find- eral femoral necks, worse on the right. She was
ing. Bone SPECT/CT demonstrated active lesion off the job after that time. Subsequent bone scan
in the left pubic bone and sclerotic change on the was performed 6 months later. Bone scan demon-
CT component (Fig. 6.2). strated almost normalized uptake uptake of both
femora and right proximal tibia. This case was
Case 6.3 stress fractures in the neck of both femora and
A 53-year-old woman, who has been working in right proximal tibia shown positive findings on
a bakery in a standing posture for a long time, bone scan (Fig. 6.3).
Fig. 6.2 A 49-year-old woman with missed left pubic SPECT/CT taken two months later, and sclerotic change
bone fracture. Negative finding is observed on the pelvic suggesting posttraumatic change (red arrow) on the CT
conventional radiograph (a). A focal hot uptake lesion is component of SPECT/CT (b). It is missed fracture on the
shown in the left pubic bone (red arrow) on bone scan and conventional radiograph 2 months ago
Case 6.4 6.2 Non-union

A 16-year-old boy was admitted for a head
trauma caused by a traffic accident. Brain CT 6.2.1 Etiology and Clinical
scan showed a depressed skull fracture with Significance
extension to the left parietal bone, left parieto-
temporosphenoid bone, and left orbital wall and Non-union is a serious complication of a fracture
epidural hemorrhage and hemorrhagic contusion. that persists for a minimum of 9 months without
At the time of arrival, he was not alert and could healing for 3 months [4]. Non-union results from
not communicate clearly. A neurologic examina- multifactorial process when the bone lacks blood
tion revealed dysarthrosis, and he was not able to supply and adequate stability or both and gets
complain his dysfunction and/or pain clearly at infected. The major patent factor is the poor
that time. Bone scan was performed to rule out blood supply. This can occur with poor nutrition,
fracture sites throughout the whole skeletal sys- smoking, and biologic causes of poor blood flow
tem. Bone scan demonstrated more fracture or and poor bone healing. The other causes are inad-
traumatic injury in the lower portion of manu- equate stabilization of facture site and fracture
brium, right proximal humerus, left scapula, and types with fracture gap greater than 3 mm; lack
left upper ribs (Fig. 6.4). of cortical continuity; highly comminuted, but-
Fig. 6.3 A 53-year-old woman with stress fractures of worse on the right (b). Bone scan taken 6 months later
the neck of both femora and right proximal tibia. Initial demonstrates almost normalized uptake of both femurs
bone scan reveals focal area of increased uptake in the and right proximal tibia (c). Stress fractures appear to
neck of both femora and right proximal tibia (red arrow) have occurred in normal bones due to persistent and
(a). Coronal CT image on the same day shows sclerotic repeated minor force in traumatic condition
change of subcortical bone of bilateral femoral necks,
c 6.3 Bone Graft
6.3.1 Etiology and Clinical Significance
The bone graft is commonly used for reconstruc-

tion of bony defect. The success of reconstruction
depends on good blood supply to the bone graft.
The vascular occlusion may result in necrosis and
failure. It is important to assess vascularity and
viability of the underlying bone.
6.3.2 Imaging
Bone scan can offer method for the assessment of

the graft’s physiologic status and viability [5].
Most allografts are not well microvascularized at
the time of surgical insertion and depend on
revascularization from surrounding blood vessel.
In the early postsurgical phase, the graft demon-
strates as a photon- deficient area. Subsequent
bone scintigraphy is necessary for the ascertain
sequential change of the increased perfusion,
blood pool, and delayed uptake as revasculariza-
terfly fragments; and soft tissue compromised tion progresses. Bone SPECT images can be use-
open fracture. ful to separate osseous activity from the adjacent
normal bone and soft tissue activity.
6.2.2 Imaging Case 6.6

A 65-year-old man visited to the outpatient den-
Bone scan is useful in assessing atrophic non- tal clinic for the evaluation of bone graft viability.
unions. If a photon-deficient area between the He had a segmental mandibulectomy with fibular
fragments ends, it indicates a very low proba- free flap for the osteosarcoma arising in the right
bility of union being achieved. The hypertro- mandible. Two weeks after operation, SPECT/
phic non-union shows persistent accumulation CT fusion imaging showed diffusely increased
of tracer at the fragment ends. It reflects bio- radiotracer uptake at the vascularized fibular
logical activity for blood flow and new bone bone graft, which implies viable bone graft sug-
formation. gesting future good prognosis (Fig. 6.6).
Case 6.5 Case 6.7

A 23-year-old woman was operatively treated with A 55-year-old man visited to the outpatient dental
open reduction and internal fixation due to frac- clinic for the evaluation of bone graft viability. He
tures after a skiing accident. The radiologist raised had a segmental mandibulectomy with fibular free
the possibility of non-union 10 months later. Then, flap for the squamous cell carcinoma arising in the
she was diagnosed with a non-union at 13 months right retromolar trigone. Two weeks after opera-
after trauma accident. The conventional radio- tion, SPECT/CT fusion imaging did not show the
graph showed fracture lines in the fibula and tibia, significant radiotracer uptake at the vascularized
and bone scan revealed photon-deficient gap in the fibular bone graft, which implies non-viable bone
fracture site of tibia (Fig. 6.5). graft suggesting future poor prognosis (Fig. 6.7).
Fig. 6.4 A 16-year-old boy with head trauma who has Bone scan demonstrates more fractures or traumatic
additional fractures demonstrated by whole-body bone injury (red arrow) in the lower portion of manubrium,
scan. Brain CT scan shows a depressed skull fracture right proximal humerus, left scapula, and left upper ribs
(blue arrow) with extension to the left parietal bone, left (b). In a patient with brain injury, bone scan can be useful
parietotemporosphenoid bone, and left orbital wall and imaging tool to evaluate further fracture sites
epidural hemorrhage and hemorrhagic contusion (a).
a b
Fig. 6.5 A 23-year-old woman with atrophic non-union tion of the right tibia (a). Bone scan reveals photon-deficient
of right tibia fracture. The conventional radiograph dem- gap in the fracture site of tibia (red arrow) suggesting atro-
onstrates fracture line (blue arrow) following internal fixa- phic non-union (b)
a b c
Fig. 6.6 A 65-year-old man with viable bone graft in the right side of mandible. SPECT (a), SPECT/CT (b), and CT
(c) demonstrate increased tracer uptake (yellow arrow) suggesting viability of the bone graft of mandible
a b c
Fig. 6.7 A 55-year-old man with non-viable bone graft in the right side of mandible. SPECT (a), SPECT/CT (b), and
CT (c) demonstrate cold defect (yellow arrow) suggesting non-viability of the bone graft of mandible
Teaching Points • Bone scan can offer method for the

• Bone scan is a highly sensitive tool for assessment of the graft’s physiologic
the diagnosis of fracture and can be status and viability. Superiority of
helpful to demonstrate missed fracture SPECT or SPECT/CT providing three-
which cannot be observed radiographi- dimensional information has been dem-
cally. Bone scan also can play an impor- onstrated to improve interpretation of
tant role in the confirmation of suspected the viability of bone grafts.
child abuse and in patients with brain
injury.
• According to the fracture sites, the
length of time of increased uptake is References
variable. Bone scan can provide infor-
1. Cunningham BP, Brazina S, Morshed S, Miclau
mation about the relative fracture age T. Fracture healing: a review of clinical, imaging and
between old and acute fractures. laboratory diagnostic options. Injury. 2017;48(Suppl
• There is a false-positive factor. It is 1):S69–75.
2. Seo Y, Whang K, Pyen J, Choi J, Kim J, et al. Missed
immobilization and the resulting osteo-
skeletal trauma detected by whole body bone scan
porosis of disuse after fracture. False- in patients with traumatic brain injury. J Korean
negative finding in bone scans can Neurosurg Soc. 2020;63:649–56.
result from a too-short time interval 3. Krumme JW, Lauer MF, Stowell JT, Beteselassie NM,
Kotwal SY. Bone scintigraphy: a review of techni-
between the trauma and obtaining of a
cal aspects and applications in orthopedic surgery.
bone scan. Old and healed fractures Orthopedics. 2019;42:e14–24.
also definitely show no increased tracer 4. Brinker MR. Nonunions: evaluation and treatment.
uptake. In: Trafton PG, editor. Skeletal trauma: basic science,
management, and reconstruction. 3rd ed. Philadelphia:
• Bone scan has been used to provide
WB Saunders; 2003. p. 507–604.
information about the biological activity 5. Kim H, Lee K, Ha S, Shin E, Ahn K-M, Lee J-H,
of the fracture site in treatment planning et al. Predicting vascularized bone graft viability using
of fracture non-union. 1-week postoperative bone SPECT/CT after maxillo-
facial reconstructive surgery. Nucl Med Mol Imaging.
2020;54:292–8.
Stress Fractures and Sports Injury
7
Su Jin Lee

and Pathophysiology
Stress fractures, which appear as fatigue or
insufficiency fractures, are common in ath-
Stress fractures are caused by repetitive stress.
letes, military recruits, and the elderly popula-
When this occurs in a normal bone, the resulting
tion. Fatigue fractures usually occur in the
fracture is called a fatigue fracture; however,
lower extremities, while insufficiency frac-
when it occurs in an abnormal bone, such as a
tures commonly involve the spine, pelvis, and
bone with osteoporosis, it is called an insuffi-
ribs. If stress fractures are suspected, plain
ciency fracture [1]. Fatigue fractures are common
radiography should be the first test performed.
in athletes, military recruits, and dancers, with
However, a bone scan is much more sensitive
most cases affecting the lower extremities [2].
than radiography for diagnosing stress frac-
Insufficiency fractures are common in the elderly
tures; therefore, if the plain radiograph shows
population and affect the spine, pelvis, and ribs,
no findings, or if an urgent diagnosis is needed,
usually as a result of minor trauma or unnoticed
a bone scan can be useful. Application of
trauma.
single-photon emission computed tomogra-
Stress fractures may occur as a result of repet-
phy/computed tomography on bone scan is
itive or prolonged muscle action on a bone that
very useful in suspected fractures of the ankle,
has not adapted to the applied stress [3].
feet, and spine. This chapter briefly summa-
Repetitive stress may cause periosteal resorption
rizes the pathophysiology of stress fractures
that outperforms the rate of remodeling, weaken-
and presents typical cases of stress fractures
ing the cortex and leading to fractures.
affecting various locations.
Histopathological studies have shown that stress
fractures are linear regions of increased bone
Keywords
turnover. The initial change in the evolution of a
Bone scan · Fatigue fracture · Insufficiency stress fracture is the appearance of large resorp-
fracture · Stress fracture tion cavities. Next, a coupled osteoblastic
response displaces some of the resorbed bone;
however, the pace of bone formation cannot keep
up with the resorption rate. A bone scan shows a
S. J. Lee (*) very distinct line of this increased uptake attribut-
Department of Nuclear Medicine, Ajou University able to the osteoblastic activity [4].
School of Medicine, Suwon, Republic of Korea
e-mail: suesj202@ajou.ac.kr
https://doi.org/10.1007/978-981-19-2677-8_7
74 S. J. Lee
7.2 Diagnosis aspect of the tibial cortex. While a stress fracture

in the acute stage showed focally increased blood
Patients with stress fractures will commonly flow, blood pool, and bone uptake, a stress frac-
complain of pain with ambulation [5]. Pain can ture in the later stage may only show increased
manifest differently depending on the location of bone uptake on delayed phase.
the fracture, such as groin pain with pelvic frac-
ture, hip pain with femoral neck injury, and knee Case 7.1
pain with proximal tibial injury [6]. A 19-year-old male soldier complained of left
Bone scans play an important role in the diag- lower leg pain for 6 weeks. The pain worsened
nosis of stress fractures because conventional with running. Whole-body bone scan (Fig. 7.1a)
radiographs require additional time to confirm and regional medial view of both lower legs
fractures; bone scans may appear abnormal (Fig. 7.1b) showed focal increased uptake sug-
6 weeks prior to the appearance of existing radio- gesting stress fractures in the proximal shaft of
logical changes [7]. Recently, the application of both tibiae. The pain was in the left lower leg;
single-photon emission computed tomography/ however, bone scan demonstrated stress fractures
computed tomography (SPECT/CT) on bone in both tibiae.
scan has been very useful in the diagnosis of sus-
pected fractures of the ankle, feet, and spine [8]. Case 7.2
Magnetic resonance imaging (MRI) is also useful A 20-year-old female soldier complained of right
for diagnosing stress fractures because it has sim- lower leg pain. Prolonged standing, running, and
ilar or slightly better sensitivity than bone scans, going uphill caused sharp pain. She underwent
with a higher specificity [9, 10]. three-phase bone scan. There was no significant
uptake at blood flow (not shown) and blood pool
phase (Fig. 7.2a), but focal uptake was noted in
7.3 Bone Scan Findings the mid shaft of the right tibia at delayed phase
of Specific Stress Fractures image (Fig. 7.2b).
7.3.1 Stress Fractures of the Tibia Case 7.3

A 26-year-old female soldier complained of
The tibia is the most common site of stress frac- chronic lower leg pain, especially in the mid tibia
tures [11]. Most tibial stress fractures occur in the area. She regularly ran up to 6 miles at a time. A
proximal or middle third of the bone and are three-phase bone scan showed no significant
either horizontal or oblique. Rarely, stress frac- increases in blood flow (not shown) and blood
tures at the distal third of the tibia have been pool (Fig. 7.3a); however, it showed increased
reported in long-distance runners. Differentiating bone uptake suggesting stress fractures in both
shin splints from stress fractures is important tibiae (Fig. 7.3b).
because the management of each is different. An
untreated stress fracture can lead to a complete Case 7.4
fracture, usually complicated by nonunion. A A 37-year-old female patient complained of pain
three-phase bone scan is a sensitive imaging in both lower legs worsening with running. A
modality for the diagnosis of tibial stress frac- three-phase bone scan demonstrated a linear pat-
tures and shin splints. Typical patterns of shin tern of increased uptake along the posteromedial
splints in three-phase bone scans are normal part of both the tibiae on delayed phase only
blood flow and blood pool and longitudinal (Fig. 7.4b), with no alteration in blood pool
increased uptake along the diaphysis commonly (Fig. 7.4a). These findings are consistent with
involving the posteromedial and anterolateral shin splints.
7 Stress Fractures and Sports Injury 75
a b
Fig. 7.1 Anterior view of whole-body bone scan (a) and regional medial view of both lower legs (b) in a 19-year-old
male soldier show focal increased uptakes suggesting stress fractures in the proximal shaft of both tibiae
76 S. J. Lee
a b
Fig. 7.2 Anterior regional blood pool and bone phase focal uptake suggesting stress fractures is noted in the mid
images of both lower legs in a 20-year-old female soldier. shaft of the right tibia at delayed phase (b)
There is no significant uptake at blood pool phase (a), but
a b
Fig. 7.3 Anterior regional blood pool and bone phase focal uptakes are noted in the mid shaft of both tibiae at
images of both lower legs in a 26-year-old female soldier. delayed bone phase (b)
There is no significant uptake at blood pool phase (a), but
a b
Fig. 7.4 Medial view regional blood pool (a) and bone increased uptake along the posteromedial part of both the
phase (b) images of both lower legs showing shin splints. tibiae on delayed phase only (b, arrow)
A three-phase bone scan demonstrates a linear pattern of
7.3.2 Stress Fractures of the Foot focal increased uptake suggesting fatigue frac-
and Ankle ture on the third metatarsal bone (Fig. 7.6a). A
sagittal MRI scan (Fig. 7.6b) showed the fracture
The majority of fibular stress fractures occur in and bone marrow edema at the third metatarsal
the distal third portion of the bone; fractures in bone.
the proximal and middle thirds of the fibula are
rare. The main sport involved in fibular stress
fractures is running and jumping-related 7.3.3 Stress Fractures of the Femur
activities.
Metatarsal stress fractures may be the most The three femoral regions that are primarily
common form of stress injury in the foot and prone to stress fractures are the neck, medial
ankle. These injuries mainly occur in athletes proximal shaft, and distal shaft [12]. Fractures
who participate in high-intensity sports, includ- may be fatigue fractures, which occur in ath-
ing running and jumping. These fractures primar- letes, or insufficiency fractures, which occur
ily occur in the second and third metatarsal especially in the elderly population. Atypical
bones. femoral fractures (AFFs), also known as bisphos-
phonate-related proximal femoral fractures, are
Case 7.5 an example of insufficiency fractures [13].
A 21-year-old male soldier complained of left
distal lower leg pain. The pain worsened with any Case 7.7
impact activities including walking. A three- An 89-year-old female patient with osteoporosis
phase bone scan showed focally increased blood visited the outpatient clinic with left thigh pain.
flow (not shown), blood pool (Fig. 7.5a), and She had a medication history of bisphosphonate
bone uptake (Fig. 7.5b) in the left distal fibula. for 5 years due to osteoporosis. An incomplete
fracture line was suspected in the mid shaft of the
Case 7.6 left femur on X-ray (Fig. 7.7a), and focal
A 29-year-old female patient underwent right increased uptake in the same area was seen on a
ankle reconstruction surgery about 1 year ago. whole-body bone scan (Fig. 7.7b). Based on her
She complained of acute worsening pain over medical history and imaging findings, AFF was
the third metatarsal area. A bone scan revealed suspected.
78 S. J. Lee
a b
Fig. 7.5 Anterior view regional blood pool and bone phase images of both ankles in a 21-year-old male soldier with
fibular stress fracture. Focally increased blood pool (a) and bone uptake (b) are noted in the left distal fibula
a b
Fig. 7.6 A bone scan in a 29-year-old female patient shows focal increased uptake on the third metatarsal bone (a), and
sagittal MRI scan (b) shows the fracture and bone marrow edema at the same bone
7.3.4 Stress Fractures of the Pelvis tures among elderly osteoporotic patients. The
typical patterns of bone scans are an H-shaped
Sacral stress fractures occur as fatigue fractures uptake (Honda sign) and its variants: unilateral
in young active persons and as insufficiency frac- vertical uptake, horizontal uptake, half H-shaped
a b
Fig. 7.7 An 89-year-old female patient with osteoporosis. An incomplete fracture line is suspected in the mid shaft of
the left femur on X-ray (a, arrow), and focal increased uptake in the same area is seen on a whole-body bone scan (b)
uptake, and bilateral vertical uptake [1]. Pelvic Case 7.9

insufficiency fractures usually occur in the sacro- An 82-year-old female patient visited the outpa-
iliac joint and in the pubis. tient clinic because she had difficulty walking
after falling out of bed. No significant abnormali-
Case 7.8 ties were found on her pelvic X-ray. Whole-body
A 64-year-old female with osteoporosis com- bone scan and pelvis SPECT/CT revealed focal
plained of lower back pain. She had no trauma uptake in the left superior and inferior pubic rami
history. Increased uptake along the bilateral ala (Fig. 7.9a–c). Whole-body bone scan addition-
was noted on the posterior image of her bone ally showed the insufficiency fracture at the right
scan (Fig. 7.8a). Another 80-year-old male com- sixth rib (Fig. 7.9a). After a bone scan, a bone
plained of buttock pain and difficulty walking mineral density test was performed, and she was
after hitting the buttock. Intense uptake was dem- diagnosed with osteoporosis.
onstrated in the right sacral ala, mid sacrum, left
ilium, and left superior and inferior pubic rami on
his bone scan (Fig. 7.8b).
80 S. J. Lee
a b
Fig. 7.8 Increased uptake along the bilateral sacral ala H-shaped uptake variant) on the posterior image of bone
(bilateral vertical uptake variant of Honda sign) is noted scan in an 80-year-old man (b). Other uptakes suggesting
on the posterior image of bone scan in a 64-year-old insufficiency fractures are also noted in the left ilium and
woman with osteoporosis (a). Intense uptake is demon- left superior and inferior pubic rami
strated in the right sacral ala and mid sacrum (half
a b
Fig. 7.9 Whole-body bone scan (a) and pelvis SPECT/ bone scan additionally shows the insufficiency fracture at
CT (b and c) in an 82-year-old woman reveal focal uptakes the right sixth rib
in the left superior and inferior pubic rami. Whole-body
4. McCarthy EF. Histopathologic correlates of a positive

Teaching Points bone scan. Semin Nucl Med. 1997;27:309–20.
5. Fredericson M, Bergman AG, Hoffman KL,
• Stress fractures are common in athletes, Dillingham MS. Tibial stress reaction in runners.
military recruits, and the elderly popula- Correlation of clinical symptoms and scintigraphy
tion; fatigue fractures usually occur in with a new magnetic resonance imaging grading sys-
the lower extremities, while insuffi- tem. Am J Sports Med. 1995;23:472–81.
6. Niva MH, Mattila VM, Kiuru MJ, Pihlajamaki
ciency fractures commonly involve the HK. Bone stress injuries are common in female mili-
spine, pelvis, and ribs. tary trainees: a preliminary study. Clin Orthop Relat
• Bone scans play an important role in the Res. 2009;467:2962–9.
diagnosis of stress fractures because 7. Norfray JF, Schlachter L, Kernahan WT Jr, Arenson
DJ, Smith SD, Roth IE, et al. Early confirmation of
conventional radiographs require addi- stress fractures in joggers. JAMA. 1980;243:1647–9.
tional time to confirm fractures. 8. Scharf SC. Bone SPECT/CT in skeletal trauma.
• Recently, the application of SPECT/CT Semin Nucl Med. 2015;45:47–57.
on bone scan has been very useful in the 9. Ishibashi Y, Okamura Y, Otsuka H, Nishizawa K,
Sasaki T, Toh S. Comparison of scintigraphy and
diagnosis of suspected fractures of the magnetic resonance imaging for stress injuries of
ankle, feet, and spine. bone. Clin J Sport Med. 2002;12:79–84.
10. Patel DS, Roth M, Kapil N. Stress fractures: diagno-
sis, treatment, and prevention. Am Fam Physician.
2011;83:39–46.
11. Gallo RA, Plakke M, Silvis ML. Common leg injuries
References of long-distance runners: anatomical and biomechani-
cal approach. Sports Health. 2012;4:485–95.
1. Elgazzar AH. Diagnosis of traumatic disorders. 12. Edwards WB, Gillette JC, Thomas JM, Derrick
Orthopedic nuclear medicine. Springer; 2017. TR. Internal femoral forces and moments during run-
p. 147–89. ning: implications for stress fracture development.
2. Liong SY, Whitehouse RW. Lower extremity and Clin Biomech (Bristol, Avon). 2008;23:1269–78.
pelvic stress fractures in athletes. Br J Radiol. 13. Toro G, Ojeda-Thies C, Calabro G, Toro G, Moretti
2012;85:1148–56. A, Guerra GM, et al. Management of atypical femoral
3. Daffner RH, Pavlov H. Stress fractures: current con- fracture: a scoping review and comprehensive algo-
cepts. AJR Am J Roentgenol. 1992;159:245–52. rithm. BMC Musculoskelet Disord. 2016;17:227.
Osteonecrosis
8
So Won Oh , Jee Won Chai ,
and Jung Mi Park
Abstract appears normal in the early stages of the dis-

ease. In this regard, bone scintigraphy and
Osteonecrosis is characterized by the death of
MRI are preferred for the diagnosis of osteo-
cellular components of the bone that results
necrosis at an earlier stage. MRI is the most
from an interruption of the subchondral blood
sensitive diagnostic modality based on the
supply. Bone infarction and avascular necrosis
high spatial resolution for the soft tissue as
are terms that may be used interchangeably.
well as bone, and bone scintigraphy is quite
The risk factors of osteonecrosis are generally
sensitive and advantageous, allowing evalua-
multifactorial, such as serious trauma, steroid
tion of multiple sites of the body. It is expected
medication, and alcohol consumption, but the
that bone SPECT/CT can improve the diag-
etiology and pathogenesis remain unclear. The
nostic accuracy of the evaluation of osteone-
common sites for osteonecrosis are the femo-
crosis, using the functional information of
ral head, knee, talus, and humeral head.
the SPECT images combined with the exact
Osteonecrosis may lead to subchondral col-
localization information of the CT images.
lapse, which threatens the viability of the
involved joint. Therefore, early diagnosis is
Keywords
essential since it allows for the treatment of
osteonecrosis and potentially improves the Osteonecrosis · Bone scintigraphy · Bone
outcome. SPECT/CT
Initial evaluation is conducted by plain
radiographs demonstrating minimal osteope-
nia followed by variable changes, but it often
8.1 Osteonecrosis of the Hip

S. W. Oh (*)
Department of Nuclear Medicine, Seoul National Significance
University Boramae Medical Center,
Seoul, Republic of Korea Avascular necrosis of femoral head (ANFH) is
J. W. Chai the bone death that results from the interruption
Department of Radiology, Seoul National University of blood supply, mostly affecting the middle-
Boramae Medical Center, Seoul, Republic of Korea aged male population. ANFH falls into two
J. M. Park classes: traumatic or non-traumatic. Non-
Department of Nuclear Medicine, Soonchunhyang traumatic ANFH is associated with use of alco-
https://doi.org/10.1007/978-981-19-2677-8_8
84 S. W. Oh et al.
hol, glucocorticoids, and presence of hematologic be used in the evaluation of the fractured femoral
disorders or metabolic disorders, but its etiology neck with a metallic device. Recently, SPECT/CT
is unclear in about 30% of patients [1]. Idiopathic is expected to enhance diagnostic performances
ANFH in the pediatric population is also known by visualization of a central cold defect with/
as Legg-Calve-Perthes (LCP) disease. The patho- without surrounding increased uptake in the fem-
logic changes are equivalent to both ANFH in oral head that is often masked by the adjacent nor-
adults and pediatric LCP disease, except cortical mal bone in the early phase of osteonecrosis.
maturity.
Case 8.1
A 52-year-old man was admitted to the orthopedic
8.1.2 Imaging Findings clinic for the treatment of right hip pain that had
been recently aggravated. He used to stand all day
Diagnosis is normally made by images obtained because of his job, but he denied previous trauma
through a non-invasive method, either with radio- history and substance abuse including alcohol.
graphs or MRI. When the disease begins, it may Except for antihypertensive medication, he had no
be undetectable on plain radiographs. However, history of treatment for chronic diseases such as
early ANFH shows cystic and/or sclerotic diabetes or hepatitis. Imaging studies were per-
changes in the femoral head followed by the cres- formed, including plain radiography, hip MRI, and
cent sign with disease progression. The crescent bone scintigraphy, and avascular necrosis (AVN)
sign describes an area of subchondral radiolu- was demonstrated in the bilateral femoral heads
cency in the femoral head that indicates subchon- (Fig. 8.1). Multiple drilling was undertaken for the
dral fracture due to bone necrosis and subsequent treatment of the right ANFH, and close observa-
attempts at repair. ANFH at a later stage shows tion was chosen for the treatment of the left ANFH.
femoral head flattening, collapse, and degenera-
tive changes. MRI is the modality of choice for Case 8.2
patients with a suspicious history and physical A 41-year-old man visited the orthopedic clinic
examination with normal radiographs. Early due to left inguinal area pain that had worsened
ANFH usually presents as an area of low signal 1 month previously. He denied a history of trauma
intensity (SI) on T1-weighted MR image and as a and chronic diseases, including diabetes, hyper-
high SI on T2-weighted MR image. tension, and chronic hepatitis. He was a chronic
Bone scintigraphy pattern depends on the alcoholic who had drunk 1 or 2 bottles of Korean
pathophysiological stage of osteonecrosis, as distilled spirits 4 or 5 days per week for 10 years.
osteonecrosis is an evolving process. Imaging studies demonstrated AVN of the left
Osteonecrosis initially appears as a photopenic hip (Fig. 8.2). He was admitted to the hospital for
area on the bone scintigraphy, and then increased total hip replacement arthroplasty.
radiotracer uptake is seen at the boundaries
between the osteonecrotic site and the normal
tissues due to osteoblastic activity. Increased
8.2 Osteonecrosis of Knee
radiotracer uptake starts to appear when bone col-
lapse happens, and periarticular uptake is seen in 8.2.1 Etiology and Clinical
both sides of the hip joints in advanced degenera- Significance
tive arthritic stage. However, diagnostic specific-
ity of bone scintigraphy is low, and sensitivity of Osteonecrosis of the knee can occur in the
bone scintigraphy is variable according to the epiphyseal or subarticular bone, often in the
stage and etiology of osteonecrosis. Although form of AVN. The literature on osteonecrosis of
MRI is the diagnosis of choice for osteonecrosis, femoral condyles is often mixed with and some-
bone scintigraphy has several roles in the manage- times dedicated entirely to spontaneous osteo-
ment of ANFH. Bone scintigraphy may be helpful necrosis of the knee (SONK). SONK was
to provide information on viability, and it could previously considered an idiopathic ischemic
8 Osteonecrosis 85
a b
Fig. 8.1 Bone scintigraphy shows a small photopenic SI in the right femoral head, as well as a small lesion in
area (black arrow) that is surrounded by diffusely the left femoral head (white arrow) (c). In contrast to the
increased uptake in the right femoral head (a). Radiograph right femoral head lesion, the small left femoral lesion
of the pelvis shows ill-defined sclerotic lesion in the right that is centrally located is easily missed by scintigraphy or
femoral head (b). MRI demonstrates a diffusely increased plain radiograph
sequela that leads to the development of a cres- dyle (MFC) [3]. Patients with SIFK complain of
cent-shaped osteonecrosis lesion. At present, a knee pain that typically gets worse at night and
more appropriate term for the condition is sug- on weight bearing, and the onset is usually acute
gested since it represents a subchondral insuffi- without prior trauma, mostly unilateral. Due to
ciency fracture of the knee (SIFK) that its similarity with clinical symptoms, SIFK is
progresses to subchondral collapse with second- often mistakenly identified as a medial meniscus
ary osteonecrosis [2]. By contrast, primary AVN tear. The natural course of SIFK varies from
results from a reduction of the blood supply, and complete recovery to total joint collapse, in cases
its clinical significance is different from where the biomechanics of the knee joint is
SONK. Moreover, MRI features of these two altered due to structural changes, and joint
lesions have been shown to be profoundly dif- destruction may eventually occur.
ferent from each other. Primary AVN of the knee
is known to share the established features of
AVN of other sites, but SONK is associated with 8.2.2 Imaging
marked bone marrow edema emanating from
the subchondral region and extending over large Typical radiographic findings, including flat-
areas [2]. tening of the MFC, subchondral bony radiolu-
SIFK is seen more frequently in women, and cency, and complicating subchondral fracture,
up to 94% of cases affect the medial femoral con- become overt in advanced stages, although
86 S. W. Oh et al.
a b
c d
Fig. 8.2 Radiograph of the pelvis shows a sclerotic area in the left femoral head superolateral aspect that is
lesion in the left femoral head with articular surface col- surrounded by irregularly increased uptake (b–d)
lapse (a). Bone SPECT/CT demonstrates a photopenic
they are often negative in the early stages. MRI with vascular disruption might be reflected by
findings can vary according to stage, and it is bone scintigraphy. In this regard, bone scintig-
important to determine the extent of the dis- raphy is a more sensitive modality and helpful
ease for advanced stages. SIFK is associated in early detection of SIFK.
with marked bone marrow edema emanating
from the subchondral region and extending Case 8.3
over large areas, often involving the entire A 63-year-old man was managed for sudden
femoral condyle. This differs from the more onset of left knee pain that developed 2 months
localized bone marrow edema lesion subjacent ago. Knee MRI was taken because his knee pain
to cartilage loss in osteoarthritis. In general, persisted for 9 months. MRI showed middle and
osteonecrosis is seen as a sharply demarcated posterior one-third large bone marrow edema in
photon defect that is surrounded by intense the left MFC with focal subcortical fracture.
uptake in the reparative and reactive zone in Bone scintigraphy showed focal intense increased
bone scintigraphy. SIFK usually shows a uptake in the left MFC. Knee MRI and bone scin-
focally increased uptake, which the likely tigraphy suggest subchondral insufficiency frac-
pathogenesis of microfracture that is related ture of the knee (Fig. 8.3).
8 Osteonecrosis 87
a b c
d e
Fig. 8.3 The knee AP view shows no significant abnor- the trabecular cancellous bone beneath the subchondral
mality in both knees (a). Knee MRI demonstrates diffuse bone plate without disruption of the articular surface
bone marrow edema: coronal and sagittal spin-echo fat- (arrowheads). Bone scintigraphy shows focal increased
suppressed proton density images (b, c) show high SI sug- uptake in the subchondral bone area of the right MFC (d
gesting bone marrow edema in the subchondral bone of anterior image of both knees, e medial image of the right
the right MFC (arrows) and low SI linear fracture line in knee)
Case 8.4 8.3 Osteonecrosis of the Hand

A 69-year-old woman visited to the outpatient and Foot
clinic due to right knee pain that developed
6 months ago, and she denied trauma history to 8.3.1 Etiology and Clinical
the knees. Physical examination revealed swelling Significance
and tenderness over the medial side of the right
knee. Imaging workups including radiographs Kienböck disease is known as osteonecrosis of
and bone SPECT/CT were performed, and it dem- the lunate or lunatomalacia, which can lead to
onstrated SIFK of the right MFC associated with progressive wrist pain and abnormal carpal
mild osteoarthritis of the medial tibiofibular com- motion, particularly in the dominant wrist of
partment (Fig. 8.4). Based on the clinical diagno- young male patients. The exact pathophysiology
sis, medication with NSAID was chosen for the has not been fully elucidated, but it is thought to
patient, instead of surgical treatment. be an interplay between altered vascular perfu-
88 S. W. Oh et al.
a In addition, the negative ulnar variance is present

as a predisposing factor in around 75% of cases
of Kienböck disease.
8.3.2 Imaging
Radiographs show that osteonecrotic changes

start with sclerosis of the lunate and leads to
lunate collapse, fracture, scaphoid flexion, loss of
b carpal height, and carpal arthritis [5]. Advanced
imaging, such as CT or MRI, is helpful, often
resulting in upgrading to Kienböck disease, espe-
cially in patients with lunate collapse not seen on
plain radiographs. Since MRI is the most sensi-
tive tool, it may facilitate the diagnosis of osteo-
necrosis in patients without other radiographic
changes. In the MRI, the pattern of lunate bone
signal change allows the condition to be
differentiated from ulnar impaction syndrome,

the major differential diagnosis.
c
Case 8.5
An 81-year-old woman visited the outpatient
clinic due to worsening left wrist pain. She had
complained of left wrist pain since she had
injured the left wrist a few decades before.
Imaging studies, including plain radiography,
MRI, and SPECT/CT, suggested osteonecrotic
changes in the lunate. Kienböck disease was
diagnosed based on the imaging studies (Fig. 8.5).
Fig. 8.4 The knee AP view demonstrates articular sur-
face depression with a focal subchondral bony radiolu- Case 8.6
cency in the right MFC accompanied by mild osteoarthritic An 83-year-old woman was taken to the emer-
changes in the medial tibiofemoral compartment, but gency room after she was found collapsed in a
there is no evidence of typical osteoarthritic changes in
the contralateral knee (a). Bone SPECT/CT shows focally nursing home. She presented with right wrist
increased uptake that matched with a subchondral bony pain accompanied by swelling, tenderness, and
lesion in the right MFC; otherwise no significant abnor- bruising. Radiographs showed a right distal
malities are observed (b, c) radius fracture, and bone scintigraphy was per-
formed to diagnose hidden fractures of the whole
sion, repetitive microtrauma, variable lunate body. Bone scintigraphy incidentally detected a
anatomy, altered loading and kinematics, and suspicious lesion in the left distal tibia, and fur-
potential systemic disease. The lunate typically ther imaging studies including radiography and
has both palmar and dorsal blood supplies; 20%– MRI followed (Fig. 8.6). Osteonecrosis of the
26% of lunates may have a singular palmar blood distal tibia was diagnosed based on the imaging
supply, increasing their risk for osteonecrosis [4]. studies.
8 Osteonecrosis 89
a b c
d e f
Fig. 8.5 The wrist PA view shows sclerotic changes of SPECT/CT shows focally increased uptake in the lunate
the lunate (a). MRI T1 and T2 fat-saturated images dem- (d coronal, e sagittal, f transverse)
onstrate T1 low and T2 high SI in the lunate (b, c).
a b c
Fig. 8.6 The lower leg AP view radiograph shows an ill- with remaining hyperintense fat signal in the center of the
defined osteolytic lesion (yellow arrows) in the left distal lesion (b). Bone scintigraphy shows the oval shape of
tibia without periosteal reaction nor cortical thickening increased uptake in the left distal tibia (black arrow) and
around the lesion (a). MR T1 coronal image demonstrates linear shape of increased uptake on the right foot indicat-
a geographic intramedullary lesion in the left distal tibia ing the radiopharmaceutical injection site (c)
90 S. W. Oh et al.
8.4 Osteonecrosis of the Jaw meticulous clinical examination, including medi-

cation history, should be considered for an accu-
8.4.1 Etiology and Clinical rate diagnosis.
Significance
Case 8.7
Bisphosphonate-induced osteonecrosis of the A 75-year-old woman visited the dental clinic
jaw is a potential complication associated with due to gingival inflammation developed 2 weeks
long-term use of bisphosphonates, especially before. She had a history of bisphosphonate med-
pamidronate and zoledronate. Medication-related ication for 5 years for the treatment of osteoporo-
osteonecrosis of the jaw (MRONJ) has become sis. Her medical history and imaging study
the preferred term since other medications, such findings strongly suggested osteonecrosis of the
as anti-resorptive and anti-angiogenic agents, jaw (Fig. 8.7).
have been implicated as etiologic agents.
Although the etiology and pathogenesis of
MRONJ remain obscure, it has been proposed Teaching Points
that the jaw bones are highly susceptible to osteo- • Osteonecrosis is an evolving process,
necrosis due to certain anatomical and physiolog- and thus bone scintigraphy findings may
ical factors [6]. Drugs are highly concentrated in differ by stage. Initially, osteonecrosis
the jaw because of high vascularity, and the appears as a photopenic area and pro-
forces of mastication and periodontal ligament gresses to increased bony uptake at the
around numerous teeth ensure rapid bone turn- boundaries between the osteonecrotic
over around the periodontium, potentially induc- site and the normal tissues. As osteone-
ing microfractures in MRONJ. crosis leads to subchondral bone col-
lapse, bone scintigraphy demonstrates
irregularly increased uptake in the
8.4.2 Imaging whole femoral head. Further, periarticu-
lar uptake is seen in both sides of the hip
Conventional orthopantomography provides an joints in advanced degenerative arthritic
excellent general assessment of the entire jaw, stage.
but mineral loss must be as high as 30–50% to be • Since bone SPECT/CT provides cross-
visible [7]. Thus, radiographs may not visualize sectional images combined with anatom-
subtle changes in the early disease, but mottled ical CT information, it is advantageous to
bone similar to diffuse osteomyelitis and widen- evaluate the centrally located structure,
ing of periodontal ligament space become overt such as the femoral head. Thus, SPECT/
in extensive bone involvement. However, radio- CT improves both sensitivity and speci-
graphic findings and clinical symptoms are often ficity, compared to bone scintigraphy.
non-specific even in the full-blown stages; thus,
8 Osteonecrosis 91
a b
c d
Fig. 8.7 Bone scintigraphy shows diffusely increased uptake in the right mandibular body (a–c). Mandible CT demon-
strates irregular bony destruction in the right mandibular body with soft tissue abscess formation (d)
considerations applied to Kienbock’s disease. Chir

