1. Imaging the Brain in Neonatal Encephalopathy
Steven P. Miller MDCM
CIHR Clinician Scientist & MSFHR Scholar
Associate Professor, Pediatrics (Neurology)
University of British Columbia

2. Neonatal Encephalopathy
Neurological emergency
Evolves over time
The 2 Questions
What is the Diagnosis?
What is the Prognosis?

3. T1 T2
DWI CT
Normal with day 10 confirmation
FLAIR NOT HELPFUL!

4. CT, MRI, or DW-MRI Chau V et al Pediatrics 2009
Patterns of Injury
Basal Nuclei Predominant
Watershed Predominant
Total
Focal- Multifocal
CT, MRI, or DW-MRI Chau V et al Pediatrics 2009

5. Basal Nuclei with Cortical InjuryCT
MRI
ADC
BN pattern agrees for all modalities, but cortical injury not seen on CT:
Basal Nuclei with Cortical Injury

6. Watershed Pattern Perinatal Events Important! WS lower bwt
BG more seizures and intensive resusc

7. Images Courtesy of Dr. Hannah Glass UCSF

8. CT
MRI
ADC A B C D
Total pattern:
Total
Chau V et al Pediatrics 2009

9. White Matter Injury
Stroke
Li A, et al. Pediatric Research, 2009

10. FIGURE 1. A-D, Axial T2WI at the level of cerebellum (A), mid-brain (B), internal capsule (C), and corona radiata (D) shows the classic MSUD edema in the deep cerebellar white matter, cerebral peduncles, posterior limb of internal capsules, and the corona radiata, respectively. Note the relatively normal splenium of the corpus callosum (D). E-H, Isotropic diffusion-weighted images at the corresponding levels show marked hyperintensity in the deep cerebellar white matter, cerebral peduncles, dorsal brainstem, posterior limb of the internal capsules, and the corona radiata, suggestive of restricted diffusion. I-L, Apparent diffusion coefficient (ADC) maps in the same location reveal decrease in the ADC values. The areas with restricted diffusion and decreased ADC value appear as dark areaa in these maps. M-P, Fractional anisotropy (FA) maps at the corresponding levels as T2WI show that the FA values are diminished in the corresponding areas. The splenium of the corpus callosum (P) was unaffected and served as a comparative benchmark for the other areas.
Parmar H et al. Journal of Computer Assisted Tomography; :

11. Day 3 CT vs DW-MRI Agreement= 66.7% Kappa= 0.56 13 1 2 7 3 6 4 Sum 16
Normal
Watershed
Basal Nuclei
Total
Multi-Focal 13 1 2 7 3 6 4
Sum 16 8
Agreement= 66.7% Kappa= 0.56
Chau V et al Pediatrics 2009

12. Dav: A Window on Timing
Time course of the diffusion abnormality following perinatal brain injury in newborn infants. Dav has been normalized to reference values for newborn infants (Dav ratio). The maximum reduction in Dav ratio of approximately 35% occurs between days 2 and 3. Pseudonormalization is noted after the seventh day.
Figure 3. Images from Patient 10 with basal ganglia injury (status marmoratus pattern) following delivery complicated by shoulder dystocia. The region of interest used for analysis is the area of hyperintensity in the posterior putamina and ventrolateral thalami shown in the T1-weighted image at 7.8 days (arrow). T2-weighted images at the same time show corresponding signal hypointensity. These findings are consistent with petechial hemorrhage developing in regions of central gray matter infarction. The Dav scan at 1.9 days clearly shows an area of reduced diffusion in the region of the lentiform nuclei and thalami (arrow). As in figure 2, the Dav maps show the injury earlier than the conventional MR images.
From McKinstry RC et al. Neurology :

13. Dav T1
Day 3
Courtesy Dr. Ken Poskitt, UBC

14. Dav T1
Day 3
Day 8
Courtesy Dr. Ken Poskitt, UBC

15. MR Spectroscopy Lactate/NAA more predictive than quantitative T2
Miller SP et al. Pediatric Research 2001
Lactate/NAA more predictive than quantitative T2
Shanmugalingam, S. et al. Pediatrics 2006;118:

