1. Neuroimaging in the Neonate
Debra B. Selip, MD
Fetal and Neonatal Medicine Center
and
Division of Neonatology
Rush University Medical Center
March 4, 2011

2. Neuroimaging in the Neonate
Wide array of imaging modalities readily available
Expanding and rapidly changing body of literature examining appropriate imaging methods and prognostic applications

3. Neuroimaging Modalities
Xray
Ultrasound
CT scan
MRI T1 T2
DWI / DTI / FA / Tractography
MR Spectroscopy
NM Scans
SPECT
PET

4. Why Image? 2 Roles: Diagnose brain injury in at risk newborns
Improve and provide acute medical management/interventions
Detect lesions associated with long-term neurodevelopmental disability
Appropriate prognosis/predictions
Appropriate tx:
Brain cooling
Phenobarb? Bumetanide?
Redirection?
Approp prognosis:
Cognitive
Motor
Psych
Neurosensory

5. Prognostic Concerns
Clinical evaluation insufficient for prognostication
Cerebral Palsy?
School Performance?
Neurocognitive & neurodevelopmental disabilities
Behavioral disabilities
Role for neuroimaging?

6. 2 Types of Neonates Preterm Infants Periventricular Leukomalacia
Intraventricular Hemorrhage
Post-hemorrhaghic Hydrocephalus
Periventricular Hemorrhagic Infarction
Intraparenchymal Hemorrhage
Cortical and Deep Gray Matter Injury

7. 2 Types of Neonates Full term Infant Stroke Intracerebral Hemorrhage
Periventricular Leukomalacia
Intraventricular Hemorrhage
Congenital Anomalies
Cortical and Deep Gray Matter Injury

8. Outline Preterm infant: ELGAN / VLBW Term Epidemiology
Neuroimaging modalities
Indications for use
Findings and clinical correlates
Conclusions
Term
Not late preterm infant. Focus on ELGA / VLBW
Late preterm – not lots info on imaging on these infants – I suspect most their difficulties are cognitive and we’re still trying to figure out their deficits and then ultimatley how to identify them early.

9. The brain is a wonderful organ; it starts working the moment you get up in the morning and does not stop until you get into the office Robert Frost

11. Epidemiology: Preterm Infant
ELGAN/ VLBW:
number preterm infants and survival:
For babies less than 32 wks
Greater than 2% of all live births
Up to greater than 85% survival
Emphasis on Outcomes:
Improvement in ND outcomes
Infants less than 26 wks:
Approximately 15% with CP
At 11 yrs:
25% severe ND disability
35% moderate ND disability
20% mild ND disability
Outcomes: no sense in saving these babies if we can’t give them a good chance “normal” life
Marlow et al. NEJM 2005
Anderson et al. JAMA 2003
Epicure, 2005

12. Epidemiology: Preterm Infants
Emphasis on Outcomes:
Infants less than 30 wks
25 – 50% cognitive, behavioral, social difficulties requiring special ed. intervention
5 – 15% cerebral palsy, severe neuro-sensory impairment or both
Overall:
At 8 years of age
50% children BW less than 1 kg in special education
20% children BW less than 1 kg repeat a grade
10 -15% children BW less than 1 kg with spastic motor CP
Marlow et al. NEJM 2005
Anderson et al. JAMA 2003

13. Typical Injury Patterns: ELGA / VLBW
IVH
Ventriculomegaly
White matter
injury
PHH
Gray matter injury
Hemorrhage
Hypoxia
Ischemia
LEADS TO
Volpe, Neurology of the Newborn, 2008
Follett et al, JNeurosci, 2001, 2004
Deng et al, PNAS, 2006

14. Evolution of Injury: ELGA / VLBW
Local necrosis with congestion or hemorrhage
Echo-lucent cysts in periventricular white matter
Echolucent cysts – tissue dissolution – 1-3 wks
Ventriculomegaly – 2-3 months
Ventriculomegaly, cysts disappear, deficient myelin and/or gliosis with collapse of cysts, echo-densities

15. Factors to Consider When Imaging Critically Ill Infants
Timing
Technique
Transport
Compatibility
Availability
Sedation
Given the modalities readily available to us and the limitations and difficulties we encounter, we’re going to examine the following  (next slide)

