NeuroRx威: The Journal of the American Society for Experimental NeuroTherapeutics

Neuroimaging in Traumatic Brain Imaging

Bruce Lee* and Andrew Newberg†

*Department of Medicine, †Division of Nuclear Medicine, Department of Radiology, University of Pennsylvania Health System,
Philadelphia, Pennsylvania 19104

Summary: Traumatic brain injury (TBI) is a common and imaging studies can determine the presence and extent of injury
potentially devastating clinical problem. Because prompt and guide surgical planning and minimally invasive interven-
proper management of TBI sequelae can significantly alter the tions. Neuroimaging also can be important in the chronic ther-
clinical course especially within 48 h of the injury, neuroim- apy of TBI, identifying chronic sequelae, determining progno-
aging techniques have become an important part of the diag- sis, and guiding rehabilitation. Key Words: Head injury, MRI,
nostic work up of such patients. In the acute setting, these PET, neuroimaging, trauma, SPECT, CT.

INTRODUCTION The reader is referred to a separate review on imaging of

animal models of TBI published in the current volume.5
Traumatic brain injury (TBI) is an extremely common
and potentially devastating problem. Studies have esti-
mated that nearly 1.6 million head injuries occur in the INDICATIONS FOR IMAGING
United States each year, resulting in over 50,000 deaths
Not all head trauma patients require neuroimaging.6
and over 70,000 patients with permanent neurological
Neuroimaging is, of course, costly and can consume
deficits.1–3 TBI accounts for up to 10% of the health care
scanner time that may be used for patients with other
budget and an estimated annual cost to society of $30
indications. Studies have found that less than 10% of
billion.4 Because prompt proper management of TBI
patients that are considered to have minor head injuries
sequelae can significantly alter their course especially
have positive findings on CT and less than 1% require
within 48 h of the injury, neuroimaging techniques,
neurosurgical intervention.7 But this implies that there
which can determine the presence and extent of the in-
are still a small number of low risk patients that would
jury and guide surgical planning and minimally invasive
benefit from neuroimaging. On the other hand, reducing
interventions, play important roles in the acute therapy of
the number of CT’s performed on minor head injury
TBI.4 Imaging also can be important in the chronic ther-
patients even by 10% may yield more than $10 million in
apy of TBI, identifying chronic sequelae, determining
savings each year.8,9
prognosis, and guiding rehabilitation.
Defining minor versus major head injuries has been
The following review will discuss the indications for
problematic. Certain circumstances suggest major injury
imaging patients with TBI, review the roles of x-ray
and almost always merit imaging such as worsening
computed tomography (CT), magnetic resonance imag-
level of consciousness, loss of consciousness for more
ing (MRI), positron emission tomography (PET), single-
than 5 min, focal neurological findings, seizure, failure of
photon emission computed tomography (SPECT), and
the mental status to improve over time, penetrating skull
angiography in the management of TBI, and discuss
injuries, signs of a basal or depressed skull fracture, or
potential future applications of these imaging modalities.
confusion or aggression on examination.7,10 –16 However,
there is debate over which other circumstances merit
imaging. Whereas numerous criteria have been devel-
oped, including the New Orleans Criteria17 and the Ca-
Address correspondence and reprint requests to Andrew B. New- nadian Head CT rules,18,19 none have been found to be
berg, M.D., Division of Nuclear Medicine, 110 Donner Building,
H.U.P., 3400 Spruce Street, Philadelphia, PA 19104. E-mail: completely foolproof. Even patients with the complete
newberg@rad.upenn.edu. absence of clinical findings and high risk circumstances

372 Vol. 2, 372–383, April 2005 © The American Society for Experimental NeuroTherapeutics, Inc.
 NEUROIMAGING IN TRAUMATIC BRAIN IMAGING 373

