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.