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agents, the proper administration of sedation or Magnetic resonance imaging (MR, MRI) is both a
anesthesia, and the use of vital monitoring. structural and a functional imaging modality [1–12].
When CT is used, intravenous enhancement MRI uses magnetic fields and radio waves. It is one of
for blood pool effect (e.g., CT angiography) or the less invasive or relatively noninvasive imaging
blood-brain barrier disruption is additionally recom- technologies (Figure 18.1f–j). Furthermore, the MRI
mended for the evaluation of suspected or known signal is exponentially derived from multiple para-
vascular malformation, neoplasm, abscess, or empyema meters (e.g., T1, T2, proton density, T2*, proton
[1–4,28,29]. Enhanced CT may help to evaluate a mass flow, proton relaxation enhancement, chemical shift,
or hemorrhage of unknown etiology and identify the magnetization transfer, and molecular diffusion).
membrane of a chronic subdural collection. By identi- MRI also employs many more basic imaging techni-
fying the cortical veins, enhanced CT may distinguish ques than other modalities (e.g., spin-echo, inversion-
prominent low-density subarachnoid collections (e.g., recovery, gradient-echo, and chemical-shift imaging
benign extracerebral collections or benign external methods). Advancing MRI capabilities have further
hydrocephalus of infancy) from low-density subdural improved its sensitivity, specificity, and efficiency [1–
collections (e.g., chronic subdural hematomas or 12,30]. These include the fluid attenuation inversion
hygromas). It also may help to differentiate infarction recovery technique (FLAIR), fat-suppression short TI
from neoplasm or abscess, serve as an indicator of inversion recovery imaging (STIR), and magnetiza-
disease activity, for example, in degenerative or inflam- tion transfer imaging (MTI) for increased structural
matory disease and vasculitis, and provide a high-yield resolution. Fast and ultrafast MRI techniques (fast
guide for stereotactic or open biopsy. Ventricular or spin-echo, fast gradient-echo, echo-planar imaging,
subarachnoid CSF contrast opacification may further parallel imaging) have also been developed to reduce
assist in evaluating or confirming CSF compartment imaging times, improve structural resolution, and
lesions or communication (e.g., arachnoid cyst or ven- provide functional resolution (e.g., fetal imaging).
tricular encystment). As a rule, MRI is the preferred Important applications include MR vascular imaging
alternative to contrast-enhanced CT in the circum- (MR angiography and venography [MRA]) and per-
stances just enumerated. fusion MRI (PMRI), diffusion-weighted imaging
Nuclear medicine (NM) is primarily a functional (DWI), CSF flow and brain/cord motion imaging,
imaging technology [1–8]. NM involves imaging of brain activation techniques, and MR spectroscopy
the biologic distributions of administered radioactive (MRS). Fast and ultrafast imaging techniques are
pharmaceuticals. Whereas positron-emission tomo- also being used for fetal/obstetric imaging [31–36],
graphy (PET) has the unique ability to provide specific morphometrics, treatment planning, and real-time
metabolic tracers (e.g., oxygen use and glucose meta- MRI-guided surgical and interventional procedures.
bolism), the wider availability, relative simplicity, The role of MRI in imaging of the developing CNS
and rapid technical advancement of single-photon- is defined by its superior sensitivity and specificity in
emission computed tomography (SPECT) allows more a number of areas compared with US and CT
practical functional assessment of the pediatric CNS. [1–12,15,19–24,26,28–36]. MRI has also obviated or
Clinical and investigative applications have included redefined the roles of invasive procedures (e.g., myelo-
the assessment of brain development and maturation, graphy, ventriculography, cisternography, and angio-
focus localization in refractory childhood epilepsy (e.g., graphy). MRI provides multiplanar imaging with
ictal perfusion SPECT, interictal PET), assessment of equivalent resolution in all planes without reposition-
tumor progression versus treatment effects in child- ing the patient. Bone does not interfere with soft-tissue
hood CNS neoplasia (perfusion and thallium SPECT, resolution, although metallic objects often produce
18
FDG-PET), the evaluation of occlusive cerebrovascu- signal void or field distortion artifacts. Some ferromag-
lar disease for surgical revascularization (e.g., perfusion netic or electronic devices (e.g., ferrous aneurysm clips
SPECT), the diagnosis of brain death (perfusion and pacemakers) pose a hazard, and MRI is usually
SPECT), the use of brain activation techniques (e.g., contraindicated in these cases. MRI usually requires
perfusion SPECT, PET) in the elucidation of childhood longer examination times than does US and CT, and
cognitive disorders, the assessment of CSF kinetics patient sedation or anesthesia is often required in
(e.g., in hydrocephalus, CSF leaks), and spinal column infants and younger children because image quality is
screening (skeletal SPECT) [1–8]. easily compromised by motion. However, MRI may be
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Section 3 Diagnosis of the Infant with Brain Injury
ml Cr
Amino
acids
Lipids
4 3 2 1 0
Frequency (ppm)
done successfully in a large percentage of stable neo- encephalopathy versus neurodegenerative disease);
nates and young infants using the “bundle and feed” unexplained seizures (especially focal), unexplained
technique. MRI may not be as readily accessible to neuroendocrine disorder, or unexplained hydroce-
critically ill pediatric patients as US or CT, and it may phalus; the pretreatment evaluation of neoplastic
not be feasible in emergencies or for intensive care processes and the follow-up of tumor response
cases unless magnet-compatible vital monitoring and and treatment effects; suspected infectious, postin-
support are available. This is particularly important for fectious, and other inflammatory or noninflamma-
unstable neonates (e.g., using an MRI-compatible incu- tory encephalitides (e.g., encephalitis, postinfectious
bator) [12] (Figure 18.2a). demyelination, vasculitis); migrational and other
MRI demonstrates superior sensitivity and speci- submacroscopic dysgeneses (e.g., cortical dysplasia);
ficity in a number of circumstances, particularly with neurocutaneous syndromes (e.g., neurofibromatosis
the addition of new structural and functional techni- 1, tuberous sclerosis); intractable or refractory epi-
ques such as FLAIR, STIR, MTI, DWI, PMRI, and lepsy; and vascular diseases, hemorrhage, and the
MRS [1–12,15,19–24,26,28–36]. The FLAIR sequence sequelae of trauma.
