Clinically feasible MTR is sensitive to cortical demyelination in MS

Abstract

Presently there is no clinically feasible imaging modality that can effectively detect cortical demyelination in patients with multiple sclerosis (MS). The objective of this study is to determine if clinically feasible magnetization transfer ratio (MTR) imaging is sensitive to cortical demyelination in MS. MRI were acquired in situ on 7 recently deceased patients with MS using clinically feasible sequences at 3 T, including relatively high-resolution T1-weighted and proton density-weighted images with/without a magnetization transfer pulse for calculation of MTR. The brains were rapidly removed and placed in fixative. Multiple cortical regions from each brain were immunostained for myelin proteolipid protein and classified as mostly myelinated (MM(ctx)), mostly demyelinated (MD(ctx)), or intermediately demyelinated (ID(ctx)). MRIs were registered with the cortical sections so that the cortex corresponding to each cortical section could be identified, along with adjacent subcortical white matter (WM). Mean cortical MTR normalized to mean WM MTR was calculated for each cortical region. Linear mixed-effects models were used to test if mean normalized cortical MTR was significantly lower in demyelinated cortex. We found that mean normalized cortical MTR was significantly lower in cortical tissue with any demyelination (ID(ctx) or MD(ctx)) compared to MM(ctx) (demyelinated cortex: least-squares mean [LSM] = 0.797, SE = 0.007; MM(ctx): LSM = 0.837, SE = 0.006; p = 0.01, n = 89). This result demonstrates that clinically feasible MTR imaging is sensitive to cortical demyelination and suggests that MTR will be a useful tool to help detect MS cortical lesions in living patients with MS.