Parents and clinicians concerned about high-risk infants and children with motor delay or cerebral palsy seek information on
cause, treatment, prognosis, and recurrence risk. Used in combination with history and examination, neuroimaging studies can
improve diagnosis and management. In premature infants, cranial ultrasound is a reliable, noninvasive diagnostic modality.
Nuclear magnetic resonance techniques including magnetic resonance imaging and diffusion weighted imaging can be used
effectively in neonatal encephalopathies. In children with motor delay and cerebral palsy syndromes including spastic diplegia,
quadriplegia, hemiplegia, and extrapyramidal movement disorders, conventional magnetic resonance imaging has become an
important determinant of diagnosis and management. The aim of this article is to help clinicians select and interpret imaging
studies of benefit in clinical care. (J Pediatr 2004;145:S19-S27)
espite a wide range of accepted medical and rehabilitative interventions for high-risk infants and children with cerebral
palsy, there is often imprecise understanding of cause, variability in determination of treatment, and inconsistency in
Over the period of the past decade, magnetic resonance imaging (MRI) and other neuroimaging modalities
have begun to provide a foundation to address these problems, translating into real
and anticipated
benefits in care.
Considering that pneumoencephalography (injected air with x-ray visualization) was the state-of-the-art method to image
the brain only 50 years ago,
current techniques are remarkable.
Clinicians have a powerful array of tools to assess brain structure
and function: ultrasound, computed tomography (CT), and multiple nuclear magnetic resonance techniques including MRI,
magnetic resonance spectroscopy (MRS), diffusion weighted imaging (DWI), diffusion tensor imaging (DTI), and functional
Structural neuroimaging studies clearly demonstrate disorder-specific findings in children with a wide range of
developmental impairments prenatally
and postnatally,
and functional modalities are being used to map regional cognitive
and to examine cortical plasticity.
Seventy to ninety percent of children with cerebral palsy have abnormalities on brain MRI.
When combined with
history and neurological examination, imaging can provide insights into cause and pathogenesis, including patterns of selective
vulnerability specific to acquired or genetic disorders; improve treatment options; refine prognosis; and address recurrence
This article reviews specific imaging techniques, developmental brain vulnerability, and the utility of imaging in high-
risk infants and children with cerebral palsy.
Selection of the appropriate neuroimaging modality is optimally determined with an
understanding of principles, indications, limitations, and side effects of each technique
(Table I). Currently, the most commonly used clinical modalities are ultrasound and MRI,
with CT of benefit in specific situations. DWI, MRS, DTI, and fMRI are emerging
nuclear magnetic techniques used in clinical care and research. Positron emission
tomography and single photon emission computed tomography are radionuclide studies
used in management of epilepsy and brain tumors.
Cranial Ultrasound
Ultrasound uses high-frequency sound waves to produce images with good clarity.
Both the anterior and posterior fontanel can be used as acoustic windows. Cranial
From the Johns Hopkins University
School of Medicine, and the Kennedy
Krieger Institute.
Division of Neurology and Develop-
mental Medicine, Baltimore,
Submitted for publication Mar 2, 2004;
accepted May 11, 2004.
Reprint requests: Alexander H. Hoon,
MD, Kennedy Krieger Institute, Johns
Hopkins University School of Medi-
cine, 707 N Broadway, Baltimore, MD
21205. E-mail: hoon@kennedykrieger.
0022-3476/$ - see front matter
Copyright ª2004 Elsevier Inc. All rights
ADC Apparent diffusion coefficient
CT Computed tomography
DTI Diffusion tensor imaging
DWI Diffusion-weighted imaging
FLAIR Fluid attenuation inversion recovery
fMRI Functional magnetic resonance imaging
HIE Hypoxic-ischemic encephalopathy
IVH Intraventricular hemorrhage
MRI Magnetic resonance imaging
MRS Magnetic resonance spectroscopy
PHI Periventricular hemorrhagic infarction
PVL Periventricular leukomalacia
ultrasonography can be serially performed with minimal
perturbation of the neonate, making it the study of choice in
high-risk preterm infants.
Although ultrasound is not as
sensitive to subtle white matter changes and hemorrhagic
lesions as MRI, it readily identifies periventricular white
matter lesions associated with later neurologic morbidity as
well as hemorrhage or malformation in the posterior fossa.
Recently, prenatal cerebral sonography has been used to
identify fetal white matter injury in women with
uteroplacental insufficiency.
Computed Tomography
The x-ray acquired images of CT depend on tissue
atomic number and electron density, with the images produced
by a map of the local x-ray absorption coefficient.
By using
computer-applied algorithms, new scanners produce high-
resolution images in a matter of minutes. CT scans can there-
fore often be obtained without sedation. Calcification, which
may not be visualized on MRI, is readily seen on CT. CTscans
are less costly than MRI and often can be obtained after a
shorter waiting period. However, x-ray exposure may be of con-
cern to parents and clinicians, especially with repeated studies.
Magnetic Resonance Imaging
Magnetic resonance imaging has become the most
widely used imaging modality in clinical pediatrics. It uses
nuclear magnetic resonance, the intrinsic magnetic properties
of protons, to produce gray-scale images in multiple
The signal generated and the resulting images
are based on proton density in tissues, and T1 and T2
relaxation times, which describe recovery and delay of nuclear
magnetism after perturbations with an oscillating radio-
frequency magnetic field. Gadolinium, an inert contrast
material, may be infused intravenously to identify vascular
structures and regions of breakdown in the blood–brain
Images are produced on the basis of T1 and T2
relaxation characteristics. T1 weighting refers to longitudinal
relaxation time. Mature white matter, which has a short T1, is
bright on T1 weighted sequences. Gray matter appears gray
and cerebrospinal fluid dark. T1 images, which are commonly
viewed in sagittal and axial planes, are useful for the
determination of normal anatomy as well as structural abnor-
malities. T2 weighting refers to transverse relaxation time.
