1. Radiological imaging of peri-natal acute ischemia
and hypoxic ischemic encephalopathy.
Dr/ ABD ALLAH NAZEER. MD.

2. Perinatal acute Stroke, similar to a stroke which occurs
in adults, is defined as a disturbance to the blood supply of the
developing brain. This description includes both ischemic
events, which results from a blockage of vessels, and hypoxic
events, which results from a lack of oxygen to the brain tissue,
as well as some combination of the two. A neonatal stroke
occurs in approximately 1 in 4000 births, but is likely much
higher due to the lack of noticeable symptoms. One treatment
with some proven benefits is hypothermia, but may be most
beneficial in conjunction with pharmacological agents.
Neonatal strokes may lead to cerebral palsy, learning
difficulties, or other disabilities. Well-designed clinical trials
for stroke treatment in neonates are lacking, but some current
studies involve the transplantation of neural stem cells and
umbilical cord stem cells; it is not yet known if this therapy is
likely to be successful.

3. Risk Factors:
Many different risk factors play a role in causing a neonatal stroke.
Some maternal disorders that may contribute to neonatal strokes
include: autoimmune disorders, coagulation disorders, prenatal
cocaine exposure, infection, congenital heart disease, diabetes, and
trauma. Placental disorders that increase the risk of stroke include
placental thrombosis, placental abruption, placental infection, and
chorioamnionitis. Other disorders that may increase the risk of a
neonatal stroke are blood, homocysteine and lipid disorders, such as
polycythemia, disseminated intravascular coagulopathy, prothrombin
mutation, lipoprotein (a) deficiency, Factor VIII deficiency, and Factor V
Leiden mutation. Infectious disorders such as central nervous system
(CNS) infection or systemic infection may also contribute.
Many infants who suffer a neonatal stroke also follow an
uncomplicated pregnancy and delivery without identifiable risk
factors, which exemplifies the necessity for further research on this
subject.

4. Perinatal arterial ischemic stroke (PAIS) has an estimated incidence
of 1 in 2,300 live births. Most often PAIS presents with convulsions. Initial
assessment is performed with (Doppler) ultrasound and amplitude-integrated
electroencephalography (aEEG). Magnetic resonance imaging (MRI) is used to
confirm PAIS. Although neonatal MRI enables prediction of motor outcome in PAIS
patients by localizing the stroke area according to the posterior limb of the internal
capsule or by visualizing pre-Wallerian degeneration, it remains difficult to
determine the viability of brain tissue after stroke. In adults it has been shown that
arterial spin labeling (ASL) perfusion MRI, a noninvasive technique, is
valuable for the assessment of acute stroke. Perfusion deficits and perfusion–
diffusion mismatches as visualized on the ASL images have been proven to
correspond with dynamic susceptibility contrast-enhanced images. Furthermore, a
relation between perfusion in the affected hemisphere and outcome has been
shown. Although noninvasive ASL perfusion imaging seems to be a promising tool in
the neonatal population, experience is still limited, and only one study has described
the use of ASL MRI in the evaluation of PAIS. ASL MRI could demonstrate areas of
hypo- and hyperperfusion in patients with PAIS. However, ASL has not yet been used
to assess changes in perfusion (abnormalities) over time in neonates with stroke. In
addition, regional cerebral oxygenation (rScO2) was monitored, compared with
reported rScO2 values in neonates (63 ± 12% , and analyzed as a function of the
perfusion signal as visualized on the ASL MR images.

5. Radiographic features
CT
diffuse edema with effacement of the CSF-containing spaces
decreased cortical gray matter attenuation with loss of normal gray-white
differentiation
decreased bilateral basal ganglia attenuation
reversal sign: reversal of the normal CT attenuation of grey and white matter,
demonstrated within the first 24 hours in a small number of these patients
it has been proposed that this finding is due to the distention of deep
medullary veins secondary to partial obstruction of venous outflow from
the elevated intracranial pressure caused by diffuse edema
the end result is that the cerebral white matter is of higher attenuation
than the cortical gray matter
white cerebellum sign: has been described in at least one study as a component
of the reversal sign and in which there is diffuse edema and hypoattenuation of
the cerebral hemispheres with sparing of the cerebellum and brainstem,
resulting in apparent high attenuation of the cerebellum and brainstem
relative to the cerebral hemispheres
linear hyperdensity outlining the cortex as well as linear cortical enhancement
(later and less evident signs), correspond to cortical laminar necrosis.