References Main. 2007;26:13–20.
5. Rioux-Forker D, Shin AY. Osteonecrosis of the
1. Sen RK. Management of avascular necrosis of fem- lunate: Kienbock disease. J Am Acad Orthop Surg.
oral head at pre-collapse stage. Indian J Orthop. 2020;28:570–84.
2009;43:6–16. 6. Varun B, Sivakumar T, Nair BJ, Joseph
2. Gorbachova T, Melenevsky Y, Cohen M, Cerniglia AP. Bisphosphonate induced osteonecrosis of jaw
BW. Osteochondral lesions of the knee: differentiat- in breast cancer patients: a systematic review. J Oral
ing the most common entities at MRI. Radiographics. Maxillofac Pathol. 2012;16:210–4.
2018;38:1478–95. 7. Koth VS, Figueiredo MA, Salum FG, Cherubini
3. Zaremski JL, Vincent KR. Spontaneous osteonecrosis K. Bisphosphonate-related osteonecrosis of the jaw:
of the knee. Curr Sports Med Rep. 2016;15:228–9. from the sine qua non condition of bone exposure to a
4. Lamas C, Carrera A, Proubasta I, Llusa M, Majo J, non-exposed BRONJ entity. Dentomaxillofac Radiol.
Mir X. The anatomy and vascularity of the lunate: 2016;45:20160049.
Complex Regional Pain Syndrome
9
Joon-Kee Yoon, Soon-Ah Park, Young Seok Cho,
Jung Mi Park, and Jang Gyu Cha
Abstract ular bone uptake in the affected extremity. In

this chapter, we introduce several cases to help
Complex regional pain syndrome (CRPS) is a
understand the findings and clinical useful-
chronic pain condition caused by a variety of
ness of TPBS in patients with CRPS.
diseases. The pathophysiology of CRPS is
uncertain, and the diagnosis depends on clini-
Keywords
cal criteria. Three-phase bone scintigraphy
(TPBS) using 99mTc-diphosphonates is helpful Three-phase bone scintigraphy · Complex
in documenting the symptoms and signs of regional pain syndrome · Reflex sympathetic
CRPS and in the differential diagnosis of dystrophy · Extremity pain
extremity pain. The typical pattern of TPBS in
patients with CRPS is diffusely increased
blood flow, blood pool, and delayed periartic-
9.1 Etiology
and Pathophysiology
J.-K. Yoon (*)
Department of Nuclear Medicine, Ajou University Complex regional pain syndrome (CRPS) refers
Medical Center, Suwon, Republic of Korea
e-mail: jkyoon3@ajou.ac.kr to a chronic pain condition in injured limbs that is
characterized by allodynia (pain in response to a
S.-A. Park
Department of Nuclear Medicine, Wonkwang non-painful stimulus), hyperalgesia (exaggerated
University School of Medicine, pain in response to a painful stimulus), color and
Iksan, Republic of Korea temperature changes in the skin, swelling, auto-
e-mail: nmbach@wku.ac.kr nomic dysfunction, sensory motor changes, and
Y. S. Cho trophic changes. Patients may complain of move-
Department of Nuclear Medicine, Samsung Medical ment disorders. A variety of diseases may cause
Center, Seoul, Republic of Korea
e-mail: ysnm.cho@samsung.com CRPS: trauma, or surgery to the extremities,
stroke, and myocardial infarction [1, 2].
J. M. Park
Department of Nuclear Medicine, Soonchunhyang CRPS is more common in women than in
University Hospital, Bucheon, Republic of Korea men and is more likely to occur in middle-
e-mail: jmipark@schmc.ac.kr aged people. It affects the upper extremities
J. G. Cha more frequently than the lower extremities.
Department of Radiology, Soonchunhyang University Manifestations of this condition in other body
Hospital, Bucheon, Republic of Korea parts are uncommon [2, 3].
e-mail: mj4907@schmc.ac.kr
https://doi.org/10.1007/978-981-19-2677-8_9
94 J.-K. Yoon et al.
In 1864, Silas Weir Mitchell first described the Table 9.1 Symptoms and signs categories in Budapest
Criteria for CRPS
specific nature of “severe burning pain” caused by
a gunshot injury. In 1946, James A. Evans termed Symptoms categories
this pain syndrome “reflex sympathetic dystrophy Sensory Hyperesthesia, allodynia
Vasomotor Temperature asymmetry, skin color
(RSD)” to elucidate the symptoms associated with changes, skin color asymmetry
the sympathetic dysfunction. Subsequently, this Sudomotor/ Edema, sweating changes, sweating
has also been called by various names such as edema asymmetry
“causalgia,” “Sudeck’s atrophy,” and “shoulder- Motor/trophic Decreased range of motion, motor
hand syndrome.” The term “CRPS” was desig- dysfunction (weakness, tremor,
dystonia), trophic changes (hair,
nated to describe RSD and similar disorders in a
nail, skin)
consensus meeting by the International Association Signs categories
for the Study of Pain (IASP) in 1994 [3–5]. Sensory Hyperalgesia (to pinprick), allodynia
CRPS is further classified into CRPS-1 and (to light touch, temperature
CRPS-2; CRPS-1, previously known as “RSD,” sensation, deep somatic pressure,
joint movement)
is not associated with major nerve injury (noci-
Vasomotor Temperature asymmetry (>1 °C),
ceptive pain), whereas CRPS-2, previously skin color changes, skin color
known as “causalgia,” is associated with periph- asymmetry
eral nerve damage (neuropathic pain). CRPS-1 Sudomotor/ Edema, sweating changes, sweating
occurs more frequently than CRPS-2. edema asymmetry
No single definite mechanism for the develop- Motor/trophic Decreased range of motion, motor
dysfunction (weakness, tremor,
ment of CRPS has been suggested. dystonia), trophic changes (hair,
Proinflammatory neuropeptides released from nail, skin)
peripheral nerve endings induce inflammatory
responses at the site of tissue injury (neuroinflam- ificity, and these are the current diagnostic stan-
mation), which reduces the pain threshold (noci- dard for CRPS (“Budapest Criteria”). In the
ceptive sensitization), leading to allodynia and Budapest Criteria, CRPS is defined as continuing
hyperalgesia [6]. For autonomic dysfunction in pain, which is disproportionate to any inciting
CRPS, a decrease in the circulating n orepinephrine event, which must report at least one symptom in
increases the peripheral catecholamine sensitivity three of four categories, and must display at least
in the affected area, which results in vasoconstric- one sign in two of four categories (Table 9.1).
tion (cool skin) and hyperhidrosis [1]. Symptoms CRPS is diagnosed when there is no other diagno-
such as motor dysfunction, neglect, and impaired sis that better explains the signs and symptoms [3].
recognition suggest the involvement of the central In 2010, a quantitative parameter, the CRPS
nervous system in the development of CRPS [6]. severity score (CSS), was also designed to assess
There have also been reports that autoimmune severity and monitor the therapeutic response of
and psychological factors contribute to the devel- CRPS. CSS is composed of 17 self-reported or
opment and progression of CRPS. observed CRPS symptoms.
9.2 Diagnosis 9.3 Three-Phase Bone

Scintigraphy
The clinical course of CRPS varies from a self- in the Diagnosis of CRPS
limiting, mild disease to chronic, and debilitating
status. The diagnosis of CRPS depends on the Although there is no validated diagnostic test for
clinical criteria. The IASP first developed the diag- CRPS, imaging tests (radiographs, bone scintigra-
nostic criteria for CRPS in 1994, which had high phy, magnetic resonance imaging [MRI]), skin
sensitivity, but limited specificity. In 2003, the temperature measurement (infrared thermography,
diagnostic criteria were redefined to improve spec- laser Doppler flowmetry), sudomotor function
9 Complex Regional Pain Syndrome 95
test, and neurophysiologic tests (electromyogra- the upper extremities. Among the three
phy, nerve conduction velocity) can help outline phases, the delayed bone phase is more reliable
the symptoms and signs of CRPS [4]. Among for the diagnosis of CRPS than the blood flow
these imaging tests, three-phase bone scintigraphy and pool phases.
(TPBS) is the most helpful diagnostic test for
CRPS. TPBS using 99mTc-labeled diphosphonates Case 9.1
consists of blood flow, blood pool, and delayed A 21-year-old man complained of painful swell-
bone phases and is widely accepted for the evalua- ing of the left lower leg. He underwent surgery on
tion of soft tissue and bone infection/inflamma- the left knee for meniscal injury. 99mTc-MDP
tion. Blood flow images can be acquired in a TPBS revealed diffusely increased blood flow in
dynamic mode over the first 60 s, whereas blood the left foot and ankle, increased blood pool, and
pool images are obtained in a static mode immedi- delayed bone uptake in the left foot, ankle joint,
ately after the acquisition of flow images. Both and metatarsophalangeal joints (Fig. 9.1). TPBS
images provide information regarding soft tissue findings were suggestive of acute stage CRPS. He
hyperemia. Delayed bone images are acquired underwent physical therapy and lumbar sympa-
2–4 h after the injection of a radiotracer, which thetic plexus block.
reflects osteoblastic activity and bone turnover.
TPBS is also useful in the differential diagnosis Case 9.2
between CRPS and other etiologies in patients A 48-year-old man underwent external ventricu-
with extremity pain. However, TPBS is not recom- lar drainage and gross total tumor resection due
mended for monitoring the treatment response. to hemorrhagic glioblastoma in the right basal
The typical pattern of TPBS in CRPS is ‘dif- ganglia. Two months after surgery, he com-
fusely increased uptake at the blood flow and plained of tenderness and swelling in his left
pool phases and increased periarticular uptake hand. Presuming CRPS, 99mTc-DPD TPBS was
at the delayed bone phase’ in the affected extrem- performed. TPBS revealed diffusely increased
ities. However, the uptake is dependent on the blood flow and blood pool in the left hand, and
clinical course of CRPS [1, 4, 7–9]. In the acute prominent periarticular bone uptake in the small
stage of CRPS, increased radiotracer uptake in all joints of the hand, left wrist joint, left elbow
three phases of TPBS is observed in the affected joint, and left shoulder joint (Fig. 9.2). He
extremities. In contrast, in the chronic stage, the received steroid pulse therapy and complex exer-
uptake pattern is more variable [10]. In the blood cise therapy due to CRPS and left hemiplegia.
flow and pool phases, the uptake is decreased or Tenderness and swelling improved on the third
normal due to vasoconstriction, whereas delayed day of therapy.
bone uptake is either increased or normal. In the
early acute stage (<6 weeks), the uptake is nor- Case 9.3
mal or minimally increased in all three phases A 51-year-old woman presented with a throbbing
[8]. An atypical pattern of TPBS, which is the pain and burning sensation in her right forearm
decreased uptake in all three phases in the after housework. As MRI findings were sugges-
affected extremity, is frequently observed in chil- tive of reactive tenosynovitis, she took medica-
dren with CRPS and can also be seen in adults tion to control her pain. Four months later,
with chronic CRPS [11, 12]. The diagnostic per- swelling, tenderness, and trophic skin changes
formance of TPBS varies according to the clini- developed. Functional changes (weakness and
cal stage, diagnostic criteria, location, and age at limited range of motion) in the right hand and
onset of CRPS [1, 2]. Scan interpretation criteria right shoulder joints were also detected. The
may also affect the diagnostic performance. The patient underwent 99mTc-DPD TPBS, which
accuracy of TPBS is higher in the acute stage revealed increased periarticular bone uptake in
than in the chronic stage. The scan findings are the small joints of the right hand, right wrist joint,
less consistent in the lower extremities than in right elbow joint, and right shoulder joints
b c
Fig. 9.1 A case of acute stage CRPS in the lower extrem- increased blood pool (b), and delayed bone uptake (c) in
ity. A 21-year-old male patient with left leg swelling after the left foot, ankle joint, and metatarsophalangeal joints.
knee surgery. 99mTc-MDP TPBS reveals diffusely MDP methylene diphosphonate
increased blood flow in the left foot and ankle (a),
a d
b c
Fig. 9.2 A case of acute stage CRPS in the upper extrem- Prominent periarticular bone uptake is also seen in the
ity. 99mTc-DPD TPBS was performed in a 48-year-old small joints of the hand, left wrist joint, left elbow joint,
patient with tenderness and swelling of the left hand and left shoulder joint (c, d), suggesting acute stage
which developed after the resection of hemorrhagic glio- CRPS. Round-shaped bone uptake due to postoperative
blastoma. 99mTc-DPD TPBS reveals diffusely increased change is seen on the right side of the skull. DPD
blood flow (a) and blood pool (b) in the left hand. 3,3-diphosphono-1,2-propanodicarboxylic acid
a d
b c
Fig. 9.3 A case of chronic stage CRPS in the upper blood pool (b) in both hands. However, periarticular
extremity. 99mTc-DPD TPBS was performed in a 51-year- uptake in the delayed bone phase (c, d) is observed in
old woman with swelling, tenderness, trophic skin the small joints of the right hand and right wrist-
changes, and limited function in the right hand. elbow-shoulder joints (c, d). DPD 3,3-diphosphono-1,2-
99m
Tc-DPD TPBS reveals symmetric blood flow (a) and propanodicarboxylic acid
(Fig. 9.3). However, the blood flow and blood DPD TPBS was used for the evaluation of
pool in both hands were symmetric. Clinical and the pain. On TPBS, the blood flow, blood pool,
scintigraphy findings favored chronic stage and delayed bone uptake decreased diffusely in
CRPS. The patient’s symptoms improved after the left lower leg (Fig. 9.4a–d), which was
medication for a few months. inconsistent with typical CRPS. The intrave-
nous injection of ketamine was continued, and
Case 9.4 the symptoms improved partially. Three
A 40-year-old man visited the hospital with a months later, the patient revisited the hospital
complaint of burning pain, allodynia, and because of persistent pain, tenderness, allo-
hypoesthesia in the left lower leg, which dynia, and trophic changes. Follow-up TPBS
occurred after a car ran over his foot. He under- revealed improved bone uptake in the left
went a lumbar sympathetic ganglion block and lower leg, whereas hypoperfusion had not
received an intravenous injection of ketamine. changed (Fig. 9.4e–h). He was diagnosed with
However, as the pain did not subside, 99mTc- CRPS and underwent lumbar epidural blocks.
Case 9.5 Case 9.6

A 46-year-old male patient with right hemiplegia A 41-year-old man complaining of pain in the
due to acute left thalamic infarction was referred left hand after a road traffic accident was referred
for 99mTc-DPD TPBS for the evaluation of possi- to undergo 99mTc-DPD TPBS. A tendon injury in
ble CRPS. 99mTc-DPD TPBS was performed at the second finger was detected on the radio-
2 weeks (early acute phase, Fig. 9.5a–c) and graphic images. CRPS was presumed becuase of
4 months (acute phase, Fig. 9.5d–f) after dis- swelling and allodynia of the left hand, and a lim-
ease onset. On TPBS in the early acute phase, ited range of motion in the left shoulder. 99mTc-
the blood flow and blood pool were asymmetri- DPD TPBS was performed 3 months after the
cally decreased in the right hand (Fig. 9.5a, b), traffic accident, and the findings were consistent
whereas delayed periarticular bone uptake was with CRPS (Fig. 9.6a–c). The patient underwent
increased (Fig. 9.5c). Conversely, in the acute a sympathetic ganglion block and an intravenous
phase, the uptake was increased in the right hand injection of lidocaine. The symptoms partially
in all three phases (Fig. 9.5d–f) which was com- improved. Fourteen months after onset, pain and
patible with CRPS. This is a representative case skin changes in the left hand were not evident,
indicating that an atypical uptake pattern can be and the motor function recovered to grade 3–4.
observed in the early acute phase of CRPS. The Compared with the bone uptake on pretreatment
delayed bone phase is more reliable in the diag- TPBS, the asymmetry in the periarticular bone
nosis of CRPS, and serial TPBS imaging may be uptake was reduced on the follow-up TPBS
helpful in such cases. (Fig. 9.6d). Scintigraphic findings were consis-
a d
b c
Fig. 9.4 A case of atypical CRPS in the lower extremity. decreased in the left lower leg. Three months later, follow-
99m
Tc-DPD TPBS was performed in a 40-year-old male up TPBS reveals that bone uptake of the left lower leg (g,
patient with burning pain, allodynia, and hypoesthesia in h) is improved. However, the blood flow (e) and blood
the left lower leg. On the baseline TPBS, the blood flow pool (f) did not change. DPD 3,3-diphosphono-1,2-
(a), blood pool (b), and delayed bone uptake (c, d) were propanodicarboxylic acid
e h
f g
a d
b c e f
Fig. 9.5 A case for the serial scintigraphic changes of in the periarticular area of small joints and the wrist (c). In
CRPS in the upper extremity. 99mTc-DPD TPBS was per- the acute phase, the blood flow (d) and blood pool (e)
formed in a 46-year-old male patient with acute left tha- were asymmetrically increased in the right hand (wrist),
lamic infarction. In the early acute phase, the blood flow and delayed bone uptake became more prominent (f).
(a) and blood pool (b) were asymmetrically decreased in DPD 3,3-diphosphono-1,2-propanodicarboxylic acid
the right hand, whereas delayed bone uptake was increased
b c d
Fig. 9.6 A case of monitoring therapeutic response using bone uptake (c) were asymmetrically increased in the left
TPBS in CRPS. A 41-year-old male patient with lefth and hand. After treatment for CRPS, the periarticular bone
pain underwent 99mTc-DPD TPBS. On pretreatment uptake in the left hand and wrist joint was less prominent
TPBS, the blood flow (a), blood pool (b), and delayed (d). DPD 3,3-diphosphono-1,2-propanodicarboxylic acid
tent with symptomatic and functional improve- after a spontaneous intracranial hemorrhage
ment. Although monitoring the treatment in the right basal ganglia 3 months earlier. The
response of CRPS using TPBS is not generally patient was diagnosed with CRPS. His TPBS
accepted, it may be helpful in some patients. revealed diffusely decreased bone uptake in his
left hand and decreased perfusion in his left
Case 9.7 fourth and fifth fingers (Fig. 9.7a–c). This finding
A 63-year-old man present with left shoulder and suggested that CRPS was associated with com-
hand swelling and pain due to left hemiplegia bined ulnar nerve palsy. His clinical symptoms,
b c
Fig. 9.7 A case of a patient with mixed CRPS-1 and gers. T2 axial MRI images (d) reveal hypertrophy (arrow-
CRPS-2. 99mTc-DPD TPBS reveals a diffusely decreased heads) and high SI (white arrow) of the left ulnar nerve.
blood flow (a), blood pool (b), and delayed bone uptake The yellow arrow points to the normal ulnar nerve
(c) in the left hand, especially in the fourth and fifth fin-
such as tingling sensations and stiffness of the left

fourth and fifth fingers, were newly developed Teaching Points
when he was followed up 3 months later. • The diagnosis of CRPS is based on clin-
Electromyography revealed left ulnar nerve ical criteria.
lesion at the elbow level. This resulted in cubital • TPBS is helpful in outlining the symp-
tunnel syndrome with axonal degeneration. The toms and signs of CRPS and the differ-
patient underwent anterior subcutaneous ulnar ential diagnosis of extremity pain.
nerve transposition surgery. Preoperative MRI of • The typical pattern of TPBS of CRPS is
the left elbow revealed hypertrophic changes and diffusely increased uptake in the blood
high SI of the ulnar nerve at the cubital tunnel on flow, blood pool, and delayed bone
the T2 axial images (Fig. 9.7d), which was con- phases in the affected extremity.
sidered as an ulnar nerve impingement. He was • The uptake pattern of TPBS varies
diagnosed with mixed CRPS-1 and CRPS-2, according to the clinical stage, diagnos-
which resulted from peripheral nerve injury tic criteria, location, and age.
(Fig. 9.7).
References 7. Demangeat JL, Constantinesco A, Brunot B, Foucher

G, Farcot JM. Three-phase bone scanning in reflex
sympathetic dystrophy of the hand. J Nucl Med.
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1998;28:116–23.
M. Patterns of three-phase bone scintigraphy accord-
2. Howard BA, Roy L, Kaye AD, Pyati S. Utility
ing to the time course of complex regional pain syn-
of radionuclide bone scintigraphy in complex
drome type I after a stroke or traumatic brain injury.
regional pain syndrome. Curr Pain Headache Rep.
Clin Nucl Med. 2009;34:773–6.
2018;22:7.
9. Shin SH, Kim SJ. Bone scintigraphy in patients with
3. Shim H, Rose J, Halle S, Shekane P. Complex regional
pain. Korean J Pain. 2017;30:165–75.
pain syndrome: a narrative review for the practising
10. Cheon M, Kang HJ, Do KH, Yang HS, Han EJ, Yoo
clinician. Br J Anaesth. 2019;123:e424–e33.
J. Diagnostic performance of three-phase bone scin-
4. Intenzo CM, Kim SM, Capuzzi DM. The role of
tigraphy and digital infrared thermography imaging
nuclear medicine in the evaluation of complex
for chronic post-traumatic complex regional pain syn-
regional pain syndrome type I. Clin Nucl Med.
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2005;30:400–7.
11. Goldsmith DP, Vivino FB, Eichenfield AH, Athreya
5. Lee GW, Weeks PM. The role of bone scintigraphy in
BH, Heyman S. Nuclear imaging and clinical features
diagnosing reflex sympathetic dystrophy. J Hand Surg
of childhood reflex neurovascular dystrophy: com-
Am. 1995;20:458–63.
parison with adults. Arthritis Rheum. 1989;32:480–5.
6. Urits I, Shen AH, Jones MR, Viswanath O, Kaye
12. Laxer RM, Allen RC, Malleson PN, Morrison RT,
AD. Complex regional pain syndrome, current con-
Petty RE. Technetium 99m-methylene diphosphonate
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bone scans in children with reflex neurovascular dys-
2018;22:10.
trophy. J Pediatr. 1985;106:437–40.
Part III
Spine and Joint Disorders
Spine
10
Tae Joo Jeon
Abstract CT mainly in the evaluation of the spine after

surgical intervention and add some brief dis-
Spine is one of the most important structures
cussion about other conditions such as spon-
supporting our body and which is continu-
dylolysis and fractures.
ously stressed by various postures as well as
gravity. These various stresses can affect the
Keywords
stability of spine and can cause many prob-
lems. Lower back pain is the most common SPECT/CT · Spine · lumbar fusion · Fracture
disease, and its overall prevalence has been Trauma · Hybrid imaging · Spondylolysis
known to be over 10% of population. Although Failed back surgery syndrome
many of patients with this symptom can be
successfully cared by conservative manage-
ment, not small portion of the patients require 10.1 Evolution of Bone SPECT
surgical intervention such as internal fixation
or spinal fusion. At this time, imaging modali- Before the 1990s, plain radiography and planar
ties such as CT, MRI, and SPECT/CT have bone scintigraphy were the imaging procedures
important roles to assess the exact conditions of choice for the evaluation of patients with
of spine before and after the surgery, predict orthopedic problems of spine, and this trend has
the prognosis, and made decision for follow- not been changed much for a long time, even
up management plan. All these modalities
after the development of SPECT technique,
have their own benefits and limitations as is because this new technique was not widely
well known, and SPECT/CT can play special applied to the clinical field of bone disease,
role due to highly sensitive detection rate of despite its high detectability of bone change by
early bone change and less metal artifacts tomographic data, due to relatively low spatial
despite the relative low special resolution. In resolution and long scan time. Meanwhile, mag-
this chapter we will review the role of SPECT/ netic resonance imaging (MRI) emerged as a
choice of modality for spine evaluation.
However, introduction of hybrid bone imag-
ing using SPECT and CT made robust change in
T. J. Jeon (*) many aspects [1]. For example, advanced recon-
Department of Nuclear Medicine, Gangnam
struction algorithm has significantly improved
Severance Hospital, Yonsei University College
of Medicine, Seoul, Republic of Korea image quality compared to conventional filtered
e-mail: tjeonnm@yuhs.ac back projection (FBP) technique. Introduction of
https://doi.org/10.1007/978-981-19-2677-8_10
106 T. J. Jeon
attenuation correction and scatter correction also 10.3 Abnormalities in Fused

contributed to achieving better image quality, and Segments
image fusion with CT data resulted in improving
localization power [2]. Under the all these pro- Spinal fusion is a complicated procedure using
gressions, some investigators suggest that diverse metallic devices, and various problems
SPECT/CT is clinical routine in spine and pelvis can occur after this surgery.
imaging [3]. One of important problems is non-union,
Furthermore, quantitative analysis technology failure of osseous bridging to inserted metal
in SPECT/CT made it possible to measure SUV even 1 year after the surgery and which com-
in Tc-99m diphosphonates bone images as F-18 monly produces pain and its incidence varies
FDG PET/CT does, and this new technology can according to patient’s factors and the properties
be applied to traumatic bone disease as well as of used materials. Secondly, fracture of metallic
oncologic cases. This new technology can make devices also can be a possible side effect, and
it possible to monitor the serial bone changes SEPCT/CT is useful to detect the secondary
after spine surgery by objectively measured data, bone change as well as the problem of metallic
not by only visual evaluation [4, 5]. device per se. The loosening of prosthesis is
also an important condition which should be
carefully checked when interpreting the bone
10.2 Diagnosis of Spine Disease SPECT/CT. The evaluation of the exact phase of
After Various Operations these problems can make it possible to choose
the best treatment option at each time point
Although we will focus on the spine after surgery [11–13].
such as interbody fusion, screw fixation, etc.,
SPECT/CT has been also reported to be useful in
the evaluation of low back pain in young people 10.4 Evaluation of Spondylolysis
with stress fracture, spondylolysis, and benign and Other Traumatic
bone lesion [6, 7]. and Degenerative Changes
In patients with spinal fusion surgery, degen-
erative changes commonly affect the segment Spondylolysis is also an important cause of back
above or below the fusion site which is an impor- pain which is defined as break in the pars interar-
tant type of failed back surgery syndrome. ticularis of neural arch. The importance of this
Usually this is known to be developed with time- disease entity is that this can commonly occur in
related process. Most common affecting sites are children to young adults as well as elderlies
facet joint and end plate of vertebra which will be because this area is weak during developmental
demonstrated by many cases later. Progression of phase before the achievement of full maturation
degenerative changes in these areas with the of skeletal system. The etiologies of spondyloly-
passage of time can lead to spondylolisthesis
sis are varied, such as continuous stress, trauma,
which may be above and/or below the fused seg- and developmental problem. The role of SPECT/
ment [8]. The incidence of this change in lumbar CT in spondylolysis is to identify the stress of
spine has been reported to be about 70% at pars interarticularis before apparent spondyloly-
10 years after the surgery, and SPECT/CT can sis and differentiate acute spondylolysis from
play an important role in early detection of this chronic non-union.
change and providing the information for appro- SPECT/CT also plays an important role in
priate management [9]. early detection of degenerative changes in end-
According to the American College of plate of vertebral bodies as well as osteophyte
Radiology (ACR) Appropriateness Criteria, bone formation, and both sclerotic change information
SPECT/CT is useful to detect and localize the from CT part and radiotracer uptake representing
pseudarthrosis lesion with pain [10]. bone metabolic activity from SPECT data will
10 Spine 107
provide us better option for interpretation of vari- 5 vertebral bodies with minimal uptake are sup-
ous spinal diseases. posed to be old compression fractures. Otherwise,
all these compression fractures have different
severity of insults if all these injuries occurred in
Teaching Points the same time. This case is one of good example
• Hybrid bone SPECT/CT image is a use- representing that SPECT/CT provides us impor-
ful modality in evaluation of spine after tant information about exact phase of bone dis-
surgery. ease by collaboration of anatomical and
• Degenerative change affecting the seg- functional data (Fig. 10.1).
ment above or below the fusion is
important type of failed back surgery Case 10.2
syndrome. An 87-year-old woman visited to the outpatient
• Failed back syndrome is a time-related clinic due to chronic back pain. She underwent
process. posterior screw fixation at the L4, 5 level of spine.
• Common affecting sites of failed back SPECT/CT images reveal no significant bone
syndrome after spinal fusion are facet uptake in the operation site, but strong uptake can
joint and endplate. be seen in Lt. facet joint of L1/2 level, and fused
• Bone SPECT/CT has high sensitivity SPECT/CT images show asymmetric sclerotic
and specificity in detecting the screw change of the Lt. facet joint as well. Facet joint is
loosening of spine. a common site of secondary degenerative change
• SPECT/CT is also useful in evaluating after spine fusion surgery as previously men-
the spectrum of spondylolysis, only tioned. Like this case, SPECT/CT can accurately
stress reaction without spondylolysis, localize the sclerotic bone changes on CT images
spondylolysis, and non-union. (a), and fusion images provide the exact
localization of affected site on axial (b) and sagit-
tal (c) plane, while planar images failed to depict
Case 10.1 the facet joint problem (d).
An 81-year-old man presented to the hospital due According to SPECT/CT finding, Lt. facet
to upper back pain developed 2 days ago. He joint lesion appears to be active phase of disease
underwent multilevel lumbar pedicle fixation sur- in spite of sclerotic change, and this cannot be
gery 1 year ago and got a slip down injury validated by CT and planar scintigraphic data
recently. Planar bone scintigraphy showed only (Fig. 10.2).
increased uptake in T12 to L1 vertebrae (a). MIP
image obtained from SPECT data reveals stron- Case 10.3
ger uptake in that lesion with additional hot A 55-year-old woman with history of total hip
lesions in the remaining lumbar spine (b). Sagittal replacement on Lt. side presented to the outpa-
reconstruction CT image revealed anterior wedg- tient clinic due to low back pain. Planar bone
ing deformity of T12 vertebral body and multiple scintigraphy shows focal hot uptake in L3 verte-
mild compression fractures of L1, 3, 5 vertebral bra (a), and coronal fusion SPECT/CT images
bodies (c). Fusion SPECT/CT images show represent more clearly defined hot uptake in the
intense uptake in T12 body and relatively strong same area (b). Sagittal reconstruction CT image
uptake in L1 body, while only mild uptakes are reveals only mild compression of upper margin
noted in L3 and L5 bodies (d). These SPECT/CT of L3 vertebral body (c); however SPECT/CT
findings were not clearly defined by planar scin- image shows intense radiotracer uptake in poste-
tigraphy only. Considering all these results, only rior portion of L3 vertebral body as well as upper
T12 and L1 vertebral bodies got recent traumatic margin of the vertebral body (d). Although upper
insults, while the other lesions in compressed L3, margin of sacrum has sclerotic bone changes on
108 T. J. Jeon
a b
c d
Fig. 10.1 Planar scintigraphy (a) shows only mild uptake ity in multiple compression fracture of vertebrae, very
in T12, L1 level compared to MIP SPECT image (b), and strong uptake in T12, strong uptakes in L1, and mild
CT scan can only provide the information of anatomic uptakes in L3, 5 vertebral bodies (d)
changes of spine (c), while SPECT reveals different activ-
CT scan (c), SPECT image reveals no visible hot Case 10.4

uptake in this area (d). All these findings mean An 83-year-old woman with history of total hip
that SPECT/CT is a very useful modality that can replacement on Rt. side and posterior screw fixa-
validate the exact extent of bone disease as well tion of L2–L4 came to the clinic due to back pain.
as the exact phase of bone injury. SPECT images Planar bone scintigraphy reveals increased uptake
are known to have higher resolution as well as only in part of L2, 3 vertebrae (a); however MIP
higher sensitivity compared to those of planar image of SPECT shows more intense uptakes in
scintigraphy in the evaluation of deep structure this area and additional hot uptake in L4, 5, and
according to using tomographic data set. Rapid Rt. acetabulum (b). Sagittal reconstruction CT
progression of hardware and software technology image shows sclerotic changes in upper and
of SPECT/CT will definitely exaggerate these lower portion of L2 and upper margin of L3 ver-
results in the near future (Fig. 10.3). tebral bodies (c). Fusion SPECT/CT images
10 Spine 109
a b
c d
Fig. 10.2 Asymmetric sclerotic changes of Lt. facet joint exact extent of hot uptake can be estimated by coronal
are noted on axial CT image (a), and axial fusion SPECT/ reconstruction image (c), while planar scintigraphy failed
CT image shows strong uptake in the Lt. facet joint, but to localize the facet lesion, and only degenerative change
only minimal radiotracer uptakes are noted in another of vertebral body can be suspected by this image (d)
small round sclerotic lesions of vertebral body (b). More
reveal localized hot uptakes in the endplate of shows periscrew lucency in Rt. side (arrow),
L2/3 vertebral body with sclerotic changes and and fusion SPECT/CT images reveal strong
additional hot uptakes in facet joints of L3/4 and focal uptakes in both screws, especially in Rt.
L4/5 (d). This is another case demonstrating typi- side (b).
cal findings of failed back syndrome with hot These findings can be due to screw loosen-
uptakes above and below level of fusion and adja- ing, and the incidence of this event is reported to
cent facet joints. In the interpretation of cases be 0.6% to 11%, and bone SPECT/CT has
with failed back syndrome, knowledge about known to have excellent sensitivity (100%) and
commonly affected site will be very helpful and specificity (89.7%) in detecting loosening of
essential (Fig. 10.4). screw in spine [14]. In the interpretation of loos-
ening, CT images must be very important like in
Case 10.5 other diseases. Although only planar scintigra-
A 70-year-old woman with history of posterior phy and plain radiography were available in the
screw and rod fixation of L2 to L4 presented to past, now SPECT/CT images provide much
the clinic due to back pain. Axial CT image (a) more useful information for this problem.
110 T. J. Jeon
a b
c d
Fig. 10.3 Nearly all part of L3 body seems to be involved reconstruction CT represents mildly increased bone den-
by hot uptake on planar scintigraphy due to blurring of sity in upper margin of L3 body (c), while SPECT/CT
image (a); however only part of L3 body was involved by image reveals some discrepancy, strong uptake in the pos-
hot uptake on SPECT image fused to CT (b). Sagittal terior portion of vertebral body (d)
10 Spine 111
a b
c d
Fig. 10.4 Planar scintigraphy shows focal hot uptakes these areas (b). Mild sclerotic bone changes of L2, 3 ver-
only in the lateral margins of L2, 3 vertebrae with mild tebral bodies are well defined by sagittal reconstruction
focal uptakes in L4, 5 vertebrae, and only minimal focal CT images (c), and increased uptakes are noted in the
uptake is noted in Lt. acetabulum (a). However, MIP lower margin of L2 and upper margin of L3 vertebral bod-
SPECT images show stronger and larger hot lesions in all ies (d)
112 T. J. Jeon
a b
Fig. 10.5 Axial CT image (a) reveals periscrew lucency According to both anatomic and functional imaging find-
of Rt. side (arrow), and strong radiotracer uptakes are ings, more exact evaluation of loosening and disease
noted in both sides of screws, especially in Rt. side (b). activity can be achieved
Especially loosening of posterior fixation of part interarticularis (b). Sagittal CT (c) and fusion
vertebral body by screw like in this case is com- SPECT/CT (d) image of Rt. pars interarticularis
monly missed by planar scintigraphy, although at the same level represents focal bone defect
longitudinal pattern of loosening case such as without significant radiotracer uptake. These
total hip replacement can be more easily findings suggest the possibility of different time
detected by planar technology only. Hybrid of event in these two spondylolysis lesions
tomographic imaging SPECT/CT provides although anatomic image reveals similar findings
tomographic images of three axial plane, and in both pars interarticularis lesions of L5
any plane of loosening of device is readily vertebra.
detectable (Fig. 10.5). SPECT/CT is also useful in the evaluation of
exact phase of various spinal fractures such as
Case 10.6 spondylolysis, vertebral pedicle fracture, and
A 50-year-old man with history of bilateral total avulsion fracture of spinal spinous process. Even
hip replacement surgery was admitted to the small uptakes in fracture lesions can be easily
clinic due to low back pain. Axial CT image detected and exactly localized by this hybrid
shows bony defects in bilateral pars interarticu- imaging technique, and the accumulation of
laris of L5 vertebra with mild sclerotic changes knowledge about this condition will make
(a). However, fusion SPECT/CT image reveals SPECT/CT provide proper treatment guideline in
asymmetric focal tracer uptake only in the Lt. the future (Fig. 10.6).
10 Spine 113
a b
c d
Fig. 10.6 Axial CT image (a) shows breaks in the pars status of bilateral pars interarticularis defects although CT
interarticularis of both sides (L5 level) with mild sclerotic scan reveals similar findings. Sagittal reconstruction CT
changes, and asymmetrically increased uptake is noted in and fusion SPECT/CT at the level of Rt. pars interarticu-
defect of Lt. side on axial fusion image (b). These findings laris reveal well-defined bony defect (c) and no significant
suggest the possibility of chronic non-union of Rt. pars uptake in this area (d)
interarticularis, and fusion images demonstrate different
a physician’s perspective of the adoption of SPECT/

