Residents Section Pat tern of the Month

Ho et al.
Cerebral Edema
Residents Section
Pattern of the Month

Residents

inRadiology
Mai-Lan Ho1
Rafael Rojas
Ronald L. Eisenberg

American Journal of Roentgenology 2012.199:W258-W273.

Ho ML, Rojas R, Eisenberg RL

Keywords: cerebral edema

DOI:10.2214/AJR.11.8081
Received October 3, 2011; accepted after revision
March 7, 2012.
1

All authors: Department of Radiology, Beth Israel

Deaconess Medical Center, Harvard Medical School, 330
Brookline Ave, Boston, MA 02215. Address correspondence
to R. L. Eisenberg (rleisenb@bidmc.harvard.edu).
WEB
This is a Web exclusive article.
AJR 2012; 199:W258W273
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his article reviews the pathophysiology and imaging appearances of cerebral

edema or increased water content. Edema is a common response to various forms
of brain injury, and the causes can be categorized as cytotoxic, vasogenic, interstitial, or combined. Identification of the dominant imaging pattern, in conjunction with additional radiologic findings and clinical history, often yields clues to the diagnosis. Table 1 lists the types of cerebral edema and their associated causes.
CT is the initial screening examination for patients presenting with new-onset neurologic
symptoms. On CT, edema manifests as decreased attenuation relative to surrounding normal
parenchyma. Standard CT brain viewing settings (window width, 100 HU; window level, 40
HU) highlight the contrast between gray and white matter, whereas narrower stroke window
settings (window width, 30 HU; window level, 30 HU) accentuate focal areas of hypodensity.
Abnormalities can be characterized in terms of location; pattern of gray-white matter involvement and associated mass effect as evidenced by midline shift; sulcal, ventricular, cisternal
effacement; and cerebral herniation. Coronal and sagittal multiplanar reformation images are
frequently useful for further localization and quantification.
MRI provides excellent soft-tissue contrast resolution and thus is often requested for evaluation
of underlying lesions. On MRI, edema produces high signal on T2-weighted imaging and low
signal on T1-weighted imaging. Diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC) sequences distinguish between cytotoxic edema (restricted diffusion) and vasogenic or interstitial edema (normal or increased diffusion). Diffusion-tensor imaging (DTI)
uses tensor analysis to calculate the degree of anisotropy on the basis of the magnitude and direction
of water diffusion in each voxel in the brain. A
commonly used parameter is fractional anisot- TABLE 1: Distribution of
Cerebral Edema
ropy, which reflects the principal directional
eigenvector of molecular motion and is used
in white matter tractography. FLAIR sequences, which suppress CSF signal, are useful for visualizing periventricular signal abnormalities due to interstitial edema. T2* gradient-recalled echo (GRE) and susceptibilityweighted imaging sequences are useful for
identifying associated hemorrhage or calcification. Time-of-flight images and abnormal
flow voids can suggest the presence of a vascular malformation. Contrast enhancement
may be seen in neoplasms, active infection or
inflammation, and vascular lesions.
Symptoms of cerebral edema are nonspecific and related to secondary mass effect,
vascular compromise, and herniation. Clinical
and radiologic changes are usually reversible
in the early stages as long as the underlying
cause is corrected. With mild edema, increased
brain volume is compensated for by decreases

Cytotoxic
Arterial infarction
Small vessel disease
Vasogenic
Neoplasm
Hemorrhage
Venous thrombosis
Arteriovenous shunts
Interstitial
Hydrocephalus
Combined
Trauma
Hypoxic-ischemic encephalopathy
Osmotic
Hydrostatic
Infection or inflammation

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in CSF and blood volume. However, rapidly progressive edema overwhelms cerebral autoregulatory mechanisms, resulting in structural compression; cerebral ischemia; and, ultimately, fatal
cerebral herniation. To prevent this, a variety of empirical medical treatments are used, including
hyperventilation, osmotherapy (mannitol and hypertonic saline), loop diuretics, hypothermia,
sedation (propofol, barbiturates), and neuromuscular paralysis (succinylcholine). Corticosteroids, which reduce the permeability of the blood-brain barrier, can also be used to control vasogenic edema. For cases refractory to medical management, such as severe trauma and major
strokes, emergency decompressive craniectomy may be performed as a last resort.
In this article, we will review the pathophysiology and imaging appearances of various
causes of cerebral edema. Characterization of edema location and distribution, along with
associated parenchymal abnormalities, is critical for early and accurate diagnosis, workup,
and intervention.

