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CHAPTER 61  Neuroimaging

ultrasound. As edema develops, usually after several hours, increased echogenicity of brain parenchyma can be seen, but this
measure is nonspecific, relative, and often is difficult to appreciate. Blood associated with a hemorrhagic infarct also will appear
as increased echogenicity. As mass effect develops secondary to
edema, ventricular and sulcal effacement can be seen. Later, vascular and perivascular mineralization can result in linear thalamic
and basal ganglia echogenicity (lenticulostriate vasculopathy or
mineralizing angiopathy).26
Ultrasound Doppler evaluation of newborn ischemia has
shown some utility. Brain perfusion can be investigated by determining the resistive index (RI). RI in the normal neonate (0.75 6 0.1)
is higher than that seen in the older infant before (0.65 6 0.5)
and after (0.55 6 0.5) fontanelle closure.25 An increase in the RI
with a decrease in the peak systolic velocity and end-diastolic velocity in infants with HIE within the first 12 hours of life as
measured in the anterior and middle cerebral arteries correlated
with a poor prognosis at 1 year of life. A decrease in RI to less
than 0.60 at 12 hours (anterior and middle cerebral arteries) and
24 hours (all insonated arteries, including basilar artery) after
neonatal asphyxia, which is thought to be a result of the decreased
vascular tone associated with loss of autoregulation, has been associated with a poorer outcome at 12 to 18 months of life.27,28
Approximately half of patients with low RI scores have normal
grayscale images. There is a host of other reasons for low RI scores,
however, including cardiac disease, extracorporeal membrane oxygenation, ongoing hypoxemia, hypercapnia, and technical issues.
It also should be noted that increased fontanelle pressure can increase the RI measure by 20%; hence, there is considerable user
dependence to this application. If hyperemia persists and as HIE
evolves, cytotoxic edema increases and leads to increased intracranial pressure and increased RI measurements. A high RI score on
the first day of life with evidence of neonatal insult suggests an in
utero injury. Although some centers have continued to pursue the
use of ultrasound, MRI has supplanted much of this evaluation.
CT detection of acute ischemic injury also depends on edema
resulting from the injury. Edema is seen as decreased attenuation
and loss of gray-white differentiation, usually detected several

hours postinsult.29 Small or early infarcts can be missed with CT,
and detection of ischemia in the newborn is made more difficult
by the generally lower attenuation of the relatively “watery” unmyelinated newborn brain. For this reason, in some instances of
neonatal ischemic injury, there may actually be an increase in the
attenuation of this watery unmyelinated white matter because of
an outpouring of serum proteins from damaged blood vessels. As
brain swelling develops in the first few days, there can be a loss of
CSF spaces seen as ventricular compression, sulcal effacement,
and loss of perimesencephalic cisterns. Acute thrombotic stroke
associated with arterial thrombosis can at times be appreciated
acutely as a hyperdense artery, most commonly the middle cerebral artery on noncontrast CT. Acute hemorrhage, such as with
hemorrhagic arterial (from reperfusion) or venous infarcts, will be
hyperdense initially on CT, evolving to isodense over the first week.
Standard MR sequences exploiting T1 and T2 relaxation times
also depend on the development of edema to appreciate acute
ischemic injury, which results in hyperintensity on T2-weighted
and FLAIR images and hypointensity on T1-weighted images.
This change typically takes at least several hours to develop, and,
although generally more sensitive than CT in adults, evaluation of
the newborn is again made somewhat difficult by the lack of myelination. As a result, ischemia can sometimes be more conspicuous on CT than on T1- or T2-weighted MRI (Fig. 61.8). The