6. MRI
Diffusion-weighted MR imaging is the earliest imaging modality to
become positive, usually within the first few hours after a hypoxic-
ischemic event due to early cytotoxic edema. During the first 24 hours,
there may be restricted diffusion in the cerebellar hemispheres, basal
ganglia, or cerebral cortex (in particular, the perirolandic and occipital
cortices). The thalami, brainstem or hippocampi may also be involved.
Diffusion-weighted imaging abnormalities usually pseudo-normalize by
the end of the 1st week .
As in younger patients, conventional T1 and T2 weighted images are
often normal or demonstrate only very subtle abnormalities. In the early
subacute period (24 hours–2 weeks), conventional T2 weighted images
typically become positive and demonstrate increased signal intensity and
swelling of the injured gray matter structures.
T1 hyperintensities signaling cortical laminar necrosis become evident
after two weeks. This hyperintense signal does not represent hemorrhage,
it's believed to be caused by the accumulation of denatured proteins in
dying cells. This hyperintensity can be seen also within a few days on
FLAIR.

7. Acute Ischemic Stroke. NECT and Axial DWI-diffusion.

8. CT of a 7 day old with history of perinatal asphyxia, shows diffuse
low attenuating supratentorial brain parenchyma with relatively
hyperdense Cerebellum - "CT Reversal sign" of Global hypoxia.

9. CT scan show bilateral
hypodensity involving
the basal ganglia and
the thalami Axial T1WI
show hyperintensity of
the basal ganglia.
Axial T2WI shows
corresponding
hypointensity .
DWI reveals
hyperintensity at the
basal ganglia,
hippocampi and
occipital lobes,
consistent with
restricted diffusion of
acute ischemic injury.

10. CT without and with iv contrast. Axial T2 with bilateral thalamic infarct.

11. Global hypoxic-ischemic brain injury.

12. Hypoxic-ischemic brain injury.

17. Images show the temporal evolution of a right-sided main branch MCA territory
infarction (patient 1) on T1-weighted images (top row) and T2-weighted images
(bottom row) obtained on days 2, 5, 12, 42, and 75 post-delivery.

18. Graph shows DWIs of a patient with an infarction within the PCA territory,
showing severe HSI on day 3 (A) and mild-to-moderate HSI on day 10 (B).

19. MRI Diffusion show bilateral fronto parietal and parieto occipital cortical restricted
diffusion. Similar restricted diffusion in caudate nuclei. Area of involvement corresponds
to cortical as well as internal border zone infarcts. Imaging wise : Bilateral border infarcts

20. A, Axial T2-weighted fast spin-echo
image (3200/85/1), with an echo train
length of 8, obtained at 13 hours of
life shows no abnormality.
B, Trace LSDI image (1520/62.5/1),
with a b max of 750 seconds/mm2,
obtained at 13 hours of life shows no
abnormality.
C, Corresponding ADC map.
D, Axial T2-weighted fast spin-echo
image obtained at 5 days of life shows
very subtle hyperintensity in the
posterior putamen bilaterally
(arrows).
E, Trace LSDI image obtained at 5 days
of life shows decreased diffusion in
corresponding areas (arrows).
F, Corresponding ADC map.
G, T1-weighted axial spin-echo image
(600/20/2) obtained at 6 weeks of life
shows hyperintensity within the
posterior putamen and ventrolateral
thalamus bilaterally (arrows).