attenuates the signal from flowing water (i.e., CSF) MRI frequently offers greater diagnostic specifi-
and increases the conspicuity of non-fluid-water- city than does CT or US for delineating vascular and
containing lesions lying in close approximation to hemorrhagic processes. This includes the clear depic-
the CSF-filled subarachnoid and ventricular spaces. tion of vascular structures and abnormalities based on
The STIR technique suppresses fat signal to provide proton flow parameters and software enhancements
improved conspicuity of water-containing lesions not requiring the injection of contrast agents (e.g.,
in regions where fat dominates (e.g., orbit, head MRA). MRA and MR venography (MRV), including
and neck, spine). The MTI method suppresses back- with contrast blood-pool enhancement (e.g., gadoli-
ground tissues and increases conspicuity for vascular nium, feraheme), may additionally be used to differ-
flow enhancement (e.g., MRA) and gadolinium entiate arterial from venous occlusive disease
enhancement. [1–12,15,19–24,26,28–36]. Using gradient recalled
MRI is the imaging modality of choice in a echo (GRE) magnetic susceptibility techniques, MRI
number of clinical situations [1–12,15,19–24,26,28– also provides more specific identification and staging
36]. These include developmental delay (e.g., static of hemorrhage and thrombosis based on the evolution
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18 Neuroimaging in the Evaluation of Pattern and Timing of Fetal and Neonatal Brain Abnormalities
of red blood cell and hemoglobin breakdown. MRI is provides definitive evaluation of muscular and cuta-
often reserved for more definitive evaluation of neous vascular anomalies (i.e., hemangiomas and vas-
hemorrhage and as an indicator or guide for angio- cular malformations) that arise in parameningeal
graphy in a number of special situations. MRI may be locations (e.g., head and neck, paraspinal) and extend
used to evaluate an atypical or unexplained intracra- to involve the CNS directly or are associated with
nial hemorrhage by distinguishing hemorrhagic other CNS vascular or non-vascular abnormalities.
infarction from hematoma and by distinguishing MR spectroscopy (MRS) offers a non-invasive in
among the types of vascular malformations (e.g., vivo approach to biochemical analysis [1–12,37–40]
cavernous versus arteriovenous malformations). (Fig. 18.2d). Furthermore, MRS provides additional
MRA may obviate the need in some cases of vascular quantitative information regarding cellular metabo-
malformation for conventional angiography in the lites, since signal intensity is linearly related to steady-
follow-up of surgery, interventional treatment, or state metabolite concentration. MRS can detect cellular
radiosurgery. biochemical changes prior to the detection of morpho-
In the evaluation of intracranial vascular anoma- logical changes by MRI or other imaging modalities.
lies (e.g., vascular malformation and aneurysm), MRI MRS may therefore provide further insight into both
may identify otherwise unsuspected prior hemor- follow-up assessment and prognosis. With recent
rhage (i.e., hemosiderin) [1–12,15,19–24,26,28–36]. advances in instrumentation and methodology, and
When CT demonstrates a nonspecific focal high den- using the high inherent sensitivity of hydrogen 1, sin-
sity (calcification versus hemorrhage), MRI may pro- gle-voxel and multivoxel proton MRS is now carried
vide further specificity, for example, by distinguishing out with relatively short acquisition times to detect
an occult vascular malformation (e.g., cavernous mal- low-concentration metabolites in healthy and diseased
formation) from a neoplasm (e.g., glioma). It may tissues. Phosphorus-31 spectroscopy has also been
further assist US or CT in differentiating benign developed for pediatric use. Currently, MRS has been
infantile collections (i.e., external hydrocephalus) used primarily in the assessment of brain development
from subdural hematomas [28,29]. MRI often also and maturation (Figure 18.3), perinatal brain injury,
(a) (b)
Cho
NAA
Cr
Cr Cho
NAA
infant adult
(c)
NAA/Cho Maturation Time Constant
Thalamus 48±10
Basal ganglia 54±12
Geniculocalcarine 78±45
Parietal 113±41
Paracentral 125±39
176±61
Frontal
Figure 18.3 1H MR spectroscopy of the developing brain with (a) infant spectra, (b) adult spectra, and (c) maturation time constants
for brain regions. (From Dermon J, Barnes PD, Spielman D. Spatiotemporal mapping of cerebral maturation in childhood using 2D MR
spectroscopic imaging. American Society of Neuroradiology, 2002.)
