AUTHOR=Yoon Keejin , Archer Derek B. , Clarke Margareta A. , Smith Seth A. , Oguz Ipek , Cutter Gary , Xu Junzhong , Bagnato Francesca TITLE=Transcallosal and Corticospinal White Matter Disease and Its Association With Motor Impairment in Multiple Sclerosis JOURNAL=Frontiers in Neurology VOLUME=13 YEAR=2022 URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2022.811315 DOI=10.3389/fneur.2022.811315 ISSN=1664-2295 ABSTRACT=Purpose

In this cross-sectional, proof-of-concept study, we propose that using the more pathologically-specific neurite orientation dispersion and density imaging (NODDI) method, in conjunction with high-resolution probabilistic tractography, white matter tract templates can improve the assessment of regional axonal injury and its association with disability of people with multiple sclerosis (pwMS).

Methods

Parametric maps of the neurite density index, orientation dispersion index, and the apparent isotropic volume fraction (IVF) were estimated in 18 pwMS and nine matched healthy controls (HCs). Tract-specific values were measured in transcallosal (TC) fibers from the paracentral lobules and TC and corticospinal fibers from the ventral and dorsal premotor areas, presupplementary and supplementary motor areas, and primary motor cortex. The nonparametric Mann–Whitney U test assessed group differences in the NODDI-derived metrics; the Spearman's rank correlation analyses measured associations between the NODDI metrics and other clinical or radiological variables.

Results

IVF values of the TC fiber bundles from the paracentral, presupplementary, and supplementary motor areas were both higher in pwMS than in HCs (p ≤ 0.045) and in pwMS with motor disability compared to those without motor disability (p ≤ 0.049). IVF in several TC tracts was associated with the Expanded Disability Status Scale score (p ≤ 0.047), while regional and overall lesion burden correlated with the Timed 25-Foot Walking Test (p ≤ 0.049).

Conclusion

IVF alterations are present in pwMS even when the other NODDI metrics are still mostly preserved. Changes in IVF are biologically non-specific and may not necessarily drive irreversible functional loss. However, by possibly preceding downstream pathologies that are strongly associated with disability accretion, IVF changes are indicators of, otherwise, occult prelesional tissue injury.