References CT in a clinical setting with a focus on trauma sur-
gery. Eur J Nucl Med Mol Imaging. 2014;41(Suppl
1. Utsumomya D, Shiraishi S, Imuta M, Tomiguch S, 1):S59–66.
Kawanak K, Morishita S, et al. Added value of SPECT/ 4. Tbotta F, Jreige M, Schaefer N, Becce F, Prior J,
CT fusion in assessing suspected bone metastasis: Laonde M. Quantitative bone SPECT/CT: high speci-
comparison with scintigraphy alone and non fused ficity for identification of prostate cancer bone metas-
scintigraphy and CT. Radiology. 2006;238:264–71. tases. BMC Musculoskelet Disord. 2019;20:619.
2. Miyaji N, Miwa K, Tokiwa A, Ichikawa H, Terauchi 5. Huang K, Feng Y, Liu D, Liang W, Li L. Quantification
T, Koizumi M, et al. Phantom and clinical evalua- evaluation of Tc-99m MDP concentration in the lum-
tion of bone SPECT/CT image reconstruction with bar spine with SPECT/CT: compare with bone min-
Xspect algorithm. Eur J Nucl Med Mol Imaging Res. eral density. Ann Nucl Med. 2020;34:136–43.
2020;10:71. 6. Matesan M, Behnia F, Bermo M, Vesselle H. SPECT/
3. Scheyerer MJ, Pietsch C, Zimmermann SM, CT bone scintigraphy to evaluate low back pain in
Osterhoff G, Simmen HP, Werner CM. SPECT/CT young athletes: common and uncommon etiologies. J
for imaging of the spine and pelvis in clinical routine: Orthop Surg Res. 2016;11:76.
114 T. J. Jeon
7. Trout AT, Sharp SE, Anton CG, Gelfand MJ, Mehlman 11. Al-Riyami K, Van den Wyngaert GG, T, Bomanji
CT. Spondylolysis and beyond: value of SPECT/CT J. Bone SPECT/CT in the postoperative spine: a
in evaluation of low back pain in children and young focus on spinal fusion. Eur J Nucl Med Mol Imaging.
adults. Radiographics. 2015;35(3):819–34. 2017;44(12):2094–104.
8. Levin DA, Hale JJ, Bendo JA. Adjacent seg- 12. Sumer J, Schmidt D, Ritt P, Lell M, Forst R, Kuwert
ment degeneration following spinal fusion for T, et al. SPECT/CT in patients with lower back pain
degenerative disc disease. Bull NYU Hosp Jt Dis. after lumbar fusion surgery. Nucl Med Commun.
2007;65(1):29–36. 2013;34(10):964–70.
9. Lee I, Budiawan H, Moon JY, Cheon GJ, Kim YC, 13. Waldman LE, Scharf SC. Bone SPECT/CT of the
Paeng JC, et al. The value of SPECT/CT in localiz- spine, foot, and ankle: evaluation of surgical patients.
ing pain site and prediction of treatment response in Semin Nucl Med. 2017;47(6):639–46.
patients with chronic low back pain. J Korean Med 14. Hydyana H, Maes A, Vandenberghe T, Fidlers L,
Sci. 2014;29(12):1711–6. Sathekge M, Nicolai D, et al. Accuracy of bone
10. Patel ND, Broderick DF, Burns J, Deshmukh TK, SPECT/CT for identifying hardware loosening
Fries IB, Harvery HB, et al. ACR appropriate- in patients who underwent lumbar fusion with
ness criteria low back pain. J Am Coll Radiol. pedicle screws. Eur J Nucle Med Mol Imaging.
2016;13(9):1069–78. 2016;43(2):349–54.
Hip
11
Sun Jung Kim and So Won Oh
Abstract after hip surgery rather than dealing with pri-

mary hip diseases.
Hip replacement and internal fixation are
major surgeries commonly performed in the
Keywords
hip region. Total hip arthroplasty (THA) is
one of the most successful and cost-effective Total hip arthroplasty · Internal fixation ·
surgical procedures. The main indications are Complications · Nuclear imaging · SPECT/
osteoarthritis, avascular necrosis, femur neck CT · Fracture
fracture, and inflammatory arthritis. The
incidence of THA has increased dramatically
over the past 20 years, despite a variety of
11.1 Loosening in THA
early and late complications. Accordingly,
the increase of revision arthroplasty has fol-
Loosening of the prostheses is one of the major
lowed. It is still challenging to identify the
complications of THA and accounts for about
cause of pain and failure in THA despite the
70% cases of revision arthroplasty [1]. Aseptic
advances in radiologic and nuclear imaging
loosening is loss of fixation of the implant, which
techniques. Internal fixation is widely used in
can be caused by inadequate initial fixation,
treatment of hip fractures. Hip fractures are a
mechanical loss of fixation overtime, or biologic
common injury, and femur neck fractures are
loss of fixation due to particle-induced osteolysis
associated with high levels of patient mor-
around the implant. The Hip Society has defined
bidity and mortality after surgery. In this
it as confirmed intraoperatively or identified
chapter, we present a brief review of cases to
radiographically as a change in implant position
assess the cause of pain and complications
or a progressive radiolucent line at the bone-
cement or bone-implant interface [2]. Thus, it is
important to check serial radiographs with clini-
S. J. Kim (*) cal follow-up.
Department of Nuclear Medicine, National Health
Insurance Service Ilsan Hospital, Reproducible assessment of periprosthetic
Goyang, Republic of Korea lucency uses the standardized zones proposed by
e-mail: sunjk32@nhimc.or.kr Gruen (zones 1–7) for the femur and DeLee and
S. W. Oh Charnley (zones I–III) for the acetabulum
Department of Nuclear Medicine, Seoul National (Fig. 11.1a) [3, 4]. A lucent zone greater than
https://doi.org/10.1007/978-981-19-2677-8_11
116 S. J. Kim and S. W. Oh
2 mm in diameter around the prosthesis is a com- power field microscopic examination in some
mon sign of loosening on radiography. materials, but the criteria for infection were not
In bone scan, loosening is suspected when reached.
there is an increased uptake in around the entire
or near entire periprosthetic area. Bone scan
(including triple phase) has slightly lower diag- 11.2 Chronic Expanding
nostic performance than radiography to detect Hematoma in THA
loosening of prosthesis: a sensitivity of 67% and
specificity of 75% for acetabular cup and 85% Chronic expanding hematoma (CEH) is a rare
and 72% for femoral stem, respectively [5, 6]. entity that often results from trauma, surgery,
Increased uptake around prosthesis on vascular anticoagulation therapy, or bleeding disorders
and blood pool image of triple-phase bone scan [7]. In addition, periprosthetic chronic expanding
(TPBS) is likely not aseptic loosening. It is hematoma after THA is very rare. To the best of
challenging to distinguish between aseptic and our knowledge, only a few cases of CEH after
septic loosening. In nuclear imaging, white THA were reported to date, which was accompa-
blood cell (WBC) scan can be useful, and 18F- nied by progressive osteolysis [8, 9]. In reported
FDG PET/CT seems to be needed by further cases, there was no clear trigger for hematoma
research. formation, and the cause was unknown. In con-
trast to pseudotumor that occurs around replaced
Case 11.1 hip joint, there was no histiocytic infiltration and
A 55-year-old man who underwent bilateral hip very little evidence of particulate or metal debris
arthroplasty visited the outpatient clinic com- on histological findings.
plaining of worsening right hip pain for 1 month. Clear preoperative diagnosis could be diffi-
The right one was operated 3 years ago and the cult to determine. The differential diagnosis to
left one 13 years ago. be considered is as follows: acute local tissue
Radiograph showed periprosthetic radiolu- reaction (ALTR) known as pseudotumor, benign
cency in entire zones around the right femoral and malignant soft tissue tumor, and deep
stem and periosteal reaction in zones 2, 3, 5, and infection.
6 of the right femur. Osteolysis was observed in
zones I and II of the left acetabulum (Fig. 11.1b). Case 11.2
Bone scan showed increased uptake in most of Eight years after the patient of Case 11.1 under-
zone around the right femur stem (Fig. 11.1c). going revision arthroplasty on the right femur,
CT showed well radiolucent zone around pros- he revisited the outpatient clinic due to worsen-
thesis of the right femur (Fig. 11.1e) and perios- ing left hip pain that developed 2 weeks prior.
teal reaction around lower prosthesis (Fig. 11.1d). He occasionally felt discomfort in the left
An osteolytic lesion was seen in zones I and II of groin after 2 years since the revision surgery. On
the left acetabulum (Fig. 11.1f, g). radiograph, the preexisting osteolytic lesion in
These findings are reasonable for loosening the left acetabulum appeared slightly larger than
of the right femoral stem and asymptomatic 8 years ago (Fig. 11.2a). Bone scan showed no
osteolysis in the left acetabulum. He under- abnormal uptake in the left acetabulum (Fig.
went revision surgery for the painful right 11.2b). CT obtained 8 months later revealed a
femur component. There were quite a few large cystic mass in the left iliac fossa extending
inflammatory debris in the femur where the from the left iliac bone to the anterior aspect of
femur stem was located. Frozen biopsy of sev- the ipsilateral hip joint coursing below the heads
eral periprosthetic soft tissues during operation of the iliopsoas muscle (Fig. 11.2d–f, h–j). The
showed polymorphonuclear leukocytes/high- cystic mass was abutting to the osteolytic lesion
11 Hip 117
a b c
d e f g
Fig. 11.1 (a) The Charnley-DeLee numbering system surgery. (d) Axial CT image of lower level of prosthesis
for acetabular cups and the Gruen zone numbering for shows periosteal bone formation (arrow), which is often
femoral stems in the anterior-posterior plane. (b) seen in periprosthetic infection. (e) Axial CT of upper
Radiograph shows periprosthetic radiolucency in entire level of prosthesis shows well radiolucent zone (yel-
zones around the right femoral stem and periosteal reac- low arrow) greater than 2 mm around prosthesis. (f), (g)
tion in zones 2, 3, 5, and 6. Osteolysis (arrow) in zones I The right acetabular cup is well fixed (yellow arrow) and
and II of the left acetabulum (inset). (c) Bone scan shows an osteolysis with thin sclerotic rim and cortical break-
increased uptake in most of zone of the right femur stem, down (green arrows) in zones I and II of the left acetabu-
suggesting loosening. Focally increased uptake in zone 4 lum on axial and sagittal CT images
of the left femoral stem is still seen even 13 years after
grown in the left superior acetabulum and iliac 11.3 Periprosthetic Joint Infection
bone (Fig. 11.2e, f, i, j). MRI showed a mixture in THA
of fresh and old blood indicating repeated bleed-
ing (Fig. 11.2g, k). He underwent surgery to Periprosthetic joint infection (PJI) is one of the
remove the cystic mass, which had separated most dreaded complications. This is because sev-
into two lumens, filled with old blood and clots. eral stages of surgery may be necessary instead
Histopathologic report revealed hematoma with of once and the subsequent increase in morbidity
thick capsule. He replaced the left acetabular and the outcome of the prosthesis may be poor.
cup and the femur head due to prolonged oste- The diagnosis of PJI is difficult and not standard-
olysis and loosening confirmed during surgery. ized. At least six different definitions of PJI were
He had no previous history of trauma and anti- released by independent societies, but most of
coagulation therapy. Laboratory data showed them do not include imaging techniques, except
normal coagulation profiles. Unlike previous for the recently released World Association
reports, osteolysis did not progress significantly. against Infection in Orthopaedics and Trauma
a b c
d e f g
h i j k
Fig. 11.2 (a) Radiograph shows an osteolytic lesion the left iliac fossa and inguinal area, displacing femoral
(arrow) larger than 8 years ago (inset, arrow head) in vessels to medial side (arrow). No contrast enhance-
zones I and II the left acetabulum. (b) Bone scan shows no ment is seen within the mass. (h), (i) Coronal and (j) sagit-
abnormal uptake in the left hip area. Cortical margin of tal CT images demonstrate the extension of the mass
the left iliac crest is not clearly visible (arrow). Slightly (arrow heads). The cystic mass appears to have eroded
increased uptake in zones 1 and 7 of the right femur (long adjacent cortical bone (long arrows) of preexisting oste-
arrow) even after 8 years of revision. Uptake in zone 4 olysis in the left iliac bone and acetabulum. (g) T1 TSE
(arrow head) of the left femur stem reduced, compared to axial and (k) T2 STIR coronal MR images show a large
previous bone scan that acquired 8 years ago before the hemorrhagic mass with dark signal intensity wall on both
revision (c, same image of Fig. 11.1 (c)). (d)–(f) Axial images (arrow head). A mixture of low to high signal
CT images show a large cystic mass (arrow heads) in intensity on both images suggests repeated bleeding
(WAIOT) definition. The WAIOT definition WBC scan—if necessary, combined with a
includes only two imaging techniques, bone scan bone marrow scan—has very high specificity for
and WBC scan, respectively, as a rule-out and identifying PJI and is the most reliable imaging
rule-in test to define PJI [10]. tool. The reported accuracy of the combined WBC
TPBS has high sensitivity but low specificity scan and bone marrow scan ranges from 83% to
for diagnosing certain disease including 98% for both hip and knee prosthesis infections
PJI. However, if TPBS is negative in all three [12]. Most of the largest researches show a high
phases, infection can be ruled out considering the NPV for WBC scan, ranging from 92% to 100%
high negative predictive value (NPV) [11]. [13]. SPECT/CT using 99m
Tc-HMPAO-WBC
11 Hip 119
without performing bone marrow scan can be the right femur on delayed phase (Fig. 11.3f). CT
most valuable imaging technique in diagnosing showed a complicated fluid collection from the
PJI [14]. As with TPBS, PJI can be excluded from anterolateral side of the right hip, which drain to
diagnosis if the WBC scan is negative. the skin (Fig. 11.3c). It was not difficult to diag-
nose PJI clinically because there was turbid dis-
Case 11.3 charge through the skin sinus tract. He had
Two years after the patient of Case 11.1 and extensive and meticulous debridement of infected
11.2 undergoing excision of CEH and revision of soft tissue and irrigation, and then an antibiotic
the left acetabular cup, he visited again the outpa- impregnated cement spacer was placed in its
tient clinic because of pain and discharge in the place (Fig. 11.3g). Surgeons confirmed during
right proximal thigh for a month. Right hip revi- surgery that the draining sinus in the skin was
sion surgery was performed due to loosening communicated to the hip joint. Microbial cultures
10 years ago. He had a draining sinus in the skin of synovium and periprosthestic soft tissue col-
of anterolateral proximal thigh (Fig. 11.3a). He lected during surgery and preoperatively were all
had already been taking antibiotics at another negative, and pathologic report revealed inflamed
clinic for 10 days. Radiograph showed no signifi- granulation tissue with abscess and necrosis. After
cant abnormal findings (Fig. 11.3b). TPBS 7 weeks, he underwent surgery to remove the anti-
showed distinctly increased vascular and blood biotic spacer and additional debridement through
pool in the right anterolateral thigh (Fig. 11.3d, e) irrigation, but exchange of prosthesis was not per-
and increased uptake around greater trochanter formed considering the patient’s various
reattachment device (GTRD), zone 1 and 7 of the circumstances.
a b d
c g
f
Fig. 11.3 (a) Sinus tract on anterolateral skin of right eral rim enhancement (short arrow) in the fluid collection.
proximal thigh. (b) Radiograph shows a thin radiolucency (d), (e) Localized increased uptake (arrow) in anterolat-
in zones 1 and 7 and periosteal bone formation in zones 1, eral proximal thigh on both vascular and blood pool phase
2, 5, and 6 of right femur without longstanding change of bone scan, which may be corresponding to the fluid
(serial radiographs not shown). (c) Enhanced axial CT collection area on CT. (f) Increased uptake (arrow) around
shows fluid collection (long arrow) with a skin sinus tract GTRD, zones 1 and 7 of the right femur on delayed phase
(arrow head) in anterolateral thigh and surrounding sub- bone scan. (g) Radiograph after surgery shows placement
cutaneous infiltration (short white arrow). There is periph- of antibiotic spacer (arrow)
11.4 Osteolysis in THA uptake in the right hip prosthesis area in all three
phases (Fig. 11.4e, f). He underwent revision
Osteolysis (OL) is expansile lytic lesion adjacent operation, and loosening of the acetabular cup
to one of the implants that is greater than or equal was confirmed at the time of surgery. Osteolytic
to 1 cm in any one dimension or increasing in bone defect in the acetabulum was filled using
size on serial radiographs or CT [2]. OL is usu- allograft bone chips, and acetabular cup and fem-
ally aseptic and the result of an inflammatory oral head were exchanged.
immune response to particulate wear debris [15].
Serial radiographs are most commonly used to
identify OL, but radiography has a sensitivity of 11.5 Failure of Impacted Bone
only 41.5% [16]. CT provides greater sensitivity Graft in THA
for OL detection than radiography and is margin-
ally superior to MRI [17]. The sensitivity and Impaction bone grafting (IBG) is now a routine
specificity for diagnosing acetabular OL by bone technique in revision THA for acetabular defects
scan were 34% and 0%, respectively [18]. The caused by OL or loosing. Bone graft provides a
significance of bone scan for diagnosing OL is substrate and scaffolding for development of
still uncertain. OL itself does not imply loosen- bone structure. Allograft is commonly used,
ing, but OL can predate aseptic loosening. It is despite of drawbacks such as lack of osteoinduc-
often difficult to predict the progression of OL tive property, disease transmission, inconsistent
because most cases are asymptomatic. Clinical incorporation, and immune reactions.
decision-making regarding asymptomatic OL in Histological studies have shown complete incor-
patients with otherwise well-functioning THA poration of allograft cancellous chips was
remains a challenge. If the amount of the remain- replaced by newly formed trabeculae [19].
ing bone stock is small, the outcome of revision Bone allografts have high opacity and attenua-
surgery is likely to be poor. Therefore, regardless tion on initial postoperative radiograph and CT,
of functional failure of THA, the operation may which gradually decrease over time, as graft incor-
be decided by considering the rate of OL, the poration progresses. This process can take up to
amount of the remaining bone stock, and the 18 months and CT can better show this process.
patient’s medical risk. TPBS can be used to evaluate the viability of
bone graft. Increased flow indicates preserved
Case 11.4 blood supply to graft region along with increased
A 78-year-old man who underwent bilateral THA blood pooling, and delayed image reveals
visited to the outpatient clinic with intermittent increased uptake ascertaining the integrity and
right hip pain. The right one was operated viability of the bone allograft. However, these
17 years ago and the left one 13 years ago. findings can be seen in various diseases. SPECT/
Serial radiographs showed the position of the CT can be useful in the assessment of graft via-
right femoral head was gradually shifting upper bility in THA because CT can increase the
outward (Fig. 11.4a–c), suggesting polyethylene specificity.
(PE) liner wear. Localized osteolytic lesions in
zones I and II of the right acetabulum have newly Case 11.5
appeared on latest radiograph (Fig. 11.4c). For A 81-year-old woman who underwent revision
femoral component, subsidence of the right THA of right hip 9 years ago was referred to the
femur prosthesis progressed gradually, and radio- clinic to evaluate the worsening right hip pain for
lucency around the flange of femoral stem was 1 month.
increasing (Fig. 11.4a–c). Pelvic bone CT showed On radiograph, one of the screws inserted into
large (5 × 4.6 × 2.6 cm in dimension) osteolysis the acetabular cup came out to the level of femur
in zones I–III of the right acetabulum, and the neck, and the density of acetabulum around the
extent of osteolysis was wider than radio- cup appeared to be rather high (Fig. 11.5a). CT
graph (Fig. 11.4d). TPBS showed no abnormal showed high attenuation area that looked like
11 Hip 121
a b c
e f
Fig. 11.4 (a–c) Serial radiographs show (1) wear of PE Coronal, sagittal, and axial CT show a large osteolysis
liner; see the length of black bars, (2) gradual progression (arrows) in zones I–III of right acetabulum. Note wear of
of subsidence of right femoral stem, (3) radiolucency PE liner on coronal image (short arrow). (e), (f) There is
around flange of the femoral stem (short arrow), (4) an no abnormal uptake in right hip region on blood pool and
osteolytic lesion above acetabular cup (arrow heads). (d) delayed image of bone scan
mosaic fragments in the acetabulum around the lar cup at the time of surgery, but the bone graft
cup (Fig. 11.5c–e). Bone scan showed slightly fragments filled in the acetabulum during revi-
increased uptake approximating to the acetabular sion 9 years ago remained unincorporated into
cup (Fig. 11.6b). SPECT/CT showed slightly the host bone (Fig. 11.5i). After removing all the
increased uptake in IBG area of the acetabu- bone fragments, new implants were placed.
lum (Fig. 11.5f–h). Radiotracer uptake in bone graft is accepted as
Although there was no clear evidence to con- an evidence of bone viability and patency of
sider the cause of the pain in clinical and imaging microvascular anastomosis. It is hard to explain
investigation, she finally underwent re-revision why this happened and what is the relation
surgery because she complained of very severe between failure of incorporation of bone graft
hip pain. There was no loosening of the acetabu- and worsening hip pain in this patient.
a b
c d
Fig. 11.5 (a) Radiograph shows an acetabular screw pro- proved to bone graft fragments filled during previous sur-
lapse (arrow head) and high attenuation (arrow) around gery. (e) In addition, axial CT image shows acetabular
the acetabular cup. (b) Bone scan shows slightly increased component retroversion (arrow). (f) Bone SPECT, (g) CT,
uptake approximating to the acetabular cup (arrow) and and (h) fused SPECT/CT images show slightly increased
greater trochanter (short arrow, shown as osteolysis on uptake in IBG area of the acetabulum. (i) There are few
radiograph). (c), (d) Coronal and sagittal CT images show traces of bone ingrowth on outer surface of retrieved cup
well high attenuation area that looks like mosaic frag- (short arrow). Removed bone fragments maintain their
ments (arrows) in acetabulum around the cup, which has shape one by one (long arrow)
11 Hip 123

11.6 Avascular Necrosis neck, which may be suspected for delayed heal-
of Femoral Head After ing, and abnormal uptake in the right femoral
Internal Fixation of Femoral head was not evident (Fig. 11.6a). However,
Neck Fractures SPECT and SPECT/CT revealed a relatively
large size of photon defect in most of anterior
One of the main complications after internal fixa- half of the right femur head with surrounding
tion of femoral neck fracture is avascular necro- irregular band-like uptake (Fig. 11.6c–e), which
sis (AVN) of the femoral head. The overall is reasonable for osteonecrosis.
incidence of AVN after internal fixation of femo- In this case, it was difficult to diagnose with
ral neck fracture is 15–25%, and about 20% of planar images alone, but it was possible to diag-
these patients required further surgical treatment. nose by obtaining SPECT/CT. Since the location
Disruption of the blood supply to the femoral of the photon defect was in anterior half of the
head at the time of injury is considered primary femoral head, it is thought that the lesion was
mechanism responsible for AVN of the femoral masked by radioactivity of posterior half of the
head following femoral neck fracture. head and distorted pelvic position. The increased
MRI is the most useful imaging modality in uptake in the femur neck area on planar
detecting early stage of AVN of the femoral image (Fig. 11.6a) represents reactive margin of
head; however, the diagnostic value of MRI in AVN, not delayed healing of the fracture.
patients undergoing internal fixation has a limi-
tation due to susceptibility artifact from metallic
implant. 11.7 Fracture-Related Infection
Bone scan has advantages in this respect and
has been widely used in diagnosing early AVN Fracture-related infection (FRI) is a serious com-
because the blood supply is one of the major fac- plication in orthopedic surgery leading to poor
tors affecting bone uptake of bone radiotracer. By bone healing and loss of function. In the case of
applying SPECT to bone scan and adding a CT open fractures, it has been reported that the inci-
image with SPECT, diagnostic ability in the dence of FRI can reach up to 30%.
detection of AVN has improved [20]. The perfor- The radiologic signs, suggesting FRI, are as
mance of bone SPECT/CT for predicting devel- follows: bone lysis (fracture site, around the
opment of AVN depends on the time point of implant), implant loosening, sequestration, non-
imaging after surgical fixation because revascu- union, and periosteal bone formation at localiza-
larization occurs; therefore, bone SPECT/CT can tions other than the fracture site.
be performed at least 3 months after surgery of Bone scan (including triple phase) has a high
femoral neck fracture to reliably predict the pos- sensitivity (89–100%) but low specificity (0%–
sibility of AVN [21]. 10%) for diagnosing FRI, so it is not recommended
in the assessment of FRI. WBC scan is the most
Case 11.6 reliable imaging tool for orthopedic infection. Due
A 60-year-old woman 5 months after undergoing to the physiological bone marrow uptake and the
multiple pinning for fracture of right femur neck lack of detailed anatomical information, it is often
was considering joint replacement surgery for the difficult to distinguish between the infection-
fused left hip joint. She took radiography, bone induced accumulation of labeled leukocytes and
scan, and SPECT/CT for preoperative evaluation. the marrow accumulation of these cells. Additional
Radiograph showed complete union of fracture bone marrow scan is sometimes needed to solve
of the right femur neck with multiple pinning still this problem. However, recent hybrid SPECT/CT
in place (Fig. 11.6b). Bone scan showed marked imaging allows for better anatomic details without
lumbar scoliosis and left hip flexion deformity an additional bone marrow scan. WBC SPECT/
due to fused hip joint. Moderately increased lin- CT showed a high diagnostic accuracy (92%) for
ear uptake was observed in the right femoral detecting an FRI in the peripheral skeleton [22].
11 Hip 125
c d
b e
Fig. 11.6 (a) Whole-body bone scan shows moderately SPECT, and (e) fused SPECT/CT images show a large
increased linear uptake (arrow) in right femur neck but no photon defect (arrow) in most of anterior half of right
abnormal uptake in right head portion. (b) Radiograph femur head with surrounding irregular band-like radio-
shows healed fracture in right femur neck with multiple tracer uptake (arrow head), suggesting reactive margin of
pinning status. (c) MIP image of bone SPECT, (d) bone osteonecrosis
Case 11.7 of the fracture site and loosening of the inserted

A 65-year-old man with hip pain visited to the screw (Fig. 11.7c). 99mTc-Hexamethlypropylene
clinic 4 months after undergoing open reduction amine oxime (HMPAO)-labeled WBC whole-
and internal fixation due to subtrochanteric frac- body imaging obtained on 4 h showed multifocal
ture of left femur. Radiograph showed non-union foci of leukocyte uptake in the left upper thigh
a b d
c
f
Fig. 11.7 (a) 99mTc-HMPAO whole-body planar images screw (yellow arrow). (d–f) SPECT, CT, and fused
show multifocal foci of leukocyte uptake in the left upper SPECT/CT images show accurate localization of leuko-
thigh. (b) Delayed planar images more clearly show the cyte uptake; the infected non-union site (white arrow),
uptakes (black arrow) seen in early whole-body image and contiguous perifemoral soft tissue abscess (long white
additional foci (yellow arrows) of leukocyte uptakes in the arrow), anteromedial aspect of the infected loosening of
left upper thigh. (c) Radiograph shows non-union of the screw (yellow arrow)
fracture site (white arrow) and loosening of the inserted
instead of less visible physiologic bone marrow cedent trauma and usually occurs in elderly
activity in the femur (Fig. 11.7a). Delayed patients with poor bone quality. However, it has
regional planar image obtained on 21 h revealed been reported in patients who were treated with
more clearly the uptakes seen in early image and corticosteroids for rheumatoid arthritis and organ
additional foci of leukocyte uptakes (Fig. 11.7b). (kidney, liver) transplantation.
99m
Tc-HMPAO SPECT/CT obtained on 4 h SIFFH presents acute hip pain and can cause
showed precise localization of leukocyte uptake femoral head collapse leading to osteoarthritis,
in the infected non-union site, contiguous peri- like osteonecrosis. For these reasons, it is often
femoral soft tissue abscess at lateral aspect of the important to differentiate it from osteonecrosis. A
non-union site, and anteromedial aspect of the majority has symptom resolution with non-
infected loosening of screw (Fig. 11.7d–f). In this operative management, and those that worsened,
case, although radiograph shows helpful findings approximately 35%, are typically managed
such as non-union and implant loosening sug- with surgical treatment, i.e. THA.
gesting infection (Fig. 11.7c), these are not spe- MRI is most commonly used for the diagno-
cific for infection. However, WBC scan and sis of SIFFH [23]. The characteristic findings
SPECT/CT provide very specific information such as low signal intensity band-like lesion rep-
leading to confirmatory diagnosis. resenting subchondral fracture and bone marrow
edema patterns are distinct from those of
osteonecrosis.
11.8 Subchondral Insufficiency Radiography is usually normal until head col-
Fracture of Femur Head lapse occurs, and CT will be helpful in finding
subchondral radiolucent line (crescent sign).
Subchondral insufficiency fracture of femur head Regarding bone scan, several cases of increased
(SIFFH) is known as a rare condition and caused uptake of femoral head have been reported.
by normal or physiological stress without ante-
11 Hip 127
a e
b c
g
d
Fig. 11.8 (a) Radiograph shows osteoarthritis in the joints. (e), (f) On SPECT and SPECT/CT, increased
right hip and no remarkable finding in the left hip region. uptake with subchondral fracture is observed in the left
(b), (c) Increased uptake in the left femur head region femur head (arrow in e [SPECT image]) and osteoarthritis
(arrow) on both vascular and blood pool images of bone (arrow head in e [SPECT image]. (g) Magnified CT
scan. Mild focal uptake of the right hip joint area in blood images of the same section show subchondral radiolu-
pool image is seen (arrow head). (d) Delayed anterior and cency parallel to articular surface (short arrow on axial
posterior bone scan images show increased uptake in the image, long arrow on sagittal and coronal image), consis-
left femur head (arrow on anterior image) and both hip tent with subchondral fracture
Case 11.8
Teaching Points
An 81-year-old woman presented with left hip pain
• You should consider the following when
for 2 months. She had no recent trauma history.
reading bone scan of patients who have
Radiograph showed no abnormal finding in the left
undergone THA: (1) It is to know the
hip and mild osteoarthritic change in the right
normal findings according to the time
hip (Fig. 11.8a). TPBS showed increased vascular
window after surgery. Bone scan may be
and blood pool activity in large area of the left
falsely positive up to 2 years after hip
femur head region (Fig. 11.8b, c). Delayed image
joint replacement. (2) It is essential to
of TPBS showed moderately increased uptake in
check serial radiographs (beginning
the left femur head, mainly anterior portion (Fig.
with the most recent) and patient’s clini-
11.8d). SPECT and SPECT/CT showed increased
cal symptoms.
uptake (Fig. 11.8e, f) associated with subchondral
• When a cystic mass is seen in the
radiolucent line (radiographic crescent sign), paral-
replaced hip joint area, CEH may be
lel to articular surface, in anteromedial portion of
added to differential diagnosis, in addi-
the left femur head on CT (Fig. 11.8g). This is con-
tion to ALTR, benign and malignant
sistent with subchondral insufficiency fracture.
tumor, and deep infection.
In patients with acute hip pain who have no
• Bone SPECT/CT can be useful in the
antecedent trauma, SIFFH should be included in
assessment of painful hip with/without
the differential diagnosis when images of all
surgery because CT can increase the
phases of TPBS show increased uptake in the
specificity.
femoral head. Additional SPECT/CT can be
helpful to detect the subchondral fracture.
spective validation study. J Clin Med. 2020;9:1965.

• WBC SPECT/CT without performing https://doi.org/10.3390/jcm9061965.
11. Signore A, Sconfienza LM, Borens O, Glaudemans
bone marrow scan can be the most valu- AWJM, Cassar-Pullicino V, Trampuz A, et al.
able imaging technique in diagnosing Consensus document for the diagnosis of prosthetic
PJI and FRI. joint infections: a joint paper by the EANM, EBJIS,
and ESR (with ESCMID endorsement). Eur J Nucl
Med Mol Imaging. 2019;46:971–88. https://doi.
org/10.1007/s00259-019-4263-9.
12. Gemmel F, Van den Wyngaert H, Love C, Welling
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Knee Prostheses
12
Yoo Sung Song
Abstract Keywords
Knee surgeries can be classified as joint- Aseptic loosening · Bone SPECT/CT · Knee
preserving surgeries such as osteotomy, liga- arthroplasty · Knee prosthesis · Periprosthetic
ment reconstruction, meniscus repair, and fracture · Periprosthetic infection ·
cartilage repair, and joint-replacing arthro- Polyethylene wear
plasties such as unicondylar knee arthroplasty
(KA), patellofemoral joint arthroplasty, and
total knee arthroplasty. While the incidence of
12.1 Assessment of Knee
knee surgeries has been increasing worldwide,
Operations
substantial portion of patients experience fail-
ure. In Korea, over 70,000 cases of primary
Uptake on single-photon emission computerized
knee arthroplasties were done in 2019, with
tomography and conventional computerized
over 5000 cases of revision arthroplasties. The
tomography (SPECT/CT) has been known to cor-
complicated knee anatomy and various etiolo-
relate with the degree of arthritis. Due to its
gies of arthroplasty failure interfere with the
unique features, SPECT/CT allows early detec-
accurate assessment of post-operative
tion of osteoarthritis by showing the loading on
complications.
different compartments of the knee. Also, the
There are many knee prosthesis-related
operation results may be assessed by evaluating
complications such as periprosthetic infec-
the change of tracer uptakes according to the
tion, aseptic loosening, polyethylene wear,
realignment of mechanical stress.
osteolysis, metallosis, instability, and peri-
prosthetic fracture. Distinguishing the peri-
Case 12.1 Post-operative Evaluation
prosthetic uptake patterns on bone scans aids
A 59-year-old woman presented to the outpa-
the differential diagnosis.
tient clinic due to bilateral knee pain. The
impression was degenerative arthritis in both
knee joints, with varus deformities. Radiographs
showed joint space narrowing at bilateral joint
Y. S. Song (*) spaces with varus alignments. Patient was
Department of Nuclear Medicine, Seoul National planned for sequential high tibial open wedge
University Bundang Hospital, osteotomy for bilateral knee joints, starting
Seongnam-si, Gyeonggi-do, Republic of Korea from the right knee joint. SPECT/CT images
e-mail: syoosung@snubh.org
https://doi.org/10.1007/978-981-19-2677-8_12
132 Y. S. Song
were acquired on post-operative day 1, immedi- acquired 3 months after left high tibial osteot-
ately after right high tibial osteotomy. Images omy. The increased uptakes in the medial com-
showed increased uptake in the right patello- partments on previous SPECT/CT showed
femoral compartment and bilateral medial com- significant improvement, implying redistribu-
partments. Two months after right high tibial tion of the mechanical load. Left knee showed
osteotomy, the patient underwent left high tibial post-operation-related uptakes in the osteotomy
osteotomy. Serial SPECT/CT images were site (Fig. 12.1).
Fig. 12.1 (a)

Preoperative radiograph, a
joint space narrowing at
bilateral joint spaces
with varus alignments.
(b) Preoperative bone
scan and SPECT/CT
images, showing
increased uptake in
bilateral medial
compartments and right
patellofemoral
compartment, consistent
with degenerative
arthritis findings. (c)
Patient received right
b
and left tibial wedge
osteotomy serially.
SPECT/CT was taken 12
months after right knee
surgery, which was 2
months after left knee
surgery. Uptakes of the
right medial
compartments have
improved. Post-operative
uptakes in the left wedge
resection site are
observed
c
12 Knee Prostheses 133
12.2 Periprosthetic Infection Patient underwent revision surgery for all

components of the left TKRA. During implant
Acute periprosthetic infection occurs in about removal, there were severe bone defects in the
2% of the patients who undergoes KA [1]. tibial compartment, with pus discharge and yel-
However, radiography has limited value in the lowish soft tissue inflammation (Fig. 12.2).
diagnosis of infection, since findings vary from
complete normal to total bone destruction [2]. Case 12.3 Periprosthetic Infection
Three-phase bone scans were reported to have a A 76-year-old man presented to the outpatient
specificity of 56% and a sensitivity of 93% in the clinic due to left knee pain that developed
diagnosis of periprosthetic infection [3]. Lack of 2 months ago. Patient received bilateral TKRA
increased uptake in the blood flow phase and the 10 years ago. Radiographs showed radiolucent
blood pool phase is an important finding to osteolysis in the left femoral compartment, with
exclude periprosthetic infection. anterior cortex scalloping. Femoral loosening
was suspected, and the patient underwent bone
Case 12.2 Periprosthetic Infection SPECT/CT. Bone SPECT/CT revealed diffuse
A 67-year-old woman presented to the outpatient increased uptake in the osteolytic lesion of the
clinic due to recently developed left knee pain. femoral compartment, with also diffuse increased
The patient had received bilateral total knee uptake in the periprosthetic area of the tibial
replacement arthroplasty (TKRA) 3 years ago. compartment. Patient underwent total replace-
Serum ESR rates (34 mm/h) and CRP levels ment of the previous knee arthroplasty. Surgical
(7.47 mg/L) were elevated, with high WBC findings revealed serous colored joint fluids, with
counts (13.0 × 109/L). Radiographs showed no bone defects in the periprosthetic area. There was
abnormal post-operative findings. Bone scan and a pus-filled cavity in the metaphyseal area of the
SPECT/CT images revealed diffuse increased femur (Fig. 12.3).
uptake in the left tibial periprosthetic area.
a b
Fig. 12.2 (a) Anteroposterior radiograph view of the Bone SPECT/CT images also show diffuse increased
knee shows no significant abnormal findings. (b) Planar uptake in the left tibial periprosthetic area, mainly in the
bone scan shows diffuse increased uptake in the left peri- anterior aspect seen on the sagittal view
prosthetic area, in the weight-bearing tibial aspect. (c)
134 Y. S. Song
Fig. 12.3 (a) Osteolysis

of the femoral a
compartment is
suspected in the
radiograph (red
arrowhead). (b) Diffuse
increased uptake of the
left femoral
compartment and
periprosthetic area of the
tibial compartment is
observed in the planar
bone scan. (c) Diffuse
rim uptake around the
osteolytic lesion of the
femoral compartment is
seen on SPECT/CT
b

c
plasty for the left knee. Surgical findings revealed

12.3 Aseptic Loosening
complete detachment of the femoral component
with migration and collapse of the medial femo-
Aseptic loosening is the most common cause of
ral condyle (Fig. 12.4).
late KA failure. It may be caused by metallic par-
ticle debris or repetitive mechanical stress.
Typical radiographic findings show peripros-
thetic radiolucency, increasing in width on 12.4 Polyethylene Wear
sequential follow-up. However, evaluating the
width has its limitations due to standardizing Polyethylene wear is also a common complica-
proper position, rotation, and knee alignment tion, due to the friction of metal compartment to
during image acquisition [4]. Three-phase bone the polyethylene or delamination of the polyeth-
scans alone cannot differentiate between infec- ylene surface. Radiographic findings show joint
tion and aseptic loosening, since all phases may space loss, usually in the medial and lateral com-
show increased uptakes. Also, interpretation of partments. Polyethylene wear may also occur in
bone scans may be difficult in patients with sus- the patellar compartment, which is better visual-
pected loosening, due to the variable peripros- ized in the axial radiographs compared to the lat-
thetic uptake related to the post-operative eral radiographs. Polyethylene wear-induced
physiological response. osteolysis may occur, resulting in aseptic loosen-
ing. However, the usefulness of bone scan in
Case 12.4 Prosthetic Loosening polyethylene wear is to evaluate the presence of
A 74-year-old woman presented to the outpatient consequent aseptic loosening.
clinic due to left knee pain that developed 1 year
ago. Patient received bilateral TKRA 8 years ago. Case 12.5 Polyethylene Wear
Radiographs showed periprosthetic lucency A 76-year-old woman presented to the outpatient
under the medial and lateral tibial baseplate in the clinic due to bilateral knee pain that developed
left knee, indicative of loosening. Bone SPECT/ 3 years ago. Patient received bilateral TKRA
CT revealed increased uptake in the left femur 15 years ago. Radiographs showed osteolysis at
medial condyle around the periprosthetic area. bilateral posterior flanges. Varus alignments with
Patient received total replacement of knee arthro- left joint space narrowing were observed. Bone
136 Y. S. Song
b c
Fig. 12.4 (a) Radiolucency is suspected in the tibial SPECT/CT image reveal diffuse increased uptake in the
base plate of the left knee, but no significant abnormalities left femur medial condyle around the periprosthetic area
in the femoral compartment. (b) Planar bone scan and (c)
SPECT/CT revealed increased uptake in bilateral 12.5 Periprosthetic Fracture

medial compartments of the tibia. Patient
received revision surgery of the previous knee Periprosthetic fractures may occur in both TKA
arthroplasty. There was no gross evidence of and high tibial osteotomy surgeries. Metal
infection on surgical findings, but evident wear- components of the prosthesis are stress focus-
ing and loosening. Bone defects were found at ing factors, frequently being the starting point
both tibia and femur, at the metal augmentation of the fracture line. Fractures are classified in
side (Fig. 12.5). reference to the anatomical components [5, 6].
TKA- related periprosthetic fractures may
a b c
Fig. 12.5 (a) Osteolysis is observed in the posterior ments, tibial aspects. (c) SPECT/CT shows diffuse peri-
flanges of both knees (red arrowheads). (b) Planar scan prosthetic uptakes in both knees, suggesting loosening
reveals diffuse increased uptakes in both medial compart- more likely than periprosthetic inflammation
involve the distal femur, proximal tibia, or the

patella. Distal femur fractures may be related 12.6 Metallosis
with mismatch of metallic component and the
femoral cortex or constrained components. Metal debris may be released into the knee
Tibial fractures may be related to loosening or joint, by gross polyethylene failure. This
malposition of components. Patellar fractures induces foreign body reaction resulting in
may be related to osteonecrosis, asymmetric inflammation and staining of the joint capsule,
resection, or metal backing on the patella. cavity, or extra-
articular tissues. Eventually,
Fracture after wedge osteotomy may result in metallosis may also be associated with peri-
nonunion or delayed union, bringing recurrent prosthetic osteolysis and loosening.
varus deformity. Radiographs may show focal metal densities,
with increased periprosthetic soft tissue densi-
Case 12.6 Periprosthetic Fracture ties. Bone scans are not usually used for the
A 53-year-old man presented to the outpatient diagnosis of metallosis but, instead, may detect
clinic due to left knee pain. The impression was accompanied loosening.
degenerative arthritis, with varus deformity.
Radiographs showed joint space narrowing at Case 12.7 Metallosis
the medial compartment of left knee, with varus A 74-year-old woman presented to the outpatient
alignments, and the patient received high tibial clinical due to right knee pain. She had received
closed wedge osteotomy for the left knee joint. bilateral TKRA 9 years ago. She was diagnosed
One month after surgery, patient complained of of loosening of the right femoral compartment
sudden knee pain after walking. Radiograph and underwent revision surgery for the right
revealed fracture in the tibia posteromedial cor- knee. On surgery, there were no gross evidence of
tex, with collapse. Patient received open reduc- infection, but frail and grey-colored granulation
tion and internal fixation for the tibial fracture, tissues were found in between the prosthesis and
with plate and screw fixation of the medial bor- femoral compartment, due to metallosis. Diffuse
der. Follow-up SPECT/CT images after bone defects were found in both tibial and femo-
3 months showed improvement of the previous ral compartments. Previous prostheses were
degenerative change in the medial compartment removed completely, and revision surgery was
and the healing status of the tibial fracture done (Fig. 12.7).
(Fig. 12.6).
138 Y. S. Song
Fig. 12.6 (a) Preoperative radiographs and bone SPECT/ after lateral closed wedge osteotomy, the medial tibia has
CT images. Joint space narrowing of the left knee with collapsed. Increased uptake along the fracture line in the
increased uptake in the medial tibial plateau. (b) 1 month tibial cortex is observed
the diagnosis by detecting asymmetric stress and

12.7 Instability
excluding other causes of knee pain.
Instability is the excessive displacement of the
Case 12.8 Instability
articular elements, in which most cases require
A 60-year-old woman visited to the hospital for
revision surgeries [7]. Instability following TKA
right knee pain. She was diagnosed of degenera-
can be divided into different types, as extension,
tive arthritis and TKRA. One year after surgery,
flexion, and genu recurvatum [8]. Causes include
she complained of severe right knee pain, with soft
ligament imbalance, component misalignment,
tissue edema. She was diagnosed of flexion insta-
component failure, bone loss, etc. Bone scans aid
a b c
Fig. 12.7 (a) Lateral knee radiograph before TKRA revi- show diffuse increased uptake around the prostheses, indi-
sion surgery. There is right knee joint effusion with loos- cating loosening and need for revision surgery. Metallic
ening around the right femoral component anterior flange debris is not suggested on neither images and only could
(red arrow). (b) Planar scan and (c) SPECT/CT image be seen in the surgical field
a b
Fig. 12.8 There are no unusual findings in the radio- increased uptake in both femoral and tibial components,
graphs, but anterior translation of the tibia is observed on indicating loosening (b)
the anterior drawer test (a). Bone scan shows diffuse
bility and mediolateral instability. Therefore, the infection, with only mild wearing and synovitis.
patient received revision of the right TKRA. On Previous prostheses were removed completely,
surgical findings, there were no gross evidence of and revision surgery was done (Fig. 12.8).
140 Y. S. Song
3. Verberne SJ, et al. What is the accuracy of nuclear