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Section 3 Diagnosis of the Infant with Brain Injury
childhood CNS neoplasia versus treatment effects, and anisotropy (FA) is a vector measurement of the direc-
metabolic and neurodegenerative disorders [39,40]. tionality of diffusion using diffusion tensor imaging
Perfusion MRI (PMRI) has been developed to eval- (DTI) methods and also varies with the microstruc-
uate cerebral perfusion dynamics through the applica- tural environment, both developmentally and patho-
tion of a dynamic contrast-enhanced T2*-weighted logically [53] (Figure 18.2b). This method is especially
MRI technique [1–4,8,12,31,41]. This technique has helpful in assessing axonal development and injury,
been used to qualitate and quantitate normal and including myelination and synaptogenesis (connec-
abnormal cerebrovascular dynamics of the developing tivity). Current clinical applications of DWI and
brain by analyzing hemodynamic parameters includ- DTI include the assessment of brain maturation, the
ing relative cerebral blood volume, relative cerebral evaluation of acute injury, and the analysis of the
blood flow, and mean transit time, all as complemen- sequelae of injury (Figure 18.4). A particularly impor-
tary to conventional MR imaging. Non-contrast- tant application of DWI is in the early detection of
enhanced methods of PMRI have also been developed diffuse and focal ischemic injury. The ADC of water is
(e.g., flow-activated inversion recovery [FAIR], arterial reduced within minutes of an ischemic insult and
spin labeling [ASL], blood oxygen level determination progressively so within the first hour. High-intensity
[BOLD]) [41]. Current and advanced applications abnormalities are demonstrated on DWI, along with
of these perfusion techniques include the evaluation low-intensity abnormalities on calculated ADC
of ischemic cerebrovascular disease (e.g., hypoxia- images, at a time when conventional MRI is negative,
ischemia, moyamoya, and sickle cell disease), the and this likely reflects cellular injury (e.g., necrosis)
differentiation of tumor progression from treatment with primary or secondary energy failure. Further
effects, and brain activation imaging [1–4,8,12,31,41]. investigations are under way regarding the roles of
One of the most active areas of research is the localiza- DWI, PMRI, and MRS in the early diagnosis and
tion of brain activity, an area previously dominated by treatment of potentially reversible ischemic injury.
NM including SPECT and PET. Motion-sensitive MRI techniques are used not only
Functional MRI (fMRI) is the terminology often to evaluate vascular flow (e.g., MRA) and perfusion
applied to brain activation imaging in which local or but also to demonstrate the effect of pulsatile cardio-
regional changes in cerebral blood flow are displayed vascular flow on other fluid tissues (e.g., CSF) and on
that accompany stimulation or activation of sensory nonfluid tissues such as the brain and spinal cord.
(e.g., visual, auditory, and somatosensory), motor, or Using cardiac or pulse gating, these MRI techniques
cognitive centers [1–4,12]. fMRI is providing impor-
tant information regarding the spatial distribution of
sensory, motor, and cognitive function and functional
impairment (Figure 18.2c). Also, it may serve as a
guide for safer and more effective interventions,
including microneurosurgery or conformal radio-
therapy, for example, in the ablation of tumors, vas-
cular malformations, and seizure foci. More recently,
fMRI is being used to evaluate brain development and
maturation in neonates and young infants, including
the effects of injury and postinjury repair and recov-
ery [12].
Using echo-planar or line-scan spin-echo techni-
ques, diffusion-weighted imaging (DWI) provides
information based on differences in the rate of diffu-
sion of water molecules, and it is especially sensitive to
cellular changes [1–12,30,40,42–53]. The rate of diffu-
sion, or apparent diffusion coefficient (ADC), is
higher for free or pure water than for macromolecular
Figure 18.4 DTI with FA map in a preterm neonate as a quantita-
bound water. The ADC varies according to the micro- tive display of white matter development (arrows) of the internal
structural or physiologic state of a tissue. Fractional capsule and corpus callosum [12].