21. The neonatal mean diffusion-weighted image (mDWI) shows an ischemic area in the middle
cerebral artery territory, which resulted in a cyst observed at 3 and 24 mo. The neonatal Z map
shows normal Z values in all regions. At 3 mo, low Z values, representing abnormal fractional
anisotropy (FA) values, were observed in the affected corticospinal tract, which corresponded
with the subsequent development of unilateral motor deficits. The Z map at 24 mo was
essentially identical. Interestingly, FA values in the fornix continued to decrease from the time of
the neonatal scan to 24 mo, suggesting delayed degeneration in this tract.

23. Restricted diffusion signal in the DCST. Left middle cerebral artery infarction (A) results
in DWI signal changes throughout the DCST. PLIC and cerebral peduncle involvement
are evident on coronal (B) and sagittal images (C). Signal in the basis pontis and
medullary pyramids can be seen on left (D) but not right (E) parasagittal sections.

24. Neonate with left middle cerebral artery stroke and chronic
hemiparesis, DWI signal is appreciated throughout the DCST including
PLIC (A), peduncle (B, C), pons (D, E), and pontomedullary junction (F).

27. Axial diffusion weighted
images from a neonate
(A) with a modified
pediatric ASPECTS of
eight (involvement of
left internal capsule,
insula, M3, M5, M6, P1,
P2, and thalamus) and a
child (B) with a modified
pediatric ASPECTS of 10
(involvement of left
caudate, lentiform,
internal capsule, insula,
and middle cerebral
artery territories M1–
M6).

28. (A) Axial diffusion-weighted image showing hyperintensity in the
territory of left middle cerebral artery. (B) MR angiography demonstrates
loss of flow distal to the left middle cerebral artery bifurcation.
A B

30. Perinatal asphyxia, more appropriately known as hypoxic-
ischemic encephalopathy (HIE), is characterized by clinical and
laboratory evidence of acute or subacute brain injury due to
asphyxia. The primary causes of this condition are systemic
hypoxemia and/or reduced cerebral blood flow (CBF). Birth
asphyxia causes 840,000 or 23% of all neonatal deaths worldwide
HIE- Acute brain injury that occur before, during or after birth.
Signs and symptoms:
Mild hypoxic-ischemic encephalopathy
•Muscle tone may be slightly increased and deep tendon reflexes
may be brisk during the first few days
•Transient behavioral abnormalities, such as poor feeding,
irritability, or excessive crying or sleepiness (typically in an
alternating pattern), may be observed
•Typically resolves in 24h.

31. Moderately severe hypoxic-ischemic encephalopathy
The infant is lethargic, with significant hypotonia and diminished deep
tendon reflexes.
The grasping, Moro, and sucking reflexes may be sluggish or absent
The infant may experience occasional periods of apnea
Seizures typically occur early within the first 24 hours after birth
Full recovery within 1-2 weeks is possible and is associated with a
better long-term outcome.
Severe hypoxic-ischemic encephalopathy
Seizures can be delayed and severe and may be initially resistant to
conventional treatments. The seizures are usually generalized, and
their frequency may increase during the 24-48 hours after onset,
correlating with the phase of reperfusion injury.
As the injury progresses, seizures subside and the
electroencephalogram becomes isoelectric or shows a burst
suppression pattern. At that time, wakefulness may deteriorate further,
and the fontanelle may bulge, suggesting increasing cerebral edema.

32. Other symptoms include the following:
Stupor or coma is typical; the infant may not respond to any physical
stimulus except the most noxious.
Breathing may be irregular, and the infant often requires ventilatory
support Generalized hypotonia and depressed deep tendon reflexes
are common Neonatal reflexes (eg, sucking, swallowing, grasping,
Moro) are absent Disturbances of ocular motion, such as a skewed
deviation of the eyes, nystagmus, bobbing, and loss of "doll's eye"
(ie, conjugate) movements may be revealed by cranial nerve
examination
Pupils may be dilated, fixed, or poorly reactive to light
Irregularities of heart rate and blood pressure are common during
the period of reperfusion injury, as is death from cardiorespiratory
failure An initial period of well-being or mild hypoxic-ischemic
encephalopathy may be followed by sudden deterioration,
suggesting ongoing brain cell dysfunction, injury, and death; during
this period, seizure intensity may increase.