Teaching Points imaging in the assessment of periprosthetic knee
infection? A meta-analysis. Clin Orthop Relat Res.
• Complications of prosthesis-related 2017;475(5):1395–410.
knee surgeries include periprosthetic 4. Fehring TK, McAvoy G. Fluoroscopic evaluation of
infection, aseptic loosening, polyethyl- the painful total knee arthroplasty. Clin Orthop Relat
ene wear, metallosis, instability, and Res. 1996;331:226–33.
5. Felix NA, Stuart MJ, Hanssen AD. Periprosthetic
periprosthetic fracture. fractures of the tibia associated with total knee arthro-
• Periprosthetic uptake patterns on bone plasty. Clin Orthop Relat Res. 1997;345:113–24.
scans aid the differential diagnosis. 6. Takeuchi R, et al. Fractures around the lateral cortical
hinge after a medial opening-wedge high tibial oste-
otomy: a new classification of lateral hinge fracture.
Arthroscopy. 2012;28(1):85–94.
7. Rodriguez-Merchan EC. Instability following total
References knee arthroplasty. HSS J. 2011;7(3):273–8.
8. Parratte S, Pagnano MW. Instability after total knee
1. Gonzalez MH, Mekhail AO. The failed total knee arthroplasty. Instr Course Lect. 2008;57:295–304.
arthroplasty: evaluation and etiology. J Am Acad
Orthop Surg. 2004;12(6):436–46.
2. Mulcahy H, Chew FS. Current concepts in knee
replacement: complications. AJR Am J Roentgenol.
2014;202(1):W76–86.
Ankle and Shoulder
13
So Won Oh and Jee Won Chai
Abstract ous pathological disorders of the two joints,

only a few clinically significant diseases of the
The ankle and shoulder are major joints that ankle and shoulder are briefly introduced,
are responsible for the active movements of including the foot.
the body; thus, various orthopedic disorders
occur in association with overuse, strain, Keywords
trauma, etc. Unlike the knee or hip, degenera-
tive arthritis infrequently involves the ankle Ankle and foot · Shoulder · Bone SPECT/CT
and shoulder, and other pathological condi-
tions such as dislocation or trauma to these
joints can cause serious disabilities and dis- 13.1 Ankle Osteoarthritis
comfort in daily activities. Plain radiography,
CT, and MRI are the main diagnostic tools for 13.1.1 Etiology and Clinical
musculoskeletal disorders, since they could Significance
provide clues to understand the pathophysiol-
ogy by means of excellent anatomical infor- The ankle is affected by osteoarthritis (OA) in
mation. Bone scintigraphy is a highly sensitive approximately 1% of the world’s adult popula-
diagnostic tool for evaluating blood flow and tion, which results in pain, dysfunction, and
bone remodeling activity. Bone SPECT/CT impaired mobility [1]. The ankle is an uncom-
has recently gained attention as a helpful mon site for OA compared with other sites such
modality for understanding orthopedic disor- as the knee, hand, and hip, as it is strongly con-
ders by combining functional information and tained in ligaments and tendons. On the contrary,
precise anatomical localization. Among vari- the ankle is particularly prone to injury because
of its flexibility in movement. Irreversible carti-
lage damage may occur at the time of injury, and
articular incongruity and instability can lead to
S. W. Oh (*)
Department of Nuclear Medicine, Seoul National chronic cartilage overloading. Thus, ankle OA is
University Boramae Medical Center, Seoul, usually a consequence of significant trauma or
Republic of Korea the cumulative effects of repeated minor physical
J. W. Chai insults. In this regard, patients with post-traumatic
Department of Radiology, Seoul National University OA are generally younger than those with pri-
Boramae Medical Center, Seoul, Republic of Korea mary OA [2].
https://doi.org/10.1007/978-981-19-2677-8_13
142 S. W. Oh and J. W. Chai
13.1.2 Imaging right subtalar joint. Post-traumatic OA of the sub-

talar joint was diagnosed, and medical treatment
Ankle OA generally refers to the degeneration of with anti-inflammatory drugs was prescribed
the talocrural joint between the talus, tibia, and (Fig. 13.2).
fibula, which is known as the true ankle joint.
The subtalar joint, however, is often considered
the second part of the ankle joint, because it con- 13.2 Osteochondral Lesion
tributes to ankle motion and shares biomechani- of the Talus
cal and pathomechanical factors of ankle
instability [3]. 13.2.1 Etiology and Clinical
Radiography is the diagnostic tool of choice Significance
for the evaluation of OA despite the advent of
new imaging techniques. Typical radiographic Osteochondral lesions of the talus (OLT) cover a
findings of OA include joint space narrowing, wide spectrum of pathologies, including sub-
subchondral sclerosis, and osteophytosis. Weight- chondral contusion, osteochondritis dissecans,
bearing mortise and lateral views of the ankle are osteochondral fracture, and OA resulting from
needed for the optimal visualization of OA fea- long-standing disease [5]. OLT clinically causes
tures [4]. ankle pain with a succession of nonspecific signs
MRI is a very helpful diagnostic tool for the such as pain without the exact localization neces-
evaluation of soft tissues in joints, such as carti- sarily related to the lesion, blocking, click, insta-
lage and tendons. Although MRI is still less bility, and joint swelling. OLT mainly occurs in
accessible than radiography, it provides insights active patients in relation to trauma, but the phys-
and clues to pathomechanics in relation to the iopathology and natural course of OLT are still
development of ankle OA, based on the excellent being debated. The location of the OLT is consid-
spatial resolution and three-dimensional ered to be associated with the mechanism of the
information. injury and direction of the applied force
(Fig. 13.3).
Case 13.1
clinic with right ankle pain that developed 3 days 13.2.2 Imaging
prior. He denied any preceding traumatic injury
to the ankle. The radiographs showed bilateral OLT may be visualized as an area of detached
pes planus and severe OA in the right talocrural bone surrounded by radiolucency, but it may not
joint. Bone SPECT/CT showed increased uptake appear on plain radiographs in the early stage.
in the anterior aspect of the right talocrural joint. Routine radiography often fails to detect OLT,
Primary ankle OA was diagnosed based on the particularly when placed posteriorly [6]. Thus,
clinical symptoms and radiographic findings cross-sectional imaging such as CT or MRI could
(Fig. 13.1). be helpful in patients with prolonged symptoms
to detect OLT and exclude other ankle and foot
Case 13.2 pathologies.
clinic with pain in the lateral aspect of the right Case 13.3
ankle, and tenderness was elicited in the right lat- A 59-year-old woman was referred to the ortho-
eral gutter area. He had an ankle injury when he pedic clinic to rule out osteochondritis dissecans
was 25 years old. Bone SPECT/CT showed dif- of the left ankle. The pain persisted for more than
fusely increased radiotracer uptake along the 10 years. Radiography revealed an osteochondral
13 Ankle and Shoulder 143
a d
b e
c f
Fig. 13.1 The ankle mortise view shows severe osteoar- ankle joint (b), compared with the normal position of the
thritis in the right talocrural joint; the joint space is dif- left ankle joint (c). Bone SPECT/CT shows increased
fusely narrowed, and subchondral sclerosis is visualized uptake in the anterior aspect of the right talocrural joint,
in the anterior tibial plafond and talar dome area (a). The with joint space narrowing and osteophytosis (d–f)
lateral ankle views show anterior subluxation of the right
lesion in the left talar dome area. MRI showed a 13.3 Anterior Ankle Impingement
multiloculated cystic lesion surrounded by bone Syndrome
marrow edema in the medial area of the left talar
dome. Bone SPECT/CT showed a cystic lesion Impingement refers to a clinical syndrome with
that was matched with focal increased uptake in pain or restricted joint motion induced by an
the medial aspect of the left talar dome. Aching abnormal entrapment or contact of structures.
pain subsided after administration of anti- Anterior ankle impingement (AAI) syndrome,
analgesic medication under the diagnosis of also known as “footballer’s ankle,” results from
OLT. Surgical curettage of the osteochondral cyst compression of anterior osteophytes of the dorsal
can be considered in cases where the symptoms talar neck and distal tibia during dorsiflexion of
persist (Fig. 13.4). the foot [7]. Repetitive repair following injury
a c
b d
Fig. 13.2 The mortise view shows no abnormal findings sclerosis (black arrows) (b). Bone SPECT/CT demon-
except os subfibulare at the right lateral malleolus (white strates diffusely increased radiotracer uptake along the
arrow) (a). The lateral view of right ankle showed diffuse right subtalar joint (c, d)
narrowing of the subtalar joint space and subchondral
leads to the formation of osteophytes that may

cause contact between opposing bone or entrap
soft tissue with consequent narrowing of the
anterior joint space. In this regard, AAI may
occur due to repetitive impaction injury to the
anterior chondral margin from hyper-dorsiflexion
or direct impact from an external object, such as
a soccer ball [8]. Patients with AAI typically
complain of chronic ankle pain with a history of
recurrent ankle sprain accompanied by a decrease
in the overall ankle range of motion, mostly
affecting dorsiflexion.
13.3.1 Imaging
Radiography can visualize bony osteophytes of

the ankle well. However, plain radiography or CT
Fig. 13.3 Sprain of the lateral collateral ligament (arrow)
may transmit the force diagonally, which can cause injury may not be valuable for the evaluation of soft tis-
to the talar dome and/or kissing tibial lesion. In conse- sue impingement. MRI can accurately detect
quence, medial-sided osteochondral lesions of the talus bony osteophytes as well as soft tissue lesions,
involving both articular cartilage and subchondral bone of such as synovitis, tenosynovitis, and concomitant
the talar dome may develop in association with the lateral
collateral ligament injury chondral injury. In addition, MR arthrography is
a d
b c f
Fig. 13.4 The mortise view shows a small radiolucent defect and thinning at the medial talar dome (b, c). Bone
lesion (black arrow) in the medial aspect of the left talar SPECT/CT shows focal increased uptake in the medial
dome (a). Left ankle MRI shows a non-displaced osteo- aspect of the left talar dome area (d–f)
chondral lesion with cystic change and irregular cartilage
highly accurate in the assessment of soft impinge-

ment when clinical signs of AAI are overt. 13.4 Plantar Fasciitis
Ultrasonography has also gained popularity as a
reliable and inexpensive modality for evaluating 13.4.1 Etiology and Clinical
impingement lesions. Significance
Case 13.4 Plantar fasciitis is the most common cause of

A 22-year-old soldier complained of right ankle heel pain and is more common in runners.
pain that developed 2 weeks prior and was aggra- Although the name itself implies inflammation, it
vated during dorsiflexion. He had undergone is currently considered that degeneration of the
arthroscopic surgery for the treatment of an plantar fascia related to repetitive micro-tears of
osteochondral lesion of the talus 6 years prior. the fascia is the main cause that lacks an inflam-
Bone scintigraphy of the right foot revealed dif- matory reaction [9]. Plantar fasciitis causes stab-
fusely increased tracer uptake in the right tibial bing pain in the heel pad that usually occurs after
plafond. Right ankle MR showed diffuse bone a period of rest and eases while walking. Causes
marrow edema in the tibial plafond. Based on of plantar fasciitis are considered multifactorial,
clinical examination and imaging, AAI syndrome with abnormal biomechanics and delayed healing
was diagnosed (Fig. 13.5). as likely contributors.
a b c
Fig. 13.5 Bone scintigraphy of the right foot shows diffusely increased tracer uptake in the right tibia plafond (a).
Right ankle MRI shows diffuse bone marrow edema (yellow arrows) in the tibial plafond (b, c)
13.4.2 Imaging 13.5 Accessory Ossicles
The diagnosis of plantar fasciitis is clinically 13.5.1 Etiology and Clinical

made, although imaging can confirm the diagno- Significance
sis or rule out other causes of heel pain. Almost
half of the patients with plantar fasciitis have heel Accessory ossicles around the foot and ankle are
spurs, but they are incidental and nonspecific to common developmental variations that occur due
clinical symptoms. Ultrasonography can show to the failure of union of secondary ossification
thickening and low echogenicity of the plantar centers. These ossicles are mostly detected inci-
fascia. The differential diagnosis of heel pain can dentally and usually remain asymptomatic, but
be Achilles’ tendonitis, retrocalcaneal bursitis, they can become painful in relation to fractures,
subtalar joint abnormalities, and fractures of the dislocations, etc. Thus, the prevalence of ossicles
calcaneus. The management of plantar fasciitis is varies, and the true prevalence of ossicles is
typically conservative, because pain is self- unknown. The most common accessory ossicles
limiting and resolves within a year. in the foot are the os trigonum, os peroneum, and
os naviculare [10]. Among them, the os navicular
Case 13.5 often receives attention when it presents with
A 45-year-old man visited the orthopedic clinic clinical symptoms.
due to sudden onset of stabbing pain on the left Os naviculare, known as accessory navicular,
heel pad. He had been followed up for the treat- usually co-exist with pes planus, which is often
ment of ankylosing spondylitis at the Department associated with painful conditions and bursa for-
of Rheumatology. Under the impression of enthe- mation, especially in young athletes. Type 2 os
sopathy of the left hill pad, imaging workups, naviculare is the most common type, and the
including ultrasonography, plain radiography, and most common presenting symptom is medial foot
bone SPECT/CT, were performed. Ultrasonography pain that is aggravated by walking or running. In
showed thickening and low echoic change of the addition, type 1 and 2 os naviculare can cause
left plantar fascia at the calcaneal insertion site, but posterior tibial tendinopathy due to the insertion
there were no abnormal findings in the Achilles site of the tibialis posterior tendon on the acces-
tendon. Plantar fasciitis was diagnosed based on sory navicular bone.
clinical examination and imaging (Fig. 13.6).
a b
c d
e f
Fig. 13.6 The lateral ankle views show plantar calcaneal (d), compared with the right side (3.2 mm) (c). Bone
spurs (black arrows) at both sides (a, b). Ultrasonography SPECT/CT shows matched increased uptake (white
shows thickening of the planar fascia at both sides. The arrows) at the left calcaneal spur only (e, f)
plantar fascia is slightly thicker (4.6 mm) in the left side
13.5.2 Imaging Case 13.6

A 19-year-old man visited the outpatient clinic
Radiography can show ossicles in the foot, but it because of bilateral ankle pain that developed
is difficult to prove a causal relationship with 2 weeks prior. The time to walk or stand had
pathological conditions and the presence of the increased since he started working as a kitchen
ossicles. MRI could be useful to identify symp- assistant 3 months ago. Radiography revealed
tomatic accessory ossicles, which can accompany bilateral type 2 accessory navicular bones. Bone
bone or soft tissue changes in and around the os, SPECT/CT showed focal increased uptake at the
and exclude other causes of foot pain, such as right accessory navicular bone. Pre-hallux syn-
tumors or fractures [11]. When acute pain devel- drome was diagnosed, and supportive manage-
ops in this region, bone scintigraphy may help ment, including anti-inflammatory agents, was
differentiate accessory ossicles from an acute prescribed (Fig. 13.7).
injury.
a b d
Fig. 13.7 The standing foot radiograph shows type 2 accessory navicular bones of both feet (a). Bone SPECT/CT
shows focally increased radiotracer uptake at the right accessory navicular bone (b–d)
13.6 Mid-foot Sprain because of its noninvasive nature and ability to

measure dynamic changes under loading [12];
13.6.1 Etiology and Clinical however, it is limited by the depth of penetration
Significance and resolution, with heterogeneous evidence
regarding the accuracy of the various measure-
The mid-foot joint complex, known as the ment techniques.
Lisfranc joint, has a specialized bony and liga-
mentous structure that provides stability by hold- Case 13.7
ing the metatarsals. A twisting fall can break or A 24-year-old man visited the outpatient clinic
dislocate these bones out of place, resulting in because of right mid-foot pain. He had an injury
Lisfranc injuries, because there is no connective while stepping on the right foot during a soccer
tissue holding the first metatarsal to the second game 3 months prior. He had been treated with
metatarsal. A Lisfranc injury is commonly seen splint application and pain medication, but pain
in football and soccer players, but it is often mis- was redeveloped on the right mid-foot in a soccer
taken for a simple sprain, especially if the injury game a week prior. Lisfranc injury was diagnosed
is a result of a straightforward twist and fall. It is based on clinical history and imaging findings
a severe injury that may take many months to (Fig. 13.8).
heal and may require surgery for treatment.
13.7 Shoulder Dislocation

13.6.2 Imaging
Variable clinical presentations and radiographic Significance
findings make Lisfranc ligament injuries difficult
to detect, especially in cases of incomplete or A Hill–Sachs defect is a compression fracture of
subtle injuries. CT and MRI usage has increased the posterolateral humeral head, and a Bankart
over the last decade, while conventional radiog- lesion is an injury at the anteroinferior aspect of
raphy is often inaccurate in reliably detecting the glenoid labral complex. Both lesions are
Lisfranc injuries. Ultrasonography has become associated with anterior shoulder dislocation,
popular for the assessment of Lisfranc injuries which typically occurs with the shoulder in
a b
Fig. 13.8 The standing foot radiograph shows no abnormality in the right foot (a). Bone SPECT/CT shows increased
uptake between the right medial cuneiform and the second metatarsal bone base (b coronal; c transverse; d sagittal)
abduction and external rotation. The biomechani- but they could be missed in the early stages or in
cal association between these lesions and anterior cases of small size defects such as glenoid rim
shoulder instability is evident, but the etiologies fractures. Thus, CT and MRI are recommended
of both lesions have not been clearly established as superior imaging options for evaluating gle-
[13]. The prevalence of both lesions is closely noid bone loss and identifying small defects. MR
related and likely to be high in patients with arthrography may provide information on the
recurrent anterior shoulder instability, although glenoid and/or humeral head defect, but it is an
the true incidence of both lesions remains invasive procedure that requires puncture of the
unknown. The choice of management depends on joint synovium. When a Hill–Sachs defect is
the clinical significance of the lesions, particu- identified, the anterior glenoid should be care-
larly with respect to anterior shoulder instability. fully assessed to defect a Bankart lesion.
For bony Bankart, immediate and appropriate
treatment is required to prevent glenoid bone Case 13.8
loss. Bankart repair is the most common surgical A 37-year-old man visited the emergency room
treatment for traumatic anterior shoulder (ER) due to left anterior shoulder dislocation
instability. 3 weeks prior. Shoulder dislocation occurred
after he fell to the ground drunk with the out-
stretched arm on the day of his visit to the ER. He
13.7.2 Imaging complained of severe pain accompanied by ten-
derness of the left shoulder, but he denied a previ-
Wedge-shaped defects may be visualized in the ous history of shoulder dislocation. He was sent
posterolateral aspect of the humeral head on the home after the application of the abduction brace
anteroposterior radiograph with internal rotation, followed by manual reduction. A week later, the
left shoulder dislocation redeveloped while he hit Bankart lesion was diagnosed. He was admitted
the left shoulder on the armrest during a car acci- to the Department of Orthopedics for arthroscopic
dent. Imaging studies including radiography, repair of bony Bankart lesion (Figs. 13.9 and
three-dimensional CT, and bone SPECT/CT were 13.10).
performed, and a Hill–Sachs lesion with a bony
a b
c d
Fig. 13.9 A wedge-shaped defect is demonstrated at the terolateral aspect of the left humeral head (c) and bony
left posterosuperior humeral head on the internal rotation Bankart lesion as a fracture at the left glenoid anteroinfe-
view (a), compared with the normal-looking right side rior area (d). White arrows indicate a Hill–Sachs lesion,
(b). CT also shows a wedge-shaped depression in the pos- and a black arrow shows a bony Bankart lesion
a b c
d e
Fig. 13.10 The maximal intensity projection image of inferior area (a). Focal increased uptakes are matched
bone SPECT shows two foci of an increased uptake in the with a Hill–Sachs lesion in the posterolateral aspect of the
left shoulder; a black arrow points the left humeral head, left humeral head (b, c) and a bony Bankart lesion in the
lateral aspect, and a star indicates the left scapular glenoid left glenoid anteroinferior area (d, e)
13.8 Rotator Cuff Tear ties when chronic RCTs develop arthropathy.
The multiplanar imaging capabilities of MRI
13.8.1 Etiology and Clinical combined with its excellent soft tissue con-
Significance trast make it ideal for imaging the rotator cuff.
MRI can be used to evaluate the integrity of
The shoulder has the highest mobility, but the the cuff overall or determine whether an exist-
least intrinsic stability of all joints in the human ing tear is repaired when other findings are
body. The glenohumeral (GH) joint lacks intrin- ambiguous. Ultrasonography is an alternative
sic osseous constraints, which are compensated modality for evaluating the rotator cuff, which
for by many static stabilizers, such as the labrum, can provide images with high image contrast
joint capsule, and GH ligaments. The rotator cuff, without the use of ionizing radiation. The
which consists of the supraspinatus, infraspina- diagnostic accuracy of shoulder ultrasonogra-
tus, teres minor, and subscapularis muscles, plays phy for RCTs can reach as high as 91% and
a crucial role in maintaining the dynamic stabil- 100% for partial- and full- thickness tears,
ity of the naturally unstable GH joint. Rotator respectively [15].
cuff tears (RCTs) commonly occur when the ten-
dons pull away from the bones in active situa- Case 13.9
tions, such as baseball or tennis. RCTs are very A 50-year-old man visited the outpatient clinic
common injuries, but the true prevalence is because of left upper arm pain that developed
unknown; asymptomatic cuff abnormalities are 3 months prior. Plain radiographs showed no
noted in 30% of patients aged >60 years and 62% abnormal bony abnormality in the left shoulder,
of those aged >80 years [14]. but shoulder ultrasonography showed a near-full-
thickness tear at the far anterior portion of the left
supraspinatus tendon. Pain persisted after taking
13.8.2 Imaging analgesic medication, and further evaluation
including MR arthrography and bone SPECT/CT
Plain radiographs are usually normal in acute was performed for the arthroscopic repair of RCT
stages and may show radiographic abnormali- (Fig. 13.11).
a c
d
b
Fig. 13.11 The radiograph shows no abnormal bony (SST) (b). Bone SPECT/CT shows focal uptake in the
abnormality in the left shoulder (a). MR arthrography anterior aspect of the left humeral head that is the inser-
shows high-grade bursal surface partial thickness tear at tion site of SST (c, d)
the anterior to mid portion of the supraspinatus tendon
Teaching Points and shoulder joints owing to high spatial

• The ankle and shoulder are major joints resolution for soft tissue as well as bone
that are responsible for the active move- and cartilage.
ments of the body; thus, various ortho- • Bone scintigraphy was not useful in the
pedic disorders can occur in association assessment of the ankle and shoulder
with overuse, strain, trauma, etc. joint disorder, but the introduction of
• Cross-sectional images such as CT or SPECT/CT is expected to help under-
MRI are advantageous to evaluate standing pathomechanics related to the
orthopedic disorders involving ankle development of orthopedic disorders.
References 8. Lavezry KP, McHale KJ, Rossy WH, Theodore

G. Ankle impingement. J Orthop Surg Res.
2016;11:97.
1. JG P. The epidemiology of osteoarthritis. In:
9. Goff JD, Crawford R. Diagnosis and treatment of
Moskowitz RW, Howell DS, Goldberg VM, Mankin
plantar fasciitis. Am Fam Physician. 2011;84:676–82.
HJ, editors. Osteoarthritis. Diagnosis and treatment.
10. Lawson JP. International skeletal society lecture in
Philadelphia, PA: WB Saunders; 1984. p. 9–27.
honor of Howard D. Dorfman. Clinically significant
2. Barg A, Pagenstert GI, Hugle T, et al. Ankle osteoar-
radiologic anatomic variants of the skeleton. AJR Am
thritis: etiology, diagnostics, and classification. Foot
J Roentgenol. 1994;163:249–55.
Ankle Clin. 2013;18:411–26.
11. Choi YS, Lee KT, Kang HS, Kim EK. MR imaging
3. Bonnel F, Toullec E, Mabit C, Tourne Y, Sofcot.
findings of painful type II accessory navicular bone:
Chronic ankle instability: biomechanics and pathome-
correlation with surgical and pathologic studies.
chanics of ligaments injury and associated lesions.
Korean J Radiol. 2004;5:274–9.
Orthop Traumatol Surg Res. 2010;96:424–32.
12. Woodward S, Jacobson JA, Femino JE, Morag
4. Kraus VB, Kilfoil TM, Hash TW 2nd, et al. Atlas of
Y, Fessell DP, Dong Q. Sonographic evaluation
radiographic features of osteoarthritis of the ankle and
of Lisfranc ligament injuries. J Ultrasound Med.
hindfoot. Osteoarthr Cartil. 2015;23:2059–85.
2009;28:351–7.
5. Posadzy M, Desimpel J, Vanhoenacker F. Staging
13. Griffith JF, Antonio GE, Yung PS, et al. Prevalence,
of osteochondral lesions of the talus: MRI and cone
pattern, and spectrum of glenoid bone loss in ante-
beam CT. J Belg Soc Radiol. 2017;101:1.
rior shoulder dislocation: CT analysis of 218 patients.
6. Verhagen RA, Maas M, Dijkgraaf MG, Tol JL, Krips
AJR Am J Roentgenol. 2008;190:1247–54.
R, van Dijk CN. Prospective study on diagnostic
14. Sambandam SN, Khanna V, Gul A, Mounasamy
strategies in osteochondral lesions of the talus. Is
V. Rotator cuff tears: an evidence based approach.
MRI superior to helical CT? J Bone Joint Surg Br.
World J Orthop. 2015;6:902–18.
2005;87:41–6.
15. Okoroha KR, Fidai MS, Tramer JS, Davis KD,
7. Vaseenon T, Amendola A. Update on anterior
Kolowich PA. Diagnostic accuracy of ultrasound for
ankle impingement. Curr Rev Musculoskelet Med.
rotator cuff tears. Ultrasonography. 2019;38:215–20.
2012;5:145–50.
Part IV
Metabolic and Endocrine Osseous
Disorders
Metabolic Bone Disease
14
Jin-Sook Ryu and Hye Won Chung
Abstract Understanding the diverse manifestations of

MBD using nuclear medicine imaging studies
Metabolic bone disease (MBD) includes a
assists in early and specific diagnosis.
wide range of clinically distinct diseases that
In this chapter, we will review the appli-
cause changes in bone structure, mineraliza-
cation of nuclear medicine imaging studies
tion, and/or mass. MBD can be inherited
in various MBDs that exhibit abnormal bone
or acquired. Skeletal dysplasia is a hetero-
loss or osteosclerosis. Osteoporosis, the most
geneous group of genetic disorders caused
common MBD, will be dealt with in a separate
by defective genes during the bone forma-
chapter.
tion process. These disorders overlap with
MBD. In MBD, most pathological processes
Keywords
accelerate osteoblast and osteoclast activity,
resulting in increased bone turnover. Although Metabolic bone disease · Bone scintigra-
MBD is common, clinical diagnosis based phy · Osteomalacia · Renal osteodystrophy
on radiological findings may be challeng- Paget’s disease · Osteopetrosis · Camurati–
ing. 99mTc-labeled diphosphonate binding to Engelmann disease
hydroxyapatite crystals depends on the degree
of local bone formation regulated by osteo-
blastic activity. Bone scan has the advantage
14.1 Osteomalacia
of high sensitivity with the capacity to easily
image the whole body. Bone scan can provide
a functional map of bone turnover, displaying
Significance
pathology that is global, focal, or multifocal.
Osteomalacia refers to a marked softening of
J.-S. Ryu (*) bones caused by impaired mineralization of the
Department of Nuclear Medicine, Asan Medical osteoid in the cortical and trabecular bones. Two
Center, University of Ulsan College of Medicine,
Seoul, Republic of Korea MBDs, osteoporosis and osteomalacia, decrease
e-mail: jsryu2@amc.seoul.kr bone mass. In osteoporosis, there is a decrease in
H. W. Chung the amount of both mineral and osteoid. However,
Department of Radiology, Asan Medical Center, in osteomalacia, the amount of osteoid (bone for-
University of Ulsan College of Medicine, mation) is not decreased. Osteomalacia is much
Seoul, Republic of Korea less common than osteoporosis. The most common
e-mail: chung@amc.seoul.kr
https://doi.org/10.1007/978-981-19-2677-8_14
158 J.-S. Ryu and H. W. Chung
symptoms of osteomalacia are bone pain, muscle tion of fibroblast growth factor 23. This process
weakness, and waddling gait. If osteomalacia results in the inactivation of the sodium phos-
occurs in growing bones prior to the closure of phate cotransporter in the proximal renal tubule
the growth plate, it is termed infantile osteomala- and renal phosphate wasting [3]. Specifically,
cia or rickets. Growing bones fail to mineralize, for localization of tumors causing osteoma-
become soft, and develop deformities [1]. lacia, somatostatin receptor imaging such as
Osteomalacia results from defects in the 68
Ga-DOTA-peptide PET/CT can successfully
bone maturation process caused by impaired identify the culprit tumor. Many of these tumors
bone metabolism. These defects are primarily are phosphaturic mesenchymal tumors contain-
caused by inadequate levels of phosphate, cal- ing somatostatin receptors [4]. Conventional
cium, and vitamin D. Vitamin D deficiency is imaging is challenging for visualizing tumors
the most common cause of osteomalacia world- because they are often small and grow slowly.
wide. In addition, hereditary disorders of vita- Moreover, these tumors are frequently located in
min D metabolism, kidney or liver disease (as atypical skeletal sites.
these organs are involved in activating vitamin
D), small bowel disease, malabsorption, certain Case 14.1
drugs, tumors, and many other rare conditions A 40-year-old woman visited an orthopedic clinic
can cause osteomalacia. with a chief complaint of left hip pain. She was
short in stature (height, 131 cm). She was being
followed up at a nephrology clinic for bilateral
14.1.2 Imaging medullary nephrocalcinosis and type I renal tubu-
lar acidosis. She had a history of insufficiency
Radiographs often show generalized osteope- fracture at the subtrochanteric area of the left
nia in patients with osteomalacia. The presence femur 2 years ago. Regarding laboratory values,
of large quantities of unmineralized osteoid can her blood levels of 25-OH-vitamin D3 (9.4 ng/
occasionally be observed as indistinct ill-defined mL), 1α25-(OH)2-vitamin D3 (8.3 pg/mL), and
trabecular bone, often giving the impression of total calcium (8.5 mg/dL) were decreased. Her
a “poor-quality” radiograph [2]. Looser zones, osteocalcin level was increased (42.3 ng/mL), and
known as pseudo-fractures, are the hallmark her serum phosphorus and parathyroid hormone
signs of osteomalacia. These zones are caused levels were within normal limits. Radiographic
by deposition of unmineralized osteoid at stress and whole-body bone scan images were obtained
sites or along nutrient vessels, which are types of (Fig. 14.1). The patient was diagnosed with
insufficiency fractures. Looser zones are radio- vitamin D-deficient osteomalacia with multiple
lucent bands perpendicular to the cortex, with insufficiency fractures and pseudo-fractures.
sclerotic borders, and are often bilateral and
symmetrical. The common locations are the inner Case 14.2
margin of the femoral neck, pubic rami, ischium, A 65-year-old woman was referred to the pain
iliac wing, lateral scapula, and ribs. However, clinic with complaints of multiple atypical body
they can be easily missed at the early stage. Bone pain. Two years previously, she developed left
scans are particularly sensitive in terms of identi- knee pain without trauma. Despite receiving
fying pseudo-fractures. treatment at orthopedic and neurologic clinics,
In particular, extensive investigation is the pain in her back and flank worsened. She
required to identify the causes of generalized had difficulty in walking due to the severe pain.
bone pain in patients with hypophosphatemia. On screening bone scan, multiple insufficiency
Among the causes, tumor-induced osteomalacia fractures were noted in the bilateral ribs, spine,
(TIO) is curable. TIO is a paraneoplastic meta- pelvic bones, left proximal femur, and both
bolic bone disorder, in which hypophosphatemia calcanei, suggesting osteomalacia (Fig. 14.2).
and osteomalacia are caused by tumoral produc- Her blood laboratory tests results were normal,
14 Metabolic Bone Disease 159
a b
Anterior Posterior
Fig. 14.1 A 40-year-old woman with type I renal tubular Additionally, medullary calcinosis is visualized in both
acidosis and vitamin D-deficient osteomalacia. The radio- kidneys. Bone scan images (c) show multiple foci of focal
graph of the pelvis (a) shows insufficiency fracture of the increased uptakes, suggesting fractures or pseudo-
left femur (red arrow). Multiple fractures with callus for- fractures in the bilateral side of the ribs; C7, T2, and S1
mation are seen in the bilateral rib cages (red arrows) on vertebrae; right ilium; left femoral neck; and proximal
the thoracolumbar spine radiograph (b). Underlying bone femur diaphysis (red arrow). Uptakes are also increased
density is decreased, and trabeculae are prominent. diffusely and unevenly in both kidneys
a b
c d g h
e f
Fig. 14.2 A 65-year-old woman with tumor-induced images of 68Ga-DOTA-TOC PET/CT reveal a focal
osteomalacia. Bone scan (a) shows multiple focal increased uptake (maximum SUV: 9.9) in the left fibular
increased uptakes, suggesting insufficiency fractures in head (red arrow). On the CT image (d) and plain radio-
the bilateral ribs, vertebral bodies of the T-L spine, both graph (g), there is an osteolytic bone mass. The cross-
ilia and pubic rami, medial subtrochanteric cortex of the sectional image of the surgical specimen (h) shows a
left proximal femur, left distal tibia, and both calcanei. well-demarcated, ovoid-shaped, solid mass with a focal
Mildly increased rim uptake is also observed at the left hemorrhagic focus in the intramedullary portion of the
fibular head (red arrow), which was initially missed. The fibular head. This mass was histologically diagnosed as a
anterior projection image (b) and fusion PET/CT (c, e, f) phosphaturic mesenchymal tumor
except hypophosphatemia (1.3 mg/dL). The 14.2 Renal Osteodystrophy

patient was referred to the endocrinologic clinic,
and further evaluation was performed to search 14.2.1 Etiology and Clinical
the cause of osteomalacia. Phosphorus supple- Significance
mentation was initiated. 68Ga-DOTA-TOC (edo-
treotide) PET/CT was performed to identify the Renal osteodystrophy, also known as uremic
culprit tumor that was inducing osteomalacia. osteopathy, refers to skeletal findings observed
An osteolytic bone tumor lesion with high tracer in patients with chronic kidney disease. The
uptake was detected in her left fibular head, sug- pathophysiology of this condition is com-
gesting a phosphaturic mesenchymal tumor with plex. Disturbances in vitamin D, phosphate,
overexpression of somatostatin receptor 2. After and calcium metabolism lead to various clini-
surgical resection of the tumor, the patients’ cal manifestations. Varying degrees of sec-
serum phosphorus level normalized, and her ondary hyperparathyroidism, osteoporosis,
symptoms improved. osteomalacia, osteosclerosis, adynamic bone
disease, and extraosseous soft tissue calcification
Case 14.3 are observed. With a decline in renal function,
A 46-year-old man visited the orthopedic microstructural changes in the bone, vascular
clinic with a 6-month history of bilateral system, and soft tissues become macrostructural
hip pain. Sequentially, the right hip, left hip, lesions. These lesions exhibit as low bone min-
and knee pain occurred without trauma. The eral density and result in skeletal fractures as
patient showed an abnormal antalgic gait. He well as vascular and soft tissue calcifications [6].
was a hepatitis B virus carrier and had been Renal osteodystrophy is usually diagnosed after
prescribed adefovir dipivoxil for 7 years for beginning of treatment for end-stage kidney dis-
the treatment of chronic hepatitis B. Five years ease. Amyloid deposition, destructive spondylo-
previously, he was diagnosed with osteoporo- arthropathy, osteonecrosis, and musculoskeletal
sis during a routine health checkup. However, infections may occur as complications of long-
no specific treatment was prescribed. On bone term hemodialysis and renal transplantation.
densitometry using dual-energy X-ray absorp-
tiometry (DXA), severe osteoporosis of the
lumbar spine and femoral neck was shown, 14.2.2 Imaging
with a T-score of −4.1 and −2.9, respec-
tively. Laboratory test results showed that his Radiographic imaging findings are diverse; thus,
blood phosphorus level was slightly decreased radiographs can provide information regarding
(2.1 mg/dL) and his alkaline phosphatase high bone remodeling and mineralization failure.
was elevated (209 IU/L). Radiography and Osteopenia is often observed at the early stage. In
bone scan with SPECT/CT revealed multiple secondary hyperparathyroidism, bone resorption
insufficiency fractures in the spine, bilateral can affect trabecular, endosteal, and cortical bone
ribs, pelvic bones, both femurs, and left tibia envelopes or structures close to joints located at
(Fig. 14.3). The patient was diagnosed with the sub-periosteal, sub-ligamentous, and sub-
drug (adefovir)-induced osteomalacia with tendinous levels. The characteristic “salt-and-
secondary multiple insufficiency fractures pepper” appearance of the skull and “brown
[5]. The drug was changed to tenofovir alaf- tumors (osteoclastomas)” in the pelvis, long
enamide. Phosphorus, vitamin D supplements, bones, or ribs are rarely encountered currently.
and romosozumab were also initiated, and his A characteristic “rugger-jersey spine (alternating
symptoms slowly improved. bands of increased density along the endplates
a d
c e f
g h
Fig. 14.3 A 46-year-old man with drug (adefovir)- suggesting insufficiency fractures in the T-L spine, bilat-
induced osteomalacia. Diffuse osteopenia with multiple eral ribs, right femoral neck, both femoral lesser trochan-
bilateral rib fractures, suspicious subchondral bone irreg- ters, bilateral iliac side of the sacroiliac joints, and left
ularities at both sacroiliac joints, and subtle sclerotic bone proximal tibia. Pelvic MR images (g, h) show bone mar-
density at the lesser tuberosities of both femurs are noted row edema with incomplete fracture lines involving the
on radiographs (a–c). Bone scan (d) and SPECT/CT of bilateral femoral lesser trochanters and the iliac side of the
the pelvis (e, f) show multiple focal increased uptakes, sacroiliac joints (red arrows)
a F/47 b M/37
c M/72 d M/60
e F/64 F/62
f
Fig. 14.4 Scintigraphic appearances of renal osteodys- forms of hyperparathyroidism are associated with ectopic
trophy in high-turnover disease. The characteristic fea- calcification or tertiary hyperparathyroidism (b). Focal
tures are generalized increased uptake with increased skeletal abnormalities may signify associated brown
contrast between the bone and soft tissue. This leads to tumors (c, left proximal humerus, red arrow). Extra-
“superscan” (a–e), increased uptake in the long bones, skeletal uptake is seen in the lungs, stomach, and kidneys
axial skeleton, periarticular bones, calvaria, mandible, (d–f) because of an increased ratio of serum calcium to
costochondral junctions (beading pattern), and sternum phosphate and amyloid deposition (f, periarticular and
with absence of uptake in the kidneys. The more severe both buttock areas)
and decreased density in the central portion of the the subsequent imaging work-up (Fig. 14.5),
vertebral body)” is often detected on lateral lum- renal osteodystrophy and insufficiency fractures
bar spine radiographs [2]. Osteosclerosis can also were detected. In addition, a markedly high
occur in conjunction. Osteoblast activation may serum parathyroid hormone level (993 pg/mL)
result in new periosteal bone formation in the was observed.
long bones and increase cortical thickness. Plain
radiographs can also reveal the early features of Case 14.5
osteomalacia, pseudo-fractures, or Looser zones A 45-year-old man with end-stage renal disease
prior to fracture occurrence. visited the orthopedic clinic complaining of hip
Currently, this disease is characterized by pain that developed 1 month previously. He had
three major types—high-turnover disease (most been undergoing hemodialysis for 7 years after
common), low-turnover disease, and mixed renal allograft failure. On the imaging work-up
disease [7]. Scintigraphy shows a diffusely with radiography and bone scintigraphy with
increased uptake in the skeleton, including the SPECT/CT, an incomplete fracture of the right
calvaria and mandible, in high-turnover disease femoral neck was noted with underlying renal
type. It accentuates the contrast between the bone osteodystrophy findings (Fig. 14.6). Laboratory
and soft tissue with an increased skeletal to renal test findings showed the total calcium level was
uptake ratio. Figure 14.4 shows the scintigraphic within the upper normal limit (10.2 mg/dL), with
appearance of renal osteodystrophy in high- a high phosphorus level (8.4 mg/dL). The serum
turnover disease. Low-turnover disease typically intact parathyroid hormone level was markedly
shows a decreased uptake unless it is complicated elevated at 5,280 pg/mL. The patient was diag-
by a focal pathology. A mixture of these findings nosed with tertiary hyperparathyroidism. On
is observed in mixed disease. parathyroid SPECT/CT with 99mTc 2-methoxy-
isobutyl-isonitrile (MIBI), multiple parathyroid
Case 14.4 nodules, including an ectopic parathyroid nodule,
A 32-year-old woman was brought to the emer- with increased uptake were detected. Total para-
gency room due to a sudden, brief seizure-like thyroidectomy with parathyroid autotransplan-
episode. She had no other specific medical his- tation was performed. The postoperative blood
tory, except a recent history of back pain and parathyroid hormone levels normalized, and the
lower extremity weakness. On initial laboratory bone pain improved thereafter.
tests, high blood creatinine (7.5 mg/dL) and phos-
phorus (5.7 mg/dL) levels, severe hypocalcemia
(total calcium 4.9 mg/dL), and anemia (Hb 7.8 g/ 14.3 Paget’s Disease
dL) were noted. Brain MRI revealed normal find-
ings. She was diagnosed with metabolic enceph- 14.3.1 Etiology and Clinical
alopathy secondary to severe hypocalcemia and Significance
renal failure. After calcium supplementation, her
leg weakness improved, and no further seizures Paget’s disease of the bone, also known as
occurred. However, low back pain persisted. In osteitis deformans, is a chronic bone disor-
Fig. 14.5 A 32-year-old woman with renal osteodystro- insufficiency fractures with cortical disruption are noted
phy secondary to hyperparathyroidism. Bone scan (a) in the left sacral ala (e), anterior column of both acetabula
shows diffusely increased whole-body skeletal uptakes, (f), and both inferior pubic rami (g). On the coronal,
especially high uptakes in the skull, sternum, costal ends T2-weighted STIR MR image, insufficiency fracture
at bilateral costochondral junctions in a beading pattern, reveals irregular hyperintense lesion in the left sacrum
and long bone ends. Bilateral kidney activities are not (arrow) (h). The lateral lumbar radiograph (i) and sagittal
detectable. These are typical “superscan” findings of renal T2- and T1-weighted MR images (j) show “rugger jersey
osteodystrophy. On the pelvic radiograph (b) and CT (c– spine” appearance in vertebral bodies along the superior
g) images, generalized osteopenia and subchondral and inferior endplates
resorption in both sacroiliac joints (d) are seen. Associated
a F/32 b
e f g
h i j
a b
e f
g h
Fig. 14.6 A 45-year-old man with renal osteodystrophy indicating a pseudo-fracture (red arrow). On 2-h delayed
and tertiary hyperparathyroidism. Bone scan (a) shows a parathyroid SPECT/CT images with 99mTc-MIBI (e–h), a
so-called “superscan” pattern, which denotes generalized total of four nodules with increased focal uptakes are
increased uptakes in whole-body bone scan, especially in observed at the posteroinferior aspect of the right thyroid
the skull and long bones of the extremities. No kidney lobe lower pole (2.5 cm), posterior aspect of the left thy-
uptake is visualized. The plain radiograph (b) and SPECT/ roid lobe mid portion (1.4 cm), inferior aspect of the left
CT images (c, d) of the pelvis reveal a linear radiolucent thyroid lobe lower pole (1.5 cm), and ectopic site at the
line at the superolateral section of the right femur neck, left cervical level IV with calcifications (green arrow)
der characterized by excessive abnormal bone 14.3.2 Imaging

remodeling and deformities. The affected bones
show signs of dysregulated bone remodeling, This disease has three phases—early resorptive
specifically excessive bone breakdown and (incipient active), mixed middle (active), and final
subsequent disorganized new bone formation. (late inactive) sclerotic phases [8]. The diagnosis
The exact cause of this disease is unknown, can typically be made using radiographs, which
although the leading theories suggest that reveal lytic lesions in early cases and coarsened,
both genetic and acquired factors are involved. expanded bones as the disease progresses to the
Paget’s disease may affect any one or multiple final phase. Bone scan is highly sensitive and use-
bones of the body (most commonly the pel- ful for determining the extent and activity of the
vis, tibia, femur, lumbar vertebrae, and skull). condition. The bone scan appearance of Paget’s
However, the entire skeleton is never involved, disease is striking, with intensely increased tracer
and the disease does not spread from bone to localization [9]. Increased uptake is observed in
bone. The common clinical manifestations are all stages of the untreated disease (Fig. 14.7).
abnormal bone structures, such as localized Physicians must be aware of the patterns of
bone hypertrophy and osteoporosis. These pro- Paget’s disease because it may be found inciden-
cesses lead to bone pain, bone deformity, and tally during screening bone scans for metastatic
fractures. Laboratory findings reveal elevated work-ups as many patients are asymptomatic
blood alkaline phosphatase levels due to intense and/or undiagnosed. If bone scan findings sug-
osteoblastic activity. gest Paget’s disease, X-ray of the affected bone(s)
F/48 F/54 F/67
F/73 F/51 M/55
Fig. 14.7 Various scintigraphic appearances of Paget’s disease involving one or multiple bones of the body
should be performed to confirm the diagnosis. Case 14.8

