The corticospinal tract in relapsing-remitting multiple sclerosis: a pilot tractography and fixel-based MRI analysis at ultra high-field

Abstract

Background: Multiple sclerosis (MS) is a progressive neurological disorder of the central nervous system associated with demyelination and axonal loss, leading to permanent disability. Mobility impairment is the most disabling symptom in MS. Changes to lower limb disability in MS are likely related to axonal damage in the corticospinal tract (CST), the main motor pathway. Using the high SNR afforded by ultrahigh field (7T) MRI, diffusion MRI can be acquired with spatial resolution approaching anatomical imaging, with high angular resolution, and within clinically feasible scan times (~10mins). This allows for analysis using higher order diffusion models such as constrained spherical deconvolution that can estimate the fibre orientation distribution (FOD) in each voxel, together with associated axonal damage markers such as fibre density (FD) and fibre cross-section (FC) that can be analysed using “fixel-based analysis”1. Objective: This preliminary study aimed to compare the degree of CST degeneration (loss of FD and FC) to clinical motor disability. Methods: Eleven relapsing-remitting MS patients (1 male and 10 females, 42 ± 12.4 years) were tested. All had minimal or no lower limb dysfunction (EDSS < 4, pyramidal and cerebellar Kurtzke's Functional System (KFS) ≤ 2). Diffusion weighted MRI was acquired using 7T MRI and a simultaneous multi-slice 2D spin-echo EPI sequence2 (TR=7000ms, TE=72.4ms, multiband factor=2, GRAPPA=3, slices=128, 1.24mm isotropic resolution, whole brain coverage, 3 b-shells: 1000, 2000, 3000 s/mm2, 103 directions, 6 b0 images). FODs were estimated for each voxel for each subject using MRtrix 3.0, and a population FOD template was generated. Probabilistic tractrography was used to identify the CST (Fig. 1). FC and FD were computed from the CST and compared to pyramidal KFS scores for each subject. Results: Loss of FD (but not FC) in the subcortical white matter of the CST was associated with increased pyramidal dysfunction (puncorrected < 0.05) (Fig. 2). Conclusion: Using ultra-high field 7T diffusion MRI we detected loss of FD in the CST that was associated with pyramidal disability. FD could provide a useful marker of disease progression leading to loss of mobility. Future studies will aim to replicate this in a larger cohort.