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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