have been found to have intracerebral hemorrhage on were more likely to have delayed brain injury on CT,34 it
imaging.20 Nevertheless, most investigators have fo- has not been clearly established if anticoagulation or
cused on several criteria: coagulopathies should affect the decision to image.28
Glasgow coma scale
The Glasgow Coma Scale (GCS), which rates a pa- IMAGING AND ACUTE MANAGEMENT
tient’s level of consciousness from 3 (worst) to 15 (no
In the acute setting, early diagnosis and aggressive
impairment) based on a patient’s ability to open his or
management may prevent secondary injury from the
her eyes, talk, and move, is often used to assess injury
complications of brain injury. Proper management can
severity. Some have suggested that any score below 15
significantly improve mortality and morbidity, while re-
warrants imaging,21,22 whereas other investigators have
ducing hospital stay and health care costs.35,36 Imaging
suggested that imaging should not be performed unless helps identify cerebral and cranial problems and deter-
the score is below 13.23–25 mine their severity and operability, especially when re-
Vomiting and headache liable, complete neurological examinations cannot be
Based on the New Orleans Criteria, all TBI patients performed. Imaging has become essential to surgical
with headache or vomiting should be imaged. More than planning by providing anatomic localization and naviga-
two episodes of vomiting is considered by Canadian CT tion information, determining extracranial landmarks to
head rules as a high-risk factor for requiring neurosurgi- help plan the skin incision, and guiding placement of
cal intervention.18,19 However, a meta-analysis found burr holes when necessary. Imaging findings also can
that the presence of headache or vomiting were not pre- provide important prognostic indicators, which may help
dictive of intracranial hemorrhage in the pediatric pop- decide the aggressiveness of management.37–39
ulation.26 Anatomical imaging with MRI is very sensitive and
accurate in diagnosing cerebral pathology in TBI pa-
Amnesia tients. However, conventional CT (which is more avail-
While amnesia is included in both the New Orleans able and cost effective, requires shorter imaging time and
criteria17 and Canadian CT head rules,18,19 transient am- is easier to perform on patients who are on ventilator
nesia is common after mild head injury. Thus, longer and support, in traction, or agitated) is the initial imaging
more severe amnesic episodes imply a greater chance of modality of choice during the first 24 h after the inju-
hemorrhage. A SPECT study found that amnesia lasting ry.8,40 – 42 The advent of fast multidetector CT has dra-
more than half an hour is associated with bilateral cere- matically reduced scanning time and allows for quick
bral hypoperfusion.27 selective rescanning of slices that are affected by motion
Ethanol or drug intoxication artifact.43 CT is also superior in evaluating bones and
The New Orleans criteria list intoxication as an indi- detecting acute subarachnoid or acute parenchymal hem-
cation for imaging. Series have found that up to 8% of orrhage.44
ethanol intoxicated patients had intracerebral injury.6,28 Conventional CT also has its limitations. Beam-hard-
Several mechanisms have been proposed. First of all, ening effects, displacement of the CT signal near metal
intoxicated patients with impaired sensoria and judgment objects, bone, calcifications, and high concentrations of
may be more likely to suffer severe mechanisms of in- contrast, can degrade the image quality and prevent ac-
juries. Secondly, chronic abuse has been found to cause curate assessment. CT can miss small amounts of blood
brain atrophy, perhaps making the brain susceptible to that occupy widths less than a slice because of volume
insult. Finally, the presence of alcohol or other drugs of averaging. CT findings may lag behind actual intracra-
abuse may potentiate the effect of TBI on neurons and nial damage, so that examinations performed within 3 h
vasculature.29 of trauma may underestimate injury.45 In the absence of
changes in neurological status, it is still under debate
Age (>60 years and infants) whether CT scans should be repeated after a normal
According to the New Orleans criteria, all head injury admission CT.46 – 48
patients over 60 years of age should undergo imaging,17 Forty-eight to 72 h after injury, MRI is generally con-
and according to the Canadian CT head rules, anyone sidered to be superior to CT. Although CT is better at
over 65 years of age is at high risk for needing neuro- detecting bony pathology and certain types of early
surgical intervention.18,19 Studies have also shown a high bleeds, the ability of MRI to detect hematomas improves
incidence of intracranial injuries among infants who had over time as the composition of the blood changes. The
no signs or symptoms, suggesting that imaging should be overwhelming majority of patients with mild brain injury
pursued more aggressively in younger children.30 –33 show no abnormality on MRI. When abnormalities are
Anticoagulation or coagulopathies. Although one present, the most common findings are hemorrhagic cor-
study showed that patients with abnormal clotting studies tical contusions, petechia, or foci of altered signal that

