Abstract Details

RIS occurs when asymptomatic white matter lesions are detected on MRI and present an opportunity to understand the earliest biological processes underlying MS onset. Existing studies have demonstrated that whole-brain and substructure volumes are lower in pwRIS vs. HCs, but the temporal sequence of atrophy, and what specific regions are preferentially affected are incompletely understood.

To evaluate regional brain volume differences using MRI in people with radiologically isolated syndrome(pwRIS) and healthy controls(HCs)

3T brain MRIs were acquired as part of the CanProCo study on 14 pwRIS(mean age: 50 years, 50% female) and 14 HCs(mean age: 40 years, 86% female) and processed using a voxel-based morphometry(VBM) pipeline. In each RIS subject, gray matter(GM) tissue class was extracted from T1-weighted MRI and co-registered and averaged to create an unbiased template.  Each subject was registered to the template and corrected for volume change due to this warping. Regional volumetric differences were assessed between RIS and HCs.  The MACruise brain parcellation pipeline was used to calculate brain parenchymal fraction(BPF), a measure of whole-brain atrophy.

Regions in the cerebellar hemispheric GM were smaller in RIS vs HCs(p<0.05).  These regions were concentrated along the lateral edges of the cerebellar hemispheres while sparing the vermis.  BPF was smaller (p<0.004), and the only other brain region demonstrating significant decrease in pwRIS vs. HCs was the right frontal medial cortex(p<0.05).

VBM analysis demonstrates that regions in the cerebellar hemispheric GM are preferentially atrophied in pwRIS vs. HCs.  These findings suggest that the cerebellum may be one of the initial regions affected in RIS and may be a major contributor to whole-brain atrophy observed in RIS. Longitudinal follow-up of this cohort will be informative to understand the temporal evolution of brain substructures affected as pwRIS develop symptoms consistent with MS, providing insight into the pathophysiology of early MS biological processes.