The uptake intensity of the affected bone on bone A 76-year-old woman with multiple body aches
scan decreases with effective therapy. After cal- was referred to our endocrinology clinic. She
citonin or bisphosphonate therapy, bone scans was diagnosed with Paget’s disease 10 years pre-
show alterations in the uptake distribution, and viously after a fracture in her left hip. However,
the uniform uptake distribution on bone scan may her condition was not managed appropriately.
change to a patchy focal uptake [10]. Thus, she developed total hearing loss 1 year ago
and developed headache and dizziness devel-
Case 14.6 oped 5 months later. Her blood alkaline phos-
A 40-year-old man with hepatitis B pre- phatase level was high at 923 IU/L. A skeletal
sented with an increased level of serum alpha- survey by plain radiography and whole-body
fetoprotein (30.5 ng/mL; normal range, <7.5 ng/ bone scan revealed multiple bone involvement,
mL). Subsequent evaluation revealed a 1-cm including involvement of the skull, with Paget’s
arterial-enhancing nodule in the liver at the left disease (Fig. 14.10). Bone densitometry using
lateral segment, suggesting hepatocellular car- DXA showed severe osteoporosis of the lumbar
cinoma on dynamic liver CT. During the preop- spine (0.665 g/cm2; T-score, −3.7). Treatment
erative work-up, bone scan revealed a diffusely was initiated for the management of Paget’s dis-
increased uptake lesion in the right pelvic bone ease, followed by imaging and laboratory tests.
(Fig. 14.8). To exclude bone metastasis, 18F-
FDG/CT was performed. The patient underwent
left lateral segmentectomy of the liver as the most 14.4 Osteopetrosis
likely diagnosis was Paget’s disease in the right
pelvic bone based on imaging findings. After sur- 14.4.1 Etiology and Clinical
gery, his alpha-fetoprotein level normalized. At Significance
the last postoperative 4-year follow-up, he was
stationary without recurrence of tumor. Osteopetrosis, literally “stone bone,” also known
as marble bone disease, is a prototype of osteoscle-
Case 14.7 rosing dysplasia. It is an extremely rare inherited
A 61-year-old man was diagnosed with prostate disorder with both autosomal-dominant and auto-
cancer during a routine health checkup. He had somal-recessive subtypes, resulting in defective
elevated serum prostate-specific antigen (PSA) osteoclasts. Hence, bone resorption fails, but there
level (4.58 ng/mL) and alkaline phosphatase is continuous bone formation, resulting in exces-
(147 IU/L) levels. In the staging work-up, intensely sive bone formation. The bones are also structurally
increased uptake in the left pelvic bone, includ- abnormal. This condition makes them prone to frac-
ing the entire left ilium, was detected on whole- ture and narrowing of the bone marrow space caus-
body bone scan. He had no bone pain. Compared ing a decrease in hematopoiesis and anemia [11].
to the pelvic CT and MRI findings, the presumed
diagnosis of the bone lesions was Paget’s disease
(Fig. 14.9). Subsequently, the patient underwent 14.4.2 Imaging
robot-assisted laparoscopic prostatectomy. During
postoperative follow-up, his blood alkaline phos- Radiographically, the hallmark of osteopetrosis
phatase level increased along with an increase in is increased density within the medullary section
the left iliac bone uptake intensity on bone scan. of the bone, with relative sparing of the cortices.
However, there was no other evidence of cancer Erlenmeyer flask deformity (club-like long bones
recurrence, with an undetectable serum PSA level. and flaring of ends due to lack of tubulation),
After initiating treatment (zoledronic acid injec- “bone-within-bone” appearance, or the “sand-
tion and oral alendronate/cholecalciferol), his wich vertebra” appearance, characterized by
follow-up alkaline phosphatase level was normal, dense endplate sclerosis with sharp margins are
and bone scans showed decreased intensity of the observed. Bone scans show a diffuse increase in
left iliac bone uptake.
b c d
e f
Fig. 14.8 A 40-year-old patient with hepatocellular car- on maximum intensity view (b) and fusion PET/CT coro-
cinoma of the left liver lateral segment and Paget’s disease nal and transaxial images (c, e) of the whole-body 18F-
in the right pelvic bone. Whole-body bone scan (a) shows FDG/CT, and sclerotic change with preserved internal
diffusely increased uptake in the right ilium and superior trabeculation and mild cortical hypertrophy is seen on CT
pubic ramus including the right acetabulum (red arrow- images (d, f). A liver nodule is not visualized due to iso-
head). The right pelvic bones are mildly hypermetabolic metabolic activity in the normal liver tissue
a b
Anterior Posterior e
Fig. 14.9 A 61-year-old patient with prostate cancer and neous contrast enhancement in the left ilium. The serial
Paget’s disease in the left iliac bone. Bone scan images (a) follow-up bone scan images (g) show an abrupt decrease
show diffuse, intensely increased bone uptake in the left of the left pelvic bone uptake intensity after treatment ini-
ilium. Diffuse osteosclerosis of the left ilium (red arrow- tiation. Serial plain radiographs (h) do not show any
head) is noted on the plain radiograph (b) and coronal and change in osteosclerosis during the follow-up period. A
axial CT images (c, d). MR images (e, f) show cortical decrease in the blood alkaline phosphatase level (i) is well
thickening and medullary cavity narrowing with heteroge- correlated with findings of bone scans
61 year 66 year 68 year
i
Alkaline Phosphatase level (IU/L) Start of Medication
skeletal uptake and symmetrically increased focal Case 14.9

uptake in the metaphyses and adjacent diaphyses An 18-year-old woman was referred to orthope-
of multiple long bones. These are typical findings dic clinic for further evaluation of sclerotic bones,
in osteopetrosis. Bone scans also contribute to which were observed on chest radiography dur-
the follow-up of these patients. Bone scans allow ing a routine school health checkup. Bone scans
longitudinal monitoring of this disease as new and skeletal surveys revealed diffusely increased
asymptomatic bone fractures may be diagnosed. tracer uptake and sclerotic changes in the spine,
Thus, serial whole-body scans may be useful for pelvis, and long bones (Fig. 14.11). Laboratory
both symptomatic and asymptomatic patients blood tests findings were normal. The patient was
with osteopetrosis [11]. diagnosed with autosomal dominant osteopetro-
a b c
d 76 year e 83 year f 87 year
g
Alkaline Phosphatase level (IU/L)
Start of Medication
Fig. 14.10 A 76-year-old woman with multiple bone increased uptakes are also noted in the upper C-spine,
involvement with Paget’s disease. Diffuse osteosclerosis T12, left seventh rib, and right side L3 body. After treat-
is detected in the skull (a), bilateral pelvic bones, sacrum, ment initiation, follow-up bone scans (e, f) show decreased
and left proximal femur (b, c) on radiographs. intensity of uptakes in the abovementioned bone lesions.
Compression fracture (green arrowhead) is noted at the A compression fracture with increased uptake in the L2
L4 body. Initial bone scan (d) shows diffuse, intensely vertebral body (red arrowhead) is shown on the last fol-
increased uptake in the skull, bilateral pelvic bones and low-up image (f). The graph (g) shows the drop in the
sacrum, left proximal femur, and L4 vertebral body. Focal blood alkaline phosphatase level after treatment initiation
a b
Anterior Posterior
c d
Fig. 14.11 An 18-year-old woman with newly diagnosed appearance. Whole-body bone scan (b, c, e) shows sym-
osteopetrosis. The chest radiograph (a) and anterior and metric diffusely increased uptakes along the cortex of the
lateral views of the whole spine (d) and lower extremities spine, sternum, both pelvic bones, and long bones of both
(f) show diffusely increased density of all bones. Dense the upper and lower extremities. This is especially promi-
sclerosis of the upper and lower endplates of vertebral nent at the proximal ends of the humeri and tibiae along
bodies with central relatively lucent bone is consistent with the proximal and distal ends of the femora. These
with a “sandwich vertebrae” or “bone within a bone” imaging findings are typical features of osteopetrosis
e f
sis type 2 with a heterozygous mutation in the 14.5 Camurati–Engelmann

CLCN7 gene, detected using diagnostic exome Disease
sequencing.
Case 14.10 Significance
A 39-year-old woman with a history of left hip
pain for several years visited the orthopedic sur- Camurati–Engelmann disease, also known
gery clinic. She requested an opinion regarding as progressive diaphyseal dysplasia, is a rare
hip surgery. Ten years prior, she was diagnosed autosomal dominant form of sclerosing bone

with osteopetrosis and was taking medication. dysplasia. It begins in childhood (predominantly
The patient underwent bone marrow transplan- before the age of <30 years) and follows a pro-
tation for hematologic failure. Further imaging gressive course. In most cases, it results from a
studies (Fig. 14.12) were performed for presurgi- defect in the transforming growth factor β1 (TGF
cal assessment. β1) gene, which causes osteoblastic overactivity
a b c
f
Anterior Posterior
Fig. 14.12 A 39-year-old patient with severe osteopetro- including joint space narrowing, subchondral cystic
sis with hematologic failure. Whole-body bone scan (a, b) changes, and subluxation of the left femoral head, are
shows diffusely increased uptakes in the whole skeleton, observed, indicating secondary osteoarthritis. Radiographs
especially in the skull and long bones. Multifocal of the lumbar spine (d) show a “sandwich vertebrae”
increased uptakes at the right posterior arc of the eighth appearance, and bone SPECT/CT images (e–g) of the
and ninth ribs, radial, and fibular shafts suggest earlier L-spine and pelvis demonstrate decreased uptakes in the
fractures. A deformity at the left hip joint reveals intensely thick dense upper and lower endplates of the vertebrae
increased periarticular bone uptakes (red arrowhead). On and increased uptake in the relatively lucent central zone
the pelvic radiograph (c), the entire bones are abnormally with narrow marrow spaces (green arrowhead)
dense. Additional abnormalities at the left hip joint,
[12]. The common symptoms include extremity 14.5.2 Imaging

pain, muscle weakness, cranial nerve impair-
ment, and waddling gait. Patients may also pres- The radiographic hallmark of Camurati–
ent with hepatosplenomegaly. A small proportion Engelmann disease is cortical thickening of the
of the patients are asymptomatic. diaphysis of the long bones. The epiphyses are
F/7 M/16
M/35 F/46 F/51
Fig. 14.13 Scintigraphic pattern of Camurati–Engelmann disease (progressive diaphyseal dysplasia) in various stages
on bone scan
spared, and narrowing or obliteration of the med- Case 14.11

ullary canal is observed in a bilateral symmetric An 11-year-old boy with Camurati–Engelmann
pattern. In severe cases, osteosclerosis is wide- type I disease visited the medical genetics clinic
spread, and the skull and axial skeleton are also for further management. At the age of 5 years,
involved [13]. On bone scan, the affected regions he was diagnosed with this disease after a work-
show high tracer uptake representing osteoblas- up for his waddling gait. Molecular analysis
tic activity, even before it is radiologically vis- revealed the presence of a TGF β1 gene mutation.
ible. Clinical, radiographic, and scintigraphic He complained of discomfort in the right ankle.
findings are generally concordant. However, Skeletal survey and bone scan revealed a typical
markedly increased uptake with minimal radio- pattern of bilateral, symmetric hyperostosis at
graphic findings can reflect early and active the diaphysis of the long bones (Fig. 14.14). The
disease (Fig. 14.13). Therefore, bone scan is a patient was followed up periodically in the clinic
valuable tool for diagnosing early-stage disease. with steroid treatment.
a b
11 year 15 year
Anterior Posterior Anterior Posterior
c d
Fig. 14.14 An 11-year-old boy with Camurati– steroid treatment, similar patterns of increased uptakes in
Engelmann type I disease. Initial bone scan (a) shows the long bones are persistent in the diaphysis of long
symmetric increased tracer uptakes in the diaphysis of the bones (arrows). Plain radiographs show cortical thicken-
long bones in the bilateral ulnae, radii, femurs, and tibiae ing of the diaphysis of the long bones in the same location
(arrows). On follow-up bone scan 4 years later (b) after shown on the bone scan (c, d)
ings of metabolic bone disease. Radiographics.

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A, Kattapuram SV, Huang AJ. Imaging find-
Osteoporosis
15
Seoung-Oh Yang, Jung Mi Park, Hye Joo Son,
Jang Gyu Cha, Jee Won Chai, and So Won Oh
Abstract rosis must not be neglected since osteoporotic

fractures have enormous impacts on patients as
Osteoporosis is the most common metabolic
well as the whole society. Osteoporotic fracture
bone disorder which is characterized by reduc-
is the most serious clinical outcome of osteo-
tion in the bone density. Osteoporosis is called
porosis, and it is more common in women than
as “the silent killer” and often diagnosed after
in men, due to decreased bone mineral density
the development of fracture because it itself has
(BMD) after menopause. Thus, active preven-
no overt clinical symptoms. However, osteopo-
tion including early diagnosis and proper treat-
ment is crucial in the management of patients
S.-O. Yang (*)
with osteoporosis. This chapter includes clini-
Department of Nuclear Medicine, Dongnam Institute
of Radiological and Medical Sciences, cally relevant cases performed by nuclear
Busan, Republic of Korea imaging (bone scan, SPECT/CT, and PET/
e-mail: soyang@dirams.re.kr CT) and other correlative radiologic images
J. M. Park for the diagnosis of the vertebral compression
Department of Nuclear Medicine, Soonchunhyang fracture, sacral insufficiency fracture, atypi-
cal femoral fracture, and medication-related
e-mail: jmipark@schmc.ac.kr
osteonecrosis of the jaw (MRONJ) in patients
H. J. Son
with osteoporosis.
Department of Nuclear Medicine, Dankook
Cheonan, Republic of Korea Keywords
e-mail: hyejooson@dkuh.co.kr
Osteoporosis · Vertebral fracture
J. G. Cha
Department of Radiology, Soonchunhyang University Insufficiency fracture · Atypical femoral
Hospital, Bucheon, Republic of Korea fracture · Medication-related osteonecrosis
e-mail: mj4907@schmc.ac.kr of the jaw (MRONJ)
J. W. Chai
Department of Radiology, Seoul National University
Boramae Medical Center, Seoul, Republic of Korea Osteoporosis is the most common musculo-
e-mail: chaijw@snu.ac.kr
skeletal disease in the world. The World Health
S. W. Oh Organization (WHO) and National Osteoporosis
Department of Nuclear Medicine, Seoul National
Foundation define osteoporosis as a metabolic bone
Seoul, Republic of Korea disease that is characterized by reduction of bone
e-mail: mdosw@snu.ac.kr mass and microstructural deterioration of bone tis-
https://doi.org/10.1007/978-981-19-2677-8_15
180 S.-O. Yang et al.
sue. Enhanced bone fragility and decreased bone Osteoporosis and osteoporotic fracture can
strength are attributed to an increased risk of frac- impose significant economic and healthcare bur-
ture (osteoporotic fracture). Osteoporotic fracture dens not only on the individual level but also on
can be induced by non- traumatic cause, which the public level. For example, osteoporotic hip
refers to a fracture resulting from a minor fall from a fracture pays a considerable amount of social
standing height or less. Osteoporotic fracture com- costs. Hip fracture requires a long period of hos-
monly occurs in the vertebra, hip, and distal radius. pitalization, and furthermore, it is associated with
serious medical complications such as pressure
sores, pneumonia, urinary tract infection, and
15.1 Etiology venous thrombosis (pulmonary embolism) that
and Pathophysiology are followed by the immobilization. In addition,
loss of labor during the hospitalization and sub-
One of the main factors affecting osteoporosis sequent rehabilitation causes enormous socio-
is aging. In general, the bone mass reaches the economical loss. The incidence of hip fractures is
maximum at the age of 30, and then the process anticipated to increase from 1.1 million in 2018
of bone formation and bone resorption that main- to 2.6 million in 2050, by the Asian Federation
tains the minerals of the bone tissue slows down. of Osteoporosis Societies [1]. Recently, osteo-
The reduction in skeletal mass results from an porotic fracture is rapidly increasing in South
imbalance between bone resorption and bone for- Korea, as South Korea already became an aged
mation; increased bone resorption or decreased society and is about to enter a super-aged society
bone formation may result in osteoporosis. by 2026. It deserves to be called as “Osteoporosis
Various factors including age, gender, family Tsunami.”
history, and ethnicity can affect the development
of osteoporosis. The balance between bone for-
mation and resorption plays a key role in deter- 15.2 Diagnosis of Osteoporosis
mining the bone mineral density (BMD). BMD
gradually decreases with age after reaching its Osteoporosis is diagnosed by the measurement
maximum at the age of 30, and the bone becomes of BMD using dual energy X-ray absorptiometry
brittle with age after the age of 50. Osteoporosis (DXA). DXA measures BMD as the ratio of bone
is more likely to occur in women than men, par- mineral content (BMC) to the area of region of
ticularly after menopause. Estrogen regulates interest (ROI). Other than single-photon absorp-
bone resorption, and its deficiency leads to a tiometry (SPA) and dual-photon absorptiometry
rapid decrease in BMD and deterioration of bone (DPA), radioisotopic modality is not used to
quality. Besides, malnutrition, smoking, lack of measure BMD. Quantitative imaging techniques
weight-bearing exercise, small body shape, and like DXA and quantitative computed tomography
drugs or diseases affecting the BMD are associ- (QCT) measure the BMD from the segmented
ated with the development of osteoporosis. bone regions of the acquired images. However,
Osteoporosis can be classified according to the measurement of BMD alone cannot accu-
the underlying causes: primary and secondary. rately predict the risk of fracture.
Primary osteoporosis occurs in relation to age, Bone scan can help in detecting early fractures
which includes postmenopausal (type 1) and and determining the stage of vertebral fractures
senile (type 2). Secondary osteoporosis is caused as a supplementary tool to radiographic imaging.
by certain medical conditions and medications Bone scan is advantageous to screen the whole
such as prolonged immobilization, steroid ther- skeleton identifying osteoporotic fractures [2].
apy, and diabetes mellitus. Senile osteoporosis is Bone scan is also helpful in the case of avascular
the most common type of osteoporosis and fol- necrosis that occurs as a complication of osteo-
lowed by postmenopausal osteoporosis. porotic fracture and in detecting osteomyelitis
15 Osteoporosis 181
or clinically unpredicted lesions that may be Densitometric vertebral facture assessment

accompanied by the fractures. However, a sen- (VFA) combined with BMD increased clinical
sitivity of bone scan decreases in elderly patients diagnosis of osteoporosis by detecting previously
with osteoporotic fractures and in patients with unknown vertebral fractures and suggested VFA
steroid medication. In addition, a specificity of with BMD for the first BMD assessment in post-
bone scan is low because increased uptakes are menopausal women [4]. Bone scan is also useful
also seen at the sites of fractures, infection, meta- to detect microtrauma in patients with low back
bolic bone disease, and metastases. pain without definite radiographic abnormalities,
Other imaging modalities can be used for the as it demonstrates multiple or single linear areas
assessment of osteoporosis. Magnetic resonance of increased uptake with reduction of the verte-
imaging (MRI) is the most sensitive exam for bral height and loss of normal vertebral contour.
diagnosing vertebral fractures, due to visualiza- Three-phase bone scan may help to determine
tion of the bone marrow swelling. Unfortunately, the stages of vertebral fractures. The intensity of
the clinical accessibility of MRI is often lim- radiotracer uptake of the vertebral fracture gradu-
ited because of high cost and/or various medi- ally diminishes until 12–24 months. On the other
cal conditions of patients, e.g., metallic devices. hand, spine MRI shows low signal intensity on
Computed tomography (CT) is also useful since it T1-weighted image and band-like pattern in 46.7%
provides three-dimensional reconstructed images. of patients with acute osteoporotic compression
However, the application of PET/CT is still lim- fracture. However, it can be difficult to differen-
ited. Schmitz et al. evaluated fluorodeoxyglucose tiate malignant fractures from benign fractures
(FDG) PET in patients with osteoporosis or pre- in cases that acute stage of compression fracture
clinical osteoporosis to differentiate pathological was accompanied by severe bone marrow edema
fractures from benign fractures, and they sug- on MRI [5, 6]. Acute vertebral fractures originat-
gested that a high FDG uptake is characteristic for ing from osteoporosis or preclinical osteoporosis
malignant and inflammatory processes [3]. tend to have not pathologically increased FDG
uptake [7]. Because high FDG uptake is charac-
teristic of malignant and inflammatory processes,
15.3 Osteoporotic Vertebral FDG-PET may be potentially useful for differen-
Compression Fracture tiating osteoporotic vertebral fractures and patho-
logic fractures. In certain clinical fracture cases
Vertebral compression fractures are the most where CT and MRI images are inconclusive in
common type of insufficiency fractures because differentiating benign from malignant etiologies,
the axial skeletons are primarily composed of PET/CT can be acquired, which can also discover
cancellous bone that is more metabolically active additional skeletal or extra-skeletal metastases.
than cortical bone. It is difficult to diagnose osteo- The standardized uptake value (SUV), a dimen-
porotic vertebral fractures with simple radiogra- sionless parameter, is commonly used as a rela-
phy, when only minimal compressions occurred tive measure of FDG tissue uptake with correction
at an initial stage of the fracture. Besides, second- for the amount of injected FDG and the patient’s
ary vertebral fractures were reported to develop weight [8].
in nearly 20% of the patients within 1 year.
Multiple vertebral fractures may lead to kypho- Case 15.1
sis, scoliosis, chronic back pain, loss of height, An 80-year-old male presented to the emergency
decreased pulmonary function, decreased move- room for the chest pain after fall-down injury.
ment and fatigue, and imbalance. In this regard, Bone scan showed intense bone uptake in recent
detection of the early stage of vertebral fracture compression fracture site of T10, L1, and L2 and
is necessary to prevent the serial development of mildly increased uptake in T11–12 suggesting
multiple vertebral fractures. old compression fracture sequela. Furthermore,
there were focal increased uptakes in the known lumbar vertebrae should be used when interpret-
fracture sites of right third and left third to sixth ing BMD of the lumbar spine (Fig. 15.1).
anterior arc and right tenth and 11th and left tenth
rib posterior arc (a). In addition to multiple com- Case 15.2
pression fractures in thoraco-lumbar (T-L) spine, A 70-year-old woman came to the emergency
degenerative spondylosis in L5-S1 with prob- room for back pain by slip down on the floor.
able lumbosacral transitional vertebra in L5-S1 Bone scan showed rib fractures in the left hemi-
was noted in the radiograph (b). In the patient’s thorax and increased radioactivity in L2 vertebral
BMD of the lumbar spines, mean T-score of body (a). Simple radiography and CT of lumbar
L3–4 was −3.0 indicating osteoporosis (c). The spine showed anterior ossifications at the level of
International Society for Clinical Densitometry disc spaces indicating diffuse idiopathic skeletal
(ISCD) recommends that BMD of more than two hyperostosis (DISH), diffuse osteoporosis, and
a b
Fig. 15.1 Bone scan shows intense bone uptake in T10, 10th ribs (a). Multiple compression fractures in T-L
L1, and L2 and mildly increased uptake in T11–12. spines and degenerative spondylosis in L5-S1 with prob-
There are focal increased uptakes in the osteoporotic able lumbosacral transitional vertebra in L5-S1 are noted
fracture sites of anterior arcs of right third and left third– in the radiograph (b). Mean T-score of L3–4 is −3.0 indi-
sixth ribs and posterior arcs of right 10–11th and left cating osteoporosis (c)
15 Osteoporosis 183
trabecular loss of L2 with preserved vertebral bones, insufficiency fractures can occur with-
height (b, c). Bone SPECT/CT showed increased out trauma. These fractures can be important
uptake in the endplate area of L2 with more because they lead to immobility and are associ-
decreased uptake in the left anterior column (d). ated with high mortality. The 1-year mortality
In the patient’s initial BMD of the lumbar spines, rate is 16.3%, and the 5-year mortality rate is
mean T-score was −2.1 indicating osteopenia. 58.1% [10]. In most cases, pubic rami fractures
She received pain management and treatment and sacral injuries are ipsilateral. CT can detect
with teriparatide (recombinant human parathy- fracture sites in 25% of all the sacral fractures
roid hormone) injection for 3 months. Follow-up and 30% of the femoral neck fractures [11]. MRI
L-spine CT showed interval increased bone den- and bone scan are more sensitive to detect the
sity and wedge-shaped vertebral collapse of L2 fractures than CT.
body, which suggested osteonecrosis 5 months Insufficiency fractures of the sacrum are also
after the acute trauma (e). common and usually occur in osteoporotic bone
Delayed thoraco-lumbar fractures appear with minimal or unremembered trauma. Sacral
often in osteoporosis or old age. Its main mecha- insufficiency fractures are also common and are
nism is hyperflexion injury. The posterior two- often difficult to diagnose radiographically or
thirds of vertebral bodies receive collateral blood by CT. Owing to its relationship with osteopo-
from four arteries derived from two interverte- rosis, the majority occur in elderly females and
bral levels, whereas the anterior one-third of the are frequently bilateral, often presenting as low
vertebral body is defined as the watershed zone back pain.
associated with a higher risk of ischemic AVN [9] Plain radiographs are generally normal, and
(Fig. 15.2). both clinician and radiologist need to consider
the possibility of sacral insufficiency fracture
Case 15.3 to allow prompt accurate diagnosis and proper
A 62-year-old woman with known lung cancer treatment. Lumbar spine MRI is among the
suffered back pain for several years. PET/CT first investigations performed and can enable
for initial staging of lung cancer showed com- the correct diagnosis to be made. Occasionally
pression fractures in T11 and L4 vertebral bod- the MR appearances can mimic tumor or osteo-
ies with low FDG uptakes (a). After 17 months myelitis. The most common pattern is the “H”
from initial PET/CT, bone scan showed increased or butterfly pattern, with a horizontal band of
horizontal radioactivity in the L2, L3, and L4 increased uptake across the body of the sacrum
vertebral bodies which suggest recent compres- and two vertical limbs of activity in the sacrum.
sion fracture (b). BMD at the total femur showed Several pattern variations may be seen, includ-
a T-score of −3.3, and lateral radiograph of the ing asymmetry of the alar activity. Less severe
L-spine showed multiple compression fractures fractures may show only horizontal linear
in T11, L2, L3, L4, and L5 after 1 week from uptake. The “H” sign on bone scan is consid-
bone scan (c, d). In this case, we can assume the ered diagnostic finding in the appropriate clini-
dating of the compression fracture that T11 and cal setting, but this sign is often absent. CT is
L4 lesions were old ones and L2, L3, and L5 useful to confirm the diagnosis and exclude
lesions were relatively acute lesions by uptake tumor or infection.
patterns on bone scan (Fig. 15.3).
Case 15.4
A 76-year-old woman with osteoporosis pre-
15.4 Insufficiency Fractures sented with fall-down injury at stairs. She took
of Pelvis and Sacrum medication for 10 years for rheumatoid arthritis
with neck and shoulder pain. Pelvic CT showed
Insufficiency (fragility) fractures of the pelvis multiple fractures at left sacral ala and superior
are common in patients with over 65 years of and inferior pubic rami with swelling of left
age after a low energy fall. In severe osteoporotic obturator and pectineus muscle by contusion (a).
a b
c d e
Fig. 15.2 Multiple rib fractures in the left hemithorax SPECT/CT shows increased uptake in L2 (arrow) with
and increased radioactivity in L2 vertebral body are seen more decreased uptake in the left anterior column (d).
on bone scan (a). Simple radiography and CT of lumbar Follow-up L-spine CT shows increased bone density and
spine show anterior ossifications at the level of disc spaces wedge-shaped vertebral collapse of L2 body (arrow) sug-
indicating DISH, diffuse osteoporosis, and trabecular loss gesting osteonecrosis, 5 months after the acute trauma (e)
of L2 (arrow) with preserved vertebral height (b, c). Bone
Bone scan showed increased bone uptakes in the fractures of T spines (b). In her BMD of the lum-
left sacral ala, left pubic ramus, and left acetabu- bar spines and femur neck, T-scores were −2.8
lum, sternal fracture, and multiple compression and −2.1, respectively (Fig. 15.4).
15 Osteoporosis 185
a b
c d
Fig. 15.3 PET/CT shows compression fractures in T11 suggest recent compression fracture (b). BMD at the total
and L4 vertebral bodies with low FDG uptakes (a). Bone femur shows a T-score of −3.3 (c). Lateral radiograph of
scan 17 months later from PET/CT shows increased hori- the L-spine shows multiple compression fractures in T11
zontal radioactivities in the L2-4 vertebral bodies which and L2-5 vertebrae (d)
Fig. 15.4 Pelvic CT shows fractures at left sacral ala and the left sacral ala, left pubic ramus, and left acetabulum
superior and inferior pubic rami with swelling of left are seen including sternal fracture and multiple compres-
obturator and pectineus muscle (a). Increased uptakes in sion fractures of T spines on bone scan (b)
15 Osteoporosis 187
Case 15.5 15.5 Atypical Femoral

A 68-year-old woman with back pain for Fracture (AFF)
2 months was given MRI order in the outpatient
clinic. MRI showed irregular permeative low Bisphosphonate, which has been used for the
T1 signal intensity with heterogeneously gado- longest time for treatment of osteoporosis,
linium enhancing lesion in the upper sacrum. has been proven to have an excellent effect of
Differential diagnoses of MRI included metasta- reducing the incidence of osteoporotic fractures
sis, infiltrative bone marrow lesion (lymphoma, by about 50% through several randomized clin-
leukemia), and recent bone contusion (a). To ical trials. Bisphosphonates are antiresorptive
evaluate the possibility of metastasis or other agents that inactivate osteoclastic bone resorp-
malignancy, PET/CT was performed. On maxi- tion, decreasing bone turnover and bone loss.
mum intensity projection (MIP) image, moder- However, since 2005, it has been reported that
ate degree of FDG uptakes (maxSUV; 2.7) in the there is a risk of deterioration of bone qual-
sacral body was noted without evidence of pri- ity due to the suppression of the normal bone
mary malignancy outside of the sacrum (b). In remodeling process. Furthermore, unusual
three-orthogonal CT images, sclerotic change in types of femur fractures have been reported
the sacrum was also seen (c). PET/CT diagnosis even with minor trauma in patients with long-
was suggestive of insufficiency fracture of the term bisphosphonate treatment [12]. It occurs
sacrum, so bone scan was done as a next imaging frequently in the femur and mandible, which
study. Bone scan showed relatively characteristic requires the most bone remodeling process in
flat H-shaped increased radioactivity of insuffi- the human body. As a clinical feature, it does
ciency fracture in the sacral body with two verte- not heal properly during the remodeling pro-
bral compression fractures (d) (Fig. 15.5). cess, so the fracture line spreads and continues
to cause unstable fractures.
Case 15.6 The characteristics of AFF are non-
In a 75-year-old female patient who underwent comminuted, transverse fractures originating at
surgery 6 months ago for rectal cancer, 18F-FDG the lateral cortex of the subtrochanteric femur
PET/CT was performed for further evaluation of with localized periosteal or endosteal thickening
metastasis. She complained pain in the back and that occurs with minimal trauma. The shape of
left hip joint at that time. In the patient’s PET/ AFF plane has distinct feature that the fracture
CT, increased FDG uptakes were observed on line is horizontal on the outside but the fracture
the sacrum mainly in the right side (maxSUV; progressing obliquely toward the inside is char-
7.3) and left acetabular roof (maxSUV; 3.1), sug- acteristic. Adults with long-term bisphosphonate
gesting possible metastasis (a). The patient also use are at increased risk of AFF, estimated 100
underwent bone scan which showed intense hot per 100,000 person-years [13].
uptakes in the right upper sacrum and left ace-
tabular roof which were consistent with the PET/ Case 15.7
CT lesions (b). Due to horizontal radioactiv- A 65-year-old woman with pain on the left thigh
ity crossing the sacral body (arrow in b), sacral visited orthopedic surgery clinic. She had a renal
insufficiency fracture was suggested. MRI was transplant 21 years ago. There is no history of
performed the next day to exclude the possibility trauma. Preoperative radiograph showed bilateral
of metastasis. MRI showed suspicious low signal cortical abnormalities in the lateral side of femo-
intensity line in the right sacral ala and low sig- ral shafts (a). Bone scan showed focal increased
nal intensity lesion in the left acetabular roof on radioactivity more prominent in the left femur (b).
T1 WI (c, d). Final imaging diagnosis was stress Surgery (intramedullary nailing) was performed
fracture more likely rather than metastasis. After to prevent overt fracture (c). After 18 months, she
8 years until now, she is well alive without evi- slipped down at home and got overt fracture in
dence of skeletal metastasis (Fig. 15.6). her right femur (d) (Fig. 15.7).
b c
Fig. 15.5 MRI shows irregular permeative low T1 signal orthogonal CT images, sclerotic change in the sacrum is
intensity with heterogeneously gadolinium-enhancing also seen (c). Bone scans (anterior and posterior spot
lesion in the upper sacrum (a). On maximum intensity view) show relatively characteristic flat H-shaped pattern
projection (MIP) image of PET/CT, moderate degree of with a horizontal band of increased uptake across the
FDG uptakes in the sacral body is noted without evidence body of the sacrum and vertebral compression fractures in
of primary malignancy outside of the sacrum (b). In three- L3 and L5 (d)
15 Osteoporosis 189
Fig. 15.6 PET/CT shows increased FDG uptakes on the tivity crossing the sacral body (arrow) (b). MRI shows sus-
sacrum mainly in the right side and left acetabular roof (a). picious low signal intensity line in the right sacral ala and
Bone scan shows intense hot uptakes in the right upper low signal intensity lesion in the left acetabular roof on T1
sacrum and left acetabular roof with a horizontal radioac- WI with mild gadolinium enhancement (c, d)
a b
c d
Fig. 15.7 Preoperative radiograph shows bilateral corti- nailing) was performed to prevent overt fracture (c) After
cal abnormalities in the lateral side of femoral shafts (a). 18 months, she slipped down at home and got overt frac-
Bone scan shows focal increased radioactivities more ture in her right femur (d). [Courtesy of Kwang-kyoun
prominent in the left femur (b). Surgery (intramedullary Kim, MD, Konyang University Hospital]
Case 15.8 15.6 Medication-Related

A 77-year-old woman with pain on both thighs Osteonecrosis of the Jaw
visited orthopedic surgery clinic. She was on (MRONJ)
bisphosphonate treatment for 6 years for osteo-
porosis. Initial radiograph of the femur showed MRONJ is a rare complication of certain medi-
focal cortical thickening in the lateral sides of cation, occurring in about 1 in 10,000–100,000
femoral shaft predominantly in the right femur patients. Bone resorption inhibitors such as
(a). Bone scan showed focal intense horizontal bisphosphonates are widely used for the treatment
radioactivity in the right femoral shaft (b). One and symptom relief of various bone diseases such
week later after taking bone scan, she had fall- as osteoporosis and bone metastasis of malignant
down injury resulting in fracture of the right tumors. Nevertheless, MRONJ is a serious com-
femur (c) (Fig. 15.8). plication that has been reported, and related stud-
15 Osteoporosis 191
a b
Fig. 15.8 Initial radiograph of the femur shows focal (b). After 1 week from bone scanning date, she had fall-
cortical thickening in the lateral sides of femoral shaft pre- down injury resulting in fracture of the right femur (c).
dominantly in the right femur (a). Bone scan shows focal [Courtesy of Kwang-kyoun Kim, MD, Konyang
intense horizontal radioactivity in the right femoral shaft University Hospital]
ies have been conducted, but a clear mechanism ing methods for diagnostic definition. Although
of development and treatment has not been estab- radiographic findings are often nonspecific, an
lished so far. Although the etiology and patho- increasing volume of evidence recognizes some
genesis of MRONJ remain obscure, it has been radiological characteristics are associated with
proposed that the jaw bones are highly susceptible MRONJ [15]. In dental panoramic radiographs
to osteonecrosis due to certain anatomical and and apical radiographs, osteolytic radiographic
physiological factors [14]. MRONJ is character- lesions with uneven borders and radiopaque
ized by pain, exposed bone, infection, and patho- osteosclerosis can be observed. In CT, osteo-
logical fracture. Incidence of osteonecrosis of the phytes or osteonecrosis is clearly observed. Bone
jaw is expected to continue to increase. Definition scan with three-phase imaging is important for
of MRONJ includes the following characteristics the diagnosis of osteonecrosis and is considered
to be defined as (1) current or previous administra- useful for the detection of early changes, but it is
tion of bone resorption inhibitors or angiogenesis difficult to detect minor inflammation and necro-
inhibitors, (2) bone exposure in the maxillofacial sis due to its low resolution. Thus, SPECT/CT
region or bone probed through internal or external improves both sensitivity and specificity, provid-
fistula of oral cavity lasting for more than 8 weeks, ing cross-sectional images combined with ana-
and (3) no history of radiotherapy or definite meta- tomical CT information. In MRI, the T1 signal
static bone tumors in the maxilla. of osteonecrosis is often decreased, and the low
MRONJ is a bone disease that frequently signal of STIR, T2, and vascular components is
affects the soft tissues, so it requires targeted imag- often attenuated.
Medications Associated with MRONJ Case 15.9

