This document discusses various MRI techniques for assessing brain development and injury in preterm and term infants. It summarizes several studies that used MRI to predict neurodevelopmental outcomes in preterm infants, finding moderate to high sensitivity and specificity. Diffusion tensor imaging is presented as a way to analyze white matter microstructure and connectivity, with examples showing regions correlated with visual function and coordination.

1. Brain MRI as a predictor of the future David Edwards © Imperial College London Page

2. Normal Severe injury T1 weighted images

3. Distribution of probability that MRI examination of the posterior limb of the internal capsule will correctly assign neurodevelopmental prognosis after neonatal encephalopathy Predictive probability = 94% (95% CI 89-99%) (  density curve: Rutherford et al Pediatrics 1998;102:323-328)

4. Diffusion weighted image (Cowan et al Neuropediatrics 1994;25:172-175)

5. 24 weeks gestation Term (Battin et al Lancet 1997;349:1741)

7. The commonest ‘lesion’ in preterm infants at term: Diffuse Excessive High Signal Intensity on T2 weighted images (DEHSI) (Maalouf et al J Pediatr 1999;135:351) DEHSI

8. © Imperial College London Page Frequency of abnormalities in MR image of preterm infants at term (Maalouf et al J Pediatr 1999;135:351)

9. Prediction of cerebral palsy aged 2 1 2 3 Focal lesions White Matter abnormal Ventricles dilated Sensitivity Specificity Cranial Ultrasound Moderate/ Severe White Matter Any White Matter MRI 4

10. Brain growth in an individual infant © Imperial College London Page Kapellou et al PLOS Medicine 2006; 3:8 .

11. Reduced cortical growth from 23 to 48 weeks gestational age is related to neurological outcome at 6 years of age © Imperial College London Page

12. Cortical growth 34 weeks to 40 weeks 29 weeks to 34 weeks

13. © Imperial College London Page a b c d An Automatic Brain Atlas for infants and children Registered to an MR image defines 83 brain regions automatically Gousias et al NeuroImage 2008:672-684

14. © Imperial College London Page Thalamic volume is reduced in preterm infants with focal brain lesions Srinivasan et al Pediatrics 2007

15. Diffusion Tensor Imaging (DTI) © Imperial College London Page

16. Diffusion Tensor Imaging (DTI) © Imperial College London Page

17. Tractography © Imperial College London Page Behrens T. E. J., Nature Neuroscience (2003) 6(7), 750-757

18. Diffusion Tensor Imaging with probabalistic MR tractography © Imperial College London Page Behrens et al Nat Neurosci . 2003 Jul;6(7):750-7 Counsell et al NeuroImage . 2007 Feb 1;34(3):896-904.

20. © Imperial College London Page -4 -2 0 2 4 e( Visual Score | X ) -.02 -.01 0 .01 .02 .03 e( Fractional Anisotropy | X ) -4 -2 0 2 4 e( Visual Score | X ) -.5 0 .5 1 e( MRI-detected Brain Lesions | X ) -3 -2 -1 0 1 2 e( Visual Score | X ) -2 -1 0 1 2 e( Post-menstrual age at Scan | X ) -3 -2 -1 0 1 2 e( Visual Score | X ) -4 -2 0 2 4 e( Gestational Age at Birth | X ) Bassi et al Brain . 2008 Feb;131(Pt 2):573-82.

21. Page Preterm infants aged 2 years: regions where FA shows linear correlation to eye-hand co-ordination score

22. © Imperial College London Page 26 weeks 40 weeks Robinson et al, submittted Thalamus Primary sensory cortex Primary motor cortex

23. © Imperial College London Page Robinson et al, submittted 26 weeks 40 weeks

24. Mapping the Thalamus using Diffusion Tractography © Imperial College London Page = frontal/temporal cortex = occipital/parietal cortex = motor neighbourhood = somatosensory area KEY normal White matter lesion Counsell et al NeuroImage . 2007 Feb 1;34(3):896-904.