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FLAIR sequence has proved to be more sensitive than T1 and T2
to ischemic changes in older myelinated children and adults.
DWI is more sensitive than T2 and FLAIR sequences and correlates well with at least short-term neurologic outcomes in neonates and infants.30 These sequences, as previously discussed, have
been shown to be acutely sensitive to the cytotoxic edema associated with ischemia.12 This cytotoxic edema results in diminished
diffusion of water in the affected area. DWI in experimental models can detect ischemia in minutes after onset as a region of restricted diffusion.31,32 These sequences have now become widely
implemented in adult and pediatric neuroimaging, where differentiation of acute ischemic stroke from other neurologic disorders
permits appropriate and timely implementation of stroke therapies. The restricted diffusion associated with ischemia evolves over

a 1- to 3-week period, at which time the diffusion image usually
normalizes. If sufficient tissue destruction has occurred, the diffusion ultimately will increase because of the greater amount of free
water following necrosis. This change in diffusion is also useful in
distinguishing a new stroke (which will show decreased diffusion)
from an older lesion (which will have increased diffusion),
whereas both lesions may be of similar signal intensity on standard T1 and T2 imaging (Fig. 61.9).
Timelines for relative T2 and diffusion changes have been
shown to differ in neonates and infants versus older children and
adults. Animal models have suggested that diffusion changes in
neonates and infants with HIE do not necessarily precede T2
changes. This finding is presumably a result of age-dependent differences in brain water content and changes therein as a result of
differences in vascular permeability in response to hypoxic-ischemic insult.33,34 The initial diffusion abnormality may increase
over the first day, and the extent of the diffusion abnormality can
encompass both the core infarct and penumbra, potentially overestimating the ultimate infarct. This potential overestimation
could be an indication for MR perfusion, which can separate the
areas of core infarction and penumbra.35 The identification of
lactate on MRS is also evolving as a useful tool that may serve as
a predictor for the severity of perinatal asphyxia, although considerable complexity is involved, which has limited application of
this technology.31,36
As previously mentioned, the pattern of hypoxic-ischemic injury varies with the etiology of the insult and the developmental
state of the brain. Early in utero insults result in tissue resorption,
without the ability to mount a gliotic response that is not seen
until the third trimester. During early brain development, insults
can result in congenital malformations. HIE or injury in the early
to middle second trimester may result in polymicrogyria with or
without associated schizencephaly. In the 24th to 25th week of
gestation range, HIE can preferentially injure the deep gray matter nuclei in the setting of total asphyxia. PVL is the pattern of
injury seen with prolonged partial hypoxia at 24 to 34 weeks.
Typically with PVL on neonatal grayscale ultrasound, there may
be increased echogenicity in the periventricular white matter, an

appearance that is indistinguishable at this stage from edema
or from parenchymal hemorrhage, which also may be seen. As
PVL progresses, cystic change occurs that progresses to coalescent
cavitation of the involved white matter. Collapse of these spaces
ultimately results in the thinning and volume loss of the white
matter, particularly in the posterior periventricular white matter.
Although cranial ultrasound affords better resolution for the visualization of cystic change of early PVL in the premature neonate,
MRI has overall greater sensitivity to white matter injury, especially in the more advanced stages of PVL, and demonstrates an


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S E C T I O N V I   Pediatric Critical Care: Neurologic

A

B

C

D

•  Fig. 61.8  ​Abusive head trauma with diffuse cerebral ischemia. (A) Axial noncontrast computed tomog-

raphy (CT), (B) axial T2-weighted, and (C) diffusion-weighted magnetic resonance imaging (MRI). (A) CT
shows a thin layer of acute subdural blood (arrowheads) and diffuse loss of gray-white demarcation in the
cerebral hemispheres. (B) Although the T2 image appears remarkably normal with appropriate lack of
myelination in this 3-month-old child, the relative brightness of the cerebral hemispheres compared with
the central gray on diffusion-weighted images (C) is consistent with a diffuse ischemic insult. (D) Gradientrecalled echo MRI in another 4-month-old with abusive head trauma demonstrates dark, low-signal areas in
the right frontal subdural space and left posterior parafalcine regions, consistent with subdural hematomas.

undulating ventricular margin with associated periventricular T2/
FLAIR signal abnormality with or without a paucity of white
matter. However, it is not yet clear whether this increased sensitivity is of significant prognostic value. Ischemic insults to the term
child demonstrate different patterns of injury, determined by the
specifics of the insult and the vulnerability of various areas. Profound hypoxia in the term infant results in injury largely to areas
that are most actively myelinating—in particular, the perirolandic
white matter and the associated corticospinal tracts and white
matter tracts associated with the occipital cortex, as well as other
areas with high energy demands, such as the putamina, thalami,
hippocampi, and brainstem. In contrast, a watershed pattern
of injury discussed in the next section develops with prolonged

partial ischemia that is not sufficient to cause an infarct of the
cerebrum, with shunting to the high-energy demand areas. Current recommendations for the encephalopathic term infant have
included early CT to assess for intracranial hemorrhage, with
consideration for MRI with DWI and GRE sequences later in the
first postnatal week to assess the extent of injury.24