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374 LEE AND NEWBERG

Currently, the advantages of cost and convenience for

CT have limited the use of MRI in the acute management
of TBI. As MRI becomes more available, newer se-
quences provide more information, and scanning time
decreases, this may change.5 Moreover, the development
of shorter MR studies using fast pulse sequences on ultra
low, low, or intermediate field strength systems and non-
ferromagnetic monitoring and ventilation devices may
allow more patients to be scanned. Additionally, inves-
FIG. 1. MRI of 66-year-old male after a motor vehicle accident tigators are using MRI to better understand the mecha-
showing a large right frontal intraparenchymal hemorrhage on nisms of secondary injury in brain trauma. This may lead
the FLAIR (left image) and T2 (right image) sequences. The
FLARE images shows diffuse, heterogeneous increased signal to preventative or preemptive treatments in the acute
intensity consistent with evolving blood products with surround- setting. Eventually, MRI may become a more useful tool
ing edema in the frontal lobe. for the early evaluation of acute brain injury.
Neither PET nor SPECT imaging is used routinely in
represent white matter shear injury. When petechia re- the acute management of head trauma. Both have limited
solve, they leave a permanent hemosiderin deposition on availability especially during off-hours and require a fair
MRI. MRI is superior to CT in detecting axonal injury, amount of time to complete. Because PET and SPECT
small areas of contusion, and subtle neuronal dam- imaging provide functional rather than detailed anatomic
age.49,50 Studies have shown that CT missed approxi- information, neither is likely to replace CT or MRI in the
mately 10 –20% of abnormalities seen on MRI.51,52 acute setting of head trauma. In addition, it is always
Moreover, MRI is better at imaging the brainstem, basal important to use PET and SPECT in conjunction with
ganglia, and thalami. However, although the greater sen- anatomical imaging. Currently, SPECT and PET are
sitivity of MRI is helpful in the subacute and chronic more useful in guiding long-term therapy by helping
settings, it has not been established whether finding the establish a patient’s prognosis.
additional lesions that MRI can detect would signifi-
cantly change acute management of head trauma.44,50,53 Hemorrhage and edema
Moreover, white matter changes can be found in a large Hemorrhage or edema can cause mass effect, which
percentage of healthy middle-aged individuals. can directly compress vascular structures, resulting in
New MRI technology and acquisition sequences have ischemia and infarct, directly impinge upon other vital
improved the sensitivity of MRI. Ashikaga and col- structures, or herniate different parts of the brain. There-
leagues54 found fluid-attenuated inversion recovery fore, hemorrhage or edema that is either worsening or
(FLAIR) MRI, a sequence that suppresses the high signal already large enough to produce mass effect should be
from CSF by using a long inversion time (T1), to be urgently evacuated. Imaging plays a crucial role in iden-
more sensitive in detecting traumatic lesions and hema- tifying, following, and governing management of these
tomas (FIG. 1). McGowan and colleagues55 demon- conditions. Because hemorrhages frequently progress
strated that magnetization transfer imaging (MTI), which and large contusions often develop delayed hemorrhage
applies radio frequency power only to the protons in the or edema, repeat imaging is usually indicated, especially
macromolecules of tissues rather than the protons in if changes in neurological status occur. The location of
water, can add sensitivity to MRI. In a study by Lewine the bleed helps determine the risk of mass effect and
and colleagues,56 magnetic source imaging, using a com- management. It also affects the relative accuracy of CT
bination of MRI and magnetoencephalography, was su- and MRI.
perior to MRI alone. In separate studies, Sinson and Brain contusions are relatively common, occurring in
colleagues and Cecil and colleagues57,58 found proton up to 43% of patients with blunt trauma and frequently as
magnetic resonance spectroscopy to be a sensitive tool in coup or contrecoup injuries in deceleration or accelera-
detecting axonal injury in the corpus callosum of TBI tion trauma.60 Contusions associated with a fall, aniso-
patients. Functional MRI can demonstrate changes in coria, low GCS scores, or older patients (⬎60) are likely
regional brain activation in patients with mild TBI.59 to benefit from prompt neurosurgical intervention.61 On
However, all of these techniques still fell far short of noncontrast CT, contusions appear as low attenuation if
100% sensitivity in most studies reported in the litera- hemorrhage is absent and mixed or high attenuation if
ture. Moreover, they are not routinely available in many hemorrhage is present. In the acute stage, CT is more
medical centers, and while the improved sensitivity may sensitive than MRI, as the clot signal can be indistin-
allow better prediction of outcomes, future studies will guishable from brain parenchyma on MRI. After the first
be necessary to determine how these improvements may few hours, the hemoglobin in the contusion loses its
impact acute management of TBI. oxygen to become deoxyhemoglobin, which is still not

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FIG. 3. CT of an 80-year-old female status post fall showing a

FIG. 2. CT of an 87-year-old female status post fall showing a large left subdural hematoma in addition to substantial sub-
large subdural hematoma along the left cerebral convexity with arachnoid hemorrhage (arrows).
significant midline shift and effacement of the left lateral ventricle.

