radiology seminar

1. Pediatric perinatal insult:
HYPOXIC ISCHEMIC
ENCEPHALOPATHY
Dr. Mohit Goel, JRIII
19/5/14

2. INTRODUCTION
 Hypoxic-ischemic injury (HII) to the brain is a devastating occurrence that
frequently results in death or profound long-term neurologic disability in
both children and adults.

3. Imaging findings in HII are highly variable and depend on a number of
factors, including :
• Brain maturity
• Severity
• Duration of insult
• Type and timing of imaging studies

4. PATHOPHYSIOLOGY
 Regardless of the specific cause of injury, the common underlying
physiologic processes that result in HII are diminished cerebral blood
flow (ischemia) and reduced blood oxygenation (hypoxemia).
 In general, infants and children are more likely to suffer asphyxial
events, which result in hypoxemia and brain hypoxia.
 With prolonged hypoxemia, cardiac hypoxia occurs, leading to
diminished cardiac output and, ultimately, to brain ischemia.

5. Hypoxic-Ischemic Brain Injury: Imaging Findings from Birth to Adulthood.
Benjamin Y. Huang, MD, MPH and Mauricio Castillo, MD. Doi: 10.1148/rg.282075066 March 2008 RadioGraphics, 28, 417-439.

6.  Areas of the brain with the highest concentrations of glutamate or
other excitatory amino acid receptors (primarily located in gray
matter) are more susceptible to excitotoxic injury that occurs as a
result of hypoxia-ischemia.
 Areas of the brain with the greatest energy demands become
energy depleted most rapidly during hypoxia-ischemia, and are
therefore injured early on.
 Because of delayed cell death from apoptosis, some injuries may
not be evident until days after the initial insult has occurred

7. Patterns of brain injury in mild to
moderate hypoperfusion.
how the vascular supply changes with
maturation and affects the pattern of brain
injury in HIE.
The premature neonatal brain has a
ventriculopetal vascular pattern, and
hypoperfusion results in a periventricular
border zone of white matter injury.
Premature Term
In the term infant, a ventriculofugal vascular pattern develops as the brain
matures, and the border zone during hypoperfusion is more peripheral with
subcortical white matter and parasagittal cortical injury.
Neonatal Hypoxic-Ischemic Encephalopathy: Multimodality Imaging Findings. Christine P. Chao, MD,
Christopher G. Zaleski, MD and Alice C. Patton, MD. Doi: 10.1148/rg.26si065504 October 2006 RadioGraphics, 26, S159-S172.

8. Causes of HIE.
Chao C P et al. Radiographics 2006;26:S159-S172
©2006 by Radiological Society of North America

9. IMAGING MODALITIES :
Accurate identification and characterization of the severity,
extent, and location of brain injury rely on the selection of
appropriate neuroimaging modalities, including
1. Ultrasonography
2. Computed tomography
3. Magnetic resonance imaging.

10.  Radiation
 Less sensitive
Why Not CT ??

11. TERM NEONATE
Antepartum risk factors
 maternal hypotension
 infertility treatment
 multiple gestation
 prenatal infection
 thyroid disease
Intrapartum factors
 forceps delivery
 breech extraction
 umbilical cord prolapse
 abruptio placentae
 tight nuchal cord
 maternal fever
Antepartum factors in combination with intrapartum
factors.

12. “1-2-3-4 sign”
Imaging Findings in Neonatal Hypoxia: A Practical Review. E. Ralph Heinz1 and James M.
Provenzale http://www.ajronline.org/doi/full/10.2214/AJR.08.1321
The four components of the 1-2-3-4 sign are :
1. Increased signal intensity in the basal ganglia on T1-weighted images
2. Increased signal intensity in the thalamus on T1-weighted images
3. Absent or decreased signal intensity in the posterior limb of the internal
capsule on T1-weighted images “absent posterior limb sign”
4. Restricted water diffusion on diffusion-weighted images.

13. SEVERE ASPHYXIA IN TERM
NEONATES
Central pattern of injury involving
the deep gray matter
 putamina
 ventrolateral thalami
 hippocampi
 dorsal brainstem
 lateral geniculate nuclei
 occasionally perirolandic
cortex.
 actively myelinating areas are
the most susceptible to
neonatal HII

14. USG
 Early findings - global
increase in cerebral
echogenicity and
obliteration of the CSF
containing spaces,
suggesting diffuse cerebral
edema.
 1st week but more readily
apparent after 7 days.
Increased echogenicity in
the basal ganglia, thalami,
and brainstem

15. USG
 Late findings include prominence of the ventricles and extraaxial CSF-
containing spaces, likely due to atrophy.
 The presence of diminished
resistive indexes (<60) in the
anterior and middle cerebral
arteries has been associated
with a poor clinical outcome,
even in the absence of other
US abnormalities.

