Myelinization. THOMAS P. NAIDICH, MD FACR Mt. Sinai Medical Center New York, NY USA

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1 Myelinization THOMAS P. NAIDICH, MD FACR Mt. Sinai Medical Center New York, NY USA

2 ALTERS BRAIN WATER LOCALLY MYELIN CONTAINS: GLYCOLIPIDS PHOSPHOLIPIDS & CHOLESTEROL

3 Maturation of the White Matter

4 Maturation of the White Matter Newborn Adult

5

6 Maturation of the White Matter

7 FIFTH MONTH: DORSAL COLUMNS & MEDIAL LEMNISCUS

8 SIXTH MONTH: STATO-ACOUSTIC SYSTEM & LATERAL LEMNISCUS

9 SEVENTH MONTH: INF. OLIVARY Nu., INF. CBLLR. PEDUN. MLF SUP. CBLLR. PEDUN.

10 SEVENTH MONTH: OPTIC CHIASM & TRACT POSTERIOR LIMB INT. CAPSULE PERI-CENTRAL CORONA RADIATA

11 EIGHTH MONTH: MID CBLLR. PEDUN. CORTICOSPINAL TR.

12 MYELINATION HAS DIFFERENT ASPECTS: INCREASED FAT & DECREASED WATER Term

13 Maturation of the White Matter Term

14 Maturation of the White Matter Term

15 Maturation of the White Matter Term

16 Maturation of the White Matter Term

17 Maturation of the White Matter Term

18 Maturation of the White Matter Term

19 Maturation of the White Matter Term

20 Maturation of the White Matter Term

21 Maturation of the White Matter Term

22 WHITE T1 MYELINATION SPIN ECHO TR / TE = 620 / 20 GENU 6 SPLENIUM 4 CORPUS MEDULLARE 3

23 3 MONTHS

24 4 MONTHS

25 6 MONTHS PLUS

26 6 MONTHS PLUS

27 9 MONTHS

28 9 MONTHS

29 BLACK T2 MYELINATION SPIN ECHO TR / TE = 2000 / 70 FRONTAL LOBE GENU ANT. LIMB 8 14 SPLENIUM 6

30 5 MONTHS

31 6 MONTHS

32 8 MONTHS 11 MONTHS

33 14 MONTHS

34 4 YEARS

35 THE SAME SYSTEMS SHOULD BE APPLIED: to the 1. CORTEX vs SUBCORTICAL WM & 2. BASAL GANGLIA vs INTERNAL CAPSULE

36 SUBCORTICAL GRAY vs. WHITE MATTER AGE 8 Months 10 Months 12 Months 15 Months 18 Months SIGNAL G = W G = W G > W G > W G > W SITES CALCARINE ALL OTHER SITES PARACENTRAL ALL BUT FRONTAL ALL SITES

37 NEWBORN 8 MONTHS

38 9-10 MONTHS

39 BASAL GANGLIA & INTERNAL CAPSULE GRAY vs. WHITE MATTER AGE WHITE GRAY SIGNAL 0-4 Mo. HIGH LOW G << W 4-10 Mo. G < W ~ 10 Mo. EQUAL EQUAL G = W > 10 Mo. LOW HIGH G > W

40 10.5 MONTHS

41 WHITE T1 MYELINATION SPIN ECHO TR / TE = 620 / 20 GENU 6 SPLENIUM 4 CORPUS MEDULLARE 3

42 BLACK T2 MYELINATION SPIN ECHO TR / TE = 2000 / 70 FRONTAL LOBE GENU ANT. LIMB 8 14 SPLENIUM 6

43 LANDMARKS FOR MYELINATION 1. These are landmarks by which all normal patients ought have myelinated the structure 2. Obtain birth history & correct to 40 wg. 3. Have schedulers get ga and schedule tests to fall on known landmarks. 4. Wasteful to get data that fall between them.

44 In the Pre-Term Infant Myelination can be Confusing PMA: 33.5 wg PMA: 38.3 wg PMA: 33.0 wg PMA: 27.1 wg These high H 2 0, cell dense areas are likely normal maturational features. Leijser LM et al. Eur J Pediatr Neurol 2009; 13: Figs.1-4 pp

45 Rutherford M et al. Early Human Development 2010; 86: Using (Conf-using?) Myelination to Detect Hypoxic-Ischemic Injury T1 T2 Normal Three Patients with Hypoxia-Ischemic Injury

46 Severity of HIE in the Basal Ganglia: T1 Normal Mild Moderate Hypoxia-Ischemia Severe Fig. 4 p. 354 in M. Rutherford et al. Early Human Dev (2010) 86: Fig. 3 p. 585 in M. Rutherford et al. Pediatr Radiol (2006) 36:

47 Maturation of the White Matter Yakovlev s Terminal Zone

48 Terminal Zone vs. Periventricular Leukomalacia 1.5T T2 2500/ T FLAIR 7000/120/2000 Liauw L et al. Eur J Rad. 2008; 65: Fig. 3 p 400

