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=Volume 13 - 2022

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 the assessment of regional axonal injury and its association with disability of people with multiple sclerosis (pwMS) can be improved by using the more pathologically specific neurite orientation density and dispersion index (NODDI) method in conjunction with high-resolution probabilistic tractography white matter tract templates.
Methods: Parametric maps of the neurite density index, orientation dispersion index, and isotropic volume fraction (IVF) were estimated in 18 pwMS and nine matched heathy 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. Unpaired t-tests assessed group-differences in NODDI derived metrics; Spearman rank correlations analyses assessed associations between NODDI metrics and other disease features.
Results: IVF values of the TC fiber bundles from the paracentral, presupplementary and supplementary motor areas were higher in pwMS than in HCs (p ≤ 0.05) and in pwMS with motor disability compared to those without motor impairment (p ≤ 0.0149). IVF in several TC tracts was associated with the Expanded Disability Status Scale score (p ≤ 0.05). 
Conclusion: IVF alterations are present in pwMS even when other NODDI metrics are still mostly preserved. Changes in IVF may not necessarily drive irreversible functional loss. However, by preceding downstream pathologies that are strongly associated with disability accretion, IVF changes could be early indicators of  tissue injury and function as target measures for early therapeutic interventions.