35. Imaging of neonatal hypoxic-
ischemic encephalopathy.
Ultrasonography is the first-line imaging
technique for the evaluation of the newborn
brain, These past few years have seen an
increasing role of MRI in the investigation of
HIE because of greater sensitivity and
specificity.
Electro-encephalogram(EEG).
Computed Tomography(CT).
MRI, MRS and DWI.

36. MRI sequences:
T1 WI, T2 WI++
FLAIR: are not very useful to detect lesion in young infant less than
24 months due to brain maturation.
IR T1-weighted: Has been very helpful in the last two decades
before generalization of high fields MRI as it gives excellent images
of brain anatomy and maturation, It also shows accurately the
differentiation between myelinated and unmyelinated WM.
Three-dimensional GE T1 weighted sequence (3DT1):
•allow 1 mm contiguous slices, which can be reconstructed in any
anatomic plane.
T2: to detect hemorrhagic lesions
DWI: It is now recommended that DWI should be performed
between 2 days and 8 days of life.
Multiple studies have shown :
DWI are more sensitive in the detection of HIE lesions than
conventional MRI especially for early diagnosis.

37. MRI Protocol:
Sagittal and axial T1 WI
Axial and coronal T2 WI
Axial T2*
3D T1
FLAIR (older child)
DWI
MRS:
Lactate peak:
•due to anaerobic glycolysis
•found within 24 h of life
Subsequently, a reduction in N-acetyl aspartate
(NAA) is evident due to neuronal loss.

38. Advanced technique: Perfusion.
Arterial Spin-Labeled (ASL) Perfusion
•Recent advances in novel research imaging
modality.
•allows noninvasive evaluation of CBF (cerebral
blood flow) using electromagnetically labeled
arterial blood water as an endogenous contrast
agent.
•Demonstrates low CBF in neonates who have
suffered HIE and in infants and children after
stroke.

39. Imaging Recommendation:
Cranial sonography (US):
•First, between 7 and 14 days,
•Repeat before discharge from the hospital
MRI, DWI, MRS
•When US is abnormal: MRI precise lesion extension
and aide in prognosticating,
• Defining injury in VLBW neonates with "normal" US.
Prognosis:
Poor outcome if :
•IVH plus PVL,
•PVL with volume loss, widespread infarction, or seizures
•PVL with enlarged cysts.

42. It is necessary to :
•know the normal cerebral appearance before
interpret pathological aspect
•distinguish hypoxic-ischemic brain damage from
normal myelination
Brain composition:
Changes in brain composition:
Changes in cellular density,
increase in complex lipids content due to the
evolving process of myelination,
decrease in water content mostly in the WM
Shortening of T1
Shortening of T2

53. Imaging Pattern:
The imaging patterns of HIE can be classified into
3 types:
Lesions predominantly located in the PVWM,
Lesions predominantly located in the basal
ganglia or thalamus,
Multicystic encephalomalcia.
The pattern of injury is postulated to depend on :
• The type of hypoxia–ischaemia (acute and
profound or prolonged and partial).
•The gestational age (term or pre-term).

54. HIE in preterm infant.
Risk Factors:
Pregnancy:
Gestational age/weight, previous preterm birth,
spontaneous preterm labor
Intrapartum:
Abruption, pre-eclampsia, premature rupture
of membranes, chorioamnionitis, group B Strep
Peri & postnatal factors:
Respiratory distress, sepsis, anemia, apnea,
bradycardia, cardiac arrest.

55. General Features:
++ PVL
+/- associated to:
Germinal matrix and IVH
PV hemorrhagic infarction
Cerebellar infarction
Definition:
•PVL is the HIE driven periventricular white matter (PVWM)
necrosis seen in very low birth weight premies (<1500g).
Epidemiology
•Birth weight < 1500 g 45% incidence of PVL (higher if
associated with IVH)
•Gestational age < 33 weeks 38% incidence of PVL
•> 50% of patients with PVL or grade III IVH develop cerebral
palsy.