The following is the list of drugs which are A 74-year-old woman was referred to the
known to cause MRONJ. Department of Endocrinology and Metabolism for
evaluation of pain and persistent abnormal expo-
1. Antiresorptives. sure of jaw after teeth extraction. She had a history
(a) Bisphosphonates: pamidronate, alen- of taking alendronate (70 mg weekly) for 5 years
dronate, risedronate, ibandronate, for the treatment of osteoporosis. She had no clini-
zolendronate. cal history of cranial or oral radiation therapy.
(b) Human monoclonal antibody of RANKL The left mandibular first and second molars
(receptor activator of nuclear factor were extracted; however, the wound did not heal
kappa-Β ligand): denosumab. and persisted. Short-term (three treatment periods
2. Sclerostin-binding monoclonal antibody: comprising of 4 days administration each) antibi-
romosozumab. otic (amoxicillin) treatment was given, but there
3. Drugs that are not used for osteoporosis but was no improvement. Curettage and debridement
known to cause drug-related osteonecrosis were performed repeatedly until the patient was
(antiangiogenic or targets of the vascular referred to the Endocrinology Clinic. Panoramic
endothelial growth factor (VEGF) pathway). radiograph showed bilateral bony destruction in
(a) Tyrosine kinase inhibitor: sunitinib, both mandibular bodies with more involvement
sorafenib. in the left side (a). She had open wound in her
(b) Humanized monoclonal antibody: left mandibular bone (arrow in b). Three-phase
bevacizumab. bone scan showed diffusely increased uptake in
(c) Mammalian target of rapamycin path- both mandibular bodies (c–e) predominantly in
way: sirolimus. the left side (Fig. 15.9).
a b
c d
e
Fig. 15.9 Bilateral bony destruction in both mandibular from left) show diffusely increased radioactivities in both
bodies is seen on panoramic radiography (a). Open wound mandibular bodies (c–e). [Courtesy of Yoon-Sok Chung,
in her left mandibular bone was noted (arrow in b). Three- MD, Ajou University Hospital]
phase bone scan (blood flow, blood pool, delayed image
15 Osteoporosis 193
In conclusion, BMD measures the bone quan- 2. Elgazzar AH. Diagnosis of metabolic, endocrine
tity and not the bone structure; it is insufficient and congenital bone disease. In: Elgazzar AH, edi-
tor. Orthopedic nuclear medicine. Springer; 2017.
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role of nuclear imaging in diagnosing osteopo- 3. Schmitz A, Risse JH, Textor J. FDG-PET find-
rotic fractures is often complementary and very ings of vertebral compression fractures in osteo-
sensitive. porosis: preliminary results. Osteoporos Int.
2002;13(9):755–61.
4. Cai S, Yu H, Li Y, He X, Yan L, Huang X, et al. Bone
mineral density measurement combined with verte-
Teaching Points bral fracture assessment increases diagnosis of osteo-
• Early diagnosis, treatment, and patient porosis in postmenopausal women. Skelet Radiol.
2020;49(2):273–80.
education about osteoporosis are impor- 5. Ahn SE, Ryu KN, Park JS, et al. Early bone marrow
tant to reduce future additional fractures. edema pattern of the osteoporotic vertebral compres-
• Compression fractures of the spine are sion fracture can be predictor of vertebral defor-
common and may show abnormal mity types and prognosis? J Korean Neurosurg Soc.
2016;59:137–42.
uptake in bone scan before radiographic 6. Yang SO, Kim S, Juhng SK. Imaging diagno-
changes. sis of osteoporotic fracture. J Korean Med Assoc.
• The insufficiency osteoporotic fractures 2010;53:67–75.
may show persistent uptake for months 7. Bredella MA, Essary B, Torriani M, Ouellette HA,
Palmer WE. Use of FDG-PET in differentiating
or years on bone scan, so it can be diffi- benign from malignant compression fractures. Skelet
cult to determine if the fracture is acute. Radiol. 2008;37:405–13.
• Combination of bone scan and MRI is 8. Shin DS, Shon OJ, Byun SJ, Choi JH, Chun KA, Cho
often complementary in the diagnosis of IH. Differentiation between malignant and benign
pathologic fractures with F-18-fluoro-2-deoxy-D-
vertebral fracture and sacral insuffi- glucose positron emission tomography/computed
ciency fracture. tomography. Skelet Radiol. 2008;37:415–21.
• The characteristics of AFF are non- 9. Maheshwari PR, Nagar AM, Prasad SS, Shah JR,
comminuted, transverse fractures origi- Patkar DP. Avascular necrosis of spine: a rare appear-
ance. Spine. 2004;29(6):E119–22.
nating at the lateral cortex of the 10. Hamilton CB, Harnett JD, Stone NC, et al. Morbidity
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quently observed in the long term of an older Atlantic Canadian cohort. Can J Surg.
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11. Cabarrus MC, Ambekar A, Lu Y, et al. MRI and CT of
graphs and bone scan. insufficiency fractures of the pelvis and the proximal
• In the diagnosis of MRONJ, three-phase femur. AJR. 2008;191:995–1001.
bone scan is important for the diagnosis 12. Yoon RS, Hwang JS, Beebe KS. Long-term bisphos-
of osteonecrosis and is considered use- phonate usage and subtrochanteric insufficiency frac-
tures? A cause for concern? J Bone Joint Surg Br.
ful for the detection of early changes. 2011;93(10):1289–95.
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Osteoporos Sarcopenia. 2018;4(1):16–21.
Fibrous Dysplasia
16
Yong-il Kim and Jin-Sook Ryu
Abstract emission computed tomography/computed

tomography · Positron emission tomography/
Fibrous dysplasia is a disease in which fibrous
computed tomography
tissues replace the normal bone medullary
space. Monostotic fibrous dysplasia accounts
for 70–85% of cases of fibrous dysplasia and
16.1 Clinical Features
develops in areas such as the rib and femur.
and Pathophysiology
Polyostotic fibrous dysplasia accounts for
15–30% of cases and develops in areas such
Fibrous dysplasia is a benign, non-genetic bone
as the femur and tibia. Bone scan is a valuable
developmental disease in which the fibrous con-
imaging technique for differentiating between
nective tissues of the bone grow abnormally and
monostotic and polyostotic fibrous dysplasia
form immature bone fragments. Fibrous dyspla-
and mostly shows the area of intensely increased
sia accounts for 5–7% of benign bone tumors and
uptake. Bone scan can be useful for assessing
is most commonly detected in children and ado-
the activity of fibrous dysplasia because the
lescents [1].
uptake decreases in the quiescent state. Fibrous
Monostotic fibrous dysplasia and polyostotic
dysplasia requires a differential diagnosis with
fibrous dysplasia comprise 70–85% and 15–30%
other diseases because small lesions can show
of cases of fibrous dysplasia, respectively [2].
false-negative results. Bone SPECT/CT can
Monostotic fibrous dysplasia develops in the rib,
be used to accurately determine the extent of
femur, tibia, skull, and facial bones (in order of
disease invasion. 18F-FDG PET/CT shows vari-
frequency) and rarely invades the spine. Polyostotic
able uptake for fibrous dysplasia.
fibrous dysplasia occurs in the femur, tibia, pelvis,
metatarsal bone, metacarpal bone, sternum, skull,
Keywords
humerus, and facial bones. Polyostotic fibrous
dysplasia often invades the spine and can be
Fibrous dysplasia of bone · Fibrous dyspla-
accompanied by systemic conditions. In cases
sia, monostotic · Fibrous dysplasia, polyos-
with precocious puberty and café au lait spots, the
totic · Radionuclide imaging · Single-photon
disease is referred to as McCune-Albright syn-
drome [3], and in cases with myxoma, the disease
Y.-i. Kim (*) · J.-S. Ryu
Department of Nuclear Medicine, Asan Medical is referred to as Mazabraud syndrome [4].
Center, University of Ulsan College of Medicine, The cause of this disease is known to be the
Seoul, Republic of Korea ongoing activation of adenylyl cyclase (G protein
e-mail: kyi821209@amc.seoul.kr; jsryu2@amc.seoul.kr
https://doi.org/10.1007/978-981-19-2677-8_16
196 Y.-i. Kim and J.-S. Ryu
effector) through the mutation of stimulatory G 16.2 Radiologic Findings

(Gs) protein genes (guanine nucleotide-binding and Nuclear Medicine
protein, alpha-stimulating activity polypeptide 1: Imaging
GNAS1), which subsequently induces cell prolif-
eration in response to cyclic adenosine mono- On X-ray images, radiolucency changes are
phosphate (cAMP) [5] (Fig. 16.1). observed according to the amount of fibrous and
Most cases of fibrous dysplasia have no clini- bone tissues in the bone marrow space, the extent
cal symptoms, and non-specific symptoms can of loss of normal trabecular patterns, and ground-
occur depending on the site of fibrous dysplasia, glass opacities. If the bone endosteum shows
which is often detected by chance on X-ray endosteal scalloping with the replacement of
images [6]. When the disease is followed up, normal tissues in the bone marrow space with
most cases do not show any disease progression. fibrous collagen tissues, the bone is expanded,
However, some symptoms can occur due to pain- and the boundaries of the bone cortex disappear.
less swelling with nasal obstruction, nasal bleed- Radiolucent lesions are sometimes observed as
ing, facial asymmetry, exophthalmos, diplopia, cystic lesions with sclerotic bone rims or show
headache, and anosmia [7]. Surgical interven- multilocular or bubble shapes. Computed tomog-
tions are necessary if the disease leads to either raphy (CT) is used to assess the extent of lesion
functional or cosmetic problems, causes severe invasion, especially in the skull and facial bones
pain, or is likely to be malignant [1]. [8].
Endocrine organs:
Endocrinopathies
MSH, LH, TSH, GnRH, etc
Autonomous hyperfunction
of specific cells leading to:
Hormone
• Precocious puberty
• Acromegaly
• Hyperthyroidism
Adenylate • Cushing’s syndrome
Receptor cyclase • Rickets/Osteomalacia
α α
β γ β γ
GDP + GTP
GDP GTP Skin: Café-au-lait spots
Overproduction of
PPi melanin by mutation-
Mutation Gαs bearing melanocytes
ATP
≠≠≠ cAMP
Bone: Ground glass

lesions
cAMP-driven arrest of
skeletal stem cell maturation
at woven bone stage
Fig. 16.1 Pathophysiology of fibrous dysplasia. differentiation of bone marrow stromal cells into abnor-
Mutations of stimulatory G (Gs) protein genes (GNAS1) mal osteoblasts, which results in the abnormal maturation
can lead to the inappropriate production of cAMP. The of the bony matrix. Adapted from [5] with permission
increased concentration of cAMP causes the incomplete
16 Fibrous Dysplasia 197
Bone scan is a sensitive nuclear medicine cell tumor, and aneurysmal bone cyst. 18F-FDG
imaging method that can detect early-stage positron emission tomography (PET)/CT shows
lesions for fibrous dysplasia and can screen for variable uptake for fibrous dysplasia based on
polyostotic fibrous dysplasia as it examines the active fibroblasts, which may cause problems in
entire body. Blood flow and metabolism are differentiating between fibrous dysplasia and
increased due to active osteoblasts; thus, the area bone metastasis [10] (Fig. 16.2).
of significantly increased uptake usually appears
on bone scan. In addition, bone single-photon
emission computed tomography (SPECT)/CT
Teaching Points
can be used to accurately assess the extent of
• Bone scan of fibrous dysplasia usually
lesion invasion [9]. When lesions enter the quies-
shows increased radiotracer uptake and
cent state during disease progression, an area of
can be useful to assess the disease
increased uptake might not appear on bone scan
activity.
even if the lesions are evident on X-ray images.
• Bone SPECT/CT is known to be helpful
Therefore, bone scan is more advantageous when
in determining the extent of fibrous
assessing the disease’s activity. However, small
dysplasia.
lesions can show false-negative results in some
• 18F-FDG PET/CT of fibrous dysplasia
cases. Hence, if an osteolytic lesion shows no
demonstrates variable radiotracer
uptake on bone scan, a differential diagnosis is
uptake.
required, which may include hemangioma, giant
Fibrous Dysplasia (FD) on imaging
Age < 21 Age > 21
FD Evaluation Symptomatic or
Asymptomatic, no
History and physical to identify: limp, bone pain, fractures, limb evidence of
complications
length discrepancy, facial asymmetry complications
Age < 5 Age > 5

years years
High clinical Low clinical Abnormal 99mTc-MDP Normal 99mTc-MDP

suspicion for suspicion for bone scan bone scan
significant FD significant FD
Significant FD Trivial FD
- Consider baseline
X-ray of affected
area(s)
- Skeletal survey
- Vision, hearing evaluation Monitor clinically - Baseline skeletal survey Low likelihood for
- Serum phosphorus, and 99mTc-MDP - Baseline head CT for significant FD;
- Tubular Reabsorption of scan at age 5 craniofacial FD Monitor clinically
Phosphate (TRP) - Serum phophorus
- 99mTc-MDP at 5 years - TRP
• Prior to age 5, a normal 99mTC-MDP bone scan dose not rule out the possibility of significant FD,
• A normal 99mTc-MDP bone scan at age 5 years or older effectively rules out clinically significant FD, and no
further radiologic monitoring is required.
Fig. 16.2 Fibrous dysplasia management algorithm. Adapted from [5] with permission
Case 16.1 finally diagnosed as McCune-Albright syn-

A 46-year-old woman underwent bone scan drome (Fig. 16.4).
and chest computed tomography (CT) to evalu-
ate her right upper chest wall area protrusion. Case 16.3
The right second rib lesion was diagnosed as A 40-year-old woman underwent bone scan and
fibrous dysplasia by excisional biopsy bone SPECT/CT to evaluate an incidentally
(Fig. 16.3). found spine and rib mass. The left third rib lesion
was diagnosed as fibrous dysplasia by a needle
Case 16.2 biopsy (Fig. 16.5).
A 10-year-old boy underwent bone scan and
lower extremity CT to assess his left calf area Case 16.4
pain. The left femur lesion was diagnosed as A 41-year-old woman underwent bone scan and
fibrous dysplasia by excisional biopsy. In 18
F-FDG PET/CT to assess her rib and spinal
addition, typical café au lait spots on the mass by chance. The right fifth rib lesion was
patient’s back/lower extremities and preco- diagnosed as fibrous dysplasia by excisional
cious puberty were found. The patient was biopsy (Fig. 16.6).
a
b
Fig. 16.3 A case of monostotic fibrous dysplasia in a arrow). On the chest CT (b), diffuse swelling is noted in
46-year-old woman. On the bone scan (a), diffusely the right second rib (blue arrow)
increased uptake is observed in the right second rib (blue
a b
Fig. 16.4 A 10-year-old boy with McCune-Albright tibia (blue arrows). On the lower extremity CT (b), an
syndrome. On the bone scan (a), multiple increased
extensive ground glass attenuated mass and other small
uptakes are found in the left side skull base, mandible, multifocal lesions are found in the left femur (blue arrows)
both humeri, left proximal radius, both femurs, and left
a b
Fig. 16.5 A case demonstrating the usefulness of bone osteolytic and sclerotic lesions with uneven increased
SPECT/CT in fibrous dysplasia. On the bone scan (a), uptake are found in the body, left pedicle, left transverse
irregularly increased uptakes are shown in the left third rib process of T3 vertebra in addition to left third rib posterior
(blue arrows). On the bone SPECT/CT images (b–d), the arc (blue arrows)
a b c
Fig. 16.6 A case of fibrous dysplasia with hypermeta- images (b–e), the right fifth rib and T5 lesions are demon-
bolic activity on 18F-FDG PET/CT. On the bone scan (a), strated as hypermetabolic osteolytic lesions [maximum
intensely increased uptakes are found in the right fifth rib standardized uptake value (SUV) of the right fifth rib; 8.1]
and T5 vertebra (blue arrows). On the 18F-FDG PET/CT (blue arrows)
6. DiCaprio MR, Enneking WF. Fibrous dyspla-

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org/10.4143/crt.2009.41.3.171.
Part V
Musculoskeletal Neoplastic Disorders
Primary Bone and Soft Tissue
Tumors 17
Jin Chul Paeng and Seoung-Oh Yang
Abstract Keywords
Primary bone and soft tissue tumors com- Bone scan · FDG PET · Primary bone tumor ·
prise many diverse pathologic types that may Primary soft tissue tumor · Sarcoma
be benign or malignant. Radiological imag-
ing including plain radiograph, CT, MRI,
and ultrasonography is the primary imaging 17.1 Pathologic Classification
method for diagnosing such tumors. Bone
scan is usually performed to determine extent Bone and soft tissue are composed of diverse
of bone invasion or distant bone metasta- cells of several origins, and each of them can
sis. FDG PET is effective for initial staging, be transformed to malignancy. According to the
monitoring treatment response, and detecting 2020 WHO classification of soft tissue and bone
recurrence. Although there are quite a large tumors, the classification of primary bone and
variation in image findings of primary bone soft tissue tumors is categorized based on the cell
and soft tissue tumors and overlap between origins (Table 17.1) [1].
benign and malignant tumors, bone scan and
FDG PET have effective roles. Particularly,
it has been consistently reported that FDG Table 17.1 WHO classification of primary bone and soft
tissue tumors
PET has a significant correlation with patho-
logic grade and patients’ prognosis, in certain Primary bone tumors Primary soft tissue tumors
Chondrogenic tumors Adipocytic tumors
pathologic types. Some representative patho- Osteogenic tumors Fibroblastic and
logic types and cases of primary bone and soft Fibrogenic tumors myofibroblastic tumors
tissue tumors are presented in this chapter. Vascular tumors of bone Fibrohistiocytic tumors
Osteoclastic giant Vascular tumors
cell-rich tumors Pericytic tumors
J. C. Paeng (*) Notochordal tumors Smooth muscle tumors
Department of Nuclear Medicine, Seoul National Other mesenchymal Skeletal muscle tumors
University College of Medicine, Seoul, tumors of bone Gastrointestinal stromal
Republic of Korea Hematopoietic tumors
e-mail: paengjc@snu.ac.kr neoplasm of bone Chondro-osseous tumors
Peripheral nerve sheath
S.-O. Yang
tumors
Undifferentiated small
of Radiological and Medical Sciences, Busan,
round cell tumor
Republic of Korea
e-mail: soyang@dirams.re.kr
https://doi.org/10.1007/978-981-19-2677-8_17
206 J. C. Paeng and S.-O. Yang
17.2 Diagnosis be detected in initial staging or surveillance. FDG

PET can also be used for determining biopsy site
Plain radiograph is usually used for the initial when the biopsy of primary site is risky or initial
evaluation of primary bone and soft tissue tumors, biopsy result is insufficient due to large necrotic
and it may provide basic information on tumor portion. FDG uptake is related to the degree of
characteristics such as location, extent, calcifica- malignancy, and high uptake is usually observed
tion, and related bone changes. Ultrasonography in high-grade or poorly differentiated tumors.
and computed tomography (CT) are effective in Thus, FDG PET finding is associated with a
some specific conditions such as superficially patient’s prognosis, although specific pathologic
located tumors or tumors in head and neck or types are cannot be differentiated on PET images
mediastinum. However, general diagnostic effi- FDG PET is also effective for treatment
cacy of ultrasonography and CT in bone and soft response evaluation. Currently, chemotherapy
tissue tumor is not optimal. Currently, magnetic and/or radiotherapy is often used for some bone
resonance imaging (MRI) is used as the essen- and soft tissue sarcomas as neoadjuvant therapy
tial imaging modality for bone and soft tis- or palliative therapy (Fig. 17.1). FDG PET shows
sue tumors. MRI can visualize the exact tumor metabolic change of a tumor and is a sensitive
extent, invasion to adjacent tissues, and meta- imaging to show response to treatment. During
static lesions in the covered field of view. MRI follow-up and surveillance after initial treatment,
can also provide much information on the patho- local recurrence is the most common treatment
logic characteristics. failure. Although MRI is the most effective imag-
ing in diagnosing recurrence, FDG PET is effec-
tive when there are metallic prostheses that cause
17.3 Nuclear Imaging severe metallic artifact and/or post-radiation
changes (Fig. 17.2).
Bone scan is usually used as one of basic image In contrast to usual cancers, bone and soft tis-
studies in bone and soft tissue tumors. The sue sarcomas often metastasize to atypical sites
purpose of bone scan is to determine extent of including peripheral bone and soft tissues. Thus,
bone invasion or distant bone metastasis. It also it is recommended to obtain total body images
shows tumor characteristics regarding osteoblas- in the case of these sarcomas, rather than usual
tic activity. Thus, baseline bone scan is neces- torso images.
sary for future follow-up and surveillance of a
patient. Most of primary malignant bone tumors
show high uptake on bone scan. However, benign 17.4 Image Findings of Common
bone tumors may show variable uptake, and the Primary Bone and Soft
degree of uptake cannot be used for differentia- Tissue Tumors
tion of malignant from benign tumors or high-
grade from low-grade tumors. Bone positron 17.4.1 Osteosarcoma
emission tomography (PET) using 18F-NaF may
also be used for the same purpose. However, 18F- Although various ossification patterns are
NaF PET is not so widely used due to high cost observed on plain radiographs, osteoblastic activ-
despite higher image quality than bone scan. ity is enhanced in most of osteosarcoma. Thus,
18
F-fluorodeoxyglucose (FDG) PET is effec- osteosarcoma shows high uptake on bone scan.
tive in the initial staging and diagnosis of recur- Additionally, high uptake is also observed in
rence. FDG PET is a sensitive imaging to detect extraskeletal metastatic sites such as the lungs.
tumors and effective in detecting metastasis. FDG PET also shows high uptake in osteosar-
Because FDG PET covers the whole body on a coma [2]. FDG PET is effective for response
single scan, unexpected distant metastasis may monitoring and recurrence detection.
17 Primary Bone and Soft Tissue Tumors 207
Fig. 17.1 Intense uptake was observed in multiple mary site progressed (yellow arrows, maximum SUV
lesions on FDG PET (maximum SUV 18.5). Despite che- 34.4), and multiple new lesions appeared (red arrows)
motherapy of second-line regimen, the tumor of the pri-
17.4.2 Chondrosarcoma The uptake of FDG by liposarcoma is usually

lower than that of other sarcoma, in line with
Chondrosarcoma usually shows intense uptake relatively favorable prognosis. Thus, discrimina-
on bone scan, whereas benign enchondroma tion between benign and malignant lipomatous
shows mild to moderate uptake [3]. Thus, bone tumors based on FDG uptake is often difficult
scan can be used for monitoring malignant trans- [5]. However, FDG uptake is well correlated with
formation of benign chondrogenic tumors. On grade of liposarcoma, and high-grade liposar-
FDG PET, although chondrosarcoma usually coma may show intense uptake. FDG uptake is
shows moderate uptake, the uptake is higher in also associated with patients’ prognosis [6].
high-grade chondrosarcoma [4].
17.4.4 Giant Cell Tumor

17.4.3 Liposarcoma
As giant cell tumor is caused by hyperprolifera-
Liposarcoma is a relatively common bone and tion of osteoclasts, it is usually shown as a radio-
soft tissue tumor. Bone scan is helpful in bone lucent mass without surrounding sclerosis or
metastasis of liposarcoma like other sarcoma. calcification on CT and a T1-low tumor with high
Fig. 17.2 On MRI, irregular enhancement pattern was nancy (maximum SUV 22.6). Atypical metastases were
observed in the back mass (arrows on MRI), which can be observed in the lung, myocardium, and thigh muscle
interpreted as a benign postoperative change. On FDG (arrows on PET)
PET, the mass showed intense uptake, suggesting malig-
enhancement on MRI. On bone scan, most giant with altered osteogenesis. It may be monostotic
cell tumor shows high uptake. The uptake is often or polyostotic forms. Fibrous dysplasia usually
combined with a central defect, which is called shows intense uptake on bone scan and variable
“doughnut sign.” Although giant cell tumor is FDG uptake on PET [9]. Malignant transforma-
classified as a malignancy, it usually shows high tion may occur in fibrous dysplasia, although it is
uptake on FDG PET with a large variability [7]. rare. Other fibrogenic, fibroblastic, and fibrohis-
tocytic tumors also show variable FDG uptake,
and the uptake is usually associated with grade
17.4.5 Ewing Sarcoma of tumors. Because a large mass may show het-
erogeneous uptake pattern due to necrosis and/or
Ewing sarcoma is classified as undifferentiated internal heterogeneous tissue components, FDG
small round cell sarcoma of bone and soft tis- PET is helpful to determine biopsy target.
sue. Ewing sarcoma usually shows intense FDG
uptake [2], with sensitivity and specificity of
FDG PET >95% [8]. Ewing sarcoma may show 17.4.7 Langerhans Cell Histiocytosis
variable uptake on bone scan, although a typical
lesion usually shows moderate uptake. Langerhans cell histiocytosis is a disorder of
abnormal proliferation of a certain immune
cell type. The bone is the most common site of
17.4.6 Fibrogenic and Fibroblastic involvement and usually presented in children or
Tumors young adults. The skull is the most common site
and it can involve any site of the skeleton. On
Fibrous dysplasia is a benign bone lesion of intra- plain radiographs, osteolytic lesion without rim
medullary fibrous proliferation, often combined is the typical finding. On bone scan, increased
uptake with internal defect is a typical finding,

and the uptake is normalized after treatment. • In primary bone and soft tissue tumors,
FDG PET is usually not necessary for diagnosis FDG PET can be used for determining
of follow-up of Langerhans cell histiocytosis. biopsy sites, initial staging, prognosis
However, FDG PET may be used in initial diag- prediction, treatment response monitor-
nosis when diagnosis is uncertain. On FDG PET, ing, and detection of recurrence.
high uptake is often observed, although it may be
variable.
Case 1
A 68-year-old male patient was diagnosed with
17.4.8 Other Tumors osteosarcoma and showed multiple metastases to
the bones and lungs. The patient received palliate
There are many other types of bone and soft tis- chemotherapy, and new nodules were detected on
sue tumors, with variable pathology. The tumors chest CT. Second-line chemotherapy was started,
may show variable findings on bone scan or FDG and FDG PET was performed after two cycles of
PET. In most tumors, FDG uptake is related to chemotherapy. On the PET images, disease pro-
tumor grade, degree of malignancy, and patients’ gression was determined (Fig. 17.1), and radio-
prognosis. Thus, FDG PET is recommended to be therapy with changed chemotherapy regimen
considered in initial staging, selection of biopsy was started.
site, evaluation of treatment response, and recur-
rence detection. However, it should be noted that Case 2
many benign bone tumors also show high uptake A 30-year-old male patient presented with a
on bone scan or FDG PET. growing mass in the upper back. He had under-
gone resection of a giant cell tumor in T-spines
5 years ago, and the new mass recurred in the
Teaching Points operation site. On MRI, a new mass was observed
• Most of primary malignant bone tumors in the soft tissue with prominent metallic artifact.
and bone involvement of malignant soft He underwent FDG PET, and the mass showed
tissue tumors show high uptake on bone intense hypermetabolism, suggesting recurrence
scan, whereas benign bone tumors may of tumor. Additionally, atypical metastases were
show variable uptake. observed in multiple organs including myocar-
• Although some tumors such as osteosar- dium (Fig. 17.2).
coma, giant cell tumor, fibrous dyspla-
sia, and Langerhans cell histiocytosis Case 3
present relatively typical findings on A 14-year-old male patient presented with a mass
bone scan, it is difficult to diagnose in the right humerus. From bone biopsy, the mass
pathologic types on bone scan. was confirmed as osteosarcoma. Bone scan and
• On FDG PET scan, there are consider- FDG PET were performed for initial staging of
able variations of uptake even in the the tumor. On both images, increased uptake
same pathologic types, and thus, it is was observed in the primary tumor, and no other
inappropriate to discriminate malignant lesion was detected. After neoadjuvant chemo-
from benign tumors or to determine therapy and limb-salvage surgery, the patient was
pathologic types on FDG PET. followed up using bone scan for surveillance of
• FDG uptake in the same pathology is recurrence. Three months after surgery, a new
usually associated with pathologic uptake on bone scan was observed in the right
grades and patients’ prognosis. humerus. On other images, it was confirmed as a
benign screw fracture (Fig. 17.3).
Fig. 17.3 On initial bone scan and FDG PET, the pri- bone scan uptake in the primary site had disappeared,
mary tumor in the right humerus shows uptake (red whereas a new uptake was observed in the screw fracture
arrows, maximum SUV 6.9). Three months after surgery, site (blue arrows)
Case 4 Case 6
A 40-year-old male patient who had been A 65-year-old female patient presented with
confirmed as hereditary multiple osteochon- aggravating cough. Multiple lung nodules were
droma complained of expansile upper back detected on chest radiograph, and FDG PET was
mass during follow-up. On bone scan, multiple performed to determine probable primary site
osteochondroma lesions showed moderately
and metastatic lesions. On FDG PET, large and
increased uptake. Particularly, intense uptake intense hypermetabolic mass was detected in the
was observed in a mass of the upper T-spine. On right psoas muscle. From the muscle biopsy, the
MRI, the mass showed was suspected as a malig- mass was confirmed as a high-grade dedifferenti-
nant tumor rather than a benign osteochondroma. ated liposarcoma (Fig. 17.5b).
On FDG PET, only mild uptake was shown
(Fig. 17.4). The mass was excised and confirmed Case 7
as grade 1 chondrosarcoma. A 19-year-old male patient presented with mul-
tiple tumors. From bone biopsy, the tumors were
diagnosed with synchronous giant cell tumors.
Case 5 After tumor removal of right femur head and total
A 45-year-old female patient presented with hip replacement surgery, he still had several giant
a left pelvic mass. The mass had slowly grown cell tumors (Fig. 17.6).
over 5 years and fat component was observed on
CT. On FDG PET, the mass showed mild uptake. Case 8
The mass was excised and confirmed as dediffer- A 44-year-old male patient presented with a
entiated liposarcoma (Fig. 17.5a). tumor in the left gluteal muscle. From the muscle
Fig. 17.4 On bone scan, multiple osteochondroma low arrows). On FDG PET, the mass showed mild uptake
lesions show high uptake (blue lines), and intense uptake (maximum SUV 2.7), although the mass was confirmed as
was observed in upper T-spine mass (red arrow). On MRI, grade 1 chondrosarcoma
the mass shows peripheral and septal enhancement (yel-
a b
Fig. 17.5 (a) A left pelvic mass with fat component on FDG PET. A large and intense hypermetabolic mass
showed mild uptake on FDG PET (maximum SUV 2.5). was detected in the right psoas muscle (maximum SUV
The mass was confirmed as dedifferentiated liposarcoma. 43.1), which was confirmed as high-grade dedifferenti-
(b) Multiple metastatic lung nodules show intense uptake ated liposarcoma
Fig. 17.6 In a patient with multiple synchronous giant showed typical finding of giant cell tumor, low T1 signal,
cell tumors, several giant cell tumors are shown. A tumor and high enhancement. FDG PET shows multiple foci of
in the left proximal tibia shows central defect on bone high uptake (maximum SUV 14.7)
scan (red arrow), which is called “doughnut cell.” MRI
biopsy, the tumor was confirmed as Ewing sar- Case 10

coma. FDG PET showed intense uptake of the A 81-year-old man presented with a large tumor
primary tumor and multiple metastatic lesions in the left medial thigh. The mass was diagnosed
including lymph nodes and bones. On bone scan, with myxoid fibrosarcoma on biopsy. On FDG
the metastatic site of bone showed moderate PET, despite intense uptake in some part (maxi-
uptake (Fig. 17.7). mum SUV 19.6), a considerable heterogeneity
was observed. When the tumor was surgically
Case 9 resected, similar heterogeneity was observed
A 35-year-old man presented with fibrous dys- on the gross tumor and microscopic findings
plasia. He showed multiple bone lesions, which (Fig. 17.8b).
showed intense uptake on bone scan. During
follow-up, a mass in the left ilium enlarged Case 11
and biopsy was performed. It was confirmed to A 2-year-old boy presented with left femoral
be a chondrosarcoma (red arrows), which was pain. On plain radiograph an osteolytic lesion
deemed a transformed malignancy from the was observed in the left proximal femur. On bone
fibrous dysplasia. Interestingly, whereas fibrous scan, high uptake was observed in the margin
dysplasia lesions showed variable FDG, malig- area with internal defect. FDG PET was per-
nant chondrosarcoma showed relatively mild formed to rule out malignancy and showed high
uptake (Fig. 17.8a). uptake in the lesion. Bone biopsy showed that it
Fig. 17.7 Ewing sarcoma in the left gluteal muscle tor lymph node and right side of sacrum (yellow arrows).
shows intense FDG uptake on PET (maximum SUV On bone scan, the sacral metastasis shows moderate
18.8). Metastatic lesions are also shown in the left obtura- uptake (red arrow)
a b
Fig. 17.8 (a) Polyostotic fibrous dysplasia in multiple SUV up to 13.7. (b) A myxoid fibrosarcoma shows intense
bones shows intense uptake on bone scan. A chondrosar- uptake in some part on FDG PET (yellow arrows, maxi-
coma transformed from the fibrous dysplasia (red arrows) mum SUV 19.6), which is matched with a considerable
shows mild uptake (maximum SUV 3.5), whereas fibrous heterogeneity in gross/microscopic pathology
dysplasia lesions show variable FDG uptake (maximum
was Langerhans cell histiocytosis. After indo- the anterior knee area, which showed intense
methacin treatment, the lesion on bone scan nor- FDG uptake. He underwent tumor resection,
malized, and pain disappeared (Fig. 17.9). and the pathologic diagnosis was clear cell sar-
coma. After 1-year follow-up, a new nodule was
Case 12 detected in the right subscapularis muscle, which
A 42-year-old male patient presented with a was confirmed as recurred clear cell sarcoma
palpable mass in the left knee and discomfort from muscle biopsy. FDG PET also showed
on walking. MRI revealed a soft tissue mass in another metastatic lesion (Fig. 17.10).
Fig. 17.9 On plain radiograph, an osteolytic lesion is internal defect. FDG PET shows also high uptake in the
observed in the left proximal femur (red arrow). On bone lesion (blue arrow)
scan, high uptake is observed in the margin area with
Fig. 17.10 On MRI, a soft tissue mass is observed in the right subscapularis muscle (maximum SUV 6.4), which
anterior knee area, which showed intense FDG uptake was confirmed as metastasis. Another small metastatic
(maximum SUV 11.6). In 1-year follow-up FDG PET, a lesion in the left lung was not detected on PET, probably
new nodule with high FDG uptake was detected in the due to partial volume effect and motion artifact
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Metastatic Musculoskeletal
Tumors 18
Young-Sil An and Seoung-Oh Yang

Bone metastasis from solid tumors may appear and Pathophysiology
at various sites, mainly cancer from the breast
and prostate. Bone metastases are mainly dis- Bone metastasis indicates that cancer cells
tributed in the axial skeleton, which contains escape from the primary cancer site and colo-
red bone marrow. The role of imaging studies nize the bone, which is seen in various primary
in bone metastasis is to establish a treatment cancers, such as the breast, prostate, lungs, and
plan for the patient and predict prognosis. For kidneys [1]. The process by which a solid tumor
nuclear medicine imaging, bone scan and 18F- can metastasize to bone includes pre-metastatic
FDG PET are the most commonly used clini- niche formation [2], circulation-mediated dis-
cally, and bone PET using 18F-NaF can also semination of tumor cells, and complex interac-
be used to evaluate bone metastasis. Here, we tion between circulating tumor cells and the bone
introduce a variety of nuclear medicine imag- microenvironment, known as the “seed and soil”
ing cases showing metastatic bone lesions, hypothesis [3, 4].
and we would like to inform you about what Cancer cells settle in the bone and cause bone
points to keep in mind when evaluating bone destruction mediated by osteoclast-mediated
metastases with nuclear medicine imaging. osteolysis, and these bone changes cause bone
pain and fracture, which lowers the patient’s
Keywords quality of life and may increase morbidity [5].
Systemic chemotherapy, radiation therapy, and
Bone metastasis · Bone scan · 18F-NaF PET orthopedic surgery can be performed to treat bone
18
F-FDG PET · Flare phenomenon metastases; however, there is no ideal treatment
Osteolytic · Osteosclerotic that can offer a complete cure. Clinical treatment
and supportive care in patients with bone metas-
Y.-S. An (*) tasis mainly focus on reducing metastatic bone
Department of Nuclear Medicine and Molecular
pain, improving the patient’s quality of life, and
Imaging, Ajou University School of Medicine,
Suwon, Republic of Korea increasing life expectancy.
e-mail: aysays@aumc.ac.kr
S.-O. Yang
of Radiological and Medical Sciences, Busan,
Republic of Korea
e-mail: soyang@dirams.re.kr
https://doi.org/10.1007/978-981-19-2677-8_18
218 Y.-S. An and S.-O. Yang
18.2 Diagnosis NaF bone PET can obtain high-resolution images

compared to bone scans and, in particular, has the
Assessing bone metastasis in cancer patients advantage of acquiring 3D images; therefore, it
using imaging tools is an essential element in can be superior to bone scan in evaluating bone
establishing a patient’s treatment plan and pre- metastasis [8]. Currently, it is not widely used
dicting prognosis. In the field of nuclear medicine, because of its weakness compared to bone scans
bone scans using bone-seeking radiopharmaceu- in terms of cost. However, bone PET is expected
ticals (99mTc-MDP, 99mTc-DPD, and 99mTc-HDP) to be more widely used clinically because it is
and 18F-FDG PET reflecting glucose metabolism more convenient for patients than bone scan
of metastatic sites are currently widely used in because the waiting time from radiopharmaceuti-
clinics to evaluate metastatic bone lesions. cal injection to image acquisition in bone PET is
Bone scan is the most commonly used clini- shorter than bone scan (1 h versus 3–4 h).
cal nuclear medicine imaging method for evalu-
18
F-FDG PET is widely used clinically to
ating bone metastasis in patients with various evaluate distant metastasis to various organs,
cancers (including breast, stomach, lung, and including the bone in cancer patients. It is gen-
prostate cancer). This imaging tool focuses on erally known that 18F-FDG PET shows bet-
the fact that osteoblastic (bone-forming) activ- ter diagnostic performance than bone scans in
ity occurs actively at the site of bone metasta- evaluating bone metastasis [9]. However, in the
sis, which can show hot uptake of bone-seeking case of osteosclerotic metastasis, the degree of
radiopharmaceuticals. Bone metastasis is known
18
F-FDG uptake may be low, and in this case, it
to predominantly occur in the axial skeleton might be necessary to evaluate the lesion com-
(spine, pelvis, skull, and ribs) where red bone plementarily by performing a bone scan [10].
marrow is widely distributed [6]; therefore, this In particular, when evaluating the response to
area should be carefully examined when read- chemotherapy, it is thought that evaluating the
ing a bone scan. In the case of extensive bone viability of the lesion on 18F-FDG PET rather
metastasis, it may involve the appendicular skel- than the activity of the metastatic lesion remain-
eton and may appear as a superscan. In addition, ing on the bone scan is better for predicting the
some metastases could be found as a single lesion patient’s prognosis [11].
in an unexpected area (e.g., single metastasis of When evaluating bone metastases using
the sternum in breast cancer); therefore, cau- nuclear medicine imaging, it is essential to con-
tion is required when evaluating bone scans. In sider the patient’s current treatment status. If a
detecting bone metastases, bone scans are gener- patient underwent imaging studies during chemo-
ally known to have high sensitivity but relatively therapy and/or hormone therapy, a flare phenom-
low specificity [6, 7]. Therefore, if metastasis is enon that may appear as if the bone metastasis
suspected on a bone scan, it may be necessary to has temporarily worsened may be observed. If the
obtain further images such as computed tomog- patient’s current clinical information is not prop-
raphy (CT), magnetic resonance imaging (MRI), erly understood, it may be mistakenly judged that
or 18F-fluorodeoxyglucose (18F-FDG) positron metastasis had progressed. The flare phenom-
emission tomography (PET) to evaluate metasta- enon is known to occur in both bone scan [12]
sis. In addition, a bone scan has a limitation in and 18F-FDG PET [13], and this is a factor that
that lesions may be missed in cases of predomi- can predict a good prognosis for patients. When
nantly osteolytic (bone destructive) metastatic reading nuclear medicine images, we must fully
bone lesions that do not have increased osteo- understand the patient’s clinical information.
blastic activity. In this chapter, we would like to introduce
Bone PET using 18F-NaF, a bone-seeking cases in which physicians should carefully con-
radiopharmaceutical that emits positrons, can sider when reading nuclear medicine images to
also be used to evaluate bone metastasis. 18F- evaluate bone metastases.
18 Metastatic Musculoskeletal Tumors 219
rib observed on a previous bone scan was more