16. MRI Diffusion-weighted imaging
 Sensitive for the detection of injury in the first 24 hours,
during which time conventional T1- and T2-weighted images
may appear normal.
 Demonstrate increased signal intensity in the region of the
ventrolateral thalami and basal ganglia particularly the
posterior putamina in the perirolandic regions and along the
corticospinal tracts

17. MRI - Pseudonormalization.
 Although diffusion-weighted images seemingly improve and
appear relatively normal by the end of the 1st week, this
finding does not imply that there has been improvement or
reversal of underlying disease.

18. MRI
 Day 1 ---- Conventional T1- and T2-weighted MR images are frequently
normal , therefore less useful than DWI
 Day 2 ---- Injured areas may demonstrate hyperintensity on both T1- and
T2-weighted images.
 2 weeks --- T2 hypointensity subsequently develops in the thalami &
posterior putamina.
 Several months --- TI hyperintensity in thalami, basal ganglia &
perirolandic cortex may persisit.
 ‘T1WI & T2WI ARE MOST DIAGNOSTICALLY USEFUL AT THE END OF
1st WEEK, WHEN DWI PSEUDONORMALIZE’.
 Chronic stage of injury - atrophy of the injured structures
- T2 hyperintensity in the ventrolateral thalami,
posterior putamina, and corticospinal tracts.

19. 13 days old, male baby
Term baby with history of respiratory distress and hypotonia at birth, followed by 2
episodes of seizures.

24. 11 days old, male baby.
History of one episode of seizure , known case of HIE

25. T1WI

28. Severe neonatal HII in a 7-day-old term infant.
T1WI shows increased signal intensity in the lentiform nuclei and ventrolateral thalami.
T2WIshows decreased signal intensity in the posterior aspects of the putamina and
ventrolateral thalami.
Huang B Y , and Castillo M Radiographics 2008;28:417-439

29. DWI shows a relative lack of hyperintensity in the locations cited earlier, findings
that represent pseudonormalization.
Only the left globus pallidus shows high signal intensity. Corresponding ADC map
shows hypointensity
Huang B Y , and Castillo M Radiographics 2008;28:417-439

30. Severe neonatal HII in a 5-day-old term infant who suffered profound birth asphyxia.
T1WI show hyperintensity in the ventrolateral thalami, basal ganglia and perirolandic
cortex.
Huang B Y , and Castillo M Radiographics 2008;28:417-439

31. T2WI obtained approximately 7 months later show diffuse atrophy as well as
hyperintensity (gliosis) in the ventrolateral thalami, posterior putamina, and
perirolandic regions.
Huang B Y , and Castillo M Radiographics 2008;28:417-439

32. PARTIAL ASPHYXIA TERM
NEONATES
In mild to moderate hypoxic-ischemic ----
 brainstem
 cerebellum
 deep gray matter structures
are generally spared since autoregulatory mechanisms maintain
perfusion.
Moderate insults of short duration in neonates cause little or no injury
to the brain
Prolonged insults in neonates result in injury to the intervascular
boundary (watershed) zones, which are relatively hypoperfused as a
result of this shunting.

33. MRI TERM NEONATE
 DWI (earliest to change)
First 24 hrs ---demonstrate cortical and subcortical WM restriction
most pronounced in the parasagittal watershed territories.
 T2WI
By day 2 --- cortical swelling with loss of gray and white matter differen.
hyperintensity in the cortex and subcortical WM in the parasagittal
watershed zones occasionally involving the hemispheres diffusely.

34. Partial neonatal HII in a 2-day-old term infant who experienced seizures shortly
after birth . T1WI & T2WI are normal.

35. DWI and corresponding ADC map show restricted diffusion in the cortex and
subcortical white matter in a parasagittal watershed distribution.

36. PRETERM NEONATE
 HII is more common in preterm neonates than in term
neonates.
 HII in preterm infants, particularly those of very low birth
weight is difficult to diagnose clinically early on because
signs may be lacking or mistaken to result from
developmental immaturity.

37. PRETERM NEONATES
Manifest predominantly as damage to the deep gray matter
structures and brainstem.
Events of mild to moderate severity manifest as germinal
matrix–intraventricular hemorrhages or periventricular
leukomalacia.