Cerebrospinal fluid is bright on T2 weighted images, and
Table I. Neuroimaging modalities
Modality Sedation Advantages Disadvantages
US Not necessary Non-invasive Operator-dependent
No radiation Acoustic window needed
Portable bedside assessment
US Doppler Not necessary Same as above As above
Quantitative cerebral flow
parameters (velocity, resistive index)
Assessment of major vessels only
CT May be required Fast scanning Radiation exposure
Readily available Iodinated contrast may be needed
MR imaging Frequently required High imaging resolution Relatively long imaging time
No exposure to radiation Motion sensitive
Contrast agent very safe Environment (noise, monitoring)
MR compatible monitoring devices
MRS Frequently required No exposure to radiation See MR imaging above
Biochemical, metabolite information Need for age-matched normal controls
May be done in addition to routine MRI
MR-DWI Frequently required MR sequence evaluating water diffusion See MR imaging above
Aids diagnosis in ischemic setting
fMRI Not used, can affect results No exposure to radiation Only preliminary data available
Task performance cooperation required
PET Not routinely used Functional metabolic imaging Not readily available
High sensitivity Radiation exposure
Low spatial resolution
Arterial sampling for quantification
Control data not available
SPECT Not routinely used Functional metabolic imaging Lower sensitivity compared with PET
Relatively high sensitivity Radiation exposure
Low spatial resolution
Control data may not be available
Data taken from reference 9.
S20 Accardo, Kammann, and Hoon The Journal of Pediatrics

August 2004
mature white matter dark. T2 weighted images, including fast
spin echo and fluid attenuation inversion recovery (FLAIR)
images, are useful in visualizing brain pathology, which
frequently appears bright.
Magnetic resonance imaging has several advantages over
CT, including better tissue contrast resolution, image
generation in multiple planes, and lack of ionizing radiation
and bone artifact. However, MRI costs more than CT and
more frequently requires sedation or previous behavioral
modification of young children. Furthermore, with the recent
trend toward anesthesia coverage when sedation is required, it
may be more difficult to schedule in a timely fashion.
Sedation should be considered carefully when required
for any study.
Adequate sedation is critical to obtaining
studies not degraded by motion artifact. Chloral hydrate is
usually used for infants and young children, intravenous
Nembutal for older children, and general anesthesia for
children who cannot remain still on their own or who fail to
respond to other forms of sedation. Experienced personnel
with knowledge of good airway management, 1:1 patient
assignment, continuous monitoring, and sufficient periods for
observation after the study is completed are required to provide
sedation safely. Children with developmental disorders may
have atypical reactions to sedation, which should be explained
to parents before the children are sedated, and may require
longer periods of observation once the study is completed.
Image interpretation requires knowledge of normal
brain anatomy and development,
recognition of findings in
specific disorders
(Table II), and an awareness of potential
study artifacts. Although clinicians can readily interpret
imaging studies, neuroradiologists are more familiar with
imaging techniques
and potential artifacts including
chemical shift, motion, susceptibility, and truncation,
and should determine study sequences and be the gold
standard for image interpretation. For example, an aware-
ness of artifacts sharpens image interpretation, as seen in
Figure 1.
Dialogue with a neuroradiologist is helpful, with
discussion of history and examination focusing interpretation.
For example, white matter abnormalities in the context of
prematurity are most likely periventricular leukomalacia
(PVL), but without that history might be interpreted as
adrenoleukodystrophy or metachromatic leukodystrophy.
Neurological findings of extrapyramidal cerebral palsy should
prompt a careful assessment of the basal ganglia and thalamus
for abnormal signal intensity or atrophy.
Imaging studies, like clinical evaluations, represent only
a single point in time and should be interpreted with this in
mind. Serial studies, analogous to repeated neurological
examinations, can provide new diagnostic insights, especially
in progressive neurological disorders,
as well as in ongoing
medical or surgical management in situations including
ventriculomegaly and hydrocephalus.
Table II. Conventional MRI findings in selected childhood motor impairment syndromes
Disorder Primary findings Other abnormalities
Angelman syndrome Normal
Ataxia-telangiectasia Cerebellar atrophy
Carbon monoxide Globus pallidus
Dopa responsive dystonia Normal
Glutaric aciduria, type 1 Caudate, putamen
GM1 Type 3 Putamen
Hypoxic-ischemic Putamen, thalamus, Cortical white matter, encephalomalacia
encephalopathy peri-rolandic
Juvenile Huntington Caudate, putamen
Kernicterus Globus pallidus
Leigh’s disease Caudate, putamen,
brainstem, white matter
Methylmalonic academia Globus pallidus Internal capsule
Mitochondrial encephalo-myopathies Caudate, putamen Cortical white matter
Pantothenate kinase-associated
neurodegeneration Globus pallidus
Proprionic academia Globus pallidus, 1/– putamen
Periventricular leukomalacia Cortical white matter Thalamus
Pyruvate dehydrogenase deficiency Globus pallidus Caudate, putamen
Rett syndrome Normal
Wilson’s disease Putamen, pons, atrophy Midbrain, thalamus, caudate
Data taken from reference 9.