Imaging of Neurovascular Disorders
Ischemic Stroke
MRI, specifically DWI sequences, is critical for detecting cerebral
ischemic infarcts (Fig. 61.10) and distinguishing acute, subacute,


CHAPTER 61  Neuroimaging

A

B

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C

•  Fig. 61.9  ​Remote and acute infarcts. (A and B) Axial T2-weighted magnetic resonance imaging (MRI)

shows cerebral volume loss with encephalomalacia and gliosis (arrows) associated with an old stroke in
this child with new onset of progressive left-sided weakness. (C) Diffusion-weighted MRI reveals a new
area of infarct (arrowheads) at the edge of the remote abnormality.

A

B

C

• Fig. 61.10  ​Basal ganglia acute infarct. Axial T2-weighted magnetic resonance imaging (A) shows subtle

increased T2 signal in left basal ganglia (arrows). More conspicuously shown on the apparent diffusion
coefficient map (B) and diffusion-weighted images (C) is restricted diffusion (arrows) associated with an
early infarct involving the left caudate and lentiform nuclei.

and remote infarcts (see Fig. 61.9). The area of restricted diffusion
on DWI is generally thought to represent irreversible injury, especially when associated with T2/FLAIR signal abnormality, although there may be some cases in which the lesions are at least
potentially reversible. In the setting of acute stroke, perfusion
MRI may have a contributory role in demonstrating the total region of brain at risk (penumbra) and predicting the ultimate extent of infarct.35 The area of perfusion abnormality beyond that of
diffusion abnormality is thought to represent the penumbra and
to be at risk but potentially salvageable.
A diagnosis of acute ischemic stroke is usually suspected based

on clinical presentation, and neuroimaging can confirm the diagnosis.37 Moreover, the imaging pattern can help determine stroke
etiology. A watershed distribution is consistent with a low flow/
hypotensive cause (Fig. 61.11). Specifically, changes of ischemic
injury are seen at the boundary regions between the major cerebral distributions—that is, between anterior and middle cerebral
territories and between middle and posterior cerebral arterial

territories. Lesions involving multiple arterial distributions suggest a central thrombotic source, although other causes such as a
vasculitis or demyelinating diseases also can have this multivessel
or multifocal picture (Fig. 61.12). Classically, embolic lesions will
tend to be seen at the gray-white junction and most commonly
in the MCA distribution. Individual variability of boundary regions38 and pathology-induced alteration in flow limit the definitiveness of arterial distribution categorization following vascular
insult.
Arterial dissections as a cause for ischemic stroke can be diagnosed with MRI and MRA or with CTA. Visualization of methemoglobin in the false lumen with fat-saturated T1-weighted or
proton density–weighted MRI sequences detects most dissections, although subtle lesions may still require catheter angiogram
for diagnosis. On CTA, the false lumen is detected by the absent
or diminished enhancement compared with the true lumen. Suspicion for dissection is raised in the setting of multiple apparent
embolic strokes in a single carotid distribution or within the


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S E C T I O N V I   Pediatric Critical Care: Neurologic

A

B

•  Fig. 61.11  ​Watershed infarct. (A) Axial T2-weighted magnetic resonance imaging shows some loss of

the gray-white interface on the left posteriorly (arrows). (B) Diffusion-weighted image shows bilateral restricted diffusion consistent with ischemic injury in a watershed distribution (arrows).

A

B

•  Fig. 61.12  ​Acute

disseminated encephalomyelitis (ADEM). T2-weighted magnetic resonance imaging
(A) and fluid-attenuated inversion recovery (B) images show multiple foci of hyperintensity. In addition to
ADEM, vasculitis and multiple emboli could have this imaging appearance.

posterior circulation when there is a history of trauma, although
spontaneous dissections are seen occasionally. As previously mentioned, the presence of emboli in multiple circulations raises the
question of a more central etiology, such as a heart valve vegetation.