26. Insulae to Lingula Superior frontal to medial orbital Superior frontal to anterior orbital Brain regions where connections are strongest in young adults Robinson et al, in progress Caudate to Substantia Nigra Postcentral to Superior Frontal

27. Thalamus to thalamus Posterior cingulate to pallidum Brain regions where connections are strongest in older adults Robinson et al, in progress Thalamus to putamen Thalamus to insula

28. © Imperial College London Page Fixation Cross fMRI; brain activation during visual stimulation

29. © Imperial College London Page Imaging brain activity in a preterm infant by fMRI Rifat et al, EHD 2005 Brain activated by visual stimulation

30. © Imperial College London Page Somatosensory fMRI in a 29 week infant Arichi et al, in progress

31. © Imperial College London Page White matter tracts starting from the most activated voxel in fMRI study confirm correct anatomical connections of activate regions Preterm Preterm at term

33. Term (median 40.5 weeks)

34. Growth of the cerebral motor system from 29 to 44 weeks gestational age © Imperial College London Page

35. Growth of the default mode and motor networks from 29 to 44 weeks gestational age © Imperial College London Page

39. Diffusion Tensor Imaging to analyse white matter: regions of interest in centrum semiovale © Imperial College London Page Counsell et al Pediatrics 2004

40. © Imperial College London Page Group analysis of somatosensory fMRI in 11 preterm infants

41. Four dimensional average brain template from 29 to 44 weeks gestational age

42. © Imperial College London Page Normal DEHSI Pathology 1.0 1.5 2.0 ADC Values Counsell et al Pediatrics 2004 Diffusion Weighted Imaging in infants with Diffuse Excessive High Signal Intensity in regions of interest within white matter

43. © Imperial College London Page Krishnan, M. L. et al. Pediatrics 2007

44. © Imperial College London Page Krishnan, M. L. et al. Pediatrics 2007 Partial regression plots demonstrating components of the multiple regression analysis by plotting residuals from partial regressions

46. © Imperial College London Page White matter regions with significant difference between preterm at term and term-born infants (blue)

47. Brain regions where white matter microstructure is linearly related to gestation at birth

48. Brain regions where white matter microstructure is linearly related to severity of respiratory disease

49. © Imperial College London Page

50. © Imperial College London Page -4 -2 0 2 4 e( Visual Score | X ) -.02 -.01 0 .01 .02 .03 e( Fractional Anisotropy | X ) -4 -2 0 2 4 e( Visual Score | X ) -.5 0 .5 1 e( MRI-detected Brain Lesions | X ) -3 -2 -1 0 1 2 e( Visual Score | X ) -2 -1 0 1 2 e( Post-menstrual age at Scan | X ) -3 -2 -1 0 1 2 e( Visual Score | X ) -4 -2 0 2 4 e( Gestational Age at Birth | X )

51. © Imperial College London Page Preterm infants aged 2 years: regions where FA shows linear correlation to developmental score

52. © Imperial College London Page Preterm infants aged 2 years: regions where FA shows linear correlation to eye-hand co-ordination score

54. The neonatal biomarker toolkit © Imperial College London Page paper n gest> Tesla age at scan sequence Miller 86 34 1.5 35-38 T1,2 1998-2003 Woodward 167 31 1.5 40 T1,2 1998-2000 More severe injury generally Dyet 119 30 1.0,1.5 >36 T1,2 1997-2000 less severe injury generally Mirmiran 88 30 and 1250g 1.5 36-40 T1,2

55. © Imperial College London Page CP Cognitive Motor paper sensitivity specificity sensitivity specificity sensitivity specificity n in group n CP Miller 86 7 (approx, not stated) Woodward 161 17 94 31 89 31 88 30 120 65 84 41 84 65 85 35 Dyet DQ<85 68 4 90 24 1 Mirmiran 61 7 72 91 61 86 89 43

56. Regions of while matter damage in 12 term infants after birth asphyxia shown by TBSS