Teaching Points likely to be a benign posttraumatic change than
• Superscan is a finding suggestive of metastasis (Fig. 18.2a). The patient underwent a
extensive metastasis. repeat bone scan after 3 months, and as a result,
• The possibility of metastasis should be multiple hot uptake lesions were newly observed
considered for hot uptake lesions with a in the skull, L2 spine, and both ilium, all of which
linear pattern of the rib. were likely metastases (Fig. 18.2c). The linear
• In the case of bone scans in breast can- pattern of hot uptake in the left posterior third rib
cer patients, metastasis should be sus- was still observed, indicating a metastatic pat-
pected even with a single lesion of the tern, but focal hot uptakes in the right anterior
sternum. seventh and posterior ninth ribs were most likely
• 18F-sodium fluoride (18F-NaF) PET/CT due to a benign posttraumatic change. Another
can detect bone metastases more sensi- notable lesion was the right humeral shaft lesion,
tively than bone scan. which showed an increased uptake activity pat-
• When reading a bone scan or 18F-FDG tern during the follow-up scan. Eventually, this
PET/CT in a patient with bone metasta- lesion caused a pathologic fracture during che-
sis, be aware of the patient’s current motherapy and was pathologically confirmed as
treatment status, and be mindful of the metastasis by operation. In this case, the linear
possibility of a flare phenomenon. hot pattern of rib lesions should be suspected
• Non-18F-FDG-avid osteosclerotic bone as metastasis, and further evaluation should be
metastasis lesions may consistently strongly considered in cancer patients.
appear as hot uptake lesions on bone
scan after treatment, but this may sug- Case 18.3
gest a good prognosis. A single hot uptake in the sternum was found in
a 39-year-old woman diagnosed with left breast
cancer during a periodic follow-up of bone
Case 18.1 scans to evaluate bone metastasis (Fig. 18.3a).
A 78-year-old woman diagnosed with advanced The patient did not have any previous history of
gastric cancer visited our department to evaluate trauma; hence, 18F-FDG PET/CT was addition-
bone metastasis and underwent a bone scan. A ally performed, and hot uptake of 18F-FDG in the
diffuse pattern of hot uptake lesions was observed sternum (Fig. 18.3b, d and e) was accompanied
in the thoracic and lumbar spines, both ribs, pel- by an osteolytic lesion on CT image (Fig. 18.3c).
vic bones, and femur on the patient’s bone scan, Additional metastatic lesions were found in the
whereas the bilateral kidneys and soft tissue left supraclavicular lymph node and liver on 18F-
activity were almost nonexistent (Fig. 18.1). This FDG PET/CT (Fig. 18.3b). It is known that a hot
finding is reasonable for superscans, suggesting uptake of the sternum in the bone scan can be
extensive metastasis. a non-specific finding, but in the case of breast
cancer, a single metastasis of the sternum should
Case 18.2 be considered and must be carefully evaluated.
A 59-year-old woman diagnosed with left
breast cancer underwent periodic bone scans to Case 18.4
evaluate bone metastasis. During her bone scan A 50-year-old woman who was diagnosed with
follow-up every 6 months after surgery and che- right breast cancer 4 years prior and was under-
motherapy, a linear pattern of hot uptake lesion going follow-up after mastectomy and chemo-
on the left posterior third rib and a faintly hot therapy was suspected to have bone metastases.
uptake lesion on the right humeral shaft area The patient underwent a bone scan, and the
were newly noted (Fig. 18.2b). The focal pat- bone scan showed focal hot uptakes on the right
tern of hot uptakes in the right posterior ninth ischium, upper cervical spine, and C7 spine,
Fig. 18.1 Extensive

diffuse hot uptakes were
observed in the axial
skeleton and femur on
bone scan, but neither
both kidneys (asterisks)
nor soft tissue activity
was observed
suggesting a possible metastasis (Fig. 18.4a). metastasis. In this case, we were able to identify
For a more detailed evaluation, 18F-NaF PET/ more metastatic lesions on 18F-NaF PET/CT than
CT performed 2 weeks later showed multiple on a bone scan.
hot uptakes in the left parietal bone; C2, C7, and
L1 spine; left acetabulum; and right ischium, all Case 18.5
of which were highly suggestive of metastases A 46-year-old woman diagnosed with right breast
(Fig. 18.4b). In the body region of the L1 spine, cancer with bone metastases underwent a bone
a sclerotic change lesion was also found on CT, scan to evaluate bone metastases. At the time of
and hot uptake was also observed on PET in the diagnosis of bone metastasis, the patient showed
same region (Fig. 18.4c–e) which suggested a hot uptake in the lower cervical spine; T7, T9,
a b c
Fig. 18.2 (a) The focal hot uptake lesion was observed in in the skull, L2 spine, and both ilium on a bone scan per-
the right posterior ninth rib, suggesting posttraumatic formed 3 months later (green arrowheads). The linear pat-
change (blue arrowhead). (b) On a bone scan performed tern of hot uptake in the left posterior third rib was still
6 months later, the hot lesion of the right posterior ninth observed (red arrowhead), and focal hot uptakes in the
rib was still seen without significant change (blue arrow- right anterior seventh and posterior ninth ribs (blue arrow-
head), and hot uptake lesions were newly appeared on the heads) were noted. The right humeral shaft lesion showed
left posterior third rib (red arrowhead) and the right an increased uptake activity during follow-up (arrows)
humeral shaft (arrow). (c) New hot uptakes were observed
a b c
Fig. 18.3 (a) A hot uptake lesion is observed in the ster- image], d [PET image], and e [PET fusion with CT]).
num on the bone scan (red arrowhead). (b–e) On 18F-FDG Also, abnormal hypermetabolic lesions in the left supra-
PET/CT, hot uptake with osteolytic lesion was observed clavicular lymph node and liver were noted (blue arrow-
in the sternum (red arrowhead in b [MIP image], c [CT head in b)
a c
b
Fig. 18.4 (a) Focal hot uptakes were seen on the right image]). The body of L1 spine lesion showed hot uptake
ischium, upper cervical spine, and C7 spine in bone scan with sclerotic change on the transaxial images (arrows in
(red arrowheads). (b–e) Multiple hot uptakes were c [CT], d [PET], and f [PET/CT fusion image]). The hot
observed in the left parietal bone; C2, C7, and L1 spine; uptakes observed in the L4 and L5 spine and mandibles
left acetabulum; and right ischium on 18F-NaF PET/CT were attributed to benign degenerative change and dental
(arrows in b [maximum intensity projection (MIP) problems, respectively (blue arrowheads in b)
T10, and T12 spine; left posterior tenth rib; and Case 18.6
both ischium on a bone scan (Fig. 18.5a), all of A 63-year-old woman who underwent mastec-
which were metastatic lesions. A follow-up bone tomy for left breast cancer visited our department
scan was performed 3 months after the start of for evaluation of bone metastasis and underwent
chemotherapy. In most of the lesions seen in the 18
F-FDG PET/CT. On initial 18F-FDG PET/CT
previous image, activity and extent were over- in this patient, hot uptake was observed in T5,
all increased, and there were newly appeared hot L2 spine, and right ilium, showing metastasis
uptake lesions in the sternum, L5 spine, both ilium, (Fig. 18.6a). The patient started chemotherapy,
right scapula, and right femoral head (Fig. 18.5b). and on 18F-FDG PET/CT performed 3 months
The patient underwent a bone scan 6 months after during chemotherapy, multiple hot uptake
the completion of chemotherapy. As a result, hot lesions were observed in the skull, C-T-L spine,
uptakes of T-spines, left posterior tenth rib, and both pelvic bones, ribs, right distal clavicle, and
both ischia still remained, but overall activity left femur, all of which were metastatic lesions
and extent decreased compared to before, and (Fig. 18.6b). Compared with previous images,
other previously seen lesions almost disappeared most of the lesions showed increased activity
(Fig. 18.5c). In this patient, a temporary worsening and extent, and many newly appearing metastatic
of bone scans performed during chemotherapy is lesions were also identified. The patient under-
referred to as the flare phenomenon. Since this is went 18F-FDG PET/CT follow-up examination
a phenomenon that occurs temporarily when bone 4 months after the end of chemotherapy, and
metastasis lesions respond to chemotherapy, it is the 18F-FDG uptake in multiple metastatic bone
necessary to evaluate whether a patient is undergo- uptake lesions that had been seen in a previous
ing treatment when reading a bone scan. study was generally reduced, showing improve-
a b c
Fig. 18.5 (a) Bone scan showed multiple hot uptake uptake lesions in the sternum, L5 spine, both ilium, right
lesions in the lower cervical spine; T7, T9, T10, and T12 scapula, and right femoral head were newly appeared (blue
spine; left posterior tenth rib; and both ischium, suggesting arrowheads). (c) Hot uptakes in T-spines, left posterior
metastasis (red arrowheads). (b) A follow-up bone scan tenth rib, and both ischia were remained with overall activ-
during the chemotherapy revealed that activity and extent ity and extent decreased than previous image (red arrow-
were overall increased in most of the lesions seen in the heads), and other previously seen lesions disappeared on
previous image (red arrowheads), and metastatic hot bone scan after the completion of chemotherapy
a b c
Fig. 18.6 (a) Hypermetabolic lesions were noted in T5, with new lesions, compared to previous image (arrow-
L2 spine, and right ilium on initial 18F-FDG PET/CT heads). (c) Only mild hypermetabolic lesion in the L2
(arrowheads). (b) 18F-FDG PET/CT during chemotherapy spine (arrowhead) was remained on 18F-FDG PET/CT
revealed multiple hot uptakes in the skull, C-T-L spine, after the end of chemotherapy
both pelvic bones, ribs, right distal clavicle, and left femur
ment with only remaining mild hypermetabolic Case 18.7

lesion in the L2 spine (Fig. 18.6c). This can be A 70-year-old woman diagnosed with left
interpreted as a flare phenomenon that can appear breast cancer who underwent mastectomy vis-
temporarily aggravated during chemotherapy in ited our department to evaluate bone metas-
patients with bone metastases. The flare phenom- tasis and underwent a bone scan. On a bone
enon is mainly observed in bone scans, but as in scan, hot uptake lesions were observed on the
this case, this phenomenon can also be seen in sternum and lower cervical spine (Fig. 18.7a),
18
F-FDG PET. It should be noted that there may and MRI was performed for further evaluation.
also be a metabolic flare phenomenon that may MRI showed signs indicative of metastasis in
appear to be temporarily exacerbated in response the sternum and manubrium (Fig. 18.7b), and
to therapy. benign endplate degeneration of cervical spines
a b c
e
d
Fig. 18.7 (a) Hot uptakes were noted in the sternum (red scan performed after the completion of chemotherapy (red
arrowhead) and lower cervical spine (blue arrowhead) on arrowhead). (d) 18F-FDG PET/CT showed osteosclerotic
bone scan. (b) MRI showed signs indicative of metastasis lesions in the sternum on CT scan (arrow in e and g) with-
in the sternum and manubrium (red arrowheads). (c) A hot out significant 18F-FDG activity (d and f)
uptake lesion in the sternum was still observed on bone
a b c
d e
Fig. 18.8 (a) There were osteosclerotic lesions in T9 and FDG PET/CT. (d and e) 18F-NaF PET/CT revealed intense
T11 spines on CT image (arrows). (b) Intensely hot uptake hot uptakes in T9 and T11 spines (arrowheads in d [MIP
lesions were observed in T9 and T11 spines on bone scan image] and e [PET/CT fusion images])
(arrowheads). (c) There were no abnormal findings on 18F-
was observed (image not shown). The patient viability of metastatic lesions is lost in response
underwent chemotherapy, and a hot uptake to chemotherapy, which can suggest a good
lesion of the sternum still remained on the bone prognosis.
scan performed 7 months after the end of the
chemotherapy (Fig. 18.7c), but 18F-FDG PET/ Case 18.8
CT performed concurrently showed osteoscle- Osteosclerotic lesions were found on the T9
rotic lesions in the sternum on CT scan without and T11 spines on a bone CT (Fig. 18.8a) of
significant 18F-FDG activity (Fig. 18.7d–g). As a 50-year-old male patient who underwent sur-
such, in the non-18F-FDG-avid osteosclerotic gery 3 months ago for sigmoid colon cancer,
bone lesions, which showed a hot uptake only and nuclear medicine examinations were per-
in the bone scan, it can be considered that the formed for further evaluation of metastasis.
In the patient’s bone scan, intense hot uptakes Oncol Rev. 2017;11(1):321. https://doi.org/10.4081/
were observed on the T9 and T11 spines, oncol.2017.321.
7. Min JW, Um SW, Yim JJ, Yoo CG, Han SK, Shim
which are the same sites as the lesions seen YS, et al. The role of whole-body FDG PET/CT, Tc
on CT, suggesting metastasis (Fig. 18.8b). 99m MDP bone scintigraphy, and serum alkaline
The patient also underwent 18F-FDG PET/CT, phosphatase in detecting bone metastasis in patients
and no abnormal findings were accompanied with newly diagnosed lung cancer. J Korean Med
Sci. 2009;24(2):275–80. https://doi.org/10.3346/
(Fig. 18.8c). Additional bone PET/CT using jkms.2009.24.2.275.
18
F-NaF showed intense hot uptakes in the T9 8. Bastawrous S, Bhargava P, Behnia F, Djang DS,
and T11 spines, which was consistent with the Haseley DR. Newer PET application with an old
bone scan findings (Fig. 18.8d and e). In this tracer: role of 18F-NaF skeletal PET/CT in onco-
logic practice. Radiographics. 2014;34(5):1295–316.
case, we showed that osteosclerotic metastasis https://doi.org/10.1148/rg.345130061.
is indicated by hot uptake on bone scan or 18F- 9. Chang CY, Gill CM, Joseph Simeone F, Taneja AK,
NaF PET, but accumulation of 18F-FDG may be Huang AJ, Torriani M, et al. Comparison of the diag-
absent. nostic accuracy of 99 m-Tc-MDP bone scintigraphy
and 18 F-FDG PET/CT for the detection of skeletal
metastases. Acta Radiol. 2016;57(1):58–65. https://
doi.org/10.1177/0284185114564438.
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T, Sugita D, et al. (18)F-FDG PET/CT for diagnosis
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WH. Distribution pattern of metastatic bone dis- lesions: comparison with bone scintigraphy. Asian
ease. A need for total body skeletal image. JAMA. Spine J. 2013;7(2):96–103. https://doi.org/10.4184/
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Hoshino A, Rodrigues G, et al. Pre-metastatic YS. Prognostic utility of FDG PET/CT and bone
niches: organ-specific homes for metastases. Nat Rev scintigraphy in breast cancer patients with bone-only
Cancer. 2017;17(5):302–17. https://doi.org/10.1038/ metastasis. Medicine (Baltimore). 2017;96(50):e8985.
nrc.2017.6. https://doi.org/10.1097/MD.0000000000008985.
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the bone in cancer metastasis. J Bone Miner Res. s00259-010-1576-0.
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jbmr.3618. John J. Metabolic flare phenomenon on 18
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Marrow Replacement Disorders
19
Joo Hyun O and Ie Ryung Yoo
Abstract bone marrow (BM), leading to the overproduc-

tion of the intact immunoglobulin molecule
Disorders of the plasma cells and lymphoid
M-protein or immunoglobulin free light chains
progenitor cells will involve the bone marrow
kappa or lambda [1–3]. MM is the second most
as well as lymphoid tissues. PET/CT utilizing
common hematological malignancy, rare before
18
F-fluorodeoxyglucose (FDG) is suitable for
the age of 40, but with increasing incidence with
detection of both intramedullary and extra-
age. There is a slight male predominance [3].
medullary diseases due to the capability of the
In majority of the MM cases, monoclonal gam-
FDG PET/CT to survey the whole body and
mopathy of undetermined significance (MGUS)
the high FDG uptake demonstrated by most of
or smoldering multiple myeloma (SMM) pre-
the aggressive tumors.
cedes. MGUS and SMM are not associated with
end-organ damage. On the other hand, overt
Keywords
MM manifests as hypercalcemia, renal failure,
Bone marrow · Multiple myeloma anemia, or bone lesions known as the CRAB
Lymphoma · Leukemia features [4–6]. During the past decade, new bio-
logic drugs were developed, and more effective
multidrug combinations were applied, and these
19.1 Plasma Cell Disorders remarkable advances have led to improved prog-
(Multiple Myeloma) nosis for the patients [7].
19.1.1 Clinical Findings

19.1.2 Image Findings
Multiple myeloma (MM) is a proliferative dis-
order of cytogenetically heterogeneous clonal Bone involvement has very important clinical
plasma cells characterized by the autonomous significance in MM, since bone damage is the
proliferation of monoclonal plasma cells in the critical cause of impaired quality of life, morbid-
ity, and mortality [8]. For such reason, the role of
imaging for detection of bone disease in MM is
J. H. O · I. R. Yoo (*)
Department of Nuclear Medicine, Seoul St. Mary’s clinically important. The International Myeloma
Hospital, The Catholic University of Korea, College Working Group (IMWG) diagnostic criteria from
of Medicine, Seoul, Republic of Korea 2014 states that more than one focal lesion on
e-mail: ojoohyun@songeui.ac.kr; magnetic resonance imaging (MRI) and more
iryoo@catholic.ac.kr
https://doi.org/10.1007/978-981-19-2677-8_19
228 J. H. O and I. R. Yoo
than one osteolytic lesion on computed tomogra- sensitivity can be lower for diffuse pattern, and
phy (CT) scan meet the criteria for bone damage differentiation from reactive BM hyperplasia
requiring treatment; CT here means either the can be problematic. The pitfalls of FDG PET/
whole-body CT (WBCT) or the CT portion of CT include false-positive results due to fracture,
the positron emission tomography (PET)/CT [2]. bone remodeling, BM biopsy or postoperative
Pre-therapy imaging has traditionally included changes, red marrow hyperplasia/expansion, or
whole-body X-ray (WBXR) and WBCT. Typical inflammation/infection. Lesions 5 mm or less in
finding is punched-out osteolytic lesion without size, especially when located in the skull, dif-
sclerotic margin. WBCT is superior to the WBXR fuse disease involvement, and non-FDG-avid
for assessing risk of fracture or lesion character- plasma cell may be causes of false-negative
ization but does have higher radiation exposure. findings [4, 19]. Mesguich et al. recommended
That the osseous lytic lesions persist over time is different FDG PET/CT assessment criteria for
the limitation of both modalities [9–11]. pre-treatment and post-treatment cases [4].
MRI is far superior for assessing the extent The modified criteria adapted by IMWG com-
of bone marrow disease compared to X-ray pared focal FDG uptake to the physiologic bone
and CT. Typical finding is hypointensity on marrow or liver uptake prior to treatment, but
T1-weighted image and slightly hyperintense considered only lesions showing uptake higher
signal on T2 sequence. Fat suppression sequence than the liver to be significant post-treatment.
is utilized to overcome the high signal intensity Diffuse BM uptake pattern should be considered
of the normal bone marrow [11, 12]. For diffuse significant when the intensity is higher than the
type of MM, MRI can be the superior choice of liver uptake and requires correlation with MRI
modality compared to PET, but the persistent findings [19] (Case 19.2). Incorporation of FDG
signal change is a limitation for use in response PET/CT is recommended for routine diagnostic
assessment [13–15]. With the more recent use of work-up of MM. Especially when the WBXR
diffusion-weighted imaging (DWI), better detec- is negative and whole-body MRI is unavailable,
tion of diffuse infiltration of the bone marrow and FDG PET/CT is useful for distinguishing active
differentiation of active and treated bone marrow MM from SMM.
lesions are feasible [16]. Solitary plasmacytoma may manifest as single
PET/CT utilizing 18F-fluorodeoxyglucose lytic bone lesion or soft tissue mass and can be
(FDG) is suitable for detection of both intra- diagnosed only when systemic BM plasma cell
medullary and extramedullary diseases due to infiltration (<10%) and end-organ damage are
the capability of the FDG PET/CT to survey the absent [20] (Case 19.3). When solitary plasma-
whole body and the fusion of both the functional cytoma is suspected, functional imaging tech-
and anatomical imaging modalities. FDG PET/ nique is recommended for accurate assessment of
CT can be valuable in the assessment of disease tumor extent and exclusion of additional occult
burden and distinguishing metabolically active lesions. Particularly when whole-body MRI is
and inactive lesions [4, 13] (Case 19.1). The unavailable, FDG PET/CT has a clear role [19,
pooled sensitivity of FDG PET/CT for detect- 21]. In addition, FDG PET/CT is a useful tool
ing BM involvement in MM is reported as 61% for predicting the prognosis, early assessment of
and 91% and the pooled specificity 69% and therapeutic response, and detection of minimal
94% [17, 18]. The sensitivity and specificity for residual disease.
detecting extramedullary disease are reported to
be 96% and 78%, respectively [17]. The FDG Case 19.1
uptake in MM may be focal, multifocal, or dif- A 63-year-old man was diagnosed with relapsed
fuse in pattern, and abnormality needn’t always MM, with multifocal hypermetabolic intramed-
be present in the corresponding CT images. The ullary and extramedullary lesions. FDG PET/CT
19 Marrow Replacement Disorders 229
a b e
c f
d g
Fig. 19.1 Maximum intensity projection (MIP) image of extension from L4 vertebral lesion (short arrow) was seen
FDG PET/CT (a) showed multifocal hypermetabolic on axial fusion PET/CT image (d). Axial fusion PET/CT
intramedullary and extramedullary lesions. In axial fusion images (e–g) showed multifocal extramedullary disease in
PET/CT (b) and CT (c) images, multifocal hypermeta- left perinephric area, right scrotal sac, and LN of left ret-
bolic lesions were noted in sacrum and pelvic bones with- ropharyngeal region (arrows)
out corresponding CT abnormality. Paramedullary
can accurately assess the extent of intramedul- 19.2 Lymphoma and Leukemia
lary lesions as well as extramedullary lesions in
unusual locations that are difficult to detect by 19.2.1 Clinical Findings
anatomical imaging (Fig. 19.1).
According to the revised World Health
Case 19.2 Organization classification of neoplasm of the
A 61-year-old man presented with acute renal hematopoietic and lymphoid tissues, lymphoma
injury and hypercalcemia. Following BM can be classified into more than 90 subtypes
biopsy, initial work-up for MM was performed depending firstly on the cell origin—mature B
(Fig. 19.2). cells, T cells, and natural killer cells [22]. The
most common aggressive lymphoma worldwide
Case 19.3 is diffuse large B cell lymphoma (DLBCL),
A 63-year-old man diagnosed with solitary plas- and bone marrow involvement is seen in up to
macytoma. Because whole-body MRI is often not 11%–25% of DLBCL cases [23, 24]. With bone
available in daily practice, FDG PET/CT is used involvement, the lymphoma stage becomes IV,
to confirm the diagnosis of solitary plasmacytoma the international prognostic index (counting
with advantage of whole-body survey (Fig. 19.3). toward number of involved extra-nodal sites)
a c d h
b f
Fig. 19.2 Skull lateral (a) and pelvis AP (b) radiographs present in the rib cage, sternum, and right clavicle,
showed multiple small osteolytic lesions without scle- which are mostly accompanied by fracture findings in
rotic rim. FDG PET/CT MIP (c) image shows diffuse the CT portion (arrows) (d–g). There were diffuse and
bone marrow activity slightly more intense than the focal BM lesions on fat-saturated T2-weighted whole
liver uptake. Multiple focal FDG uptake lesions are spine sagittal MRI (h)
a c f
b
e
Fig. 19.3 MRI (a, b) showed large mass with T2 high CT (d) and CT (e) images showed large osteolytic lesion
and T1 intermediate signal intensity in sacrum (arrows). with intense heterogeneous FDG uptake and paramedul-
On posterior view of whole-body bone scintigraphy with lary extension. MIP image (f) of PET/CT showed no evi-
99m
Tc-HDP (c), photon defect area with rim activity was dence of other intramedullary and extramedullary lesion
noted in sacrum (short arrows). Axial fusion FDG PET/ nor diffusely increased marrow activity
score increases, and worse prognosis and out- tinguish regressed but viable lymphoma/leuke-
come are expected. Leukemia is by definition mia involvement of the bones from benign bone
malignancy with extensive involvement of the marrow hyperplasia.
bone marrow, and bone marrow biopsy becomes It should be noted that bone involvement is
essential for accurate diagnosis and subtype not limited to the axial skeleton or long bones.
classification. Lymphoma and leukemia can be present in any
Clinically, the gold standard for diagnosis bone, from skull to phalanges of feet.
of bone marrow involvement has been biopsy The radiology findings could be nonspecific
obtained from posterior iliac crest. However, it and may be normal, lytic, sclerotic, or mixed in
is now widely known that bone marrow biopsy the plain X-ray and CT [28]. Though MRI is not
from iliac bone alone can present false-negative usually performed for the purpose of detection
results. Conversely, FDG PET/CT can be nega- of lymphoma or leukemia involving the bones,
tive for abnormal bone uptake, while the bone the high resolution of MRI images allows more
marrow biopsy is positive. Such discordant find- accurate assessment of extent of disease involve-
ings between the two tests are not uncommon, ment in structures such as spinal cord and head
and iliac bone marrow biopsy alone cannot fully and neck region. Involved bone marrow may
represent the wide spectrum of tumor behavior show low signal intensity on T1 and high signal
[25–27]. In cases with fibrosis of the bone mar- on T2 [29].
row, aspiration biopsy may not be feasible, and
bone biopsy could be required. Case 19.4
A young man with acute lymphocytic leukemia
initially achieved complete remission follow-
19.2.2 Image Findings ing chemotherapy and allogeneic bone marrow
transplant. However, 2 years after the transplant,
Depending on the subtype of lymphoma and the patient started experiencing pain in the right
leukemia, FDG uptake can vary from impercep- hip. The radiating pain without sensory change
tible to remarkably intense. Most of the aggres- worsened over a couple of weeks, and the patient
sive forms demonstrate high FDG avidity. visited the emergency room due to severe sharp
There is no objective FDG uptake threshold or pain that kept him awake at night. The patient
imaging criteria for determining bone involve- denied any recent fall or excessive exercise.
ment of lymphoma or leukemia. Most readers The subsequent image findings were consistent
would consider intense discrete FDG uptake in with leukemic involvement in the right femur.
the bones to be positive for malignant involve- Following therapy with anti-CD22 monoclonal
ment, in the absence of obvious signs of benign antibody and radiotherapy, the patient is in remis-
findings such as fracture or post-surgical remod- sion (Fig. 19.4).
eling (Case 19.4). Leukemia can often appear
as diffuse intense FDG activity throughout the Case 19.5
axial and appendicular skeleton before treat- A 49-year-old man who was initially diagnosed
ment, similar to the bone marrow uptake follow- with nodal marginal zone lymphoma 2 years ago
ing growth stimulating factor, or multiple focal received chemotherapy and reached complete
FDG uptake areas resembling bone metastases remission. During surveillance period, palpable
(Case 19.5). Lymphoma and leukemia with nodes were discovered in the axillary area, and
known bone marrow involvement can also show restaging work-up was performed. Biopsy from
FDG uptake similar to the liver or even lower. the liver revealed diffuse large B cell lymphoma,
After chemotherapy, it becomes difficult to dis- activated B-cell type (Fig. 19.5).
a d e
Fig. 19.4 No abnormal findings were noted to account diminished FDG uptake, but focal FDG uptakes newly
for the pain in the X-ray of the hips (a). Coronal view MRI developed in multiple bones including right mandible, left
of the hips showed intramedullary bone lesion in right humerus, left scapula, left iliac bone, and left femur (d,
proximal femur with circumferential periosteal reaction arrowheads). FDG PET/CT performed after inotuzumab
consistent with leukemic infiltration (b). Fusion PET/CT and radiotherapy shows markedly diminished FDG
showed intense FDG uptake in the corresponding femoral uptakes in multiple bone sites (e)
lesion (c). After radiotherapy the right femur lesion shows
Case 19.6 of lower leg showed swelling and redness sug-

A 45-year-old patient started experiencing fre- gestive of cellulitis. Initial MRI findings were
quent gum bleeding and fatigue since 1 month suggestive of cellulitis and myositis with abscess.
ago. The patient also noticed black and blue Biopsy confirmed myeloid sarcoma from under-
marks more often throughout the body. The skin lying acute myeloid leukemia (Fig. 19.6).
a b c
d e
Fig. 19.5 There are multiple focal FDG uptakes through- Follow-up FDG PET/CT performed after chemotherapy
out the axial and appendicular skeleton, as well as the shows good response, without discrete FDG uptake in the
liver and the nodal stations in the MIP image (a). The interim MIP image (c). There are mild FDG uptakes in the
FDG uptake pattern is heterogeneous in the iliac bones ribs in the interim PET/CT image (arrowheads in c, d),
(b), and depending on the position of the needle, the corresponding to fracture line in the CT portion (e)
biopsy could yield false-negative result, as in this patient.
Teaching Points • In patients with suspected solitary plas-

• The bone marrow is involved in myeloid macytoma, FDG PET/CT is indispens-
and lymphoid neoplasms. able for confirming the diagnosis, if
• CT or MRI is often used for preliminary whole-body MRI is unavailable.
assessment of bone lesions, but FDG • FDG PET/CT has complimentary role
PET/CT has the advantage of allowing to bone marrow biopsy and is a useful
assessment of multiple bones. tool for staging, monitoring response to
• FDG PET/CT shows high sensitivity for therapy, and restaging in lymphoma/
detection of extramedullary lesions. leukemia.
• FDG PET/CT is a valuable tool for both
newly diagnosed and relapsed multiple
myeloma.
• FDG PET/CT is the preferred modality
for monitoring response to therapy in
multiple myeloma patients.
a d
Fig. 19.6 Photograph of lower leg shows erythema and Biopsy confirmed myeloid sarcoma in left lower leg,
purpura at lower level (a). Diffuse reticular thickening which shows intense FDG uptake even after antibiotics
with enhancement of subcutaneous layer, patchy edema therapy (c). The MIP images show additional extramedul-
with enhancement of peroneal longus and soleus muscles, lary involvement in the muscles of left thigh and both
and peripherally enhancing nodular lesion were sugges- lungs, as well as diffuse bone marrow involvement (d)
tive of cellulitis and myositis with abscess on MRI (b).
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Part VI
Miscellaneous Features in Musculoskeletal
Nuclear Imaging
Soft Tissue Uptake of Bone Scan
Agents 20
Yun Young Choi and Soo Jin Lee
Abstract 20.1 Heterotopic Ossification
Unexpected soft tissue uptake of bone scan Heterotopic new bone formation is the presence
agents is often a source of uncertainty and of bone in soft tissue, where it does not normally
doubt to inexperienced physicians, but some- exist. Vast majority of conditions are acquired fol-
times provides information that enhances the lowing trauma, and rarely it can be congenital
diagnostic value of the study. This chapter (e.g., myositis ossificans progressiva). The
reviews several remarkable cases showing soft pathogenetic mechanism is believed to be due to
tissue uptake associated with extraosseous het- transformation of certain primitive cells of mes-
erotopic new bone formation, soft tissue calci- enchymal origin in the connective tissue septa
fication, abnormal intracellular flux of ionic within muscles into bone-forming cells [1]. Bone
calcium after damage to cell membrane integ- scan is more sensitive than plain film in detecting
rity, and expansion of the interstitial fluid heterotopic ossification. Three-phase bone scan
component. can be used for determining the optimum time for
surgical removal. As heterotopic bone formation
Keywords progresses from immature to mature, all the three
phases of bone scan typically show progressive
Heterotopic ossification · Dystrophic calcifi- decreased uptake, leading to steady state over a
cation · Metastatic calcification · Tumoral period of 2–3 months. Then, it could minimize the
calcinosis · Rhabdomyolysis · Bone scan · risk of recurrence after excision [2].
Bone SPECT/CT
Case 20.1
Evolution of heterotopic ossification after trauma
(Fig. 20.1).
Y. Y. Choi (*) 20.2 Soft Tissue Calcification

Department of Nuclear Medicine, Hanyang University
College of Medicine, Seoul, Republic of Korea Besides heterotopic ossification, major types of
e-mail: yychoi@hanyang.ac.kr extraosseous calcification include dystrophic cal-
S. J. Lee cification and metastatic calcification.
Department of Nuclear Medicine, Hanyang University
https://doi.org/10.1007/978-981-19-2677-8_20
240 Y. Y. Choi and S. J. Lee
A B
Fig. 20.1 A 33-year-old man with the right acetabular of the focal intense uptake lesions detected immediately
fracture. Bone scan taken 2 weeks after trauma shows after trauma (C, upper row) and 1 year later (D, lower
focal intense uptake mainly in the posterior aspect of right row): majority of the uptake lesion became mature hetero-
acetabulum (A), which is markedly decreased after topic bone (open arrows), and part of the lesion has been
1 year (B). Serial SPECT/CT images show the evolution resolved (arrow)
20.2.1 Dystrophic Calcification neoplasm, or necrosis. Increased calcium-

binding capacity of the exposed denatured pro-
Dystrophic calcification involves the calcifica- teins of the injured cells which preferentially
tion of damaged tissue and occurs in the setting bind with phosphate ions, in turn react with
of normal serum calcium and phosphate level. calcium and form calcium deposits. Examples
Tissue damage might be from inflammation, include calcification in infarcted myocardium,
20 Soft Tissue Uptake of Bone Scan Agents 241
atheromas, amyloid tissue, and the center of 20.2.2 Metastatic Calcification

tumors [3].
Metastatic calcification is the calcification of via-
Case 20.2 ble, undamaged, normal tissue as a result of
Tumor uptake: dystrophic calcification hypercalcemia and/or hyperphosphatemia asso-
(Fig. 20.2). ciated with increased calcium phosphate product,
locally or systemically. This can be due to (1)
Case 20.3 metabolic abnormalities as renal failure, hypervi-
Foreign body uptake: dystrophic calcification of taminosis D, and hyperparathyroidism and (2)
paraffinoma (Fig. 20.3). increased bone demineralization from bone
Oblong soft tissue uptake in subcutaneous tumors or disseminated metastasis.
areas around both knees and calfs on SPECT/CT Tumoral calcinosis is a form of metastatic cal-
images (arrows in B-a & B-a′) are matched cification, which shows large, calcified, periar-
with soft tissue masses with spotty calcifications ticular soft tissue masses of calcium phosphate
on CT images (arrows in B-b & B-b′), proven to near the large joints such as hip, shoulder, and
be paraffinoma. The patient had a history of par- elbow, outside the joint capsule. This can be
affin injection decades ago. observed in the primary form (idiopathic, con-
A B a
Fig. 20.2 A 72-year-old woman with left shoulder pain. SPECT/CT images (B-a, white arrowheads), matched
Doughnut-shaped focal uptake is incidentally detected in with dystrophic calcification on non-enhanced CT image
the left upper abdomen (arrow) on whole-body bone (B-b, white arrowheads). The mass was surgically
scan (A). Abdominal CT taken on the next day shows gas- removed and proven to be malignant GIST. Careful evalu-
tric submucosal tumor. Curvilinear increased MDP uptake ation of soft tissue uptake made a contribution to early
is noted at the margin of gastric submucosal tumor on diagnosis of malignant tumor
A B a b
a’ b’
Fig. 20.3 An 88-year-old woman with right breast cancer and proximal legs on SPECT/CT images (arrows in a & a′)
shows incidentally detected soft tissue uptake along bilateral are soft tissue masses with spotty calcifications on CT
lower extremities on whole-body bone scan (A). Oblong images (arrows in b & b′), proven to be paraffinoma (B).
soft tissue uptake in subcutaneous areas around both knees The patient had a history of paraffin injection decades ago
genital) but also be found in various conditions since intracellular muscle protein is released and
including primary or secondary hyperparathy- excreted by dark-colored urine. Variable degrees
roidism, scleroderma, hypervitaminosis D, of muscle death cause abnormal influx of cal-
chronic renal failure on dialysis, etc [4]. cium ions into muscle cells after damage to cell
membrane integrity, which allows bone scan
Case 20.4 agents to form stable complexes inside muscle
Metastatic calcification: tumoral calcinosis in cells and results in variable degree of abnormally
secondary hyperparathyroidism due to end-stage increased uptake in damaged muscles shown on
renal disease undergoing dialysis (Fig. 20.4). bone scan. Rhabdomyolysis can lead to serious
complications such as renal failure [5].
20.3 Causes of Soft Tissue Uptake Case 20.5

Other than Calcification Various features of rhabdomyolysis are associ-
ated with causative factors: excessive physical
20.3.1 Rhabdomyolysis activity, chronic use of clutch, lying unconscious
on a hard surface under the influence of alcohol,
Rhabdomyolysis is a condition that follows mus- and drug induce, etc. (Fig. 20.5).
cle damage due to various causes including viral
or bacterial infection, certain drugs, alcohol Case 20.6
abuse, trauma, and excessive physical activity, Focal uptake in resolving hematoma after contu-
characterized by excess myoglobin in urine, sion of abdominal wall (Fig. 20.6).
A a
c d e
B
f g h
Fig. 20.4 A 66-year-old woman with hypercalcemia and nodules: two are posterior to thyroid upper pole (a, white
hyperphosphatemia. She had end-stage renal disease and arrows) and one is inferior to thyroid gland (b, white
underwent peritoneal dialysis for 13 years. Serum-intact arrow), suggestive of parathyroid hyperplasia. Multiple
PTH was elevated as high as 987.1 pg/ml (normal, periarticular uptake lesions are noted, especially involving
14–64 pg/ml), and secondary hyperparathyroidism was both shoulders and knees (arrows) on whole-body bone
suspected clinically. Parathyroid scan (A) shows multifo- scan (B). Shoulder SPECT/CT images show focal intense
cal nodular lesions revealing delayed washout on the uptake lesions around the right shoulder (c–e), which are
regional image of neck taken 2 h after Tc-99m MIBI proven to be mass-like calcifications outside the joint cap-
injection (arrows). SPECT/CT images show three hot sule (f–h) on CT images
a b
c d
Fig. 20.5 (a)–(c) Cases with severe exercise-induced 42-year-old man with weakness, especially right side, on
rhabdomyolysis with exercise-related muscle pain and the next day of heavy drinking and over-night sleep out-
dark-colored urine and elevated muscle enzyme and urine doors on a mountain rock (s-CK > 20,000; CK-MB, 42.8;
myoglobin. Areas of rhabdomyolysis shows focal u-myoglobin, 759.2). (f) A 35-year-old man, who is a
increased uptake lesions on whole-body bone scan images severe alcoholic with uremic encephalopathy and
(arrows). (a) A 24-year-old man with anterior thigh pain methicillin-sensitive S. aureus bacteremia, shows multifo-
after squat exercise 2 days ago, serum-creatine kinase cal rhabdomyolysis. Multiple factors could be concerned
(s-CK) > 20,000, urine-myoglobin 9478 (normal, 0–21). for causatives of rhabdomyolysis, but neuropsychiatric
(b) A 25-year-old man with both upper arm pain 2 h after medication was concerned for the causative factor clini-
exercise, s-CK > 20,000, urine myoglobin >3000. (c) A cally (s-CK, 53728; CK-MB, 233.4). (g) A 77-year-old
21-year-old man with back pain after kettlebell exercise man with diabetes nephropathy on hemodialysis for
2 days ago, s-CK > 20,000 urine myoglobin >1200. (d) A 3 years had drug-induced rhabdomyolysis. He had general
31-year-old man with clutch-induced rhabdomyolysis, weakness 3 weeks after administration of statin
due to a fracture of right foot 18 months ago. (e) A
e f

a b
Fig. 20.6 A 57-year-old woman was hit by a motorcycle left lower anterior abdominal wall on whole-body (a) and
a day before. She complained about left hip and elbow regional (b) images of bone scan, which is proven to be
pain. Linear increased soft tissue uptake is noted along the resolving hematoma on abdominal CT image (c)
20.3.2 Expansion of the Interstitial 20.3.3 Primary or Metastatic Tumor

Fluid Compartment Uptake Associated with
Tumor Hypervascularity
Another common mechanism of soft tissue
localization bone scan agents is associated Malignant tumors show various spectra of uptake
with expansion of interstitial fluid compart- ranges from ill-defined and barely detectable to
ment (e.g., lymphedema, ascites, pleural intense and sharply marginated. Multiple factors
effusion). may play the role in localization of bone scan
agents. Histologic evidence of calcium correlates
Case 20.7 most strongly with avid tracer uptake, but tumor
Expansion of the interstitial fluid compartment: vascularity also plays a secondary but important
lymphedema (Figs. 20.7 and 20.8) [5]. role [3, 6].
Case 20.8 Case 20.9

Expansion of the interstitial fluid compartment: Tumor uptake: neovascularization of hypervascu-
ascites (Fig. 20.9). lar tumor (Fig. 20.10).
a b
Fig. 20.7 Lymphedema of upper extremity in breast can- (a, arrow) is noted on whole-body bone scan. On lympho-
cer. A 51-year-old woman complained of swelling in her scitigraphy, non-visualization of normal lymphatic flow
right upper extremity. She had a history of right breast and skin backflow in right upper extremity (b, arrows),
cancer and underwent radiation therapy 4 years ago. suggestive of secondary lymphedema
Diffuse soft tissue uptake of swollen right upper extremity
Case 20.10 Case 20.11