Neuroimaging in Cerebral Palsy S21
Brain Development and Vulnerability
The elegant and genetically determined choreography of
brain development leads to precise temporal and spatial
structural organization.
Neural tube closure at one month
of gestational age is followed by forebrain cleavage. During
the second to fifth months of gestation, there are bursts of
neuronal proliferation, followed by waves of cortical neuronal
migration, leading to the normal six-layered cortex. This is
followed by proliferative organizational events including
elaboration of synapses and myelination
as well as elimina-
tion of cells
(apoptotic cell death) and synapses
pruning), leading to motor, cognitive, and behavioral
capabilities characteristic of children.
Selective vulnerability refers to the susceptibility of
specific cell types and brain regions to injury during times of
active development.
Early insults or genetic abnormalities
affecting fetal brain development often affect the brain
globally and result in midline abnormalities including
and agenesis of the corpus callosum,
and migrational abnormalities including
heterotopias and lissencephaly.
During the late second to early third trimester, the
primary vulnerability is in the cortical and subcortical white
matter, where developing oligodendroglia are susceptible to
Recognized antecedents include hypoxia-ischemia,
infection, and maternal metabolic abnormalities involving
thyroid function and glucose homeostasis.
Under the general
heading of white matter damage, the spectrum of terminology
for lesions seen on ultrasound and sustained during this period
of development includes periventricular hemorrhagic infarction
(PHI), PVL, periventricular echodensities and echolucencies, and
hyperechoic or hypoechoic lesions. The MRI correlates are PVLor
As the fetus approaches term, primary vulnerability to
hypoxia-ischemia shifts from white matter to neurons in the
cerebral cortex, basal ganglia, and thalamus, related to
disruption of glutamate synapses, excitotoxic injury, and cell
death from necrosis and apoptosis.
Characteristic patterns of
selective vulnerability seen on MRI include hyperintense signal
in the putamen and ventrolateral thalamus from acute, total
asphyxial events, as seen in three children in Figure 2; parasa-
gittal cortical infarction; and multicystic encephalomalacia.
Postnatally, there is wide variability in vulnerability in
supratentorial and infratentorial structures. This is often
related to the type of genetic disorder or acquired insult.
Clinical Syndromes
Although there are several clinical situations in which
imaging is of benefit, pediatricians and other clinicians
commonly consider utility in high-risk premature infants, in
neonatal encephalopathies, and in infants and young children
with motor delay or cerebral palsy. Appropriate timing and
selection will often improve the clinical utility of imaging
High-risk Premature Infants
Infants may be born prematurely in association with
anomalies in early brain development, including hydroceph-
alus, neuronal migration disorders, and absence of the corpus
callosum. However, the most common antecedent of the
motor, cognitive, and behavioral disorders seen in children
born prematurely is PVL or PHI,
as seen in Figure 3.
Ultrasound has been recommended for infants less than 30
weeks between 7 and 14 days of age and near term-corrected
age to identify intraventricular hemorrhage (IVH), PVL, and
low-pressure ventriculomegaly.
Twenty to twenty-five
percent will have one or more of these lesions, with
significantly increased risks of later major developmental
Premature infants may also sustain posterior
fossa hemorrhages
and decreased cortical gray matter
volumes associated with white matter injury.
cerebellar volumes in children have been associated with
deficits in cognition, but not motor neurological signs.
The childhood motor spectrum of children with white
matter injury, primarily PVL, ranges from mild neurological
dysfunction to quadriplegic cerebral palsy. A common pre-
sentation is often spastic diplegia, with lower extremity
spasticity, truncal hypotonia, and upper extremity athetosis
or dystonia. MRI findings include thinning of the corpus
callosum, ventricular dilatation with scalloping at the margins,
gliotic response in white matter, and white matter volume
MRI is of benefit both to exclude other abnormalities,
some of which have genetic implications, and to assess the
extent of white matter loss and gliosis. Volumetric MRI has
shown a relationship between increasing ventricular size (as
Fig 1. Pulsation artifact (arrow) in a coronal FLAIR MRI, which
might be misinterpreted as a choroid plexus tumor in the left
S22 Accardo, Kammann, and Hoon The Journal of Pediatrics

August 2004
a measure of brain volume loss) and subsequent motor and
cognitive impairments.
Neonatal Encephalopathy
Neonatal encephalopathy describes term infants with
abnormal neurological function involving tone, reflexes,
consciousness, feeding, respiration, and seizures.
Although it
is often assumed that the most common cause is obstetric error,
more than 100 years ago Freud
recognized that problems in
prenatal development might lead to perinatal distress.
Recent research has shown that there is an extensive
differential diagnosis for neonatal encephalopathy including
brain malformations, genetic or metabolic disorders, indirect
and direct infections, kernicterus, hypoxic-ischemic en-
cephalopathy (HIE), maternal thyroid disorders, severe
pre-eclampsia, thrombophilic disorders, and placental vas-
culopathy, and that the percentage varies widely in different
Furthermore, two distinct subgroups exist: one
with encephalopathic signs with or without seizures, and
a second with isolated seizures.
Infants in the latter group
have an increased likelihood of arterial strokes associated with
thrombophilic disorders. Neonatal MRI, CT, and DWI may
be of benefit in diagnosis, with potential implications for
treatment, prognosis, and recurrence risk.