60. Cranial ultrasound, coronal
view, day 1, showing severe
echogenicity in the white
matter. MRI (T2SE (TR
6284/TE 120) and ADC)
performed on day 3
showing increased signal
intensity in the white
matter on T2SE and low
signal intensity in the deep
white matter on the ADC
map with sparing of the
anterior periventricular
white matter and
asymmetrical distribution
in the parieto-occipital
white matter. The child died
and was subsequently
diagnosed to have
molybdenum cofactor
deficiency.

61. Cranial sonography
in 5-day old term
with HIE with
increase in
echogenicity of
white matter
consistent with
edema.
CD ultrasound
shows reversal of
diastolic flow,
reflecting
increased vascular
resistance
secondary to
edema.

62. PVL in a preterm infant. (a) Coronal head US image obtained in the 1st week of life shows
increased echogenicity in the periventricular white matter (arrows). (b) Follow-up US
image obtained 2 months later shows development of cystic changes in these regions and
dilatation of the adjacent lateral ventricles, findings that are consistent with PVL.

63. CT images show
decrease
In basal ganglia
density related to
Cytotoxic edema.
Subtle loss of the
normally sharp
Transition from grey
matter to
White matter at the
corticomedullary
Junction .
Cerebral edema seen
with effacement
of the cortical sulci
and the sylvian
Fissures.

67. PVL in a preterm
neonate. Axial T1-
weighted (a) and T2-
weighted (b) MR images
obtained on day 4 of life
demonstrate T1
hypointensity and T2
hyperintensity in the
periventricular white
matter. Note the
punctate foci of high
signal intensity on the T1-
weighted image (arrows
in a). These foci should be
distinguished from foci of
hemorrhage, which
would demonstrate
greater T2 shortening on
the corresponding T2-
weighted image.

68. 28-week-old, 1100-g infant. Initial MR images, A (T2-weighted SE [3000/120/1]) and B–D (T1-
weighted SE [400/15/2]), at 38 weeks corrected age show multiple spots of periventricular T1 and
T2 shortening (black arrows) with cyst formation (white arrows) and an irregular contour to the
ventricular wall. Follow-up MR images, E and F (T2-weighted SE [3000/100/1]), at 15 months
postconceptional age reveal marked irregularity of the ventricular wall, white matter loss, and
periventricular T2 prolongation (arrows). The infant developed a spastic diplegia.

69. 28-week-old 1355-g infant. Initial MR images, A and B (T2-weighted SE [3000/120/1]) and C and D (T1-weighted SE
[400/15/2]), at 38 weeks corrected age show large germinal matrix region hemosiderin deposit (arrowhead) with
adjacent multiple encephaloclastic cysts (arrows), diffuse hemosiderin deposition along the lateral ventricle,
ventriculomegaly, and absence of periventricular parenchymal signal change. Follow-up MR images, E and F (T2-weighted
SE [3000/100/1]), at 12 months corrected age reveal right periventricular hemosiderin deposition (arrowheads),
ventriculomegaly, and parenchymal destruction involving the left deep gray matter. Also note the periventricular T2
prolongation (arrows) with white matter volume loss. The infant developed a spastic diplegia with hemiparesis.

76. HIE in term infant.

89. Severe HII in a 6-yearold
child. (a) Unenhanced CT scan
obtained at the level of the basal
ganglia after cardiopulmonary
arrest that lasted 30 minutes is
essentially unremarkable. (b) On
an unenhanced CT scan obtained
just inferior to but
contemporaneously with a, the
cerebellum appears slightly
hyperattenuating relative to the
rest of the brain. This finding is
another example of the white
cerebellum sign as an early CT
indicator of HII. (c, d) Diffusion-
weighted (c) and T2-weighted (d)
MR images obtained 4 days later
show high signal intensity with
corresponding T2 abnormalities in
the caudate nuclei (white arrows),
lentiform nuclei (black arrows),
and occipital lobes (* in c).

90. CT Scan show Hyperdense thalami.
Cortical atrophy.
Ex vacuo dilatation of lateral ventricle with undulating walls suggestive of Gliosis
and paucity of periventricular white matter - Periventricular leukomalacia.