38. SEVERE ASPHYXIA IN PRETERM
 Injury to the thalami, basal ganglia, hippocampi, cerebellum, and
corticospinal tracts can be seen.
 The thalami, anterior vermis, dorsal brainstem are most frequently
involved.
 Involvement of basal ganglia is less severe compared with
involvement of the thalami particularly among neonates born at less
than 32 weeks gestation.
 Germinal matrix hemorrhages and periventricular white matter injury
also may be seen.

39. USG IN PRETERM
NEONATES
 May be normal particularly in the first 2 days.
OR
 Demonstrate increased echogenicity in the thalami by 48–72
hours

40. MRI
 1st day Conventional MR may be normal or show only subtle
abnormalities.
 Diffusion abnormalities are usually evident in the thalami within 24
hours .
 After 2 days, T2 prolongation can be seen in the thalami and basal
ganglia.

41. MRI
 3rd day - T1 hyperintensity will be seen in the injured areas.
 3–5 days - DW abnormalities most apparent subsequently begin
to pseudonormalize .
 7 days - T2 hypointensity develops in the injured areas
T1 hyperintensity persists into the chronic stage.

42. T1WI
19 days old, male baby
Preterm, AGA. History of cardiac arrest at 30 hours of life. Baby was ventilated.

43. T2WI

44. MILD TO MODERATE ASPHYXIA PRETERM
 Weighing less than 2000 gms
 Prevalence of intraventricular hemorrhage approximately
25%
 Bleeding occurs within the first 24 hours of life.
 Prevalence is inversely related to gestational age and weight
at birth.
 Majority of intraventricular hemorrhages are associated with
germinal matrix hemorrhages.

45. Sonographic grading system proposed by Burstein and Papile et.al:
Grade I
restricted to subependymal region / germinal matrix which is seen in the
caudothalamic groove
Grade II
extension into normal sized ventricles and typically filling less than 50% of the
volume of the ventricle
Grade III
extension into dilated ventricles
Grade IV
grade III with parenchymal haemorrhage
90% mortality.
It should be noted that it is now thought that grade IV bleeds are not simply
extensions of germinal matrix haemorrhage into adjacent brain, but rather
represent sequelae of venous infarction
Grading of neonatal intracranial haemorrhage

46. Grade I

47. Grade II

48. Grade III

49. Grade IV hemorrhage.

50. PVL Classification
 Grade I – Transient Periventricular echo densities
persisting for > 7 days
 Grade II - Transient Periventricular echo density
evolving into small, localized fronto-parietal cyst
 Grade III - Periventricular echo densities evolving into
extensive periventricular cystic lesions
 Grade IV – Densities extending into the deep white matter
evolving into extensive cystic lesions

51. Grade I PVL

52. Grade III PVL
PARA SAG COR

53. Grade III PVL

54. MRI - PVL
 Early WM injury will manifest as periventricular foci of T1
hyperintensity (without corresponding T2 hypointensity) within larger
areas of T2 hyperintensity.
 These foci are usually evident by 3–4 days, subsequently giving way
to mild T2 hypointensity at 6–7 days .
 In contrast, hemorrhage (reported to be present in 64% of cases of
PVL) initially manifests with much lower signal intensity on T2-
weighted images.

55. 1 yr male with history of right side focal seizurs with global developemental delay.
USG AF done during neonatal period revealed bilateral germinal matrix hemorrhage.

56. T1WI FLAIR
1 yr male with history of hypoxic cerebral palsy with mental retardation and global
developmental delay.

57. POSTNATAL INFANTS &
YOUNG CHILDREN
 Hypoxic-ischemic injuries in infants and young children are
usually the result of drowning, choking, or non accidental
trauma.
 As myelination nears completion by about 2 years of age,
injuries similar to the pattern seen in adults begin to appear.

58. SEVERE ASPHYXIA IN POSTNATAL
INFANTS & YOUNG CHILDREN
1 and 2 years of age ---- Result in injury to the
 Corpora striata
 Lateral geniculate nuclei
 Hippocampi
 Cerebral cortex (particularly the anterior frontal and parieto-occipital
cortex), with relative sparing of the thalami and perirolandic cortex.
 Immediate perinatal period but before 1 year of age --- can
demonstrate features of both birth asphyxia and later infantile
asphyxia, with involvement of the basal ganglia (predominantly
posteriorly), lateral thalami, and dorsal midbrain, as well as cortical
injury.

59. CT
< 24 hours of an insult --- may be negative or may demonstrate only
subtle hypoattenuation of the deep gray
matter structures .
Subsequent CT --- will demonstrate
 diffuse basal ganglia abnormalities along with diffuse cerebral
edema, manifesting as cortical hypoattenuation
 loss of normal “gray-white” differentiation
 cisternal and sulcal effacement.
4–6 days --- may show hemorrhagic infarctions of the basal ganglia.
Chronic phase ---- diffuse atrophy with sulcal and ventricular
enlargement .