width, asymptomatic, located along the convexities, and

well visualized on T1-weighted MRI, but the concentra-
produce minimal midline shift.
tion of red blood cells and fibrin can cause low signal on
Whereas intraventricular hemorrhages are also uncom-
T2-weighted images. Over the next several days, as the
mon (2.8%), they can be associated with significant mor-
contusion liquefies and the deoxyhemoglobin oxidizes to
bidity and mortality. In one series, nearly half of patients
methemoglobin that is strongly paramagnetic, the contu-
with intraventricular hemorrhage developed elevated in-
sion becomes more easily visualized on MRI.62
crease intracranial pressure, and 10% required ventricu-
Subdural hematomas (FIG. 2) are also relatively com-
lar drainage. On noncontrast CT, blood is of higher at-
mon (10 –20% of patients with head trauma) and are
tenuation than the low attenuation CSF. CSF can
associated with high mortality (50 – 85%).61 The prox-
confound interpretation on conventional MRI sequences.
imity of the skull can create beam hardening effects and
CSF pulsation artifacts may be misinterpreted as intra-
also cause small hematomas to spread in a convex man-
ventricular hemorrhage. However, studies have sug-
ner making volume averaging problems more likely. Us-
gested that FLAIR and fast spin echo FLAIR MRI may
ing subdural CT windows (i.e., wider soft tissue win-
be superior to noncontrast CT.63
dows) can compensate for this problem. In the subacute
stage, after the initial several days, subdural hematomas Increased intracranial pressure
approach the attenuation of normal brain parenchyma Increased increased intracranial pressure (ICP) may
and MRI becomes more effective than CT in detection.63 require ICP monitoring and treatment by osmotic agents,
Subarachnoid hemorrhages (SAH; FIG. 3) are more drainage, or hyperventilation. The absence of findings on
common in children and the elderly, who have relatively CT certainly does not exclude elevated ICP, but the
large subarachnoid spaces, and occur in up to 11% of presence of any of the following should raise suspicion
TBI patients. It is often seen adjacent to a contusion. CT for intracranial hypertension: loss of gray-white junction
is superior to conventional MRI sequences in detecting which indicates cerebral edema, midline shift, a hematoma
acute SAH because the blood in acute SAH has a low mass, subdural hematoma, herniation, or change in ventric-
hematocrit and low deoxyhemoglobin, which makes it ular shape or size. Miller and colleagues65 found a linear
appear similar to brain parenchyma on T1- and T2- association between ICP and CT findings. CT also can
weighted spin echo images. However, FLAIR sequences guide percutaneous placement of ICP monitors.66
may find small acute or subacute SAH missed by CT and
conventional MRI.54,63,64 Cerebral herniation
Epidural hematomas are relatively uncommon (1– 4% Cerebral herniation is a potentially devastating occur-
of head trauma patients) and are often associated with rence that can lead to compression of vital structures, vas-
skull fractures. No intervention is required in stable epi- culature, and cranial nerves. Although herniation most fre-
dural hematomas that are less than 1.5 cm in maximum quently occurs in the setting of diffuse cerebral edema, it

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376 LEE AND NEWBERG

DTPA, CT cisternography, and MRI using a three-di-

mensional-constructive interference steady-state se-
quence. Whereas radionuclide studies are sensitive for
detecting the presence of CSF leaks, alone they are poor
at providing precise anatomic localization, which is
needed to guide surgical repair. Radionuclide cisternog-
raphy and contrast-enhanced CT cisternography have
been traditionally used. Studies have suggested that high-
definition CT alone may be adequate at detecting small
FIG. 4. CT scan of 35-year-old male with recent motor vehicle fractures that are the sites of CSF leaks, while sparing
accident demonstrating longitudinal fracture of the right petrous
bone (thin arrow) that extends into the skull base (thick arrow).
patients the discomfort of an intrathecal injection and
nasal pledgets.75,76
can occur with normal ICP when a small volume clot in- Foreign bodies
volves the border of two intracranial components.67 With the rising prevalence of firearms injuries, it is
CT and MRI can effectively diagnose cerebral herni- increasingly common to find foreign bodies in the head.
ation. However, in some cases, MRI may be superior. Depending on their size and velocity, foreign bodies can
The better soft tissue definition of MRI and its multipla- cause damage by several mechanisms: direct laceration,
nar imaging ability are particularly important in descend- shock-wave transmission (pulsations that emanate from
ing transtentorial herniation (caudal decent of the brain the front of a projectile), and cavitation (the motion of
through the tentorial incisura).67– 69 Moreover, beam the foreign body creates a suction force in its path).77 In
hardening artifacts from the skull base and partial vol- addition to finding foreign objects and determining if
ume averaging effects can interfere with CT interpreta- removal is necessary, imaging can help track the path
tion of tonsilar herniations (inferior displacement of the and subsequent movement of the foreign body and an-
cerebral tonsils through the foramen magnum into the ticipate the corresponding complications. Non-contrast
cervical spinal canal).67,70 Efforts have been made to CT remains the imaging modality of choice. Because
correlate quantitative measures of herniation on imaging metallic objects can cause significant streak artifacts, if
(i.e., the degree of shift of structures) with clinical out- necessary and possible, reimaging the patient while an-
comes. For example, in subfalcine herniation (midline gling the gantry to avoid the metallic object can alleviate
shift or cingulated herniation), the degree of displace- this problem. Studies on the use of MRI have been
ment of the septum pellucidum from the midline is pre- limited and have not found MRI to add information to
dictive of patient prognosis. In studies of descending affect acute management. Moreover, although many
transtentorial herniation, the degree of vertical descent commercial bullets are nonferromagnetic, if there is a
did not always correlate well with neurological signs. chance that ferromagnetic metal is present, MRI should
Because quantitative measures may be cumbersome and not be used.77
not be practical in clinical settings, qualitative measures
may be adequate in governing management.67,69,71,72 Vascular injury
Trauma can disrupt arterial walls and lead to dissec-
Fractures tions, aneurysms, or fistulae. The actual incidence of
Depending on the location, size, and type of fracture, vascular damage in head trauma is unclear because many
fractures may need to be surgically repaired to relieve or lesions are asymptomatic and nowadays angiography is
prevent CSF leakage, infection, hemorrhage, or vascular only performed when damage is suspected. Imaging is
compromise. Although plain films of the skull may de- used to identify the presence of the vascular lesion, in-
tect fractures, CT is the imaging modality of choice form the decision to repair by determining lesion size,
(FIG. 4). Open skull fractures depressed more then the location, and collaterals, and guide the type and approach
full thickness of the skull should be surgically elevated.73 of the intervention.
Fractures involving the paranasal sinuses, mastoid air Although contrast angiography has been the gold stan-
cells, or the entire thickness of the calvarium can allow dard for diagnosis of vascular lesions, MRI, MRA, and
air to enter the intracranial space. Such pneumocephalus CT angiography (CTA) are growing in use and capabil-
is often absorbed over time, but when persistent, raises ity.78 Unlike conventional angiography that only images
suspicion of a CSF lead. Patients with basilar skull frac- the lumen of blood vessels, MRA and CTA can provide
tures should receive a follow-up CT scan to exclude information about the arterial walls and MRI about the
pneumocephalus. Air appears as an area of low attenua- adjoining brain parenchyma.78 CTA offers better resolu-
tion on CT and signal void on MRI.74 tion and fewer flow-related artifacts than MRA.79 – 81
Several imaging modalities have been used to identify Treatment of vascular lesions can be via either open
CSF leaks: radionuclide with 111-Indium or 99m-Tc surgical or endovascular approaches. Imaging can delin-