Hypoxic-ischemic encephalopathy is a recognized cause
of neonatal encephalopathy, as initially categorized by Sarnat
Fig 2. Axial T2 and FLAIR images from three children who developed extrapyramidal cerebral palsy after acute asphyxial insults at term
leading to neonatal encephalopathy. The findings of hyperintense lesions in the posterior putamen and ventrolateral thalamus are characteristic
of this syndrome and are a commonly seen example of the selective vulnerability of deep gray nuclei to acute asphyxial insults.
Fig 3. This imaging sequence is from a child with triplegic cerebral palsy (involvement of both legs and one arm). A, Coronal ultrasound
showing hyperechoic lesion in right periventricular region (arrows) consistent with periventricular hemorrhagic infarction (grade 4 IVH); and
hyperechoic lesion in left ventricle (arrowhead) consistent with grade 3 IVH in a 28-week preterm infant on the third day of life. B, Clot
resolution (arrows) on the right and hyperechoic periventricular signal on the left in the same infant at 6 weeks of age. C, Coronal T2 MRI at 18
months of age showing porencephalic cyst (arrows), ventricular dilatation, and thinning of the corpus callosum. Reprinted with permission.
Neuroimaging in Cerebral Palsy S23
and Sarnat.
It is now determined by four findings: fetal
distress, neonatal encephalopathy, subsequent development of
cerebral palsy, and absence of other cause.
It may result from
acute, total insults, or from partial, prolonged insults.
Imaging with acute, total insults often shows basal ganglia
injury in the putamen and ventrolateral thalamus associated
with developing glutaminergic circuits, whereas partial, pro-
longed insults may be associated with multicystic en-
cephalomalacia/diffuse atrophy. Watershed injury may also
be seen, especially after acute fall in blood pressure.
identification of infants with HIE is the subject of much
interest now because of research in neuroprotective in-
MRS and DWI have also been proposed as
methods to identify children who would benefit from these
Kernicterus, which may lead to choreoathetoid cerebral
palsy in childhood, can cause a newborn encephalopathy
similar to HIE.
Bilirubin is a toxin that targets the globus
rather than the putamen-thalamus, as in HIE.
This is another example of the concept of selective
vulnerability, and supports the importance of imaging to
determine lesion location. Although RhoGAM and WinRho
administration has greatly decreased Rh incompatibility as
a cause, other causes are hemolysis, neonatal meningitis, and,
rarely, breast feeding.
Cerebral Palsy
Cerebral palsy describes a group of motor impairment
syndromes secondary to genetic and acquired disorders of the
developing brain.
Spastic, extrapyramidal, and mixed forms
are generally recognized. Spasticity is defined by hypertonicity
that increases with increased velocity of movement. Bilateral
spastic cerebral syndromes such as spastic diplegia and spastic
quadriplegia have greater involvement of legs than arms,
whereas unilateral spastic hemiplegia may be either arm-
dominant or leg-dominant. Extrapyramidal cerebral palsy
syndromes are characterized by rigidity, elicited clinically by
passive stretch independent of velocity or dystonia, which is
often action-induced twisting or fixed postures. Arm use is
typically more affected than leg function.
Although neurological findings may be similar in
various cerebral palsy syndromes, etiological underpinnings
may be diverse. As a generality, children with spastic
syndromes often show white matter injury, whereas extrapy-
ramidal syndromes frequently have basal ganglia abnormalities
on imaging. However, in these syndromes, differential
diagnosis is often broad, including a number of recognizable
genetic and acquired disorders, as seen in Tables III and IV.
Imaging can be very important in distinguishing these
disorders, with important implications for treatment, prognosis,
and recurrence risk. For example, extrapyramidal cerebral palsy
may result from genetic metabolic disorders such as glutaric
aciduria type 1 (caudate/putamen),
mitochondrial disorders
such as Leigh syndrome (globus pallidus/caudate/putamen),
kernicterus (globus pallidus), or HIE (putamen/thalamus).
Likewise, although spastic diplegia is most closely linked
to PVL, it may also be secondary to congenital HIV;
dopa-responsive dystonia; hereditary spastic paraplegia; or
spinal pathology, arginase deficiency, and Sjo¨gren-Larsson
syndrome, with characteristic appearances on imaging.
However, although there is often a relationship between
the type and severity of imaging abnormalities and degree of
clinical impairment, exceptions exist, as seen in Figure 4.
Telling parents that treatment is directed toward their
Table III. Differential diagnosis of syndromes with spasticity
Spastic diplegia Spastic quadriplegia Spastic hemiplegia
Periventricular leukomalacia (PVL) PVL (severe) Prenatal stroke
Dopa responsive dystonia (DRD, Segawa disease) Brain malformations Schizencephaly
HIV TORCH Perinatal stroke
Hydrocephalus HIE
Grade 4 IVH
Arginase deficiency Hydrocephalus Postnatal stroke
Sjogren-Larsson syndrome Non-accidental trauma
Other bacterial/viral
*Partial, prolonged insult
Periventricular-intraventricular hemorrhage.
Table IV. Differential diagnosis of extrapyramidal
movement disorders
Dystonia/Athetoid Choreic
Kernicterus Genetic
Glutaric aciduria, type 1 Post-pump
Propionic acidemia Propionic acidemia
Methylmalonic acidemia
Wilson disease
Juvenile Parkinson
Juvenile Huntington
Progressive disorders (other)
*Acute, total insult.
S24 Accardo, Kammann, and Hoon The Journal of Pediatrics

August 2004
children and not the scan abnormalities can often be reassuring
to them, especially when they appreciate that brain structure is
distinctly different from normal.