16. Ultrasound: Diagnostic Capabilities
Hemorrhagic
Hydrocephalus
Periventricular hemorrhaghic infarction
Non-hemorrhagic
Echodensities
Echolucencies
Ventricular enlargement
Edema
Sensitivity much increased with multiple scans
Echolucencies – less frequently seen in white matter but much more predicitive of long term clinical morbidity. Most ominous in the first 2 wks of life.
Risk for PHH – most prognostic question
Late U/S findings with ventricular enlargement, cystic changes in white matter or hydrocephalus – increased risk of CP
Later scans more prognostic
Echolucencies strongly assoc with CP more so than MR
Echodensities freq transient
Reasons to change from Papile grading system to descriptions.
DeVries et al, JPediatric, 2004

17. El-Dib, M. et al. Am J Perinatol. 2010.

18. Grades of IVH – grade 1 to 4
El-Dib, M. et al. Am J Perinatol

19. El-Dib, M. et al. Am J Perinatol. 2010.

20. Ultrasound: Prognostic Capabilities
Major abnormalities
Gr 3 IVH, PHI, Cystic PVL
Predictive of CP and NM delay at follow up
Predictive of impaired cognitive outcome but with less sensitivity and specificity
Mild abnormalities
Prediction of CP or cognitive deficits is problematic
Not predictive of NORMAL outcome
El-Dib, M. et al. Am J Perinatol

21. Ultrasound: Prognostic Capabilities
Diffuse PVL: low sensitivity
Misses greater than 50% diffuse white matter injury
Hemorrhage conveys less prognostic info than evidence of white matter damage and PHH
Cerebellar Injury
30 -60% preemies who develop CP had lesions on US during perinatal period

22. Ultrasound: Prognostic Capabilities
Recent literature
gr1 and gr2 IVH in infants <26 GA with poorer ND/NC outcomes
Significant assoc. btwn gr 3 – 4 IVH, Cystic PVL, mod- sev ventriculomegaly, and CP at 2 - 9yrs in babies < 1500g
Patra, K et al. JPeds, 2006

23. Ultrasound: Prognostic Capabilities
Grade 4 IVH and ventriculomegaly strong assoc with MR and neuropsych disorders at yrs in infants <1500g
Odds Ratio: 10 fold increase in adverse outcome with above sonographic findings

24. Ultrasound: Limitations
Poor contrast for lesions of brain parenchyma
Limited field of view
Insensitive for identification of hemorrhage adjacent to bone
Fair cerebellar views
Operator dependent

25. Ultrasound: Conclusions ELGAN / VLBW
Routine screening <30 wks
Screen btwn days
80% IVH
Screen 36 wks PMA
White matter injury
Diagnostic utility quite good
Prognostic role limited to more severe injury patterns
Serial HUS may increase predictive abiltiy

26. He who joyfully marches to music in rank and file has already earned my contempt. He has been given a large brain by mistake, since for him the spinal cord would suffice.
Albert Einstein

28. MRI: ELGAN / VLBW T1 T2 DWI/ DTI/ FA / tractography / fMRI Volumetrics
Early MRI
Corrected term (40 – 42 wks CGA)
Utility in preterm brain
Utility in term corrected brain
Abnormalities of myelination of PLIC correlate very closely with cerebral palsy
T1/t2 – subacute injury
DTI/DWI – acute injury
T.M. O’Shea et al. EarlyHumDev, 2005.

29. MRI: ELGAN /VLBW Superior evaluation of: Identifies:
Brain structures
Gray / white matter
Brain stem / posterior fossa
Identifies:
More abnl findings 1st wk of life
More hemorrhagic lesions
More extensive cysts
Subtle / Diffuse white matter injury
Prognostic benefit: CP
Learning disabilities
Behavioral problems

31. MRI : Prognostic Capabilities
Woodward et al. Neonatal MRI to Predict
Neurodevelopmental Outcomes in Preterm Infants.
NEJM, August 2006.
167 infants < 30 wks
At 2 yrs
17 % severe cognitive delay
10 % severe psychomotor delay
10% CP
11% neurosensory impairment
21% moderate – severe cerebral white matter injury
Attempt to correlate clinical outcomes from children 2 yrs and MRI findings at term (PMA)
New Zealand and Australia