Cytotoxic Edema

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Cytotoxic edema results from derangements in adenosine triphosphate (ATP)-dependent

transmembrane sodium-potassium and calcium pumps and is usually caused by cerebral ischemia or excitotoxic (secondary to excessive neurotransmitter stimulation) brain injury. This
leads to intracellular accumulation of fluid in neurons, glial cells, axons, and myelin sheaths.
The gray matter is affected first because of its high metabolic activity and greater astrocyte
density. Ultimately, both the gray and white matter become involved, with corresponding loss

Fig. 1Middle cerebral artery (MCA) infarct.

A, Unenhanced CT image of early MCA infarct shows
subtle edema in right lentiform nucleus, consisting
of putamen (white arrow) and globus pallidus (black
arrow).
B, Unenhanced CT image of subacute MCA infarct
shows cytotoxic edema that causes loss of left
insular ribbon (arrow).
C, Unenhanced CT image shows hyperdense MCA
sign on right (arrow).

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of differentiation on CT. There is overall restriction of diffusion of water molecules
across the cell membrane and within the cytoplasm resulting in regional high signal on
DWI and low signal on ADC images. Initially, the blood-brain barrier remains intact and
extracellular water does not increase, yielding normal DTI maps and fractional anisotropy. Severe or repeated insults overwhelm
transmembrane ion pumps, causing cell death
with breakdown of the blood-brain barrier
and resulting vasogenic edema. Late complications include neuronal apoptosis, atrophy,
and gliosis.

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Arterial Infarction
Acute arterial infarction produces a hypoxic state with rapid ATP depletion secondary to depolarization, inflammation, oxidative or nitrosative stress, and apoptosis. Cytotoxic edema develops within 30 minutes of
arterial occlusion, peaks between 24 and 72
hours after infarction, and persists for up to
24 hours after reperfusion. On CT, loss of
Fig. 2CT angiography of infarct. Volume-rendered
reconstruction image of circle of Willis shows filling
gray-white matter differentiation corresponds
defects involving distal left internal carotid artery
to a major vascular distribution. Early signs
(arrowhead), A1 segment of anterior cerebral artery
of middle cerebral artery infarction include
(thin arrow), and M1M2 segments of middle cerebral
obscuration of the lentiform nucleus (Fig.
artery (thick arrow).
1A) and loss of the insular ribbon (Fig. 1B);
these areas of normally high gray-white contrast are supplied by small perforating branches. A
large intravascular thrombus may also appear as increased attenuation on unenhanced scans
(hyperdense artery sign) (Fig. 1C). Progressive edema results in an increase in overall volume,
manifested by effacement of sulci, ventricles, and cisterns.
Emergent evaluation of acute stroke begins with unenhanced CT, which screens for focal
edema, hemorrhage, and mass effect. If imaging or clinical findings suggest acute stroke, further assessment can be performed with contrast-enhanced CT angiography or time-of-flight MR
angiography. These modalities generate multiplanar and volume-rendered reconstructions of
the intracranial circulation, which are useful for characterizing vascular abnormalities, including occlusions, stenoses, dissections, aneurysms, and anatomic variants (Fig. 2).
MRI can also be used in the acute stroke setting, although technical and personnel requirements restrict its application in many centers. DWI is the most sensitive sequence for detection of hyperacute infarction (< 30 minutes after presentation), preceding the identification of
changes on CT (6 hours) and T2-weighted imaging (612 hours). Restricted diffusion in
acute infarcts corresponds to areas of increased and decreased signal on DWI and ADC
maps, respectively. As infarcts evolve into the subacute and chronic stages, there is progression to vasogenic edema and encephalomalacia. This is reflected by progressive increase in
T2/FLAIR intensity, with concomitant normalization of diffusivity (Fig. 3). Unenhanced
time-of-flight MR angiography or arterial spin labeling can also be performed. However,
spatial resolution is inferior compared with CT, and the images are prone to motion, susceptibility, and flow artifacts.
Complementary modalities for quantifying cerebral blood flow include SPECT and xenon
CT. In SPECT, 99mTc-labeled HMPAO (hexamethylpropylene amine oxime) is taken up by
cerebral tissue in concentrations proportional to blood flow. Xenon CT uses xenon gas, which
is radiodense and lipid-soluble. Once dissolved in the blood, it can pass through the bloodbrain barrier into the parenchyma. Images are obtained before, during, and after inhalation.
Neuroangiography is considered the reference standard for evaluation of the cerebral circulation. However, it is an invasive procedure with associated risks, most importantly, cerebral embolism. Nevertheless, neuroangiography is the standard of care for patients requiring