Advanced imaging modalities are continually being
developed and refined, including MRS, DWI, DTI, and
These techniques have the potential to show
connections between neuronal activity and brain function,
map white matter development, and facilitate early identifi-
cation and treatment of high-risk infants.
Magnetic resonance spectroscopy uses software
modifications to existing MRI hardware to provide an
assessment of brain biochemistry.
When the water signal is
suppressed, metabolites present in tissue in lower con-
centrations become detectable as spectra. Some of the
metabolites that can be detected include N-acetyl aspartate
(a neuronal marker), creatine (a bioenergetic marker), choline-
containing compounds (which may be released when cell
membranes are disrupted), lactate (associated with increased
anaerobic tissue metabolism), and neurotransmitters including
gamma aminobutyric acid. MRS can be used to identify
changes associated with HIE
as well as mitochondrial
disorders such as mitochondrial encephalopathy, lactic
acidosis, and stroke-like episodes.
Diffusion weighted imaging uses the diffusion, or slow,
random movement of water molecules (Brownian motion)
that occurs normally in the central nervous system, and is
routinely used to identify ischemic brain injury in infants,
children, and adults.
The apparent diffusion coefficient
(ADC) characterizes the movement of multiple water
molecules over a single small image region, called a voxel.
The ADC is influenced by the type of tissue present in the
voxel (CSF, gray matter, or white matter), the myelination and
orientation of white matter tracts, and the presence of
ischemic change. In acute ischemia, the ADC is diminished,
with the region appearing bright on DWI images. DWI shows
promise for the early identification of brain injury in
infants with neonatal encephalopathy secondary to HIE,
who might potentially benefit from early neuroprotective
Diffusion tensor imaging is a nuclear magnetic reso-
nance modality using anisotropy, which is the variability in
water diffusion in different directions based on structural
tissue organization, to map white matter pathways.
Although this is primarily a research modality at this time,
it will find increasing clinical applicability.
It has been used
to identify white matter injury in the neonatal period
as well
as later in childhood in children with cerebral palsy.
Preliminary data in a small number of children have suggested
that the primary mechanism of spasticity is injury in sensory
pathways connecting parietal and occipital cortex rather than
the corticospinal tracts.
If validated in future studies, DTI
may alter our understanding of pathogenesis in cerebral palsy
and other developmental disorders and potentially lead to
improved treatment for affected infants and children.
Functional MRI is a technique used to study brain
organization during cognitive and motor activities.
Taking advantage of the paramagnetic effect of de-
oxyhemoglobin, fMRI provides high-resolution images with-
out radiation or contrast. Blood oxygen level–dependent
imaging, a commonly used technique, produces images as
a result of changes in the local vascular deoxyhemoglobin
concentration. In children with hemiplegic cerebral palsy, the
technique has demonstrated cortical reorganization.
It is
anticipated that alone and in combination with other imaging
modalities, fMRI will improve the understanding of the neural
pathways in movement.
Clinicians may wonder whether the adage ‘‘when all else
fails, examine the patient’’ remains valid, with the wide range
of genetic testing and imaging techniques now readily
available. Although history and examination remain the
foundation of clinical care, imaging has emerged as an
Fig 4. Coronal T1 weighted MRI from a child with normal
intelligence and left hemiplegia shows moderate-severe bilateral
colpocephaly, absence of the septum pellucidum, and white matter
loss. If viewed without relevant clinical information, the prediction
from this image might be of a child with moderate-severe motor and
cognitive impairments.
Neuroimaging in Cerebral Palsy S25
important modality to further diagnosis and treatment.
Ongoing dialogue with colleagues in radiology, neuroradiol-
ogy, and anesthesia when necessary will facilitate appropriate
sedation, technique selection, and image interpretation,
leading to improved care. Whenever possible, parents should
be involved in the study and discussion of their child’s imaging
and appreciate when films are explained to them with clarity.
We acknowledge Michael Johnston, MD, for his review of
the manuscript, and Doris Lin, MD, for her comments on the
1. Maenpaa H, Salokorpi T, Jaakkola R, Blomstedt G, Sainio K,
Merikanto J, et al. Follow-up of children with cerebral palsy after selective
posterior rhizotomy with intensive physiotherapy or physiotherapy alone.
Neuropediatrics 2003;34:67-71.
2. Chang CH, Albarracin JP, Lipton GE, Miller F. Long-term follow-up
of surgery for equinovarus foot deformity in children with cerebral palsy. J
Pediatr Orthop 2002;22:792-9.
3. Bartlett DJ, Palisano RJ. Physical therapists’ perceptions of factors
influencing the acquisition of motor abilities of children with cerebral palsy:
implications for clinical reasoning. Phys Ther 2002;82:237-48.
4. Krach LE. Pharmacotherapy of spasticity: oral medications and
intrathecal baclofen. J Child Neurol 2001;16:31-6.
5. Hoon AH Jr, Reinhardt EM, Kelley RI, Breiter SN, Morton DH,
Naidu SB, et al. Brain magnetic resonance imaging in suspected extrapyra-
midal cerebral palsy: observations in distinguishing genetic-metabolic from
acquired causes. J Pediatr 1997;131:240-5.
6. Chen R, Cohen LG, Hallett M. Nervous system reorganization
following injury. Neuroscience 2002;111:761-73.