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18 Neuroimaging in the Evaluation of Pattern and Timing of Fetal and Neonatal Brain Abnormalities
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Section 3 Diagnosis of the Infant with Brain Injury
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18 Neuroimaging in the Evaluation of Pattern and Timing of Fetal and Neonatal Brain Abnormalities
simple shunting of hydrocephalus. Intraoperative gui- MRS, DWI, DTI, and PMRI with fMRI are also con-
dance may be provided by real-time and Doppler US. tributing to the evaluation and treatment of these
Patients with craniosynostosis are best evaluated with patients [4,12,30]. MRI is now the preferred modality
three-dimensional (3D) CT. Those with multiple for the screening and definitive evaluation of the dys-
suture involvement, especially when it is associated genetic, neoplastic, and vascular manifestations of the
with craniofacial syndromes, may require more exten- neurocutaneous syndromes (Figure 18.11). After
sive evaluation beyond 3D CT, including CT venogra- initial screening with US or CT, MRI is also considered
phy, MRI, and MR venography (jugular venous steno- the primary technology for treatment planning and
occlusive disease with collateralization). follow-up of vascular malformations and developmen-
MRI is often required to structurally delineate tal tumors [1,2,4,30]. Although arachnoid cysts are
the more subtle macrostructural anomalies arising as often readily delineated by US or CT, MRI is usually
disorders of migration and cortical organization necessary for confirmation (i.e., to exclude solid tumor)
(category III: Figure 18.9) or as disorders of prolifera- and for surgical planning. FLAIR or DWI may readily
tion, differentiation, and histiogenesis (category IV: distinguish an arachnoid cyst from other lesions
Figure 18.10) [1,2,4,5,33,54]. The perfusional and (e.g., dermoid-epidermoid and fibrillary astrocytoma).
metabolic characteristics of these anomalies (e.g., Maturation (i.e., myelination and cortical maturation)
focal cortical dysgenesis and hemimegalencephaly) and disorders of maturation (category VI) may be pre-
may be investigated with SPECT and PET, respec- cisely assessed only by MRI [1,2,4,5,30,33,54] (Figure
tively, in children with medically refractory partial 18.1f–j). The MRI findings, however, are often nonspe-
epilepsy who are candidates for surgical ablation. cific regarding causation, particularly in the first year
For added precision, the SPECT or PET data may be of life, because of the watery character of the immature
fused with the MRI data to provide a higher-resolu- brain. DTI and MRS may add specificity to the
tion spatial display of the functional information. diagnostic evaluation of these infants [1–12,37–40]
(Figures 18.2–18.4).
(a) (b)
Neurovascular Disease
Neurovascular disease characteristically presents as
an acute neurologic event (e.g., neonatal encephalo-
pathy). However, a recently discovered but fixed
deficit (e.g., hemiplegia, spastic diplegia, hypotonia)
may be the first indication of a remote prenatal
or perinatal neurovascular injury. Imaging assists
in the clinical evaluation and differentiation of
Figure 18.9 Microlissencephaly: neonatal (a) sagittal and (b) axial
T1 MRI, showing microcephaly with agyric cortex. hypoxia-ischemia, hemorrhage, and occlusive vascular
disease [1–12,30].
(a) (b)
Figure 18.14 Noncystic PVL with foci of gliosis (arrows) as high intensities on (a) sagittal and (b) axial T1 MRI plus cerebellar mineralization or
hemorrhages (arrows) as low intensities on (c) axial T2* GRE MRI.
Figure 18.15 Diffuse PVL (high intensities – arrows) on (a) near-term axial T2 and (b,c) older infant axial FLAIR MRI.
(d)
Figure 18.16 Partial prolonged HIE: acute phase with watershed injury (arrows) on (a) sagittal T1, (b) axial T2, and (c) axial DWI; (d) chronic
phase with cortical atrophy and ulegyria (arrow) on axial CT.
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Section 3 Diagnosis of the Infant with Brain Injury
seen in the late preterm to early midterm GA (e.g., 36– acute, and subacute phases [1–12] (Figures 18.12–
38 weeks) or with more severe injuries. Fetal or neo- 18.20). The edema of nonhemorrhagic HIE (e.g., partial
natal brain injury may also occur with more profound prolonged type) usually evolves over 1–7 days and often
HIE insults (e.g., anoxia or circulatory arrest) and peaks between 36 and 72 hours (2–4 days by US and
involve the thalami, basal ganglia (especially puta- CT) following the insult(s) and depending on reperfu-
mina), brainstem (especially midbrain), cerebellar sion (and other “insults”). US may show hyperecho-
vermis, hippocampi, paraventricular white matter, genicity, and CT may show hypodensities with
and perirolandic cortex [1–12,55,57,76–80] (Figures decreased gray–white matter differentiation. Complete
18.18 and 18.19). This type of injury may also vary loss of gray–white matter differentiation may correlate
with GA (thalamic greater than putaminal involve- with peak edema [60,61]. In the early phases of the
ment in the preterm GA; putaminal, hippocampal, injury, the neuroimaging findings may be nonspecific
and paracentral injury more common in the term as to causation. The differential diagnosis includes
GA). Combined partial prolonged plus profound HIE, multifocal occlusive vascular infarction, infection,
HIE patterns (e.g., total asphyxia) may also occur metabolic derangement (e.g., hypoglycemia, hyperbilir-
[1–12,76–80] (Figure 18.20). ubinemia, and fluid-electrolyte imbalance), metabolic
US, CT, or MRI (e.g., DWI) may demonstrate evol- or connective tissue disorder, and venous thrombosis
ving edema, necrosis, or hemorrhage in the hyperacute, (e.g., coagulopathy) [1–12]. Associated hemorrhage
Figure 18.17 Very severe partial prolonged HIE: acute–subacute phase with (a) low-density cerebral peak edema (arrows) on axial CT and
(b) high-intensity cerebral restricted diffusion (arrows) on axial DWI; (c) chronic phase with cystic encephalomalacia (arrows) on axial T1.
