Short-Range Structural Connections Are More Severely Damaged in Early-Stage MS

Abstract

Background and purpose: Long-range connections are more severely damaged and relevant for cognition in long-standing MS. However, the evolution of such coordinated network damage in patients with MS is unclear. We investigated whether short- and long-range structural connections sustained equal damage in early-stage MS.

Materials and methods: Sixteen patients with early-stage MS and 17 healthy controls were scanned by high-resolution, multishell diffusion imaging on 7T MR imaging and assessed cognitively. We investigated macrostructural properties in short- and long-range fibers and of microstructural metrics derived from 2 quantitative diffusion MR imaging models: DTI and neurite orientation dispersion and density imaging.

Results: Patients had significant WM integrity damage-that is, higher radial diffusivity and a lower intracellular volume fraction in the focal WM lesions. Compared with the healthy controls, the patients had noticeable microstructure changes in both short- and long-range fibers, including increased radial diffusivity, mean diffusivity, and axial diffusivity. Z scores further indicated greater damage in the short-range fibers than in the long-range fibers.

Conclusions: Our findings demonstrate that more severe demyelination preceding axonal degeneration occurs in short-range connections but not in long-range connections in early-stage MS, suggesting the possibility that there are cortical lesions that are undetectable by current MR imaging.

FIG 1.

Overview of the image acquisition and processing pipeline.

FIG 2.

The fiber microstructure metrics of whole-brain short- (black) and long-range (gray) connections in patients with MS and HCs. log2 indicates the length of fibers was denoted in a logarithmic manner with base 2.

FIG 3.

Severity of lesion damage (z score) compared between short- and long-range connections. The * represents a significant difference between short-and long-range fibers (P < 0.05); ** represents P < 0.01. # represents P < 0.05 using the one sample t test on a convergence of the average value to zero to compare with HCs. ## represents P < 0.01, FDR-corrected.