7. Sampath P, Long DM, Brem H. The Hunterian Neurosurgical
Laboratory: the first 100 years of neurosurgical research. Neurosurgery
8. Barkovich JA. Techniques and methods in pediatric neuroimaging. In:
Pediatric neuroimaging. 3rd edition. Philadelphia: Lippincott Williams and
Wilkins; 2000. p. 1-12.
9. Hoon AH, Belsito KM, Nagae-Poetscher LM. Neuroimaging in
spasticity and movement disorders. J Child Neurol 2003;Suppl 1:S25-39.
10. Hoon AH, Melhem ER. Neuroimaging: applications in disorders of
early brain development. J Dev Behav Pediatr 2000;21:291-302.
11. Bekker MN, van Vugt JM. The role of magnetic resonance imaging in
prenatal diagnosis of fetal anomalies. Eur J Obstet Gynecol Reprod Biol 2001;
12. Barkovich AJ. Magnetic resonance imaging: role in the understanding of
cerebral malformations. Brain Dev 2002;24:2-12.
13. Cabeza R, Nyberg L. Imaging cognition II: An empirical review of 275
PET and fMRI studies. J Cogn Neurosci 2000;12:1-47.
14. Gaillard WD, Balsamo LM, Ibrahim Z, Sachs BC, Xu B. fMRI
identifies regional specialization of neural networks for reading in young
children. Neurology 2003;60:94-100.
15. Johnston MV, Nishimura A, Harum K, Pekar J, Blue ME. Sculpting the
developing brain. Adv Pediatr 2001;48:1-38.
16. Truiwit CL, Barkovich AJ, Koch TK, Ferriero DM. Cerebral palsy: MR
finding in 40 patients. Am J Neuroradiol 1992;13:67-78.
17. Candy EJ, Hoon AH, Capute AJ, Bryan RN. MRI in motor delay:
important adjunct to classification of cerebral palsy. Pediatr Neurol 1993;9:
18. Johnston MV, Hoon AH. Possible mechanisms in infants for selective
basal ganglia damage from asphyxia, kernicterus, or mitochondrial encepha-
lopathies. J Child Neurol 2000;15:588-91.
19. Rivkin MJ. Opening the window into brain development in children
more widely with magnetic resonance imaging. Pediatrics 2003;11:1432-3.
20. So EL. Integration of EEG, MRI, and SPECT in localizing the seizure
focus for epilepsy surgery. Epilepsia 2000;41(suppl 3):S48-54.
21. Ment LR, Bada HS, Barnes P, Grant PE, Hirtz D, Papile LA, et al.
Practice parameter: neuroimaging of the neonate (report of the Quality
Standards Subcommittee of the American Academy of Neurology and the
Practice Committee of the Child Neurology Society). Neurology 2002;58:
22. Merrill JD, Piecuch RE, Fell SC, Barkovich AJ, Goldstein RB. A new
pattern of cerebellar hemorrhages in preterminfants. Pediatrics 1998;102:E62.
23. van Gelder-Hasker MR, van Wezel-Meijler G, de Groot L, van Geijn HP,
de Vries JI. Peri- and intraventricular cerebral sonography in second- and third-
trimester high-risk fetuses: a comparison with neonatal ultrasound and relation
to neurological development. Ultrasound Obstet Gynecol 2003;22:110-20.
24. Carlsson CA. Imaging modalities in x-ray computerized tomography
and in selected volume tomography. Phys Med Biol 1999;44:R23-56.
25. Wehrli FW, MacFall JR, Glover GH, Grigsby N, Haughton V,
Johanson J. The dependence of nuclear magnetic resonance (NMR) image
contrast on intrinsic and pulse sequence timing parameters. Magn Reson
Imaging 1984;2:3-16.
26. Hart HR Jr, Bottomley PA, Edelstein WA, Karr SG, Leue WM,
Mueller O, et al. Nuclear magnetic resonance imaging: contrast-to-noise ratio
as a function of strength of magnetic field. AJR Am J Roentgenol 1983;141:
27. Malviya S, Voepel-Lewis T, Prochaska G, Tait AR. Prolonged recovery
and delayed side effects of sedation for diagnostic imaging studies in children.
Pediatrics 2000;105:E421.
28. Hinton VJ. Ethics of neuroimaging in pediatric development. Brain
Cogn 2002;50:455-68.
29. Johnston MV, Hoon AH. Excitotoxicity and patterns of brain injury
from fetal or perinatal asphyxia. In: Maulik D, ed. Asphyxia and fetal brain
damage. New York: Wiley-Liss; 1998. p. 113-25.
30. Anupindi S, Jaramillo D. Pediatric magnetic resonance imaging
techniques. Magn Reson Imaging Clin N Am 2002;10:189-207.
31. Gelal FM, Grant PE, Fischbein NJ, Henry RG, Vigneron DB,
Barkovich AJ. The role of isotropic diffusion MRI in children under 2 years of
age. Eur Radiol 2001;11:1006-14.
32. Greenspan SL, Mathews VP. Pearls and pitfalls in clinical neuroradi-
ology. Semin Neurol 1998;18:221-36.
33. Brismar J, Ozand PT. CTand MRof the brain in disorders of the propionate
and methylmalonate metabolism. AJNR Am J Neuroradiol 1994;15:1459-73.
34. Eichler FS, Barker PB, Cox C, Edwin D, Ulug AM, Moser HW, et al.
Proton MR spectroscopic imaging predicts lesion progression on MRI in
X-linked adrenoleukodystrophy. Neurology 2002;58:901-7.
35. Volpe JJ. Neurology of the newborn. 3rd edition. Philadelphia: WB
Saunders; 1995.