16. 34 Hours Barkovich AJ, Miller SP et al. AJNR 2006 Cho NAA
Home delivery complicated by LGA infant and shoulder dystocia. After prolonged delivery, infant was cyanotic, limp. Infant was given CPR for 40 minutes before spontaneous respirations. Seizures at about 5 hours, treated with phenobarbital
New involvement of white matter pathways on second study. Studies performed at day 2 and day 7.
A-C. Axial Dav maps at 34 hours show reduced diffusivity (Dav reduced by about 50%, black arrows) in the ventrolateral thalami, posterior limbs of internal capsules, and corticospinal tracts in centrum semiovale. No other areas of reduced diffusivity are identified.
D. Proton MRS from the left basal ganglia at 34 hours shows mild lactate (Lac) elevation.
E-H. Axial Dav maps at 148 hours show that diffusivity in the deep gray nuclei has normalized (values were within 5% of normal). However, new areas of reduced diffusivity are seen in what are believed to be the optic radiations (medium white arrows in E), corpus callosum (small white arrows in F and smaller white arrows in G), cingulum (medium white arrows in H), and superior longitudinal fasciculus (larger arrows in G).
I. Proton MRS from left basal ganglia at 148 hours shows that lactate (Lac) has increased in comparison with NAA, choline, and creatine. NAA is the most reduced metabolite.
Barkovich AJ, Miller SP et al. AJNR 2006

17. 34 Hours Day 7 Barkovich AJ, Miller SP et al. AJNR 2006 Cho NAA
Home delivery complicated by LGA infant and shoulder dystocia. After prolonged delivery, infant was cyanotic, limp. Infant was given CPR for 40 minutes before spontaneous respirations. Seizures at about 5 hours, treated with phenobarbital
New involvement of white matter pathways on second study. Studies performed at day 2 and day 7.
A-C. Axial Dav maps at 34 hours show reduced diffusivity (Dav reduced by about 50%, black arrows) in the ventrolateral thalami, posterior limbs of internal capsules, and corticospinal tracts in centrum semiovale. No other areas of reduced diffusivity are identified.
D. Proton MRS from the left basal ganglia at 34 hours shows mild lactate (Lac) elevation.
E-H. Axial Dav maps at 148 hours show that diffusivity in the deep gray nuclei has normalized (values were within 5% of normal). However, new areas of reduced diffusivity are seen in what are believed to be the optic radiations (medium white arrows in E), corpus callosum (small white arrows in F and smaller white arrows in G), cingulum (medium white arrows in H), and superior longitudinal fasciculus (larger arrows in G).
I. Proton MRS from left basal ganglia at 148 hours shows that lactate (Lac) has increased in comparison with NAA, choline, and creatine. NAA is the most reduced metabolite.
Barkovich AJ, Miller SP et al. AJNR 2006

18. Hypothermia: protects the Basal Nuclei
Basal nuclei OR 0.36 (P=0.02)
White matter OR 0.3 (P=0.01)
Cerebral Cortex OR 0.62 (P=0.25)
Rutherford M et al. Lancet Neurol 2009 E Pub

19. Imaging at BC Children’s
Day 3
MRI: T1, T2
DWI
MRSI
Day 10
If cooled
If exam and imaging discordant
NEED CONSISTENCY FOR INTERPETATION!

20. Differential Diagnosis

21. Take Home Neonatal Encephalopathy is a neurological emergency
What is the diagnosis?
What is the prognosis?
Neuroimaging key
Need standardized protocols and high quality review
Neonatal Encephalopathy is a neurological emergency that evolves over time

22. UBC UCSF Support CIHR Michael Smith Foundation
Neonatal Brain Disorders Center
Donna Ferriero MD
A. James Barkovich MD
Hannah Glass MD
Sonia Bonifacio MD
David V Glidden PhD
MR Science Center
Daniel Vigneron PhD
Support
CIHR
Michael Smith Foundation
NIH:NS35902, RR01271(PCRC)
Hospital for Sick Children Foundation
Canada Foundation for Innovation
CFRI and UBC
BC Children’s Hospital Foundation
Neurology
Steven Miller MD
Vann Chau MD
Sandy Belanger RN
Mark Chalmers RRT
Janet Rigney
Alan Hill MD PhD
Elke Roland MD
Bruce Bjornson MD
Neonatology
Anne Syness MD
Brian Lupton MD
Ruth Grunau PhD
Rebecca Sherlock MD
Radiology
Ken Poskitt MD
Michael Sargent MD

24. Miller SP, et al. J Peds 2005