(e)
Ch
NA
Cr
L
Figure 18.18 Profound HIE: acute phase with (a) bilateral basal ganglia and thalamic hyperechogenicity (arrows) on US; (b) hypodensities
(arrows) on CT; high intensities (arrows) on (c) axial DWI and (d) T1/FLAIR MRI; and (e) inverted lactate doublet (L) on MRS.
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18 Neuroimaging in the Evaluation of Pattern and Timing of Fetal and Neonatal Brain Abnormalities
Figure 18.19 Profound HIE: chronic phase with (a–c) bilateral hippocampal, putaminal, thalamic, and paracentral high intensities (arrows)
on axial FLAIR MRI.
Figure 18.20 Term combined HIE: subacute phase with (a) basal ganglia and thalamic high densities (short arrows) plus cerebral low
densities (long arrows) on CT; chronic phase with (b) basal ganglia and thalamic hypointense mineralization (arrows) on axial GRE plus
(c) hypointense cystic encephalomalacia (arrows) on axial T1 MRI.
may be subarachnoid, germinal matrix, and intraven- misinterpretation regarding pattern of injury and
tricular hemorrhage (e.g., preterm fetus or neonate), timing [40]. Doppler with resistive indices (e.g., RI <
choroid plexus/intraventricular hemorrhage (e.g., term 60) or MRS (e.g., elevated lactate, elevated glutamate,
fetus or neonate), and cerebral or cerebellar hemorrhage elevated lipids, decreased N-acetyl-aspartate [NAA])
(e.g., hemorrhagic infarction). Their imaging character- may provide additional early indicators of timing and
istics are described in the next section. outcome [2,6,7,8,14,37,40,81]. The more subtle
According to the evidence-based medical litera- ischemic PVL lesions (e.g., cystic phase) may be better
ture, the sensitivity and specificity of MRI depend on delineated by US (2–6 weeks after insult) than by CT
the techniques used and the timing of the imaging or MRI, in which the density and intensity character
[2,4,6,7,40,45,78]. Conventional MRI may show char- of immature white matter often obscures the injury.
acteristic T1 hypointensities/T2 hyperintensities (12– However, CT and MRI often show gray matter injury
48 hours), followed by T1 hyperintensities (as early as better than US, and MRI demonstrates noncystic
2–4 days), and then T2 hypointensities (as early as 6–7 white matter injury better than US or CT [4,8,19–
days). These T1 and T2 changes may last for a number 24,26]. Further developments of PMRI, DWI, and
of weeks to a month. DWI may be abnormal before MRS have further improved the diagnostic sensitivity
conventional MRI and show restricted diffusion and specificity of MRI [4,8,12,30,40]. In fact, DWI
with decreased ADC as increased intensity on DWI has demonstrated restricted diffusion in the acute
and decreased intensity on ADC maps [2,7,8,40,45]. phase of PVL when US, CT, and conventional MRI
Diffusion abnormalities may tend to evolve for up to are negative or nonspecific. Such advances may facil-
2–3 weeks. Knowledge of these evolving intensity itate the early institution of neuroprotective measures
features is particularly important in order to avoid (e.g., therapeutic hypothermia or cooling) to treat
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Section 3 Diagnosis of the Infant with Brain Injury
potentially reversible primary injury (necrosis, apop- Hemorrhage may occasionally be associated with infec-
tosis) and secondary injury (reperfusion, transneural tion (e.g., herpes simplex virus 2). Vascular malforma-
degeneration) in HIE [82]. These advanced MRI tech- tions producing intracranial hemorrhage are rare in
niques may also assist in distinguishing HIE from neonates and young infants and usually not encoun-
other causes of encephalopathy, including common tered until later childhood (i.e., arteriovenous malfor-
metabolic derangements (e.g., hypoglycemia and mations [AVMs], cavernous malformations,
hyperbilirubinemia), rarer inborn errors of metabo- developmental venous anomalies, and telangiectasias)
lism, and nonmetabolic conditions (e.g., infection). [1–12,28,29]. Aneurysms are exceedingly rare in chil-
The long-term result of HIE is a static encephalo- dren but may be developmental, associated with a
pathy (i.e., CP), and imaging may demonstrate injury syndrome (e.g., Turner syndrome), or related to
in the chronic phases (>14–21 days after the insult), trauma (e.g., dissection) or infection (i.e., mycotic
including porencephaly, hydranencephaly, atrophy, aneurysm). Vein of Galen malformations are subclas-
chronic periventricular leukomalacia, cystic encepha- sified as choroidal, mural, and AVM types. They rarely
lomalacia, gliosis, and mineralization in a characteristic hemorrhage and more commonly present in infancy
distribution as described earlier [1–12] (Figures 18.12– with congestive heart failure, cerebral ischemia, or
18.20). The chronic changes are best demonstrated by hydrocephalus.