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Fig. 3MR images of patient with infarct who has

mitochondrial encephalomyopathy, lactic acidosis,
and strokelike episodes (MELAS).
A, T2-weighted image reveals increased signal in
both occipital lobes, right (thick arrow) greater than
left (thin arrow).
B, Diffusion-weighted image also shows bilateral
hyperintensities, right (thick arrow) greater than left
(thin arrow).
C, Apparent diffusion coefficient image shows
decreased signal on right (thick arrow) but normal
signal on left (thin arrow). Therefore, right-sided lesion
is acute infarct with true restricted diffusion. Leftsided lesion represents subacute or chronic infarct
with T2 shine-through on diffusion-weighted images.

C
interventions, such as intraarterial thrombolysis and thrombectomy, angioplasty or stenting,
and aneurysm or arteriovenous malformation (AVM) clipping or coiling (Fig. 4).
Stroke prognosis depends on patient age, duration of symptoms, cause and severity of occlusion, affected vascular territory, and presence of collateral circulatory pathways. In the
first 3 hours after the onset of symptoms, nonhemorrhagic ischemic stroke is treated with
systemic IV tissue plasminogen activator (tPA). After this time window, IV tPA is no longer
effective. Within 6 hours, intraarterial tPA can be directly administered during angiography.
Mechanical devices, such as the MERCI (Mechanical Embolus Removal in Cerebral Ischemia, Concentric Medical) retriever, can be used for additional thrombectomy. Antiplatelet
agents, such as clopidogrel (Plavix, Sanofi-Aventis) and aspirin, minimize parenchymal damage and decrease the risk of future stroke.

Small Vessel Disease

Small perforating vessels branch from the circle of Willis and vertebrobasilar circulation to
supply the basal ganglia, deep white matter, cerebellum, and brainstem. Hypertension and atherosclerosis predispose to injury of these penetrating end arteries, resulting in lacunar infarcts
or hemorrhage. Advanced age, radiation injury, meningoencephalitis, vasculitis, and autoimmune disorders are additional risk factors. Amyloid angiopathy is a special form of microangiopathy in which -amyloid peptide accumulates within vessel walls, predisposing to multifocal

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Ho et al.
and lobar hemorrhagic strokes. Depending
on the region affected, the clinical presentation may be silent or include some combination of motor, sensory, and ataxia or movement symptoms. The time course may be
acute, chronic, or fluctuating. If there is significant white matter involvement, subcortical
dementia (Binswanger disease) may develop,
with deterioration of executive functions.
True cortical signs, including memory loss
and aphasia, are not present.
On CT, small vessel ischemic disease
manifests as multiple white matter hypodensities in the subcortical and periventricular
white matter in the region of small penetrating end arteries. Focal lacunes can also be
seen in the basal ganglia and supratentorial
regions (Fig. 5A). Spontaneous hemorrhage,
which is common in patients with hypertension, is generally located in the basal ganglia
Fig. 4Angiography of infarct in same patient as
or thalami. In the presence of sepsis or conin Figure 3. Injection of left common carotid artery
genital heart disease, shower emboli can also
before treatment (left) reveals filling defect in distal
produce watershed infarcts at the borders
left internal carotid artery (ICA) (arrowhead), with
failure of opacification of anterior cerebral artery
between vascular zones. MRI shows T2/
(ACA) and middle carotid artery (MCA). After
FLAIR hyperintensity in ischemic areas
chemical and mechanical thrombolysis (right), there
(Fig. 5B). Diffusion restriction is present in
is complete opacification of ICA, ACA (thin arrow),
the acute phase but normalizes in the suband MCA (thick arrow).
acute and chronic phases.
Other causes of microangiopathy show varying distributions of cerebral involvement. In
amyloid angiopathy, multifocal and lobar hemorrhagic strokes are common. GRE/susceptibility-weighted imaging is useful for detecting foci of occult microhemorrhage (Fig. 6).

Vasogenic Edema
Vasogenic edema is caused by breakdown of the tight endothelial junctions comprising the
blood-brain barrier, secondary to either physical disruption or release of vasoactive compounds.

Fig. 5Small vessel ischemic disease.

A, Unenhanced CT image at level of centrum semiovale shows diffuse subcortical white matter hypodensity as
well as more focal hypodensities (arrows) representing lacunes.
B, FLAIR image shows multiple periventricular hyperintense foci.

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Fig. 6Amyloid angiopathy.