Tumor uptake: hypervascular tumor with internal Unusual bowel uptake (Fig. 20.12).
necrosis (Fig. 20.11).
Case 20.12
Incidental uptake in bladder diverticulum
20.4 Artificial Uptake of Bone (Fig. 20.13).
Scan Agents
Case 20.13
Urinary activity and bowel activity are most fre- Urinoma due to urine leakage from percutaneous
quently shown artifactual soft tissue uptake [7]. nephrectomy (PCN) catheter (Fig. 20.14).
a b
Fig. 20.8 Lymphedema of lower extremity in cervix can- occured suddenly, 10 years after operation. There is subtle
cer. A 59-year-old woman presented progressive right soft tissue uptake in the right medial thigh on bone
lower extremity swelling over several years. She had a scan (a), which is aggravated to diffuse, intense soft tissue
history of radical hysterectomy and pelvic lymph node uptake of right lower extremity 2 years later (b), sugges-
dissection due to cervix cancer 10 years ago. She com- tive of secondary lymphedema
plained of heaviness of the right lower extremity, which
A B
Fig. 20.9 A 53-year-old man with hepatocellular carci- ascites in perihepatic subdiaphragmatic space (white
noma shows increased soft tissue uptake in abdomen arrows) and right paracolic gutter (arrow heads) on
(black arrows) on bone scan (A), which matched with MRI (B)
A B a
Fig. 20.10 A 37-year-old woman with hepatocellular vascular hepatocellular carcinoma on arterial (B-a,
carcinoma. Focal soft tissue uptake in right upper abdo- arrows) and portal phase (B-b) and peripheral enhance-
men (arrow heads) presenting uptake of huge hepatocel- ment on delayed phase (B-c), suspected to be associated
lular carcinoma on whole-body bone image (A). with increased soft tissue uptake on bone scan
Abdominal CT images show neovascularization of hyper-
B
a d g
b e h
c f i
Fig. 20.11 A 34-year-old woman with azotemia due to images (B-b & B-e). The tumors do not show definite cal-
post-renal AKI presented huge endometrial cancer in cific densities on non-contrast CT images (B-c & B-f).
abdomen. Uneven soft tissue uptake in left pelvic cavity Incidentally detected lung uptake in RML lateral segment
(arrow), left upper abdomen (arrow heads), and right tho- (B-g, arrows), without definite anatomic abnormality on
rax (curved arrow) on whole body bone scan (A). SPECT/ lung window CT image (B-h), but progress to multiple
CT of abdomen shows increased MDP uptake along the lung and pleural metastasis, revealing multiple small lung
margin of necrosis in the hypervascular endometrial can- nodules with pleural effusion in right hemithorax on lung
cer (B-a, white arrowheads) and well-enhancing hepatic window CT image taken 2 weeks later (B-i)
metastatic nodules (B-d, white arrows) on enhanced CT
A B
Fig. 20.12 A 55-year-old woman shows abnormal bowel mally after intravenous CT contrast injection or other
uptake in left abdomen on bone scan (A, arrows), which is pathologic conditions including primary intestinal lym-
in the colonic loops on coronal SPECT/CT image phangiectasia, protein-losing enteropathy, and systemic
(B, white arrows). Diffuse colonic uptake can be seen nor- amyloidosis
A B
Fig. 20.13 A 79-year-old man with a right femur neck tiny calcific densities are scattered in the dependent portion
fracture. There are three hot spots in the bladder on the MIP of the bladder, and focal radioactivity retention is seen
image of SPECT/CT (B, arrows), which were not evident between the calcifications (C, white arrows). Bladder diver-
on the whole-body image (A). On the SPECT-CT image, ticulums were detected by the cystoscopic examination
a b
Fig. 20.14 A 50-year-old woman complained of right linear increased uptake in soft tissue, which was suspected
pelvic pain for 1 week. She had a total gastrectomy due to to be PCN catheter activity (a). Pelvic SPECT/CT was
stomach cancer 8 years ago. Right PCN catheter was taken for evaluation of pelvic pain (b, c). There is focal
inserted 3 weeks before, because of right hydronephrosis radioactivity retention in the right back muscle adjacent to
resulting from peri-ureteral metastasis. Asymmetric the catheter route, which is swollen compared to the con-
radioactivity retention is noted in the right kidney, with tralateral side, due to intramuscular urinoma
References
Teaching Points
• In this section, we reviewed various 1. Urist MR, Nakagawa M, Nakata N, Nogami
clinical cases of non-osseous soft tissue H. Experimental myositis ossificans: cartilage and
bone formation in muscle in response to diffusible
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heterotopic ossification, dystrophic cal- Med. 1978;102:312–6.
cification of tumor and foreign 2. Shehab D, Elgazzar AH, Colllier BD. Heterotopic
body, metastatic calcifcation in tumoral ossification. J Nucl Med. 2002;43:346–53.
3. Peller PJ, Ho VB, Krasdorf MJ. Extraosseous
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leakage including lymphedema Radiographics. 1993;13:715–34.
and ascites, hypervascular tumor uptake, 4. Steinbach LS, Johnston JO, Tepper EF, Honda GD,
and artifical activity in bowel and of Martel W. Tumoral calcinosis: radiologic-pathologic
correlation. Skelet Radiol. 1995;24:573–8.
urine. 5. Gray HW, Krasnow AZ. Soft tissue uptake of bone
• The mechanisms of non-osseous uptake agents. In: Collier BD, Fogelman I, Rosenthall L, edi-
of bone scan agents including soft tissue tors. Skeletal nuclear medicine. St. Louis, Missouri:
calcification, abnormal intracellular flux Mosby-Year book; 1996. p. 374–99.
6. Silberstein EB. Nonosseous localization of bone seek-
of ionic calcium, expansion of the inter- ing radiopharmaceuticals. In: Silberstein EB, editor.
stitial fluid component, hypervascular- Bone scintigraphy. Mount Kisco, NY: Futura; 1985.
ity of tumor, and artificial uptake were p. 347–70.
presented. 7. Loutfi I, Collier BD, Mohammed A. Nonosseous
abnormalities on bone scans. J Nucl Med Technol.
• Some of the questionable lesions on pla- 2003;31:149–53.
nar bone scan were correctly identified
on additional SPECT/CT.
Musculoskeletal Nuclear Imaging
Pitfalls 21
Yun Young Choi , Ji Young Kim ,
and Seoung-Oh Yang
Abstract enhanced sensitivity of SPECT and additional

anatomic information from CT.
Factors related to clinical history and physical
In this section, clinical cases of some classical
examination (previous trauma or recent radio-
artifacts associated with technical and patient-
nuclide studies), related to patient’s condition
related factors and clinical cases of whole-body
(age, body habitus, underlying diseases, medi-
bone scan with equivocal diagnosis at presenta-
cations, hydration status, lack of cooperation
tion, which were correctly diagnosed with addi-
during scanning), related to radiopharmaceu-
tional SPECT/CT, will be presented.
ticals (radiochemical impurities, introduction
of air into vial during preparation), related
Keywords
to technique (intra-arterial injection, extrava-
sation, suboptimal image due to inadequate Pitfall · Artifact · Bone scan · Bone SPECT/CT
count collection, full bladder), and related to
interpretation (normal and abnormal pattern
recognition) are well-known possible sources 21.1 Instrument-Related
of diagnostic errors [1].
Recently, SPECT/CT has been introduced, 21.1.1 Improper Photopeak Window
and the additional role of SPECT/CT has been Setting
stressed: enabling accurate diagnosis through
Gamma cameras are equipped with pulse height
analyzer which allows the operator to select an
optimal range of energies for accepting photons
Y. Y. Choi (*)
for the bone scan images, which are centered at
Department of Nuclear Medicine, Hanyang
University College of Medicine, photopeak energy of Tc-99m. The typical energy
Seoul, Republic of Korea window for Tc-99m bone scan agents is 10–20%
e-mail: yychoi@hanyang.ac.kr window centered at 140 keV [2].
J. Y. Kim Co-57 flood sources are used for daily quality
Department of Nuclear Medicine, Hanyang control of field homogeneity, which has an energy
peak (122 keV) similar to that of Tc-99m. The
energy peak of the gamma camera should be reset
S.-O. Yang
after the daily QC before imaging bone scan. If
Department of Nuclear Medicine,
Dongnam Institute of Radiological and Medical it is not done, subsequent scanning using Tc-99m
Sciences, Busan, Republic of Korea
https://doi.org/10.1007/978-981-19-2677-8_21
258 Y. Y. Choi et al.
a b
Fig. 21.1 What happened between two images (a, b) the photopeak energy window was found to be centered
taken 10 min apart? On initial image (a), diffusely erroneously lower at 122 keV, the energy of Co-57,
increased soft tissue activity with poor visualization of the instead of that of Tc-99m
bones is noted. A technical problem was concerned, and
bone scan agents will show low-resolution images, mechanism. Intra-arterial injection should be
resulting from loss of photopeak count and considered when exaggerated diffuse increased
increased lower energy scatter counts [3, 4]. bone uptake is seen in an extremity distal to injec-
tion site, especially with no demonstrable history
Case 21.1 Off-photopeak energy window and radiographic findings. Differential diagnosis
(Fig. 21.1) includes reflex sympathetic dystrophy [6], frost-
bite injury, and tourniquet effect [7].
21.2 Technique-Related Case 21.2 Intra-arterial injection (Fig. 21.2)
21.2.1 Intra-arterial Injection

21.2.2 Injection into Central Venous
The uptake mechanism of bone-seeking agent is Catheter
influenced not only by osteoblastic activity but
also by other factors including blood flow, sym- Injection into the central venous catheter results
pathetic tone, and bone surface area. Intra-arterial in residual radioactivity within the plastic tubing
injection may cause increased delivery of bone- or reservoir. Therefore, sufficient saline flushing
seeking agent to the area distal to injection site into the venous catheter is required in those cases.
and results in increased bone uptake. “Glove phe-
nomenon” was previously described in cases with Case 21.3 Radiotracer retention along che-
increased uptake in distal forearm bone and soft moport catheter (Fig. 21.3)
tissue after intra-arterial injection on the antecu-
bital region. “Sock” pattern was also introduced
as an intra-arterial injection artifact of lower limb 21.2.3 Tourniquet Effect
[5]. The explanation for hyperfixation mechanism
could be secondary to the increased arterial blood It has been known that release of tourniquet
flow at the first step of the radiotracers binding results in increase of blood flow and radiotracer
21 Musculoskeletal Nuclear Imaging Pitfalls 259
a b
Fig. 21.2 A 75-year-old man performed a bone scan for prominent in radial side, where the radial artery supplies
evaluation of back pain. Intense uptake in left hand distal dominantly. The above finding is due to injection of bone-
to IV site in left wrist is noted (a). On regional image (b), seeking agent into the left radial artery, instead of vein
increased uptake of the radiopharmaceutical is more
uptake in distal parts of injection site. The phe- The opposite finding of decreased localiza-
nomenon is associated with reactive hyperemia tion of radionuclide in an extremity can also
induced by transient ischemia during perfu- occur due to tight elastic stockings or elastic
sion and blood pool phases of three-phase bone bandage wrappings, representing ischemic con-
scan, due to prolonged compression [8, 9]. On dition [12].
delayed bone scan, diffusely increased uptake in
the extremity distal to injection site can be shown Case 21.4 Tourniquet effect (Fig. 21.4)
in cases with maintaining the tourniquet in place
during injection [10–12]. Case 21.5 Elastic bandage wrapping (Fig. 21.5)
a
b
Fig. 21.3 A 43-year-old woman undergoing chemother- Also unusual curvilinear increased tracer retention was
apy for breast cancer with multiple bone metastasis. noted overlapped with sternum and manubrium (arrow)
Whole-body bone scan shows multiple focal increased (a), which was proven as radiotracer retention along che-
uptake at lower C-spine, left first rib, right fifth rib, L2, moport catheter on regional SPECT/CT image (b)
and right ischial tuberosity suggested as bone metastasis.
21.2.4 Extravasation lymph node has been reported [14, 15]. The lym-
of Radiopharmaceutical phatic system is an accessory route for drainage
of interstitial fluid. Large molecular weight sub-
Extravasation and subcutaneous infiltration of stances, which cannot be directly absorbed into
radiopharmaceutical into surrounding soft tissues capillaries, are readily accommodated by lym-
induce increased activity at the site of injection, phatics and incorporated into the chylous net-
which can make star artifacts on bone scan if work draining into regional nodes. Tc-99m MDP
large amounts have been leaked [13]. Incidental is a large molecular weight substance and there-
visualization of the ipsilateral axillary or elbow fore is preferentially captured by the lymphatic
21.3 Patient-Related
21.3.1 Influence of Recent Nuclear

Medicine Study
Unexpected abnormal uptake lesions can be

noted by the influence of recent nuclear medicine
study. Prior administration of a higher-energy
radionuclide or of a preceding examination
with another Tc-99m radiopharmaceutical that
accumulates in an organ could obscure or con-
found skeletal activity [17]. Therefore, relevant
information that may assist in interpretation of
imaging findings including the history of recent
nuclear medicine studies should be checked with
the patient before injection of radiopharmaceuti-
cal [17, 18].
Case 21.8 Influence of recent nuclear medi-

cine study (Fig. 21.8)
In lymphoscintigraphy using a very small

dose, compared to bone scan, most of injected
colloid material remains at the intradermal or
Fig. 21.4 An 82-year-old woman complained of pain in subdermal injection site and could be seen as
chest wall and upper back after sitting on a massage
machine several times. She was injected in her right ante- focal uptake even 48 h after injection. This could
cubital vein after binding tightly with rubber tourniquet. be postulated that intradermal injection of a small
Diffusely increased uptake in right arm distal to right dose of Tc-99m colloid has not been cleared via
elbow injection site is incidentally detected. This finding tthe kidney or liver.
is associated with tight binding of tourniquet. Focal
uptake lesions detected on the right and left anterior tho-
racic cage were confirmed as acute fractures, and another
focal uptake in T5–6 level was revealed as acute compres- 21.3.2 Attenuation Artifact
sion fracture
Photon-deficient areas detected on the bone scan
system. Axillary lymph node uptake should be are commonly attenuation artifacts caused by
differentiated from superimposed bony structure metallic objects external to the patients, such as
by adding oblique spot views, and not be misin- jewelry, pacemakers, coins in pockets, metallic
terpreted as a pathologic focus [15, 16]. belt buckles, snaps, zippers, and external breast
prosthesis. Therefore, patients should be asked to
Case 21.6 Axillary lymph node uptake of remove metallic objects wherever possible before
extravasated radiopharmaceutical (Fig. 21.6) performing the scan [19]. Photon-deficient areas
due to avascular change may be differentiated in
some cases.
21.2.5 Improper Preparation
of Radiopharmaceuticals Case 21.9 Attenuation artifact (Fig. 21.9)
Case 21.7 Free pertechnetate in stomach and Case 21.10 Differential diagnosis of photon-
small bowel loops (Fig. 21.7) deficient lesions (Fig. 21.10)
a c
Fig. 21.5 A 52-year-old woman had pain and tenderness complex regional pain syndrome. But the patient’s secret
in the lateral malleolar area of left ankle after slipping was revealed on SPECT/CT image (d). She had applied
down. Eleven days after trauma, she underwent a three- elastic bandage and short leg cast (arrow heads) during
phase bone scan. Asymmetric diffusely decreased perfu- three-phase bone scan, which is proved on SPECT/CT
sion (a), blood pool activity (b), and bone uptake (c). image
Above findings could be noted in the chronic phase of
21.3.3 Optimum Timing of Bone Scan tial false-negative result is concerned, because it
After Trauma may take up to a week for the scan to become
positive in a small percentage of the elderly
The whole-body bone scan is a highly sensitive patients [20, 21].
modality in the evaluation of fractures, and the
majority of fractures will manifest a positive Case 21.11 Optimum time of bone scan after
three-phase bone scan immediately, but poten- trauma (Fig. 21.11)
a b
Fig. 21.6 A 36-year-old woman complained of polyar- lary area (a, arrow), axillary lymph node activity, which
thralgia. Star artifact in right elbow, which resulted from was newly visualized compared to prior bone scan taken
leakage of radiopharmaceutical at the IV site, was 3 months before (b)
masked. There is a focal uptake lesion in the right axil-
Fig. 21.7 A 44-year-old woman with breast

cancer and liver metastasis underwent bone scan a b
for evaluation of metastasis. Incidentally detected
stomach and small bowel activity in initial bone
scan (a) but disappeared on followed bone scan
after 6 months (b). Incidentally detected bowel
uptake including stomach could be from free
pertechnetate and metastatic calcification. The
patient didn’t show any clinical condition for
metastatic calcification and presents
disappearance of bowel uptake on the following
image; it was concerned for free pertechnetate
activity due to improper preparation
a b d
Fig. 21.8 A 65-year-old woman complained with both cial conditions could be considered. Past history of the
legs swelling for 3 weeks. She had a 4-year history of patient was reviewed, and it was found that she had lym-
rheumatoid arthritis and underwent right total knee phoscintigraphy (d) 2 days before the whole-body bone
replacement 3 months before. On the whole-body bone scan. Tc-99m phytate (1 mCi syringe was prepared for
scan (a) and regional images (b), there are increased each site; residual activity in each syringe was about
uptake lesions in both ankles and left hind-foot. 0.25 mCi, so net injected dose was 0.75 mCi) was given.
Unexpectedly, focal spotty uptake lesions are noted in Intradermal injection of such a small dose of Tc-99m col-
second and third MTP joint area of both feet. There is no loid could be remained after 2 days, because it has not
demonstrable joint lesion on plain radiograph of both feet been excreted via the kidney or liver
(c). The definition of lesions is too clear; therefore artifi-
a b
c d
Fig. 21.9 Whole-body bone scan of an 18-year-old girl after bone marrow aspiration biopsy (b). Focal decreased
with intestinal lymphoma shows diffusely decreased uptake associated with attenuation artifacts due to metal-
uptake in L3–5 level on posterior image (a), which has lic button (c) and coin (d) is noted
proven to be attenuation artifact due to sandbag applied
a b
c d
Fig. 21.10 A 75-year-old man with lung cancer shows in (b). The 16-year-old boy has left femur shaft fracture
focal defect in left proximal femoral shaft (a), while a and dislocation (c); therefore the cold defect is thought to
16-year-old boy shows cold defect in right femur mid be avascular change. On followed bone scan and radio-
shaft (b). These two patients have similar whole-body graphic images (d), cortical bone uptake is seen in medial
bone anterior images, showing cold defects in femur. One femur, matched with periosteal bone formation, but still
is an attenuation artifact, and the other is a true lesion. noted is cold defect in lateral cortex, suggestive of avascu-
Guess what? The tip is looking carefully at the posterior lar state. After 1 year, healed fracture with minimal lateral
images. There is no defect in the left proximal femur on angulation is noted
posterior image in (a), while there is still noted cold defect
a b
Fig. 21.11 A 58-year-old man had back pain after slip- and bone scan was repeated after 1 week (c). L1 showed
ping down. Plain radiograph shows multiple compression intense uptake, and T11 and T12 did not show increased
fractures in lower T- and upper L-spine (a). Bone scans activity compared to initial study. Those findings are sug-
taken after 2 days show subtle uptake in T11-L1 level (b). gestive of acute compression fracture of L1 and old com-
The patient was concerned of acute compression fracture, pression fractures of T11 and T12 level
Teaching Points relevant clinical information, (2) proper

• In this section, we reviewed some clini- preparation of patients, (3) meticulous
cal cases of instrument-related, positioning of patients and adequate
technique-related, and patient-related acquisition, (4) familiarity of the normal
pitfalls and artifacts on bone appearance of different age groups and
scintigraphy. normal variants, (5) awareness of tech-
• Some of these pitfalls and artifacts were nical pitfalls, and (6) knowledge of
correctly diagnosed with additional strengths and limitations of each
SPECT/CT. modality.
• The factors for best possible quality and
interpretation include (1) obtaining the
References tigraphy in the long bone proximal to a tourniquet: an

injection artifact. Clin Nucl Med. 2010;35:349–50.
11. Weiss SC, Conway JJ. An injection technique artifact.
1. Naddaf SY, Collier BD, Elgazzar AH, Magdy
J Nuc Med Technol. 1984;12:10–2.
MK. Technical errors in planar bone scanning. J Nucl
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13. Shih WJ, Collins J, Kiefer V. Visualization in the ipsi-
EANM practice guidelines for bone scintigraphy. Eur
lateral lymph nodes secondary to extravasation of a
J Nucl Med Mol Imaging. 2016;43:1723–38.
bone-imaging agent in the left hand: a case report. J
3. Sokole EB, Plachcinski A, Britten A,
Nucl Med Technol. 2001;29:154–5.
Georgakopoulou ML, Tindale W, Klett R. Routine
14. Ongseng F, Goldfarb R, Finestone H. Axillary lymph
quality control recommendations for nuclear medi-
node uptake of technetium-99m-MDP. J Nucl Med.
cine instrumentation. Eur J Nucl Med Mol Imaging.
1995;36:1797–9.
2010;37:662–71.
15. Wallis JW, Fisher S, Wahl RL. 99Tcm-MDP uptake
4. Giammarile F, Mognetti T, Paycha F. Injection
by lymph nodes following tracer infiltration: clini-
artefact displaying “sock” pattern on bone scan:
cal and laboratory evaluation. Nucl Med Commun.
“glove” sign equivalent resulting from bisphos-
1987;8:357–63.
phonate-(99mTc) injection in the foot venous
16. Wyngaert T, Strobel K, Kampen WU, et al. The
system. Eur J Nucl Med Mol Imaging. 2014;41:
EANM practice guideline for bone scintigraphy. Eur J
1644–5.
Nucl Med Mol Imaging. 2016;43:1723–38.
5. Bozkurt MF, Uğur O. Intra-arterial Tc-99m MDP
17. Donohoe KJ, Henkin RE, Royal HD, et al. Procedure
injection mimicking reflex sympathetic dystrophy.
guideline for bone scintigraphy:1.0. J Nucl Med.
Clin Nucl Med. 2001;26:154–6.
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6. Gunay EC, Erdogan A. Asymmetrically increased
18. Gnanasegaran G, Cook G, Adamson K, Fogelman
uptake in upper extremities on 99mTc-MDP bone
I. Patterns, variants, artifacts, and pitfalls in con-
scintigraphy caused by intra-arterial injection:
ventional radionuclide bone imaging and SPECT/
DIFFERENT uptake patterns in three cases. Rev Esp
CT. Semin Nucl Med. 2009;39:380–95.
Med Nucl. 2011;30:372–5.
19. Martin P. The appearance of bone scans following
7. Lecklitner ML, Douglas KP. Increased extremity
fractures, including immediate and long-term studies.
uptake on three-phase bone scans caused by peripher-
J Nucl Med. 1979;20:1227–31.
ally induced ischemia prior to injection. J Nucl Med.
20. The skeletal system. In: Taylor A, Schuster DM,
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Alazraki N. A clinician’s guide to nuclear medicine.
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21. Weiner GM, Jenicke L, Muller V, Bohuslavizki
9. Orzel JA, Rosenbaum DM, Weinberger E. “Tourniquet
KH. Artifacts and non-osseous uptake in bone scin-
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Roentgenol. 1989;152:896.
2001;35:185–91.
10. Sohn MH, Lim ST, Jeong YJ, Kim DW, Jeong HJ,
Yim CY. Abnormally increased uptake on bone scin-
Index
A scintigraphy, 7, 18–26, 50, 55, 68, 84–91,

Accessory navicular, 146–148 94–101, 105, 107, 108, 145–147, 152, 164,
Acute hip pain, 126, 127 230, 267
Acute local tissue reaction (ALTR), 116, 127 SPECT, 64, 68, 105–106, 122, 125, 151
Adenylyl cyclase, 195 SPECT/CT, 7–15, 42, 43, 45, 65, 86–88, 90, 106,
AFF, see Atypical femoral fracture 107, 109, 124, 127, 133, 135, 138, 142–152,
Allodynia, 93, 94, 97, 98 175, 183, 184, 197, 198, 200
Ankle and foot, 15, 142 Bowel uptake, 247, 252, 263
Ankle osteoarthritis, 141–142 Brain injury, 64, 69, 71
Ankylosing spondylitis, 29–31, 42, 146 Budapest criteria, 94
Anterior ankle impingement (AAI), 143–145 Bursitis, 8–10, 32, 146
Antibiotic loaded polymethylmetharcylate (PMMA), 5
Arthritis, 8, 18, 19, 29–39, 42, 43, 46, 88, 131, 132, 137,
138 C
Artificial uptake, 247, 252–255 Camurati–Engelmann disease, 174–177
Aseptic loosening, 115, 116, 120, 135, 140 Causalgia, 94
Attenuation artifact, 261, 265, 266 Charcot foot, 6–8
Atypical femoral fracture (AFF), 77, 187, 190, 193 Charcot neuropathy, 6
Avascular necrosis (AVN), 84, 124, 180 Chondrosarcoma, 207, 210–213
Avascular necrosis of femoral head (ANFH), 83, 84 Chronic expanding hematoma, 116–117
Chronic prosthetic joint infection, 5–6
Clubbing, 49, 50
B Complex regional pain syndrome (CRPS),
Bankart lesion, 148–151 93–101, 262
Bisphosphonate-induced osteonecrosis of the jaw Compression fracture, 107, 108, 148, 172, 181–188, 193,
(BONJ), 90 261, 267
Bladder diverticulum, 247, 253 Computed tomography (CT), 3, 4, 7–10, 15, 17–19, 22,
Bone 23, 25, 30, 36, 37, 39, 41–46, 50–52, 54, 55,
allograft, 120 60, 64–71, 73, 74, 79–81, 83, 84, 86–91,
erosion(s), 19, 21–26, 33, 34, 37 105–113, 116–122, 124–128, 131–139,
fracture, 63–67, 77, 171 142–152, 158, 160–162, 164, 166, 168–170,
graft, 63–71, 120–123 175, 178, 180–189, 191, 195–201, 206, 207,
marrow, 5, 11, 18, 19, 23, 25, 26, 118, 119, 124, 126, 209, 210, 218–225, 228–233, 240–243, 246,
128, 168, 174, 181, 187, 196, 218, 227–231, 250–255, 260, 262, 267
233, 234, 265 CRPS severity score (CSS), 94
marrow edema, 7, 18–20, 22, 24, 25, 30, 32, 77, 78, Cubital tunnel syndrome, 101
85–87, 126, 143, 145, 146, 162, 181 Cyclic adenosine monophosphate (cAMP), 196
metastasis, 50–52, 55, 168, 190, 197, 206, 207,
217–220, 222, 224, 231, 260
PET, 218, 224 D
scan, 4–7, 9–16, 30–39, 42–47, 50–55, 58, 59, 64–71, Diabetic foot infection, 3–4
73–81, 116–122, 124–127, 132–140, 158–162, foot ulcer, 3, 4
164, 166–173, 175–178, 180–193, 197–201, ischemia, 3, 4
206–214, 218–225, 239–255, 257–267 Texas diabetic foot ulcer classification, 3
© The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature 269
Singapore Pte Ltd. 2022
https://doi.org/10.1007/978-981-19-2677-8
270 Index
3,3-Diphosphono-1,2-propanodicarboxylic acid (DPD), Hypertrophic osteoarthropathy (HOA), 49–60

96–100 Hypertrophic pulmonary osteoarthropathy
Dystrophic calcification, 239–241, 255 (HPO), 49
E I
Elastic bandage wrapping, 259, 262 Impaction bone grafting (IBG), 120
Epidural abscess, 10, 11, 14–16 Improper preparation of radiopharmaceuticals, 261
Ewing sarcoma, 208, 212, 213 Infection, 3–19, 25, 29, 64, 95, 116, 118, 124–127, 133,
Extravasation of radiopharmaceuticals, 135–137, 139, 140, 180, 181, 183, 191, 228, 242
260–261 Infectious, 5, 16, 17, 19
Extremity pain, 95, 101, 175 Instability, 138–142, 149
Insufficiency fracture, 63, 73, 77–81, 85, 86, 126–128,
158–162, 164, 178, 181, 183–187, 193
F Internal fixation, 68, 70, 124, 125, 137
Failed back surgery syndrome, 106, 107 Intra-arterial injection, 258
Fatigue fracture, 63, 73, 77, 78, 81 Ischemia, 3, 4, 259
FDG PET, 25, 54, 181, 206–214
Femoral neck fracture, 124, 183
18
F-FDG PET, 19, 22, 45, 46, 51, 187, 197, 198, 201, J
218, 219, 221–225 Joint effusion, 7, 18, 19, 32, 33, 36, 37, 139
Fibrous dysplasia, 195–201, 208, 209, 212, 213
of bone, 195–201
monostotic, 195, 198, 208 K
polyostotic, 195, 197, 208, 213 Kienböck disease osteonecrosis of jaw, 87–88
Flare phenomenon, 218, 219, 222, 224 Knee arthroplasty, 5, 133, 135, 136
18
F-NaF PET, 219, 220, 222, 224, 225 Knee prosthesis, 118
Foot ulcer, 3, 4
Foreign body, 137, 241, 255
Fracture, 6–8, 11, 45, 63–71, 73–81, 84–88, 106–108, L
112, 124–127, 136–138, 142, 146–150, Langerhans cell histiocytosis, 208–214
158–162, 164, 167, 168, 171, 172, 175, 178, Lateral malleolar bursitis, 8
180–188, 190, 191, 193, 209, 210, 217, 219, Leukemia, 187, 229–234
228, 230, 231, 233, 240, 244, 253, 261, 262, Liposarcoma, 207, 210, 211
266, 267 Lisfranc injury, 148
Fracture-related infection (FRI), 124–126, 128 Loosening, 13, 106, 107, 109, 112, 115–117, 119–121,
Free technetium, 261, 263 124–126, 133, 135–137, 139, 140
Looser zone, 158,164
Lumbar fusion, 106, 107
G Lymphedema, 246–248, 255
68
Ga-DOTA-peptide PET/CT, 158 Lymph node uptake, 261
Giant cell tumor, 197, 207–210, 212 Lymphoma, 187, 229–234, 265
Glove phenomenon, 258
Gout, 35–39
Graft failure, 164 M
Marble bone disease, 168
Mazabraud syndrome, 195
H McCune-Albright syndrome, 195, 198, 199
Heterotopic ossification, 239, 255 Medication-related osteonecrosis of the jaw (MRONJ), 2,
Hill–Sachs defect, 148, 149 190–193
HMPAO-labeled, 125 Metabolic bone disease, 157–179, 181
Hybrid imaging, 64, 112 Metallosis, 137–138, 140
Hyperalgesia, 93, 94 Metastatic calcification, 239, 241–242, 263
Hyperemia, 9, 18, 19, 21–23, 25, 32, 64, 95, 259 Microfracture, 7, 63, 65, 86, 90
Hyperhidrosis, 94 Missed fracture, 65, 66, 71
Hyperparathyroidism, 161, 163, 164, 166, 178, Monostotic fibrous dysplasia, 195, 198
241–243
Index 271
mTc methylene diphosphonate (MDP), 50–52, 55, 95,

99
R
96, 218, 241, 251, 260 Radionuclide imaging, 259, 261
Multiple myeloma, 227–229, 233 Reflex sympathetic dystrophy (RSD), 94, 258
Musculoskeletal nuclear imaging pitfalls, 257–267 Renal osteodystrophy, 161–164, 166, 178
Revision THA, 120
Rhabodomyolysis, 242–246, 255
N Rheumatoid arthritis, 31–39, 42, 126, 183, 264
Non-inflammatory arthritis, 41–47 Rickets, 158, 196
Non-union of fracture, 63–71, 106, 107, 113, 124–126 Rotator cuff tear (RCT), 151–152
Nuclear imaging, 116, 193, 206, 257–267 Rugger-jersey spine, 161, 164
O S
Off-photopeak energy window, 258 Sarcoma, 207, 208, 214, 232, 234
Optimum time of bone scan after trauma, 262 Scintigraphy, 18, 97, 107–112, 164, 261, 264, 267
Os naviculare, 146 Septic, 10, 16, 115, 116, 120, 135, 140
Osteoarthritis, 18, 36, 41–47, 86, 87, 126, 127, 131, arthritis, 5, 17–26, 42
141–143, 175 Shoulder, 19, 21, 32, 45–47, 52, 94–98, 100, 141–152,
Osteochondral lesion of the talus (OLT), 142–143, 145 183, 241, 243
Osteolysis, 115–118, 120–122, 133–135, 137, 217 instability, 149
Osteolytic, 89, 116, 118, 120, 121, 133, 134, 160, 161, shoulder-hand syndrome, 94
191, 197, 200, 201, 208, 212, 214, 218, 219, Single-photon emission computed tomography/computed
221, 228, 230 tomography (SPECT/CT), vii, 4, 6–15, 18,
Osteomalacia, 157–162, 164 42–45, 64–66, 68, 70, 71, 74, 79–81, 84, 86–90,
Osteonecrosis, 21, 83–91, 124–126, 137, 161, 183, 184, 106–110, 112, 113, 118, 120–122, 124–128,
190–193 131–139, 142–152, 161, 162, 164, 166, 175,
Osteopetrosis, 168–175 181, 183, 184, 191, 196–198, 200, 206, 218,
Osteoporosis, 32, 36, 63, 71, 73, 77, 79, 80, 90, 157, 161, 228, 240–243, 251–255, 260, 262, 267
167, 168, 179–193 Skeletal dysplasia, 168
Osteosarcoma, 68, 206–207, 209 Spine, 11–15, 30, 55, 64, 73, 74, 81, 105–113, 158–162,
Osteosclerosing dysplasia, 168 164, 168, 171–173, 175, 181–186, 193, 195,
Osteosclerotic, 218, 219, 224, 225 198, 218–221, 223–225, 230
SPECT, 107
Spondylolysis, 105–107, 112
P Spontaneous osteonecrosis of the knee (SONK), 84, 85
Paget’s disease, 164–170, 172 Stress fracture, 64, 65, 67, 73–81, 106, 187
Paraffinoma, 241, 242 Subchondral insufficiency fracture of femur head
Periosteal reaction, 49 (SIFFH), 126–128
Periprosthetic Subchondral insufficiency fracture of the knee (SIFK), 85–87
fracture, 136–137, 140 Superscan, 163, 164, 166, 218, 219
infection, 117, 133–135, 140 Synovial, 5, 18–25, 32, 36, 37, 49
joint infection (PJI), 5, 117–119, 128 hyperplasia, 32
Phosphaturic mesenchymal tumor, 158, 160, 161
Plantar fasciitis, 145–46
Polyehtylene (PE) liner wear, 120, 121, 135–136, T
140 Tenosynovitis, 32, 95, 144
Polyostotic fibrous dysplasia, 195, 197, 213 Three phase bone scan, 4–7, 10–15, 64, 74, 77, 133, 135,
Pre-hallux syndrome, 147 181, 192, 193, 239, 259, 262
Primary bone tumor, 205 Three-phase bone scintigraphy (TPBS), 7, 18–25,
Primary soft tissue tumor, 205 94–101, 116, 118–120, 127
Progressive diaphyseal dysplasia, 174, 176 Total hip arthroplasty (THA), 115–123, 126, 127
Prosthesis, 45, 106, 116–120, 136, 137, 261 complications of, 115
Prosthetic joint infection (PJI), 5–6, 117–119 Tourniquet effect, 258–259
Pseudo-fracture, 158, 159, 164, 166 Trauma, 18, 45, 63, 64, 67–69, 71, 73, 79, 84, 85, 87, 93,
Pseudotumor, 116 106, 116, 117, 126, 127, 141, 142, 152, 158,
Pyogenic spondylitis, 10–16 161, 183, 184, 187, 219, 239, 240, 242, 262
epidural abscess, 10, 11, 14–16 Triple phase bone scan (TPBS), 116, 118–120, 127
272 Index
Tuberculous, 11–15, 19–26 V

arthritis, 19–26 Vertebral fracture, 180, 181, 193
spondylitis, 11–15 Vitamin D deficiency, 158
Tumoral calcinosis, 241, 242, 255
Tumor hypervascularity, 246–247
W
White blood cell (WBC)
U imaging, 4–6, 14, 15, 116, 118, 119, 124–126, 128, 133
University of Texas diabetic foot ulcer scan, 4, 5, 14, 16, 35, 116, 118, 119, 124–126
classification, 3 Whole body bone scan, 50–55, 69, 74, 75, 77, 79, 80,
Urinoma, 247, 254 125, 158, 166, 168, 169, 173, 175, 241–244,
247, 251, 260, 262, 264, 265

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Atlas of Nuclear

Case Oriented Approach

Yun Young Choi Jin-Sook Ryu

ISBN 978-981-19-2676-1 ISBN 978-981-19-2677-8 (eBook)

Busan, Republic of Korea Seoung-Oh Yang

Part I Inflammatory and Infectious Disorders

1 Musculoskeletal Infections�������������������������������������������������������������� 3

Part II Traumatic and Circulatory Disorders

Part III Spine and Joint Disorders

12 Knee Prostheses�������������������������������������������������������������������������������� 131

Part IV Metabolic and Endocrine Osseous Disorders

14 Metabolic Bone Disease ������������������������������������������������������������������ 157

Part V Musculoskeletal Neoplastic Disorders

Part VI Miscellaneous Features in Musculoskeletal

Young-Sil An Department of Nuclear Medicine and Molecular Imaging,

Su Jin Lee Department of Nuclear Medicine, Ajou University School of

Fig. 1.3 Pretibial soft tissue a b c

Fig. 1.10 Three-phase bone scan shows increased perfu-

1.5 Pyogenic Spondylitis bral osteomyelitis, septic discitis, and epidural

Fig. 1.13 Contrast-

Case 1.7 in the left side of screw of L3 body (Fig. 1.14c,

• SPECT/CT allows accurate anatomical involvement of bony inflammation or

References infections, particularly chronic and low-grade infec-

Septic arthritis is a painful infection in a joint Septic · Infectious · Arthritis · Tuberculous

2.2 Diagnosis Scintigraphy with 99mTc-labeled phosphonates

F-FDG PET (fluorine-18 fluorodeoxyglucose

Fig. 2.1 (a, b)

Fig. 2.3 (a) Plain

and patchy bone marrow edema. Mid-carpal Case 2.5

References 5. Eriksen EF, Ringe JD. Bone marrow lesions: a uni-

Inflammatory arthritis is a joint inflammation Rheumatoid arthritis · Ankylosing spondylitis

3.1.2 Radiographic Imaging

Case 3.2 3.2 Rheumatoid Arthritis

phalangeal joints of both hands. Bone scan shows

Case 3.6 increased uptake in both wrists, left first metacar-

inflammation. In pseudogout, the associated Case 3.8

References 9. López-Mejías R, Carmona FD, Genre F, Remuzgo-­

Abstract 4.1 Etiology

4.2 Diagnosis Case 4.1

observed in the medial compartment and patellar Case 4.3

Case 4.4 (Fig. 4.4c, d, f and g). Moreover, a possible

References toms and cartilage volume loss in knee osteoarthritis

Abstract 5.1 Etiology and Clinical

Plain X-ray images of the extremities are often Case 5.2

Case 5.7 Case 5.8

Fig. 5.5 (continued)

demonstrated on SPECT/CT. Clin Nucl Med.

Abstract duce a variety of cases performed by nuclear

Case 6.4 6.2 Non-union

c 6.3 Bone Graft

6.3.1 Etiology and Clinical Significance

The bone graft is commonly used for reconstruc-

Bone scan can offer method for the assessment of

6.2.2 Imaging Case 6.6

Case 6.5 Case 6.7

Teaching Points • Bone scan can offer method for the

Abstract 7.1 Etiology

7.2 Diagnosis aspect of the tibial cortex. While a stress fracture

7.3.1 Stress Fractures of the Tibia Case 7.3

uptake, and bilateral vertical uptake [1]. Pelvic Case 7.9

Busan, Republic of Korea Seoung-Oh Yang

Part I Inflammatory and Infectious Disorders

1 Musculoskeletal Infections�� 3

Part II Traumatic and Circulatory Disorders

Part III Spine and Joint Disorders

12 Knee Prostheses�� 131

Part IV Metabolic and Endocrine Osseous Disorders

14 Metabolic Bone Disease �� 157

Part V Musculoskeletal Neoplastic Disorders

Part VI Miscellaneous Features in Musculoskeletal

1.5 Pyogenic Spondylitis bral osteomyelitis, septic discitis, and epidural

2.2 Diagnosis Scintigraphy with 99mTc-labeled phosphonates

3.1.2 Radiographic Imaging

Case 3.2 3.2 Rheumatoid Arthritis

References 9. López-Mejías R, Carmona FD, Genre F, Remuzgo-

Abstract 4.1 Etiology

4.2 Diagnosis Case 4.1

Abstract 5.1 Etiology and Clinical

Case 6.4 6.2 Non-union

c 6.3 Bone Graft

6.3.1 Etiology and Clinical Significance

6.2.2 Imaging Case 6.6

Abstract 7.1 Etiology

7.2 Diagnosis aspect of the tibial cortex. While a stress fracture

7.3.1 Stress Fractures of the Tibia Case 7.3

8.1.1 Etiology and Clinical

Case 8.4 8.3 Osteonecrosis of the Hand

8.4 Osteonecrosis of the Jaw meticulous clinical examination, including medi-

9.2 Diagnosis 9.3 Three-Phase Bone

attenuation correction and scatter correction also 10.3 Abnormalities in Fused

12.2 Periprosthetic Infection Patient underwent revision surgery for all

SPECT/CT revealed increased uptake in bilateral 12.5 Periprosthetic Fracture

13.1.2 Imaging right subtalar joint. Post-traumatic OA of the sub-

13.4.2 Imaging 13.5 Accessory Ossicles

The diagnosis of plantar fasciitis is clinically 13.5.1 Etiology and Clinical

13.5.2 Imaging Case 13.6

13.6 Mid-foot Sprain because of its noninvasive nature and ability to

13.7 Shoulder Dislocation

except hypophosphatemia (1.3 mg/dL). The 14.2 Renal Osteodystrophy

der characterized by excessive abnormal bone 14.3.2 Imaging

sis type 2 with a heterozygous mutation in the 14.5 Camurati–Engelmann

[12]. The common symptoms include extremity 14.5.2 Imaging

Case 15.5 15.5 Atypical Femoral

Case 15.8 15.6 Medication-Related