60. CT
 Within the first 24 hours, a small number of these patients may
demonstrate the “Reversal sign,” in which there is reversal in the
normal CT attenuation of gray matter and white matter.
 “White cerebellum sign” --- 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.

61. Unenhanced CT shows diffuse cortical swelling and hyperattenuation in the
white matter relative to areas of preserved cortex, i.e ‘Reversal sign’ --poor
prognosis.
A small amount of extraaxial hemorrhage adjacent to the left frontal lobe is also
seen.
Huang B Y , and Castillo M Radiographics 2008;28:417-439

62. Unenhanced CT demonstrates the ‘White cerebellum sign’. The cerebellar
hemispheres are hyperattenuating relative to the supratentorial structures, which
are hypoattenuating due to edema.
Huang B Y , and Castillo M Radiographics 2008;28:417-439

63. Unenhanced CT scan obtained at the level of the basal ganglia after
cardiopulmonary arrest that lasted 30 minutes is essentially unremarkable.
Huang B Y , and Castillo M Radiographics 2008;28:417-439

64. DWI and T2WI obtained 4 days later show high signal intensity with
corresponding T2 abnormalities in the caudate nuclei, lentiform nuclei, and
occipital lobes.
Huang B Y , and Castillo M Radiographics 2008;28:417-439

65. MRI
 MR imaging is frequently performed in children with HII.
Diffusion-weighted images will usually be abnormal within the first 12–24
hours, initially demonstrating bright signal intensity in the posterolateral
lentiform nuclei ; thalamic involvement (when present) will usually involve
the ventrolateral nuclei.
 Over the next 48 hours, there is typically significant progression of
involvement to include the remainder of the basal ganglia and the
cortex

66. MRI
 Conventional T1- and T2WI obtained in the first 24 hours are
often normal and may appear so for up to 2 days.
 By 48 hours, T2-weighted images will usually demonstrate
diffuse basal ganglia and cortical signal intensity abnormality

67. MILD TO MODERATE ASPHYXIA
IN POSTNATAL INFANTS & YOUNG
CHILDREN
 As in term neonates, milder anoxic events in older infants will
generally result in watershed zone injuries involving the
cortex and subcortical white matter.
 White matter lesions are more common in children under 1
year of age. Relative sparing of the periventricular white
matter will be seen.

68. Unenhanced head CT scan shows bilateral cortical and subcortical
hypoattenuation in the parasagittal watershed regions

69. DWI obtained at the same level shows corresponding high-signal-intensity
areas compatible with watershed infarcts.

70. OLDER CHILDREN & ADULTS
 HII in adults is more often a result of cardiac arrest or cerebrovascular
disease, with secondary hypoxemia.
 Drowning and asphyxiation remain common causes of HII in older children.
 Mild to moderate global ischemic insults to the brain usually result in
watershed zone infarcts.
 Severe HII in this population primarily affects the gray matter structures: the
basal ganglia, thalami, cerebral cortex (in particular the sensorimotor and
visual cortices, although involvement is often diffuse), cerebellum, and
hippocampi

71. MRI
 As in younger patients, conventional T1- and T2-weighted images are
often normal or demonstrate only very subtle abnormalities.
 Early subacute period (24 hours–2 weeks) --- conventional T2WI
typically become positive and demonstrate increased signal intensity
and swelling of the injured gray matter structures. DWI abnormalities
usually pseudonormalize by the end of the 1st week .
 2nd week --- Gray matter signal intensity abnormalities at conventional
MR imaging may persist into the end of the.
 Chronic stage --- T2WI may demonstrate some residual hyperintensity
in the basal ganglia, and T1WI may show cortical necrosis , which is
seen as areas of high signal intensity in the cortex

72. Axial T2W and DWI show diffuse WM hyperintensity. On the corresponding ADC
map, the white matter is hypointense

73. MR SPECTROSCOPY
 MR spectroscopy is perhaps more sensitive to injury and more
indicative of the severity of injury in the first 24 hours after a
hypoxic-ischemic episode, when conventional and diffusion-
weighted MR imaging may yield false-negative findings or lead
to significant underestimation of the extent of injury.

74.  MR spectroscopy will demonstrate substantial lactate elevation
(appearing as a doublet centered in the deep gray nuclei, parieto-
occipital region, or white matter of the parasagittal watershed
zones by as early as 2–8 hours .
 A glutamine-glutamate peak may also be detected , probably
reflecting the release of glutamate that occurs in HII.

77. THANK YOU