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 NEUROIMAGING IN TRAUMATIC BRAIN IMAGING 377

eate anatomy and guide open surgical approaches.82,83 variety of physical, emotional, psychological, and social
Adjoining injury can block or hinder open surgical ap- difficulties that require multi-disciplinary therapy.92–94
proaches. Therefore, endovascular repair, which is also In fact, TBI patients may be unaware that specific neu-
less invasive, is frequently preferable. Dissections, aneu- rological deficits may be causing problems.95
rysms, and fistulae may be treated with endovascular coil
Chronic and delayed hemorrhage
embolization or stent-grafts. When the affected vessel
Hemorrhage can start or continue beyond the initial
cannot be treated, the parent artery may need to be oc-
few days after trauma. Reaccumulation of blood may
cluded.84 – 86
occur after evacuation, which can be best detected by
Cerebral ischemia CT. CT can detect other postoperative complications as
Almost all of the complications of head trauma can well, such as subdural empyema, brain abscess, brain
lead ultimately to cerebral ischemia, which if untreated stem hemorrhage, cerebral edema, tension pneumo-
can result in significant morbidity and mortality. Some- cephalus, and intracerebral hemorrhage. CT is also the
times head trauma complications are not readily identi- imaging modality of choice in revealing delayed cerebral
fiable, and decreased cerebral perfusion is the only sign hematoma, which should be suspected in anyone who
that a correctable problem exists. Cerebral ischemia can exhibits worsening level of consciousness, new third
occur in the absence of CT findings or before CT find- nerve palsy, or increasing ICP, can detect delayed extra-
ings evolve. Because conventional CT is poor at detect- axial hematomas, but may miss small subdural hemato-
ing cerebral ischemia, investigators have explored the mas caught by MRI.74,96
use of other modalities to detect alterations in cerebral As time progresses, hematomas decrease in attenuation
perfusion.78,87 until they becomes isodense with normal brain paren-
Perfusion CT, currently used in acute stroke and other chyma 3–10 weeks after the bleed, making it difficult to
cerebrovascular disorders, may have a role in the routine detect on CT.97,98 Because old blood still emits high
evaluation of head trauma patients. In perfusion CT, signal intensity on T1-weighted imaging, MRI is better at
nonionic iodinated contrast material is administered in- detecting chronic hemorrhage.99,100 Chronic subdural he-
travenously, and multiple sequential CT images of the matomas rarely spontaneously resolve, and therefore,
head track the flow of contrast material through the surgical or nonsurgical (e.g., mannitol, glucocorticoids)
brain.78 Comparisons with stable xenon CT and PET treatment may be necessary.
have found that perfusion CT accurately assesses brain Prognosis and CT
perfusion.88,89 Wintermark and colleagues90 found per- There is a significant need for objective measures to
fusion CT to be more sensitive (87.5% vs 39.6%) than predict the clinical course of TBI patients. Clinical vari-
conventional noncontrast CT in detecting cerebral con- ables, including GCS scores, extent of amnesia, duration
tusions. They also found abnormalities on perfusion CT of ventilatory support, and duration of intensive care unit
to correlate with unfavorable clinical outcomes. stay, have weak relationships with subsequent neuropsy-
However, cerebral perfusion can be difficult to inter- chiatric testing.101 Although some anatomic imaging
pret in the acute phase when cerebral blood flow is findings such as the presence of blood or subarachnoid
uncoupled from metabolism. Injured areas may be hypo-, hemorrhage, intraventricular hemorrhage, edema, mid-
iso-, or hyperperfused. Hyperemia can be global, which line shift, effacement of the basal cisterns, and location
has been linked with increased intracranial pressure, of lesions have been found to be predictive of overall
deep coma, and poor prognosis, or focal, which may or survival, they are not adequately predictive of functional
may not be associated with lower mortality.91 Further- outcome, even when clinical data are added.102–106
more, the perfusion abnormalities may result from pri- Ultimately, functional outcome depends on how many
mary vascular problems or from neuronal dysfunction neurons are preserved after injury. However, the location
and these two etiologies may be difficult to distinguish of damage and the ability of existing neurons to reorga-
using functional imaging studies. nize their connections to recover function are also criti-
cal. Neuronal injury is caused by direct injury, compres-
IMAGING AND CHRONIC MANAGEMENT sion, ischemia, and diffuse axonal injury (DAI). DAI,
which occurs in up to 48% of patients with closed head
In the chronic management of head trauma, imaging injuries, is caused by the shear force generated by the
has several potential roles: identifying postoperative neu- rapid deceleration in motor vehicle accidents.60 The
rophysiologic sequelae, evaluating the underlying func- force may either tear the axons or alter axoplasmic mem-
tional abnormalities associated with late complications branes, which subsequently impairs axoplasmic transport
of head trauma, predicting long-term prognosis, guiding and results in delayed damage to axons. DAI usually is
rehabilitation, and developing new therapies to prevent diffuse and bilateral, frequently involves the lobar white
secondary injury. TBI patients can suffer from a wide matter at the gray-white matter interface and may be