49 Terminal Zone vs. Periventricular Leukomalacia 1.5T T2 5408/ T FLAIR 7000/120/2000 Liauw L et al. Eur J Rad. 2008; 65: Fig. 2 p 399

50 Advanced Imaging

51 Axonal Maturation & Myelination in the Developing Brain 0-2 Yr. FA Axial Diff Radial Diff FA 0-1 Yr FA, radial D & Axial D 1-2 Yr FA, radial D & Axial D Neonates 1-Yr-olds 2-Yr-olds (22 days) Gao et al. AJNR 2009; 30:

52 Axonal Maturation & Myelination 0-2 Years The in FA and the greater in radial diffusivity than axial diffusivity indicate that Myelination is dominant in the 1 st Yr., and pruning is dominant in the 2 nd Yr. The order is central to peripheral and posterior to anterior. FA fract. aniso. SCC splenium BCC body GCC genu CST corticosptr OR IC optic radiat. internal cap PPW parietal WM FPW frontal WM Gao AJNR 2009; 30:

53 MENTAL MATURITY: PROGRESSIVE MYELINATION 5 Yr 8 Yr 12 Yr 16 Yr 20 Yr S. F. Gilbert Developmental Biology 8th Ed.

54 Increasing Global WM Volume with Age 200 Children Coronal Axial Red-yellow: w Age 5-18 Years. Boys > Girls Wilke M et al. Exp Brain Res 2007; 178: Fig. 8

55 Increasing Regional WM Volume with Age 200 Children Coronal Axial Red-yellow: w Age 5-18 Years. Boys > Girls Wilke M et al. Exp Brain Res 2007; 178: Fig. 9

56 Focal age-related increase in FA at ages yrs. in R CC R CSTr, & R SLF w radial Diffusivity but no axial Diffusivity suggesting WM compactness rather than myelination.

57 Normal Growth Patterns in Children: Tensor-Based Morphometry Children 7-15 years old show significant in WM volume & (?) GM loss Technical Problem Partial Volumes Hua X. et al. Human Brain Mapping 2009;30:

58 White Matter Volume in 408 Adolescents Years Old Corrected for total brain volume, age-related WM volume showed a steeper of WM vol. in M vs. F related to androgen activity, # of CAG repeats in Androgen Receptor gene AR & its efficiency. Inverse effect on MTR affects axon diameter, not myelination.

59 Magnetization Transfer Ratios in Cerebral White Matter Gender Differences in 408 M & F Years Old Perrin et al. The J of Neuroscience 2008; 28: Frontal Parietal Temporal Occipital

60 F-T Connections Mature Late Lebel C. NeuroImage 2008;40: F1 p1046 Maturation of WM Tracts Ages 5-30 Years (FA) N = 202 DTI: 23M

61 Maturation of WM Tracts Ages 5-30 Years (FA) N = 202 DTI: 6M and beyond Lebel C et al. NeuroImage 2008;40: Fig 2 p 1047

62 Maturation of WM Tracts Ages 5-30 Years (FA) No change in FA Fornix, Corona radiata & Centrum semiovale Mature Late Fronto-Temporal connections N = 202 Bar = Standard Error Line length = age to 90% of plateau value Lebel C et al. NeuroImage 2008;40: Fig 6 p 10517

63 Maturation of WM Tracts Ages 5-30 Years The relative effects of myelin, axon diameter, NeuroFilament & microtubules on FA, axial & radial diffusivity are unclear. The g ratio of axon diameter to axon + sheath diameter is ~ stable (~ 0.65), but does w axon diam. & varies in axons of one tract. There are no data on the g ratio of M vs. F. Axon caliber depends on # & spacing of NF. No. depends on NF synthesis. Spacing depends on PO 4 of NF side-arms that depends on Myelin-associated glycoproteins from the ODG. Differences in M vs. F hormones could alter the g ratio, and thus WM bulk, FA, axial & radial diffusivity. Axon caliber is one element changing w myelination, age (and gender?) perhaps accounting for the changes in measured MR parameters w age. Paus T. Brain & Cognition 2010; 72:26-35

64 Thank You

65 Thank You

66 Myelination

67 Maturation of WM Tracts Ages 5-30 Years (Diff) N = 202 DTI: 6M Lebel C et al. NeuroImage 2008;40: Fig 5 p 1050

68 Maturation of WM Tracts Ages 5-30 Years (FA) N = 202 N = 202 Line length = age to 90% of plateau value Bar = Standard Error Lebel C et al. NeuroImage 2008;40: Fig 6 p 1051

69 Maturation of WM Tracts Ages 5-30 Years (Diff) N = 202 DTI: 23M Lebel C et al. NeuroImage 2008;40: Fig 4 p 1049

70

71 2 YEARS

72 3 MONTHS

73 3 MONTHS

74 NEWBORN

75 14 MONTHS

76 EX: Normal 9 Month EX: Normal 9 Month

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