A, Unenhanced CT image identifies hyperdense
region of acute hemorrhage (asterisk) centered in
right basal ganglia, suggestive of hypertensive cause.
Hematoma is surrounded by thin rim of vasogenic
edema and extends into right frontal horn. Foci of
chronic encephalomalacia are noted in both frontal
lobes (arrows).
B, T2-weighted MR image shows susceptibility in
area of hemorrhage (asterisk), with hyperintense
surrounding edema. There is also hemorrhage
layering in both occipital horns (arrows).
C, T2*-weighted gradient-recalled echo MR image
again shows acute hemorrhage in right frontal horn
(asterisk). There are multiple foci of susceptibility
throughout cerebral parenchyma and sulci (white
arrows), signifying chronic microhemorrhage and
superficial siderosis. There is focal encephalomalacia
in right frontal lobe (black arrow), corresponding with
findings on CT.

C
As a result, intravascular proteins and fluid exude into the extracellular space. Expanded extracellular fluid yields decreased T1 signal, increased T2 signal, and decreased fractional anisotropy. The white matter is preferentially affected because of its lower density with multiple unconnected parallel axonal tracts.
In the early stages, vasogenic edema may be reversible with reconstitution of the bloodbrain barrier. Excess fluid can be resorbed via bulk flow of CSF and lymphovascular clearance, and extracellular protein is either digested by macrophages or transported back into
cells via transmembrane carriers. However, chronic or recurrent injury often produces irreversible myelin damage. In addition, mass effect from edema can reduce cerebral perfusion
pressure, leading to ischemia and cytotoxic edema.

Neoplasm
Both benign and malignant neoplasms are associated with vasogenic edema, which results
from tumor angiogenesis with disruption of the blood-brain barrier. Neoplastic lesions may
be primary or secondary, unifocal or multifocal, and their imaging appearances vary with the
underlying histology. On CT, vasogenic edema appears as regional hypodensity confined to
the white matter. Due to low soft-tissue contrast, the responsible lesions are often incompletely characterized but may show focal areas of hemorrhage, calcification, or necrosis. MRI
is usually ordered for tumor characterization and should include unenhanced and contrast-

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Fig. 7Neoplastic vasogenic edema.

A, In patient with type 1 edema associated with intracranial melanoma metastases, contrast-enhanced T1weighted image reveals enhancing masses (arrows) in right frontal and left parietal lobes.
B, FLAIR sequence in same patient as in A shows surrounding edema that is well circumscribed and confined to
immediate vicinity of masses (arrows).
C, In patient with type 2 edema in multifocal glioblastoma multiforme, contrast-enhanced T1-weighted image
reveals multiple enhancing foci (arrows) in left occipital lobe.
D, FLAIR sequence in same patient as in C shows diffuse infiltrative edema (arrows), reflecting tumor
microinvasion. There is extension across midline through splenium of corpus callosum (asterisk), characteristic
of glioblastoma multiforme.

enhanced T1-weighted imaging, T2-weighted imaging, FLAIR, GRE/susceptibility-weighted

imaging, DWI, ADC, and DTI sequences.
Two distinct types of peritumoral vasogenic edema have been described. Type 1 is seen in the
immediate vicinity of low-grade and nonglial tumors, such as meningiomas and metastases. This
type is thought to be secondary to parenchymal compression, with secondary ischemia and necrosis that persist even after tumor removal (Fig. 7A). Type 2 occurs with high-grade glial tumors, which are highly infiltrative and cause additional derangements of the blood-brain barrier.
This pattern of edema spreads throughout the ipsilateral cerebral hemisphere, with fingerlike
projections reflecting tumor microinvasion (Fig. 7B). After resection, there may be partial or
complete resolution of edema over several months. Compared with type 1 edema, there is increased diffusivity on DWI and decreased fractional anisotropy on DTI, likely reflecting greater

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parenchymal destruction by malignant cell infiltration. When seen in small or benign tumors, this
atypical pattern of edema is highly suspicious for malignant degeneration.
Definitive surgical management consists of complete resection, possibly with adjuvant chemotherapy and radiation. Corticosteroids used to reduce vasogenic edema likely operate by
suppressing tumor angiogenesis factors such as vascular endothelial growth factor. Other
experimental molecular agents have been used to target tumor cell growth, invasion, migration, and apoptosis.

Hemorrhage

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Vasogenic edema is frequently seen adjacent to large areas of intracranial hemorrhage secondary to hypertension, trauma, coagulopathies, amyloid angiopathy, vascular abnormalities, stroke,

Fig. 8Cerebral venous thrombosis.