91. Full-term infant with acute
sentinel event (ruptured
uterus) with MRI pattern
suggestive of acute near
total asphyxia. a Inversion
recovery sequence (TR
5038/TE 30/TI 600) does
not show a normal signal
within the posterior limb
of the internal capsule, but
areas of increased signal
intensity within thalami
and basal ganglia. DWI (b–
d) shows restricted
diffusion in the
ventrolateral thalami,
lentiform nuclei, cerebral
peduncles, and in the
perirolandic cortex. Also
note involvement of the
hippocampi.

92. Full-term infant with ‘white
brain’ pattern of injury. a, c
T2SE (TR 6284/TE 120)
shows increased signal
intensity in the white matter
with loss of cortical ribbon.
There is relative sparing of
the basal ganglia and
immediate periventricular
white matter. DWI (b, d)
confirms the abnormalities
and shows a striking
discrepancy in signal
intensity with the
cerebellum. Note high-
signal intensity of the
mesencephalon (c) on T2SE
and symmetrical restricted
diffusion in the cerebral
peduncles and also in the
cerebellum (d).

93. A 14yo with delayed milestones showing bilateral peri rolandic cortical and
occipital cortical Gliosis suggestive of Perinatal Hypoxic Ischemic injury

94. End-stage PVL in a 9-yearold child who presented with motor and cognitive delay and
seizures. The patient was born at 32 weeks gestational age. Axial fluid-attenuated
inversion recovery MR images demonstrate increased signal intensity and a few tiny
cysts in the immediate periventricular white matter. In b, there is enlargement of the
atria of the lateral ventricles with a decrease in volume of the adjacent white matter,
and the walls of the lateral ventricles have a wavy appearance.

95. Color coded white matter
directions and FA images. The
inset indicates the level of
horizontal sections displayed in
A and B. Genu most anterior
region of the corpus callosum,
ALIC anterior limb of the
internal capsule, PLIC posterior
limb of the internal capsule,
Splenium the most posterior
portion of the corpus callosum,
Isthmus region of the corpus
callosum just anterior of the
splenium. (A) The colors indicate
the direction of white matter
fibers with blue left-right, red
anteroposterior and green
cranial-caudal (point out from
the plane of the page). (B) The
intensity corresponds to FA.
Black corresponds to FA 0 and
the higher the FA value the
whiter the image.

96. Hypoxic-ischemic encephalopathy. From left to right: Bilateral basal
ganglia hyperintense rounded signal in axial FLAIR T2 images, with
restricted diffusion hyperintense in DW images and with low ADC values.

97. Delayed leukoencephalopathy after acute carbon monoxide intoxication.

98. Fibre tractography of hypoxic-ischemic leuckoenecephalopathy.

99. Sagittal image of a child
with PVL grade 1.
Transverse and sagittal image
of a child with PVL grade 2.

100. Sagittal image demonstrating
extensive PVL grade 3
Coronal and transverse images
demonstrating PVL grade 4.

107. Born at 37 weeks,
following antenatal
diagnosis of fetal
supraventricular
tachycardia. MRI, T2SE
(TR 6284/TE 120)
performed on day 3,
shows a large left-sided
middle cerebral artery
infarct of antenatal
onset, with evidence of
Wallerian degeneration
and presence of cysts
within the area of
infarction. Diffusion
tensor tractography
shows loss of fibers with
the corticospinal tract of
the affected hemisphere

111. MR spectroscopy.
Biochemical analysis of the (compromised
anaerobic) cerebral tissues.
Elevated lactate and diminished N-acetyl-
aspartate NAA concentration.
Elevation of choline relative to creatine.
Lactate-choline ratio of 1 indicate a
greater than 95% probability of adverse
neurodevelopmental outcome.

112. MR spectroscopy
of a single
voxel at 35 msec,
demonstrate
non-specific
accumulation
of metabolite at
1.2-1.3 ppm.
Spectrum at an
echo time of 144
msec shows
inversion of the
same metabolite,
which is
characteristic for
lactate.

120. Thank You.