MRI. In general, for pattern of injury and timing pur- US or CT remains the primary imaging choice in
poses, two pieces of imaging evidence are optimally acute situations [1–12,29]. As mentioned earlier,
desired: (1) late imaging, preferably MRI, beyond 2–3 there may be subarachnoid hemorrhage, germinal
years of age when the brain is greater than 90% mature matrix and intraventricular hemorrhage (e.g., prema-
(no more water of immaturity), in order to get a final, ture fetus or neonate), choroid plexus/intraventricu-
permanent injury pattern for causative etiology and lar hemorrhage (e.g., term fetus or neonate), and
GA timing, and (2) early postnatal (and/or prenatal) cerebral or cerebellar hemorrhage (e.g., hemorrhagic
imaging, preferably MRI, in order to evaluate evolution infarction). The hemorrhage usually appears hypere-
in the acute, subacute, and chronic phases so that choic on US and high density on CT in the acute to
timing as to “day range” relative to the perinatal and subacute phases (range 3 hours–7 days) unless there is
peripartum periods may be assessed [1–12,40]. associated coagulopathy. With evolution and resolu-
tion, the hemorrhage becomes isoechoic to hypoe-
Intracranial Hemorrhage choic and isodense to hypodense (>7–10 days).
Intracranial hemorrhage may result from parturitional MRI may offer more specific characterization of
trauma, HIE, a coagulopathy (e.g., thrombocytopenia, the hemorrhagic component with regard to timing
disseminated intravascular coagulopathy [DIC], extra- (Table 18.3). Acute intracranial hemorrhage, particu-
corporal membrane oxygenation [ECMO]), and vaso- larly subarachnoid, may be specifically diagnosed by
occlusive disease (e.g., thrombophilia with venous CT or lumbar puncture for CSF analysis. Although
thrombosis), or it may be idiopathic [1–12,28,29,83]. FLAIR may identify subarachnoid hemorrhage as a
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18 Neuroimaging in the Evaluation of Pattern and Timing of Fetal and Neonatal Brain Abnormalities
Figure 18.21 (a) Hyperechoic grade III and (b) grade IV GMH-IVH (arrows) and (c) posthemorrhagic hydrocephalus on coronal US.
G G
Figure 18.22 (a) Hyperechoic grade IV IVH with periventricular Figure 18.23 Vein of Galen (G) vascular malformation (choroidal
hemorrhagic infarction (arrows) on coronal US; (b) posthemorrhagic type) on (a) sagittal T2 and (b) lateral MRA.
hydrocephalus with porencephaly (long arrow) on axial CT with
shunt catheter (short arrow).
Real-time Doppler US provides intraprocedural gui-
dance and monitoring. The long-term sequelae of
hyperintensity and GRE may identify acute hemor- intracranial hemorrhage are often better demonstrated
rhage in any location as a hypointensity, MRI often by MRI than by CT (e.g., hydrocephalus, atrophy,
provides better specificity beyond the acute phases encephalomalacia, porencephaly, calcification, and
[2,4,29,84] (Table 18.3). Hemorrhagic manifestations hemosiderin).
and sequelae of HIE in premature infants readily
detected by US include germinal matrix hemorrhage
(GMH grades I–IV), intraventricular hemorrhage Occlusive Neurovascular Disease and Sequelae
(IVH), periventricular hemorrhagic infarction (aka Occlusive neurovascular disease in the fetus, new-
grade IV), and posthemorrhagic hydrocephalus born, and infant may be arterial or venous in origin
[1–13,25] (Figures 18.21 and 18.22). Choroid plexus and typically results in focal or multifocal lesions
hemorrhage and hemorrhagic infarction in term within the distribution of the occluded vessel or ves-
infants are also easily demonstrated. Portable US sels [1–12] (Table 18.4). Arterial occlusive disease
may effectively delineate the potential hemorrhagic or may be partial or complete and may be due to embo-
ischemic sequelae of ECMO. Although CT has been lization, thrombosis, or stenosis. The result may be
more reliable, high-resolution US using transfontanel ischemic infarction or hemorrhagic infarction fol-
and transcranial approaches, including the mastoid lowed by atrophy. Arterial occlusive disease may
view, may detect extracerebral hemorrhage (subdural occur as a prenatal or perinatal event (emboli of
and subarachnoid) and posterior fossa collections (cer- placental origin, fetal heart, or involuting fetal ves-
ebellar or subdural) [1–13,25]. Color Doppler US, sels), as a complication of infection (e.g., meningitis),
MRA, and CTA are all able to identify and distinguish with congenital heart disease, or from a hypercoagu-
the types of Galenic malformations and provide follow- lopathy (e.g., thrombophilias and prothrombotic dis-
up (Figure 18.23). Angiography is more specifically orders) [85–93]. The thrombophilias may be genetic
directed to the definitive interventional or surgical or acquired and include protein C and S deficiencies,
management of these and other vascular anomalies. activated protein C resistance, antiphospholipid
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Section 3 Diagnosis of the Infant with Brain Injury
Migraine
Ergot poisoning
antibody (e.g., lupus and anticardiolipin), antithrom-
Subarachnoid hemorrhage bin III deficiency, factor V Leiden, prothrombin gene
Drugs mutation, methylene tetrahydrofolate reductase
Cocaine (MTHFR), homocysteine, factors VIII/IX/XI, anemia,
Amphetamines polycythemia, and others. These are risk factors that
L-asparaginase
are often provoked by “triggers” that may include acute
systemic disease (e.g., dehydration, infection, trauma,
Oral contraceptives
hypoxia-ischemia) and chronic systemic disease (e.g.,
Hypercoagulopathy (thrombophilias) hematologic disorders, connective tissue disorders,
Protein S deficiency lupus) [90]. Other causes include trauma (e.g., dissec-
Protein C deficiency tion), arteriopathies (e.g., moyamoya), and metabolic
Antithrombin III deficiency disorders (e.g., mitochondrial cytopathies). Conditions
Factor V (Leiden) and prothrombin mutations commonly associated with cortical or dural venous
sinus occlusive disease include infection, dehydration,
Antiphospholipid antibody (lupus, anticardiolipin)
perinatal encephalopathy, cyanotic congenital heart
Heparin cofactor II deficiency disease, polycythemia, other hypercoagulable states,
Dehydration/hypernatremia DIC, and trauma [1–12,85–94]. Color Doppler US
HIE/DIC may be used as a noninvasive tool for initial identifica-
Sepsis/DIC tion and monitoring of these infants. MRI is more
Polycythemia/hyperviscosity sensitive and specific than US or CT for ischemic
infarction, hemorrhagic infarction, and venous throm-
Nephrotic syndrome
bosis [2–5,7,12,30,88,90] (Figures 18.24 and 18.25).