A, Unenhanced CT image shows cord sign of hyperdense thrombus within left transverse and sigmoid sinuses
(arrows). There is subtle adjacent vasogenic edema (asterisk).
B, Rotational maximum-intensity-projection image of MR venogram shows marked attenuation of left transverse
and sigmoid sinuses (arrows). Abnormal signal indicative of thrombus was confirmed on T1-weighted imaging.

Fig. 9Arteriovenous malformation (AVM).

A, Unenhanced CT image shows lobulated hyperdense lesion with calcified phleboliths (arrow). Note mild
surrounding vasogenic edema (asterisks).
B, CT angiography image shows AVM involving entire left cerebral hemisphere, with nidus in left frontal lobe.

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Fig. 10Dural arteriovenous fistula.

A, Unenhanced CT image shows marked vasogenic
edema in left temporal lobe, with linear areas of
sparing (arrows).
B, T2-weighted MR image shows increased signal
corresponding to edema. Multiple serpiginous
internal flow voids are noted, with dilated
perimedullary (thin white arrow), transcortical (black
arrow), and cortical (thick white arrow) veins.
C, Contrast-enhanced T1-weighted MR image shows
avid enhancement of dural arteriovenous complex.

and metastases. The mechanism is presumed to involve exudation of serum proteins during clot
formation, leading to perihematoma inflammation and blood-brain barrier breakdown. Edema
manifests as surrounding hypoattenuation on CT scans and as T2/FLAIR hyperintensity on MR
images. At times, it may produce mass effect up to twice the volume of the original lesion (Fig.
6). Medical management may be instituted to reduce elevated intracranial pressure. Impending
herniation may require surgical evacuation and decompressive craniectomy.

Venous Thrombosis
Cerebral venous thrombosis is a rare form of infarction in which there is obstruction of
venous outflow, leading to parenchymal congestion and breakdown of the normal blood-brain
barrier. Risk factors include trauma, thrombophilic conditions (dehydration, pregnancy, cancer, medications, hypercoagulopathies), and chronic inflammation or infection. Patients may
present with headache, vision changes, and seizures. Strokelike symptoms can also occur but
are typically more indolent and poorly lateralized in comparison with arterial disease.
On unenhanced CT, hyperdense clot within the affected vein may produce a cord sign.
Surrounding vasogenic edema is not confined to a typical arterial distribution (Fig 8A). Hemorrhagic transformation is common and appears heterogeneous and gyriform. CT venography
confirms the presence of filling defects, with the classic empty delta sign produced by thrombus in the superior sagittal sinus. MR venography can also be used for assessment for cerebral
venous thrombosis. However, because T2 flow-related artifacts are common, T1-weighted

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sequences should be examined to verify signal changes in the region of suspected thrombus (Fig. 8B).
Treatment of cerebral venous thrombosis
involves anticoagulants; on rare occasions,
systemic or angiographic thrombolysis may
be required. Even in cases of hemorrhagic
transformation, the potential benefits of anticoagulation almost always outweigh the risks.
Without treatment, increasing perfusion pressures are transmitted back into the arterial system, leading to arterial infarction with associated cytotoxic edema. Severe cases may require ventriculostomy or decompressive craniectomy to prevent fatal herniation.

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Arteriovenous Shunts
Cerebral arteriovenous shunts can be classified as AVMs or arteriovenous fistulas (AVFs). Fig. 11Ependymitis granularis. FLAIR MR image
These lesions are characterized by abnormal shows small triangular areas of hyperintensity
(arrows) around anterolateral frontal horns. This
communication between the cerebral arterial represents normal anatomic variant.
and venous systems. AVMs are congenital malformations characterized by an intervening capillary bed or central nidus. In contrast, AVFs have
direct arteriovenous communications and are more often acquired than congenital. These may occur secondary to venous thrombosis or obstruction from trauma, infection, hypercoagulable states,
neoplasms, or vascular disease.
Mechanisms of cerebral edema in arteriovenous shunts are incompletely understood. Potential causes include impaired venous drainage, arterial steal phenomena, and rupture with
hemorrhage. Venous hypertension can be caused by hemodynamic shunting, thrombosis,
mass effect, or hydrocephalus. Elevated venous pressures lead to outflow obstruction, edema,
and ultimately ischemia.
On unenhanced CT, arteriovenous malformations may be visible as lobulated hyperdense
masses with internal calcified phleboliths. CT, MRI, or conventional angiography reveals a
serpiginous tangle of vessels with a central nidus connecting the feeding arteries and draining
veins (Fig. 9). AVFs are characterized by direct connections between the cerebral, dural, or

Fig. 12Normal pressure hydrocephalus.