32. Woodward et al. NEJM. Aug 2006

33. MRI: Prognostic Capabilities Cont…d
Majority of preemies have
Loss of volume
Cystic abnormality
Enlarged ventricles
Thinning of the corpus callosum
Delayed myelination
Can these term findings be associated with definitive outcomes at 2yr, 4yrs, 6yrs, etc

34. Study Results 28% no white matter injury 5% mild white matter injury
17% moderate white matter injury
6% severe white matter injury
Correlation of MRI at term with outcome at 2 yrs of age (corrected)
More signif the white matter injury, the greater the neuro dev impairment
Normal or mild MRI result = free of severe impairments at 2yrs.
Mod –severe MRI white matter injury – severe neurodev deficits
Most common impairment noted severe cognitive delay (approx 20% of kids scored more than 6mo below corrected age)

35. The chief function of the body is to carry the brain around.
Thomas A. Edison

37. CT Scan: ELGAN / VLBW Good imaging modality Limited use due to:
Hemorrhage
Cerebral volume / Ventricles / Extra-axial space
Bones
Limited use due to:
Ionizine radiation / risk of future malignancy
Cognitive impairment
Correlations btwn clinical outcome and image results weak
Ionizing radiation – o.1% risk life long fatal malignancy from head CT at age 12 months estimated
Risk of development of brain tumor found to be 10 fold higher in infants exposed to cranial irradiation under 5 mo. In comparison to over 7 mo.

38. MRI vs Ultrasound vs CT in the ELGAN/VLBW: Conclusion
Ultrasound Early
MRI Later
Ultrasound early
MRI later
Forget the CT Scan

39. Imaging the Term Infant
Hypoxic Ishcemic Encephalopathy
Neonatal Stroke
Arterial Ischemic Stroke
Cerebral Venous Thrombosis
Intracerebral Hemorrhage
Periventricular Leukomalacia
Intraventricular Hemorrhage
Congenital Anomalies

40. Ultrasound: Term Infant
Not ubiquitously helpful
Poor parenchymal evaluation
Poor anatomic views
Poor for stroke
Good for IVH evaluation
Doppler views
Vascular
Hydrocephalus vs Ventriculomegaly
RI = (systolic ACA blood flow – diastolic ACA blood flow)
diastolic ACA blood flow
Marker of acute edema, increased ICP

41. CT Scan: Term Infant Significant findings Global picture of injury
Calcifications
Hemorrhage
Low attenuation in basal ganglia and thalamus
Global picture of injury
Extremely fast
Emergent situation
Limited use due to:
Risk of future malignancy
Risk of future cognitive impairment
Usu in infant with midline shift on HUS who needs emergent neurosurg intervention

42. MRI: Term Infant No ionizing radiation Multi-planar imaging
More sensitive and specific for CNS evaluation than CT or US
Grey matter
White matter
Modality of choice

43. MRI: Hypoxic Ischemic Encephalopathy
Water and the brain
T1 – 7 days
T2 – 7 days
DWI: one of the earliest indicators of tissue injury (within hours) – best 2 – 4 days
No ionizing radiation
Volumetric data of sensorimotor and mid-temporal cortices are assoc with full scale verbal and performance IQ scores
PLIC most reliable region compared to histopath
Evolving patterns of injury over time
MR Spect: functional eval - creatinine and lactate peaks
>50% basal ganglia and thalamic region injury

44. MRI: Pattern of Brain Injury
2 main types
Basal Ganglia-Thalamus
Acute near total asphyxia
CP / cognitive injury readily apparent
Watershed Predominant
Prolonged partial asphyxia
Ant – Mid cerebral artery
Post –Mid cerebral artery
Childhood symptoms / Deficits at 30 mo.

45. MRI: HIE Prognostic Capabilities
Neurodevelopmental handicap at 1-2 yrs of age if:
Basal ganglia or thalamic abnormality
50 – 94% with CP, mental retardation, seizure disorder
Well established

46. I was taught that the human brain was the crowning glory of evolution so far, but I think it's a very poor scheme for survival.
Kurt Vonnegut

48. MR Spectroscopy: Term Infant
Non-invasive in vivo biochemical analysis
Cellular metabolic information
Detection of biochemical changes before morphological changes apparent
NAA
Lactate
Creatine
Choline
Prognosis
Early H-MRS studies promising

49. Summary Appropriate modality for particular investigation
Pre-term Imaging US
MRI
MR Spect?
Full-term Imaging CT