Periventricular gradients in axonal and myelin microstructure are present in people with multiple sclerosis having low and high disability

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Abstract
Background: MS imaging studies have demonstrated an ependymal “surface-in” distribution of white matter damage. The origin of this effect and how it impacts myelinated axons in people with MS (PwMS) is poorly understood. Objectives: To investigate (1) whether there is clear evidence of tract-wise, periventricular damage, based on fractional anisotropy, mean diffusivity, axonal water fraction (AWF) and myelin volume fraction (MVF), in PwMS, (2) if such tissue damage is associated with T 1 -“black-hole” (T 1 -BH) and/or non-BH lesions, and (3) if periventricular quantitative MRI abnormalities are correlated with lateral ventricle (LV) and choroid plexus (CP) enlargement. Methods: We applied structural, MT-weighted, and multi-shell diffusion MRI in healthy controls and PwMS to quantify periventricular gradient damage to axons and myelin. We also evaluated the correlation between such gradient damage and both non-BH and T 1 -BH lesion loads, and brain volume changes. Results: Clear periventricular gradients exist in both AWF and MVF measures in the Association and Projection Tracts. They are strongly correlated with T 1 -BH lesion load, and with LV and CP enlargement in PwMS with EDSS > 2. Conclusions: Tract-specific, periventricular gradients in PwMS exist prominently in AWF and MVF, are strongly associated with T 1 -BH lesion loads, and correlate with LV and CP enlargement.
Funding Information
  • Canada First Research Excellence Fund
  • Canadian Institutes of Health Research (FRN# MOP-84367)
  • Multiple Sclerosis Canada Biomedical Research Operating Grant (Fund #3613)
  • National Sciences and Engineering Research Council of Canada (NSERC) Discovery grant (RGPIN-2018-05047)

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