A, Unenhanced CT image shows marked lateral ventricular enlargement out of proportion to sulci.
Hypodensities surrounding frontal and occipital horns (arrows) reflect transependymal migration of CSF.
B, FLAIR MR image again shows central ventricular dilation and grade 1 periventricular hyperintensities
(arrows). Scattered foci of microvascular disease are also present.

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Fig. 13Traumatic brain injury.

A, Unenhanced CT image shows hemorrhagic
contusions with internal blood products and
surrounding edema in inferior frontal lobes, left
(asterisk) greater than right.
B, Unenhanced CT image in same patient as in
A shows hemorrhagic contusion in left anterior
temporal lobe (asterisk).
C, Unenhanced CT image of different patient with
diffuse axonal injury shows multiple punctate
hemorrhages (arrows) centered at gray-white
junction.
D, FLAIR image in same patient as in C shows multiple
regions of signal abnormality indicating edema
(arrows).
E, Gradient-recalled echo image in same patient as in
C shows additional foci of microhemorrhage (arrows).

E
pial arteries and veins. On MRI, slow-flow malformations show increased T2 (fluid) signal,
whereas high-flow malformations and fistulas produce T2 signal voids (flow artifact) (Fig.
10). Although the primary pattern of edema is vasogenic, hemodynamically significant lesions may produce ischemia with associated cytotoxic edema.

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Most AVMs can be managed expectantly. However, AVFs and large AVMs require intervention because of significant hemodynamic effects. Transcatheter embolization or surgical excision may be performed, depending on lesion size, location, and pattern of venous drainage.

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Interstitial Edema
Interstitial (hydrocephalic) edema occurs in the setting of increased intraventricular pressures, which cause rupture of the ventricular ependymal lining. This allows transependymal
migration of CSF into the extracellular space, most commonly the periventricular white matter. Fluid composition is identical to CSF, with similar ionic concentrations and negligible
protein levels (as opposed to vasogenic edema). Various causes of interstitial edema include
obstructing masses, meningitis, subarachnoid hemorrhage, and normal pressure hydrocephalus. In contrast, ependymitis granularis refers to small triangular areas of abnormal signal
around the anterolateral frontal horns (Fig. 11). This normal anatomic variant results from
regionally decreased myelin, increased extracellular fluid, or focal breakdown of the ependymal lining with gliosis. On CT, the combination of ventriculomegaly and increased periventricular hypodensity is suggestive of the diagnosis of interstitial edema (Fig. 12A). MRI is
a more sensitive imaging modality, showing hypointensity on T1-weighted imaging and periventricular hyperintensity on T2-weighted imaging/FLAIR (Fig. 12B). Periventricular hyperintensity can be graded according to its severity. Grade 1 (discontinuous) appears as focal
signal abnormalities adjacent to the frontal and occipital horns and the atria of the lateral
ventricles. Grades 2 and 3 (continuous and periventricular halo) completely surround the
ventricles and are of varying thickness. Grade 4 (diffuse white matter abnormality) extends
to the gray-white matter junction. Because of the extracellular location of edema, DTI maps
may show regionally decreased fractional anisotropy. However, the average overall diffusivity is normal on DWI and ADC maps.
In symptomatic patients, decompression with resection of the obstructing lesion (noncommunicating hydrocephalus) or ventriculostomy catheter placement (communicating hydrocephalus) allows normalization of ventricular pressures. In turn, this enables normal antegrade resorption of interstitial fluid across the ependymal lining and back into the ventricular
system. Without intervention, the findings ultimately progress to cerebral atrophy and gliosis.

Fig. 14Hypoxic-ischemic encephalopathy.

A, MR image of patient with carbon monoxide inhalation injury shows T2 signal abnormalities in both globus
pallidi (arrows). Slow diffusion was identified on diffusion-weighted imaging and apparent diffusion coefficient
sequences, indicating cytotoxic component.
B, Unenhanced CT image in patient with global cerebral edema after cardiac arrest shows diffuse loss of
gray-white differentiation from combined cytotoxic and vasogenic edema. Brain is markedly swollen, with
effacement of sulci and ventricles and crowding of basal cisterns (arrows) producing pseudo-subarachnoid
hemorrhage appearance.