Vasculopathy/Vasculitis
Acquired vasculopathies can be a result of known infectious or
noninfectious causes or of unknown pathophysiology, such as in
primary cerebral vasculitis, which tends to involve medium and
small vessels, or moyamoya syndrome, which demonstrates greatest

involvement of the central cerebral vessels. Vasculopathy involving
large and medium-sized vessels can be seen on MRA, although
more subtle irregularities and small-vessel involvement still
requires a catheter angiogram, which remains the gold standard
imaging modality.
In transient cerebral angiopathy of childhood, classically a
basal ganglia infarct resulting from M1 MCA segment narrowing
and occlusion of lenticulostriate vessels is seen, with cortical
injury being less common. Narrowing typically of the terminal

carotid and proximal M1 MCA segment of the affected side often
can be delineated on MRA. A lack of well-developed collaterals


CHAPTER 61  Neuroimaging

also will be noted, in contrast to the typical presentation of moyamoya syndrome, where the vessel occlusion has been more slowly
progressive over a longer period. Moyamoya “syndrome” denotes
the pattern of vessel involvement that can be associated with type 1
neurofibromatosis, radiation injury, sickle cell disease, trisomy 21
syndrome, or other pathology. When this pattern is idiopathic,
the term moyamoya disease is used. More commonly, moyamoya
syndrome/disease will be bilateral, and MRI will demonstrate
evidence of chronic ischemic insult. The enlarged lenticulostriate
collaterals generally will be appreciable on both MRA (correlating
with the “puff of smoke appearance” initially described with catheter arteriography) and as flow voids through the basal ganglia
and basal cisterns on MRI (Fig. 61.13). These apparent flow voids
need to be distinguished from enlarged perivascular spaces that
also are seen in this region.
Vasculitic changes can accompany infections, including meningitis, either through direct invasion of vessels or by an immune
response to the particular pathogen. Parenchymal injury, if present, is mediated by ischemic changes. The pattern of involvement

B

A

in the immune-mediated mechanism may be fairly symmetric, as
can be seen in acute disseminated encephalomyelitis (ADEM) or
some metabolic diseases. Noninfectious vasculitides, including
those associated with systemic disease—for example, systemic lupus erythematosus and, in particular, primary CNS vasculitis—

can be more problematic in diagnosis. Classically, a catheter angiogram and occasionally a brain biopsy have been used to
evaluate the possibility of primary CNS vasculitis. Most cases of
symptomatic vasculitis will demonstrate abnormality on standard
MRI (T2, FLAIR, and DWI) sequences; thus, a completely normal MRI makes the likelihood of CNS vasculitis low. Occasionally, however, there can be a vasculitic process in the presence of a
normal MRI.39 Furthermore, cases have been reported of biopsyproven CNS vasculitis in which the MRI was abnormal and results of a catheter angiogram were normal.40 Because medium and
small vessels often are involved in the setting of CNS vasculitis, to
which MRA has less sensitivity, a catheter angiogram may be indicated in the setting of very strong concern for vasculitis with a
normal MRA and occasionally even a normal MRI.

C

E

D
•  Fig. 61.13  ​Moyamoya

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syndrome in a 15-year-old girl. (A) Axial T1-weighted magnetic resonance
imaging (MRI) shows flow voids (circle) associated with enlarged lenticulostriate collaterals. (B) Axial fluidattenuated inversion recovery image shows gliosis in the right anterior periventricular white matter (arrow)
with leptomeningeal linear hyperintensities corresponding to collaterals. (C) Axial T1 postcontrast MRI
demonstrates enhancing right lenticulostriate and leptomeningeal collaterals (arrows). (D) Coronal maximum
intensity projection image from a magnetic resonance angiogram shows no flow distal to the terminal​
internal carotid artery (ICA) and nonvisualization of right and left proximal posterior cerebral arteries.​
(E) Lateral view from a right ICA catheter angiogram showing occlusion of the ICA below the siphon​
(arrow) and extensive thalamostriate collateral vessels (arrowheads).