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378 LEE AND NEWBERG

reversible. Although DAI is rarely fatal, it can result in

significant neurological impairment. The number of le-
sions correlates with poorer outcomes, and lesions in the
supratentorial white matter, corpus callosum, and corona
radiate correlate with a greater likelihood that the patient
will remain in a persistent vegetative state. Whereas
hemorrhagic axonal injury can be seen on CT as multiple
foci of high attenuation, nonhemorrhagic injury can be
missed. In fact, CT is abnormal in less than half of all
patients with DAI.52,107
Prognosis and MRI
MRI is generally more sensitive than CT for detecting
neuronal damage. Patients with widespread MRI abnor-
malities or brain stem injuries usually show no signifi-
cant neurological recovery, even when they have normal FIG. 5. FDG-PET scan of 33-year-old male status post motor
CT scans and intracranial pressures. However, aside vehicle accident demonstrates hypometabolism affecting the
temporo-parietal and occipital (thin arrows) regions as well as
from such obvious cases of devastating injury, a consis- the caudate and putamen (thick arrows), which are findings sug-
tent relationship between MRI lesions and clinical or gesting diffuse axonal injury.
neuropsychological outcomes has not been demonstrat-
ed.108,109 with lesions on CT and vice versa.119,120 In general,
Various newer MR technologies may provide better SPECT is more sensitive than CT in detecting lesions in
information for prognosis and rehabilitation guidance. TBI patients.121,122 However, it is not always clear
Investigators have used MTI to detect white matter ab- whether the abnormalities observed on SPECT corre-
normalities in multiple sclerosis, progressive multifocal spond to direct or indirect injury, or possibly abnormal-
leukoencephalopathy, and Wallerian degeneration. ities from prior trauma or other neuropsychiatric condi-
Through MTI, a magnetization transfer ratio can be de- tions. CBF abnormalities are commonly seen in mild TBI
rived and quantitatively measure the structural integrity patients with chronic symptoms, even if no structural
of tissues. MTI changes have been found to be more damage is apparent.123 Often the size of the lesion on
sensitive than T2-weighted MRI in detecting histologic SPECT exceeds the size of the lesion on CT or MRI.
axonal damage in animal models.110,111 Bagley and col- SPECT appears to be better than CT or MRI in deter-
leagues112 found associations between MTI abnormali- mining long-term prognosis.122,124 A negative initial
ties and neurological deficits. SPECT scan after trauma seems to strongly predict a
Proton MR spectroscopy can detect the amount of favorable clinical outcome.125 A worse prognosis is as-
creatinine, choline, myo-inositol, and N-acetylaspartate sociated with larger lesions, multiple defects, and lesions
(NAA) in a selected tissue volume.113 NAA, whose func- in the brainstem, temporal lobes, parietal lobes, or basal
tion has not been clearly established, has been found to ganglia. Abnormal SPECT can be predictive of neuro-
be a marker for neuronal loss in a wide variety of con- psychological deficits.126 Studies have found that de-
ditions including spinal cord injury, amyotrophic lateral creased blood flow to various parts of the brain correlate
sclerosis, Parkinson disease, Huntington disease, isch- with various types of behavior: the frontal lobes with
emic stroke, progressive multifocal leukoencephalopa- disinhibitive behavior, the left cerebral hemisphere with
thy, epilepsy, and multiple sclerosis, as reviewed sepa- increased social isolation, and the right hemispheric ar-
rately in the current volume.5,113 Animal models of brain eas with increased aggressive behavior.127 Deficits in
injury have shown NAA levels to decrease within hours frontal lobe and thalamic perfusion have been linked to
after injury.5,114,115 Several investigators have found lower impairments in executive functioning.128 However, no
NAA to creatinine ratios as measured by MR spectroscopy consistent correlation between SPECT abnormalities and
to correlate with poorer clinical outcomes.58,116,117 Finally, neuropsychological test scores has been established.129
functional MRI studies by McAllister and colleagues59 Because MRI detects lesions missed by SPECT and vice
found persistent changes in the brain activation patterns versa, a combination of MR and SPECT may be even
of mild TBI patients compared with controls when given better for determining prognosis.130
various working memory tasks.
Prognosis and PET
Prognosis and SPECT As reviewed separately in the current volume,131 PET
SPECT can detect abnormalities in cerebral blood flow measures the cerebral metabolism of various substrates,
(CBF) as reviewed separately in the current volume.118 most commonly fluorodeoxyglucose in the measurement
Not all alterations in cerebral blood flow are associated of glucose metabolism, which should correspond to neu-