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18 Neuroimaging in the Evaluation of Pattern and Timing of Fetal and Neonatal Brain Abnormalities
Figure 18.24 Middle cerebal arterial infarction (arrows): (a) acute phase with edema on axial DWI; (b) subacute phase on CT; (c) chronic phase
on axial T2 with hemiatrophy.
(c) (d)
Figure 18.26 (a) Large neonatal bilateral subgaleal hematomas
(arrows) on CT with soft tissue algorithm. (b) Right frontal cranial
depression in another neonate (arrows) on CT with bone algorithm.
Figure 18.27 (a,b) Parturitional trauma and partial prolonged hypoxic-ischemic injury with scalp swelling, molding, and intracranial
hemorrhage on CT (arrows). (c) Asymmetric cerebral watershed injury with atrophy, cystic encephalomalacia, and ulegyria on followup T2 MRI
(arrows).
fissures, accessory sutures, intrasutural bones, and spinal injury (e.g., intraspinal hemorrhage, cord con-
lacunar change) or from craniotabes in maternal- tusion, cord edema, transection, brachial plexus
fetal vitamin D–deficiency rickets [29,98]. MDCT injury, and ligamentous injury) and the sequelae of
with 3D surface reconstructions potentially may be spinal injury (e.g., hydrosyringomyelia, cystic myelo-
needed. MRI is probably necessary when neurologic pathy, and myelomalacia).
deficits are present and the CT is negative or nonspe-
cific. In this situation, MRI may reveal lesions such as
brainstem infarction, traumatic axonal (shear) injury, Infections and Inflammatory Processes
cortical contusion, or hypoxic-ischemic injury, as well US or CT is often used initially to delineate CNS
as sequelae such as gliosis, microcystic encephaloma- infection or inflammation (e.g., fetal inflammatory
lacia, and hemosiderin deposition (Figure 18.27). response syndrome [FIRS]) and its sequelae or com-
MRI is often more specific than CT for hemorrhage plications. However, MRI is clearly superior for early
beyond the hyperacute/acute stage (Table 18.3). Color detection, including the use of diffusion imaging,
Doppler US, contrast-enhanced CT, or MRI may dis- and for demonstrating the precise nature and extent
tinguish external hydrocephalus (dilated subarach- of involvement using T2, FLAIR, GRE, and gadoli-
noid spaces) from chronic subdural hematomas (e. nium-enhanced sequences (e.g., CMV) [1–12,101–
g., child abuse and its mimics) when nonenhanced 103]. This includes meningoencephalitis due to
CT demonstrates nonspecific extracerebral collec- TORCH infections (i.e., toxoplasmosis, other [e.g.,
tions [29]. Furthermore, hemosiderin as demon- syphilis], rubella, cytomegalovirus [CMV], herpes
strated by MRI is confirmation of a previous simplex virus [HSV2], and human immunodeficiency
hemorrhage. In children with atypical intracranial virus [HIV]), and neonatal meningitis (e.g., group B
hemorrhage on CT (e.g., hemorrhage out of propor- Streptococcus, Listeria, and gram-negative bacteria)
tion to the history of trauma or hemorrhage of vary- (Figures 18.28–18.33). Less common but increasingly
ing ages), MRI may show an existing vascular prevalent causes of subacute and chronic CNS inflam-
malformation, a hemorrhagic neoplasm, or other mation are granulomatous meningoencephalitic
findings indicating the need for distinguishing child infections (e.g., tuberculosis, spirochete, fungal, and
abuse from its mimics [29]. parasitic), particularly in immunocompromised
Initial evaluation of spine trauma (e.g., fracture/ hosts. The imaging pattern is often asymmetric and
dislocation) may include plain films or US, but progressive. Such findings may include subarachnoid
MDCT (including 2D reformatting and 3D surface exudate, ventriculitis, edema, cerebritis, infarction,
reconstructions) is preferred. Abnormality on preli- hydrocephalus, effusion, empyema, abscess, and in
minary imaging, changing clinical signs, or unex- the chronic phase cystic encephalomalacia, atrophy,
plained brain injury may provide the indication for gliosis, and calcification.