36. Capone GT. Human brain development. In: Capute AJ, Accardo PJ,
eds. Developmental disabilities in infancy and childhood. 2nd edition.
Baltimore: Paul H Brookes Co; 1996. p. 25-75.
37. Paus T, Collins DL, Evans AC, Leonard G, Pike B, Zijdenbos A.
Maturation of white matter in the human brain: a review of magnetic
resonance studies. Brain Res Bull 2001;54:255-66.
38. Ryan CA, Salvesen GS. Caspases and neuronal development. Biol
Chem 2003;384:855-61.
39. Johnston MV. Neurotransmitters and vulnerability of the developing
brain. Brain Dev 1995;17:301-6.
40. Sarnat HB, Flores-Sarnat L. Neuropathologic research strategies in
holoprosencephaly. J Child Neurol 2001;16:918-31.
41. Bale JF, Miner L, Petheram SJ. Congenital cytomegalovirus infection.
Curr Treat Options Neurol 2002;4:225-30.
42. Kato M, Dobyns WB. Lissencephaly and the molecular basis of
neuronal migration. Hum Mol Genet 2003;12:R89-96.
43. Leviton A, Dammann O. Maternal intrauterine infection, cytokines and
brain damage in the preterm newborn. Pediatr Res 1997;42:1-8.
44. Back SA, Luo NL, Borenstein NS, Levine JM, Volpe JJ, Kinney HC.
Late oligodendrocyte progenitors coincide with the developmental window of
vulnerability for human perinatal white matter injury. J Neurosci 2001;21:
45. Saliba E, Marret S. Cerebral white matter damage in the preterm
infant: pathophysiology and risk factors. Semin Neonatol 2001;6:
S26 Accardo, Kammann, and Hoon The Journal of Pediatrics

August 2004
46. Asao C, Korogi Y, Kondo Y, Yasunaga T, Takahashi M. Neonatal
periventricular-intraventricular hemorrhage: subacute and chronic MR
findings. Acta Radiol 2001;42:370-5.
47. Roelants-van Rijn AM, Groenendaal F, Beek FJ, Eken P, van Haastert
IC, de Vries LS. Parenchymal brain injury in the preterm infant: comparison
of cranial ultrasound, MRI and neurodevelopmental outcome. Neuropedi-
atrics 2001;32:80-9.
48. de Vries LS, Eken P, Groenendaal F, van Haastert IC, Meiners LC.
Correlation between the degree of periventricular leukomalacia diagnosed
using cranial ultrasound and MRI later in infancy in children with cerebral
palsy. Neuropediatrics 1993;24:263-8.
49. Johnston MV. Excitotoxicity in neonatal hypoxia. Ment Retard Dev
Disabil Res Rev 2001;7:229-34.
50. Menkes JH, Curran J. Clinical and MR correlated in children with
extrapyramidal cerebral palsy. Am J Neuroradiol 1994;15:451-7.
51. Barkovich AJ. MR and CT evaluation of profound neonatal and
infantile asphyxia. J Neuroradiol 1992;13:959-72.
52. Edwards AD, Yue X, Cox P, Hope PL, Azzopardi DV, Squier MV,
et al. Apoptosis in the brains of infants suffering intrauterine cerebral injury.
Pediatr Res 1997;42:684-9.
53. Volpe JJ. Neurobiology of periventricular leukomalacia in the premature
infant. Pediatr Res 2001;50:553-62.
54. Leviton A, Paneth N, Reuss ML, Susser M, Allred EN, Dammann O,
et al. Maternal infection, fetal inflammatory response, and brain damage in
very low birth weight infants. Developmental Epidemiology Network
Investigators. Pediatr Res 1999;46:566-75.
55. Paneth N, Kazam E, Monte W. Brain damage in the preterm infant.
London (UK): Cambridge University Press; 1994.
56. Mercuri E, He J, Curati WL, Dubowitz LM, Cowan FM, Bydder GM.
Cerebellar infarction and atrophy in infants and children with a history of
premature birth. Pediatr Radiol 1997;27:139-43.
57. Inder TE, Huppi PS, Warfield S, Kikinis R, Zientara GP, Barnes PD,
et al. Periventricular white matter injury in the premature infant is followed by
reduced cerebral cortical gray matter volume at term. Ann Neurol 1999;46:
58. Allin M, Matsumoto H, Santhouse AM, Nosarti C, AlAsady MH,
Stewart AL, et al. Cognitive and motor function and the size of the
cerebellum in adolescents born very pre-term. Brain 2001;124:60-6.
59. Skranes JS, Nilsen G, Smevik O, Vik T, Brubakk AM. Cerebral MRI of
very lowbirth weight children at 6 years of age compared with the findings at 1
year. Pediatr Radiol 1998;28:471-5.
60. Melhem ER, Hoon AH Jr, Ferrucci JT Jr, Quinn CB. Periventricular
leukomalacia: relationship between lateral ventricular volume on brain MR
images and severity of cognitive and motor impairment. Radiology 2000;214:
61. Leviton A, Nelson KB. Problems with definitions and classifications of
newborn encephalopathy. Pediatr Neurol 1992;8:85-90.
62. Freud S. Infantile cerebral paralysis. Coral Gables: University of Miami
Press; 1968.
63. Johnston MV. MRI for neonatal encephalopathy in full-term infants
(commentary). Lancet 2003;361:713-4.