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 NEUROIMAGING IN TRAUMATIC BRAIN IMAGING 379

FIG. 6. FDG-PET scan of a 38-year-old male with head injury 15 FIG. 8. FDG-PET scan of a 49-year-old female with MVA 6
years ago with encephalomalacia in the left temporal lobe dem- years ago and persistent headache and memory problems with
onstrates marked hypometabolism in the left temporal lobe (thin bilateral decreased temporal lobe metabolism (arrows).
arrow) and right cerebellar hypometabolism (thick arrow) con-
sistent with crossed cerebellar diaschisis.
PET imaging can also uncover other potentially con-
founding neuropsychiatric conditions such as depression
ronal viability. PET can also be used to diagnose patients
or drug induced effects (FIG. 9). Furthermore, several
with DAI to determine the extent of damage and prog-
studies have shown that the glucose metabolic abnormal-
nosis (FIG. 5). PET studies may help delineate reversible
ities observed on PET are associated with a number of
and irreversible lesions to direct therapeutic interven-
possible mechanisms and therefore may not provide suf-
tions toward preventing further damage. The major lim-
ficient data to assess global function and level of con-
itation of PET imaging is that it cannot distinguish be-
sciousness in head injury patients.138,139
tween functional abnormalities associated and not
associated with structural damage. In general, studies Imaging and new therapies
have found that cerebral dysfunction can extend far be- Imaging is playing a crucial role in defining the mech-
yond the boundary of anatomical lesions and may even anisms of secondary injury in TBI and, in turn, poten-
appear in locations remote from the trauma. Alavi and tially identifying targets of new therapies.140 TBI is
colleagues132 showed that approximately 33% of ana- found to initiate an inflammatory cascade that results in
tomical lesions were associated with larger and more the release of amino acids, such as glutamate and aspar-
widespread metabolic abnormalities. As much as 42% of tate, and free radicals, that may lead to further tissue
PET abnormalities were not associated with any anatom- damage.141 Other potential culprits include nitrous oxide,
ical lesions observed on anatomical images. The meta- endogenous opioid peptides such as naloxone, cat-
bolic effects of cortical contusions, intracranial hema- echolamines, acetylcholine, thyrotropin-releasing hor-
toma, and resultant encephalomalacia are primarily mone (TRH), lactate, and adenosine.142,143 Cytokines
confined to the site of injury (FIG. 6), whereas those of such as tumor necrosis factor (TNF) and interleukins 1,6,
subdural and epidural hematomas often are widespread and 8, also have found to increase following TBI.144,145
and may even affect the contralateral hemisphere. DAI PET, functional MRI, MR spectroscopy, and SPECT,
results in diffuse hypometabolism.132,133 have been and will continue to be crucial in identifying
Alavi and colleagues132 found that GCS scores of 13 the concentrations and locations of these various mole-
and lower were associated with whole brain hypometab- cules in animal and human brains following injury. In
olism on 18F-fluorodeoxyglucose (FDG)-PET. Studies animal models, imaging has been used to determine the
have shown that PET can uncover areas of cerebral hy- effectiveness of glutamate and N-methyl-D-aspartate re-
pometabolism that are associated with neurological and ceptor blockers and antioxidants on TBI.146,147 Ischemia
behavioral dysfunction but not detected on CT, MRI, or and reperfusion injury are thought to play important
EEG (FIGS. 7 and 8).134,135 Moreover, some of these roles, and imaging has been important in understanding
areas eventually develop structural abnormalities such as perfusion changes after TBI as well helping develop
encephalomalacia and atrophy on CT. Separate studies therapies to alter perfusion.148,149 Using PET to measure
by Gross136 and Ruff137 found PET hypometabolism to CBF, oxygen metabolism, and the oxygen extraction
significantly correlate with overall clinical complaints
and overall neuropsychological test results. However,

