A novel approach with "skeletonised MTR" measures tract-specific microstructural changes in early primary-progressive MS

Abstract

We combined tract-based spatial statistics (TBSS) and magnetization transfer (MT) imaging to assess white matter (WM) tract-specific short-term changes in early primary-progressive multiple sclerosis (PPMS) and their relationships with clinical progression. Twenty-one PPMS patients within 5 years from onset underwent MT and diffusion tensor imaging (DTI) at baseline and after 12 months. Patients' disability was assessed. DTI data were processed to compute fractional anisotropy (FA) and to generate a common WM "skeleton," which represents the tracts that are "common" to all subjects using TBSS. The MT ratio (MTR) was computed from MT data and co-registered with the DTI. The skeletonization procedure derived for FA was applied to each subject's MTR image to obtain a "skeletonised" MTR map for every subject. Permutation tests were used to assess (i) changes in FA, principal diffusivities, and MTR over the follow-up, and (ii) associations between changes in imaging parameters and changes in disability. Patients showed significant decreases in MTR over one year in the corpus callosum (CC), bilateral corticospinal tract (CST), thalamic radiations, and superior and inferior longitudinal fasciculi. These changes were located both within lesions and the normal-appearing WM. No significant longitudinal change in skeletonised FA was found, but radial diffusivity (RD) significantly increased in several regions, including the CST bilaterally and the right inferior longitudinal fasciculus. MTR decreases, RD increases, and axial diffusivity decreases in the CC and CST correlated with a deterioration in the upper limb function. We detected tract-specific multimodal imaging changes that reflect the accrual of microstructural damage and possibly contribute to clinical impairment in PPMS. We propose a novel methodology that can be extended to other diseases to map cross-subject and tract-specific changes in MTR.

Keywords: magnetization transfer imaging; primary-progressive multiple sclerosis; tract-based spatial statistics.

Figure 1

Red voxels show the regions of significant reduction in skeletonised MTR over one year, overlaid onto the FSL fractional anisotropy template in MNI coordinates.

Figure 2

Blue voxels indicate the areas of significant correlation between the decrease in skeletonised MTR over the follow‐up period and the changes in upper limb function scores (z‐NHPT). The map is overlaid onto the FSL fractional anisotropy template in MNI coordinates.

Figure 3

Significant MTR changes over one year (blue) and probabilistic distribution of new/enlarged lesions over the same follow‐up period in the patient group (red‐yellow). The red‐yellow color scale indicates the percentage of patients who developed a new/enlarged lesion in a given voxel. This figure shows that MTR changes were not confined to areas of new/enlarged lesions, but were also detectable in the NAWM, possibly generated with the contribution of mechanisms of Wallerian degeneration. The maps are overlaid onto the FSL T1 template in MNI coordinates.