64. Cowan F, Rutherford M, Groenendaal F, Eken P, Mercuri E, Bydder
GM, et al. Origin and timing of brain lesions in term infants with neonatal
encephalopathy. Lancet 2003;361:736-42.
65. Sarnat HB, Sarnat MS. Neonatal encephalopathy following fetal
distress. Arch Neurol 1976;33:696-705.
66. American College of Obstetricians and Gynecologists. Neonatal
encephalopathy and cerebral palsy: defining the pathogenesis and pathophys-
iology. Washington, DC; 2003.
67. Johnston MV. Selective vulnerability in the neonatal brain. Ann Neurol
68. Wagner CL, Eicher DJ, Katikaneni LD, Barbosa E, Holden KR. The
use of hypothermia: a role in the treatment of neonatal asphyxia? Pediatr
Neurol 1999;21:429-43.
69. Debillon T, Daoud P, Durand P, Cantagrel S, Jouvet P, Saizou C, et al.
Whole-body cooling after perinatal asphyxia: a pilot study in term neonates.
Dev Med Child Neurol 2003;45:17-23.
70. Hansen TW. Kernicterus: an international perspective. Semin Neonatol
71. Yilmaz Y, Alper G, Kilicoglu G, Celik L, Karadeniz L, Yilmaz-De-
girmenci S. Magnetic resonance imaging findings in patients with severe
neonatal indirect hyperbilirubinemia. J Child Neurol 2001;16:452-5.
72. Gourley GR. Breast-feeding, neonatal jaundice and kernicterus. Semin
Neonatol 2002;7:135-41.
73. Kaplan M, Hammerman C. Glucose-6-phosphate dehydrogenase
deficiency: a potential source of severe neonatal hyperbilirubinaemia and
kernicterus. Semin Neonatol 2002;7:121-8.
74. Hoon AH, Johnston MV. Cerebral palsy. In: Asbury AK, McKhann
GM, McDonald WI, et al, eds. Diseases of the nervous system: clinical
neuroscience and therapeutic principles. Cambridge: Cambridge University
Press; 2002. p. 568-80.
75. Strauss KA, Morton DH. Type I glutaric aciduria, part 2: a model of
acute striatal necrosis. Am J Med Genet 2003;121C:53-70.
76. Macaya A, Munell F, Burke RE, De Vivo DC. Disorders of movement
in Leigh syndrome. Neuropediatrics 1993;24:60-7.
77. Johnston MV, Hoon AH. Possible mechanisms in infants for selective
basal ganglia damage from asphyxia, kernicterus, or mitochondrial encepha-
lopathies. J Child Neurol 2000;15:588-91.
78. Huppi PS, Inder T. Magnetic resonance techniques in the evaluation of
the perinatal brain: recent advances and future directions. Semin Neonatol
79. Shevell MI, Ashwal S, Novotny E. Proton magnetic resonance
spectroscopy: clinical applications in children with nervous system diseases.
Semin Pediatr Neurol 1999;6:68-77.
80. Zarifi MK, Astrakas LG, Poussaint TY, Plessis Ad A, Zurakowski D,
Tzika AA. Prediction of adverse outcome with cerebral lactate level and
apparent diffusion coefficient in infants with perinatal asphyxia. Radiology
81. Wilichowski E, Pouwels PJ, Frahm J, Hanefeld F. Quantitative proton
magnetic resonance spectroscopy of cerebral metabolic disturbances in
patients with MELAS. Neuropediatrics 1999;30:256-68.
82. Bydder GM, Rutherford MA. Diffusion-weighted imaging of the brain
in neonates and infants. Magn Reson Imaging Clin N Am 2001;9:83-98.
83. Schaefer PW, Grant PE, Gonzalez RG. Diffusion-weighted MR
imaging of the brain. Radiology 2000;217:331-45.
84. Neil J, Miller J, Mukherjee P, Huppi PS. Diffusion tensor imaging of
normal and injured developing human brain—a technical review. NMR
Biomed 2002;15:543-52.
85. Hagmann P, Thiran JP, Jonasson L, Vandergheynst P, Clarke S,
Maeder P, et al. DTI mapping of human brain connectivity: statistical fibre
tracking and virtual dissection. Neuroimage 2003;19:545-54.
86. Tummala RP, Chu RM, Liu H, Truitt NI, Hall WA. Application of
diffusion tensor imaging to magnetic-resonance-guided brain tumor re-
section. Pediatr Neurosurg 2003;39:39-43.
87. Huppi PS, Murphy B, Maier SE, Zientara GP, Inder TE, Barnes PD,
et al. Microstructural brain development after perinatal cerebral white
matter injury assessed by diffusion tensor magnetic resonance imaging.
Pediatrics 2001;107:455-60.
88. Hoon AH Jr, Lawrie WT Jr, Melhem ER, Reinhardt EM, Van Zijl PC,
Solaiyappan M, et al. Diffusion tensor imaging of periventricular leukomalacia
shows affected sensory cortex white matter pathways. Neurology 2002;59:752-6.
89. Menon RS. Imaging function in the working brain with fMRI. Curr
Opin Neurobiol 2001;11:630-6.
90. Di Salle F, Formisano E, Linden DEJ, Goebel R, Bonavita S, Pepino A,
et al. Exploring brain function with magnetic resonance imaging. Eur J Radiol
91. Briellmann RS, Abbott DF, Caflisch U, Archer JS, Jackson GD. Brain
reorganisation in cerebral palsy: a high-field functional MRI study. Neuro-
pediatrics 2002;33:162-5.
Neuroimaging in Cerebral Palsy S27