FIG. 9. FDG-PET scan of a 69-year-old boxer with visual and

FIG. 7. FDG-PET scan of a 43-year-old female with head injury memory problems evaluated for dementia pugilistica. The find-
2 years ago now with cognitive and memory dysfunction as well ings demonstrate moderate global cortical hypometabolism and
as language problems demonstrates hypometabolism in the en- preservation of subcortical and occipital structures most con-
tire left hemisphere (arrow) related to the head trauma. sistent with depression, not DAI.

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380 LEE AND NEWBERG

fraction (OEF) in severe brain injury, Yamaki and col- 12. Bock K, Duus JO, Hindsgaul O, Lindh I. Analysis of conforma-
tionally restricted models for the (1– 6)-branch of asparagine-
leagues150 found that long-lasting anaerobic glycolysis linked oligosaccharides by n.m.r.-spectroscopy and HSEA calcu-
with high OEF and a relatively low ratio of oxygen lation. Carbohydr Res 228:1–20, 1992.
metabolism to glucose metabolism predicted poor out- 13. Birn B, Gadegard E, Lind PO, Bergsoe K, Metze E, Birn H, et al.
[Social and behavioral subjects in dental care training]. Tandlae-
comes. SPECT and PET imaging have been used to mea- gebladet 80:555–559, 1976.
sure improvements in cerebral blood flow associated with 14. Ingebrigtsen T, Romner B. Management of minor head injuries in
hyperbaric oxygen therapy151 and hyperventilation152 ther- hospitals in Norway. Acta Neurol Scand 95:51–55, 1997.
apy in TBI patients. 15. Ingebrigtsen T, Romner B. Routine early CT-scan is cost saving
after minor head injury. Acta Neurol Scand 93:207–210, 1996.
16. Schunk JE, Rodgerson JD, Woodward GA. The utility of head
CONCLUSIONS computed tomographic scanning in pediatric patients with normal
neurologic examination in the emergency department. Pediatr
In the future, the already significant role of imaging in Emerg Care 12:160 –165, 1996.
17. Haydel MJ, Preston CA, Mills TJ, Luber S, Blaudeau E, DeB-
guiding therapy may grow. Technological improvements lieux PM. Indications for computed tomography in patients with
continue to reduce scanning time and improve resolution. minor head injury. N Engl J Med 343:100 –105, 2000.
New methods are being developed to quantify damage 18. Stiell IG, Lesiuk H, Wells GA, Coyle D, McKnight RD, Brison R,
et al. Canadian CT head rule study for patients with minor head
on images and perhaps improve predictive power. A injury: methodology for phase II (validation and economic anal-
growing number of minimally invasive, image-guided ysis). Ann Emerg Med 38:317–322, 2001.
techniques are replacing open surgical techniques. Imag- 19. Stiell IG, Lesiuk H, Wells GA, McKnight RD, Brison R, Clement
C, et al. The Canadian CT Head Rule Study for patients with
ing is increasingly vital to the development of new ther- minor head injury: rationale, objectives, and methodology for
apies and may be used to measure patient response to phase I (derivation). Ann Emerg Med 38:160 –169, 2001.
these therapies. Imaging has and will continue to influ- 20. Quayle KS, Jaffe DM, Kuppermann N, Kaufman BA, Lee BC,
Park TS, et al. Diagnostic testing for acute head injury in children:
ence therapy and may improve outcomes for what is when are head computed tomography and skull radiographs in-
clearly a significant health care problem. dicated? Pediatrics 99:E11, 1997.
21. Ingebrigtsen T, Romner B, Kock-Jensen C. Scandinavian guide-
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