Delineation of cortical pathology in multiple sclerosis using multi-surface magnetization transfer ratio imaging

The purpose of our study was to evaluate the utility of measurements of cortical surface magnetization transfer ratio (csMTR) on the inner, mid and outer cortical boundaries as clinically accessible biomarkers of cortical gray matter pathology in multiple sclerosis (MS). Twenty-five MS patients and 12 matched controls were recruited from the MS Clinic of the Montreal Neurological Institute. Anatomical and magnetization transfer ratio (MTR) images were acquired using 3 Tesla MRI at baseline and two-year time-points. MTR maps were smoothed along meshes representing the inner, mid and outer neocortical boundaries. To evaluate csMTR reductions suggestive of sub-pial demyelination in MS patients, a mixed model analysis was carried out at both the individual vertex level and in anatomically parcellated brain regions. Our results demonstrate that focal areas of csMTR reduction are most prevalent along the outer cortical surface in the superior temporal and posterior cingulate cortices, as well as in the cuneus and precentral gyrus. Additionally, age regression analysis identified that reductions of csMTR in MS patients increase with age but appear to hit a plateau in the outer caudal anterior cingulate, as well as in the precentral and postcentral cortex. After correction for the naturally occurring gradient in cortical MTR, the difference in csMTR between the inner and outer cortex in focal areas in the brains of MS patients correlated with clinical disability. Overall, our findings support multi-surface analysis of csMTR as a sensitive marker of cortical sub-pial abnormality indicative of demyelination in MS patients.