spinal MRI [2,4,29], including a STIR sequence. An Recurrent infectious or noninfectious CNS infec-
existing spinal anomaly or mass should be ruled out. tion (e.g., meningitis) may require investigation for a
MRI is the procedure of choice to fully evaluate acute parameningeal focus (e.g., sinus or mastoid infection,
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18 Neuroimaging in the Evaluation of Pattern and Timing of Fetal and Neonatal Brain Abnormalities
Figure 18.28 Congential CMV on (a) fetal T2 and (b) neonatal T1 plus (c) GRE MRI including dysplastic (microcephaly, undergyration) and
encephaloclastic (cavitations) components plus T1 hyperintense/T2 hypointense mineralization (arrows).
P
H P
H
(a) (b)
(a) (b)
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Section 3 Diagnosis of the Infant with Brain Injury
Figure 18.35 Bilirubin encephalopathy and kernicterus on MRI with (a,b) globus pallidus and subthalamic T1 hyperintensity (arrows) in
subacute phase and (c) T2 hyperintensity (arrows) plus atrophy in chronic phase.
general, the differential diagnosis, depending on the irregularly involves the subcortical arcuate fibers, and
clinical picture and timing of the imaging, may also may spare the cerebellum. Examples are the infectious
include profound HIE, hypoglycemia, toxic exposure and postinfectious demyelinating diseases (e.g.,
(e.g., methane, cyanide), osmolar myelinolysis, striatal TORCH, HIV, SSPE, and ADEM) and the vasculitides
necrosis, and meningoencephalitis. (e.g., lupus). Nonspecific white matter abnormalities
may be seen with a variety of metabolic, neurodegen-
Disorders Primarily Affecting White Matter erative, infectious, postinfectious, toxic, and vascular
Disorders that primarily or predominantly affect the processes. In this situation, the clinical findings must
white matter are known as the leukoencephalopathies be relied on. An important example is posterior rever-
[2,5,39,107–109]. Traditionally, leukoencephalopathies sible leukoencephalopathy (e.g., hypertension, trans-
have been divided into dysmyelinating and myelino- plant, cyclosporine, renal disease). Also, it is
clastic disorders. In dysmyelinating disorders, an intrin- important to remember that the most common causes
sic (inherited) enzyme deficiency results in the of cerebral white matter abnormalities (particularly
disturbed formation, destruction, or turnover of the periventricular) and prominent Virchow-Robin spaces
essential components of myelin. They are also referred in children with developmental delay are the static
to as the leukodystrophies. The pattern of damage is leukoencephalopathies (e.g., maldevelopmental, under-
symmetric in both hemispheres, has diffuse margins, myelination, postinflammatory, postischemic, and
often spares the arcuate fibers, and consistently involves idiopathic).
the cerebellar white matter. The leukodystrophies are
primarily associated with the lysosomal and peroxiso-
mal disorders (e.g., metachromatic leukodystrophy, Disorders Affecting Both White Matter
Krabbe leukodystrophy, and the adrenoleukodystrophy and Cortical Gray Matter
complex [ALD]) and with diseases of white matter (e.g., A number of metabolic disorders involve both gray
Pelizaeus-Merzbacher, Canavan, Alexander, and and white matter [2,5,39,107–109]. Disorders asso-
Cockayne). Included in the differential diagnosis is ciated with cortical atrophy along with white matter
infantile-onset leukoencephalopathy with swelling involvement include lysosomal disorders such as the
(macrocephaly) and mild clinical course. Early central lipidoses and mucopolysaccharidoses (also associated
white matter involvement may suggest Krabbe (also skeletal dysplasia) and mitochondrial disorders such
abnormal thalami), ALD, phenylketonuria, maple as Alper disease and Menkes disease. If there is a
syrup urine disease (MSUD: Figure 18.34), or Lowe diffuse cortical dysgenesis (e.g., lissencephaly, poly-
syndrome. The lack of myelination (hypomyelination) microgyria) associated with white matter abnormal-
may suggest Pelizaeus-Merzbacher disease or Menkes ities, then peroxisomal disorders such as Zellweger
disease. In myelinoclastic disorders, the myelin sheath syndrome should be considered along with congenital
is intrinsically normal until it yields to exogenous or infections (e.g., cytomegaloviral) and the congenital
endogenous myelinotoxic factors. The pattern of muscular dystrophies (e.g., Fukuyama, Walker-
damage is asymmetric, is sharply demarcated, Warburg, Santavuori) (Figure 18.36).
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Section 3 Diagnosis of the Infant with Brain Injury
(d) (e)
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18 Neuroimaging in the Evaluation of Pattern and Timing of Fetal and Neonatal Brain Abnormalities
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Section 3 Diagnosis of the Infant with Brain Injury
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