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Combined Edema
Several disorders produce a mixed pattern of cytotoxic and vasogenic edema. This may be
due to multifocal or systemic disease or to pathophysiologic alterations associated with disease
progression. Causes include trauma, hypoxic-ischemic encephalopathy, metabolic or toxic conditions, multisystem organ failure, hypertensive crises, and infection or inflammation. On CT
and MRI, there is global loss of gray-white matter differentiation and effacement of the sulci,
ventricles, and basal cisterns. If the underlying cause is not addressed, progression to transtentorial and fatal brainstem herniation is inevitable. Aggressive intervention is indicated, including
surgical decompression if the condition is refractory to medical management.

Trauma

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Cerebral contusions are caused by direct head trauma, which classically affects the inferior
frontal and anterior temporal lobes. Coup injuries occur when a moving object impacts the
stationary head, with injury immediately subjacent to the site of trauma. Contrecoup injuries
occur when the moving head strikes a stationary object, causing inertial transmission of force
to the side opposite the area impacted. Both cytotoxic and vasogenic edema are present, reflecting reactive intracellular metabolite accumulation and traumatic opening of the bloodbrain barrier. Vessel injury may cause hemorrhage (Fig. 13A).

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Fig. 15Posterior reversible encephalopathy

syndrome.
A, Unenhanced head CT shows hypodensities in
posterior occipital lobes (arrows) with primarily
vasogenic pattern, although there are focal areas of
cortical involvement.
B, FLAIR MR image again shows symmetric
hyperintensities (arrows) with both white and gray
matter involvement.
C, Contrast-enhanced T1-weighted MR image shows
faint gyriform enhancement (arrows) in this region,
thought to occur secondary to hypertension-induced
transient vasodilation with breakdown of blood-brain
barrier.

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Severe acceleration-deceleration forces, such as in high-speed motor vehicle accidents,
may produce diffuse axonal injury. This occurs via differential shearing mechanisms and
preferentially affects the gray-white matter junction, corpus callosum, and brainstem. When
seen in children and the elderly, this constellation of findings should suggest nonaccidental
trauma, particularly when the history is inconsistent with the degree of injury. Skeletal fractures, intracranial hemorrhages, and retinal hemorrhages are also characteristic and show
both spatial and temporal heterogeneity.
On CT, areas of edema or hemorrhage may be fairly subtle. MRI is more sensitive, showing
T2/FLAIR hyperintensity in regions of edema and GRE/susceptibility-weighted imaging
susceptibility within foci of microhemorrhage (Fig. 13B). Restricted diffusion on DWI and
ADC sequences indicates ischemia. DTI with tractography determines the degree of injury to
white matter tracts. Over time, lesions evolve and become less conspicuous. In the late stages,
residual hemosiderin and chronic atrophy may be identified.
Treatment of diffuse axonal injury is primarily supportive. Intracranial pressure should be
continuously monitored in patients with initial Glasgow Coma Scale score below 9, abnormal
CT findings, age greater than 40 years, motor posturing, or systolic blood pressure below 90
mm Hg. Emergent ventriculostomy or craniectomy may be required for decompression.

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Hypoxic-Ischemic Encephalopathy
Hypoxic-ischemic encephalopathy is a pattern of brain injury resulting from partial oxygen
deprivation. The pathophysiology involves energy-dependent mitochondrial injury leading to
eosinophilia, macrophage digestion, cortical atrophy, and gliosis. It is most frequently seen in
preterm neonates secondary to birth asphyxia but can occur at any age. Causes include hypoxic
(reduced environmental oxygen as may occur at high altitudes or secondary to diving or strangulation), hypoxemic (reduced blood oxygen, as with anemia, pulmonary or cardiac shunt, or
carbon monoxide poisoning), ischemic (inadequate blood flow, as in infarction, shock, cardiac
arrest, increased intracranial pressure), and histotoxic (impaired oxygen metabolism, as with
Reye syndrome secondary to aspirin use in children, cyanide, triethyl tin, lead, hexachlorophene, methionine sulfoxime, cuprizone, isoniazid, and dinitrophenol) conditions.
The injury may be focal, diffuse, or global, with the degree of severity ranging from transient edema to irreversible infarction and necrosis. Acute lesions appear hypodense on CT
and hypointense on T1-weighted imaging and hyperintense on T2-weighted imaging because
of associated edema or encephalomalacia. Contrast enhancement is variable and indicates a

Fig. 16Radiation necrosis.

A, FLAIR MR image shows extensive bifrontal edema (thin arrows) with primarily vasogenic distribution and
involvement of genu of corpus callosum (thick arrow). Frontal sinuses are also opacified.
B, Contrast-enhanced T1-weighted image shows mild linear rim enhancement (arrows) and central areas of
hypoenhancement.

