The Hospital for Sick Children
Translational Medicine, Mouse Imaging Centre

Author Of 2 Presentations

Imaging Poster Presentation

P0546 - Axonal and myelin volume fractions and imaging g-ratio in pediatric MS and MOG-associated disorders. (ID 1520)

Abstract

Background

Previous studies have described extensive microstructural brain tissue abnormalities in pediatric MS patients. However, available techniques do not distinguish the extent to which such abnormalities are due to axonal loss or demyelination. Further, little is known about microstructural brain tissue changes in MOG-associated disorders (MOGad).

Objectives

To apply a combined analysis of magnetization transfer saturation (MTsat) and multi-shell diffusion-weighted imaging (DWI) with computation of myelin and axonal volume fractions (MVF and AVF) and imaging g-ratio (the ratio between inner and outer diameter of the myelin sheath); to investigate the specific relationship between these metrics in the corpus callosum (CC) and within brain white matter lesions (WML) of pediatric MS and MOGad.

Methods

We acquired standardized 3T brain MRI in 26 healthy controls (HC) (58% females (F), mean age [years (y) (range)] 15y (9-19)); 16 MS (69% F, 17y (14-18), disease duration (DD) 3y (1-7), time from last relapse (TLR) 2y (0-6)); and 11 MOGad (72% F, 12y (8-18), DD 3y (0-6), TLR 1y (0-3), 8/11 relapsing). WML and CC were segmented according to establishes procedures. DWI processing was performed with FSL and DMIPy; MTsat, MVF, AVF, and g-ratio were computed using the Jargon data management system. We used general linear models to model average MVF, AVF, and g-ratio in the CC and WML of each group, including the factors age, DD, and the interaction term group*DD. Models including sex were tested, and all exhibited lower AIC.

Results

Relative to HC, MS showed decreased CC MVF (-0.018/y, p=0.0304) and AVF (-0.0069/y; p=0.053) and corresponding increased CC g-ratio (0.0084/y, p=0.059) with increased DD. Relative to HC, MOGad showed decreased CC MVF (-0.017/y, p=0.0304) and AVF (-0.0081/y, p=0.014) with increased DD, without significant CC g-ratio changes. Both MS and MOGad showed decreased average WML MVF compared to HC WM (-0.19, p<10-8; and -0.2, p<10-8). MOGad also showed decreased average WML AVF (-0.067, p=0.0048) compared to HC. Average WML g-ratio was higher in MS than MOGad (0.17, p=0.0102), but not significantly different from HC in either group. WML MVF, AVF, and g-ratio did not change significantly with DD in MS or MOGad compared to HC.

Conclusions

Both pediatric MS and MOGad exhibited MRI correlates of axonal loss and demyelination in the CC and WML. Our measures of axonal loss in MOGad reinforces recent work warning of potentially long-term impacts on the brain from non-MS demyelinating pathologies.

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Imaging Poster Presentation

P0607 - MRI Characterization of Damage in and Around Lesions in Pediatric MS and MOG-Associated Disorders (ID 1847)

Abstract

Background

Multiple sclerosis (MS) and MOG-associated disorders (MOGad) are characterized by hyperintense white matter (WM) lesions on T2/FLAIR MRI. Conventional imaging is sensitive but does not inform on the specific pathological substrate. Magnetization transfer saturation provides a good myelin measure, and multishell diffusion is sensitive to the axon + myelin assembly. Together, these can be modelled to estimate myelin volume fraction (MVF), axonal volume fraction (AVF) and imaging g-ratio.

Objectives

To quantify gradients of damage to axons and myelin in lesions and surrouding normal appearing white matter, in pediatric MS and MOGad.

Methods

15 MS [67% females (F), mean (range) age [years (y)]: 17y (14-18), disease duration (DD) 3y (0-6), time from last relapse (TLR) 2y (0-6)] and 7 MOGad [86% F, 13y (8-18), DD 3y (0-6), TLR 1y (0-3), 6/7 relapsing] participants received 3T brain MRI. MVF, AVF and g-ratio were computed according to established procedures. T2 lesions were segmented according to standardized pipelines and WM masks by multi-atlas segmentation. Euclidean distance transforms labelled voxels in normal-appearing WM with the distance to the nearest lesion voxel, and voxels inside lesions with the distance to the nearest non-lesional WM voxel. Mean MVF, AVF and g-ratio were computed on each isodistant surface. Data were modeled using linear mixed models with distance, diagnosis, and their interaction. Knots were used at 0 and 2mm distance.

Results

MVF decreased towards the center of lesions (MOGad: -0.03/mm; MS: -0.05/mm; p values (ps)<0.002; difference n.s.) as did AVF (MOGad: -0.03/mm; MS: -0.01/mm; ps<0.0002; difference p=0.02); this graded damage extended to 2mm outside lesions. Beyond this, AVF continued to increase (MOGad: 0.001/mm; MS: 0.0003/mm; ps<10-6; difference p<10-6). Inside lesions, g-ratio increased towards the center in MS (0.03/mm, p<10-6) and decreased in MOGad (p=0.15; MOGad-MS difference p<10-4). G-ratio rose with distance outside lesions (MOGad: 0.001/mm; MS: 0.0004/mm; ps<10-4; difference p<10-5). AVF and g-ratio were similar between groups (within 2%) at 20mm from lesions; MVF was higher in MS (14%, p=0.08).

Conclusions

MS and MOGad showed myelin and axonal loss of decreasing severity with distance from lesion center, and this damage extended outside visible lesions. However, MOGad exhibited more severe axonal loss within and near lesions. The corresponding decreasing g-ratio relative to MS may indicate preferential loss of small axons in MS, or relatively better remyelination in MOGad.

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