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American Journal of Roentgenology 2012.199:W258-W273.

Fig. 17Cerebral abscess.

A, T1-weighted contrast-enhanced image reveals lobulated fluid collection with irregular enhancing rim (arrow)
in right parietal lobe.
B, FLAIR image shows surrounding vasogenic edema (arrow).

poorer prognosis as a reflection of ongoing injury. There is a cytotoxic pattern of edema, with
restricted diffusion on DWI and ADC maps. The deep gray matter is typically most severely
affected because of its high metabolic requirements (neuronal cell bodies and glia) and watershed arterial distribution. Classic locations include the hippocampus; globus pallidus; and,
to a lesser extent, the caudate nucleus, putamen, and thalamus (Fig. 14A). The cerebellum and
brainstem are fairly resistant to hypoxia, and involvement of these regions indicates highergrade injury. Advanced hypoxic-ischemic encephalopathy can produce a vasogenic edema
pattern that involves white matter axons and myelin sheaths. This affects the periventricular
and subcortical white matter, corpus callosum, and external and internal capsules (Fig. 14B).
The severity of imaging findings in hypoxic-ischemic encephalopathy correlates with the
clinical likelihood of developing delayed neuropsychiatric syndrome.

Osmotic Edema
Osmotic cerebral edema results when solute concentrations differ between the brain parenchyma and blood plasma. This produces an abnormal osmotic pressure gradient resulting in
net flow of fluid from serum into the brain. Causes include conditions that dilute the plasma
(including water intoxication, dialysis disequilibrium, hyponatremia, syndrome of inappropriate antidiuretic hormone secretion, diabetic ketoacidosis, hepatorenal failure, and other
metabolic conditions) and disorders that increase tissue osmolarity (hemorrhage, infarct, contusion). Both intracellular (cytotoxic edema) and extracellular (interstitial and vasogenic
edema) components have been described.

Hydrostatic Edema
Hydrostatic edema occurs in the setting of an acute increase in intracranial pressure and
may develop in neurosurgical patients, hypertensive crises, hypertensive nephropathy,
eclampsia, pheochromocytoma, and Cushing syndrome. The increase in intravascular pressure causes reactive spasm of cerebral vessels, resulting in cerebral ischemia and cytotoxic
edema. Eventually, cerebrovascular autoregulation is overwhelmed and there is flooding of
the cerebral capillary bed, resulting in interstitial or vasogenic transudation of fluid into the
extracellular space.

Infection or Inflammation
Cerebral infection may be caused by bacteria; viruses; fungi; and other entities, such as prions.
Among the imaging manifestations are abscess, meningitis, ventriculitis, and encephalitis.

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Cerebral Edema
Inflammatory causes include demyelinating disorders (multiple sclerosis spectrum, posterior
reversible encephalopathy syndrome (Fig. 15), progressive multifocal leukoencephalopathy),
vasculitis, autoimmune syndromes, epilepsy, migraine, radiation (Fig. 16), and drug reactions.
These entities produce vasogenic edema due to damage of the blood-brain barrier. Areas of
internal restricted diffusion may also be present and may signify proteinaceous or hemorrhagic contents (typically hyperintense on T1-weighted imaging) or ischemia with cytotoxic
edema (hyperintense on T2-weighted imaging and hypointense on T1-weighted imaging).
Contrast enhancement is most avid in the acute phase and declines over time. In cases of cerebral infection, heterogeneous soft-tissue enhancement is suggestive of a phlegmon, whereas
organized fluid with dense rim enhancement is concerning for abscess (Fig. 17).
Suggested Reading

a scientific statement from the American Heart

Association. Stroke 2009; 40:36463378
4. Moritani T, Ekholm S, Westesson PL. Brain edema. In: Moritani T, Ekholm S, Westesson PL,
eds. Diffusion-weighted MR imaging of the brain,
2nd ed. Berlin, Germany: Springer-Verlag, 2009:
3752
5. Rabinstein AA. Treatment of cerebral edema.
Neurologist 2006; 12:5973

American Journal of Roentgenology 2012.199:W258-W273.

1. Nag S, Manias JL, Stewart DJ. Pathology and new

players in the pathogenesis of brain edema. Acta
Neuropathol 2009; 118:197217
2. Marmarou A. A review of progress in understanding the pathophysiology and treatment of brain
edema. Neurosurg Focus 2007; 22:E1
3. Latchaw RE, Alberts MJ, Lev MH, et al. Recommendations for imaging of acute ischemic stroke:

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