Reduced White Matter Fiber Density in Patients with Multiple Sclerosis

Area of Science:

• Neuroimaging
• Biomedical Engineering
• Neurology

Background:

• Understanding white matter (WM) damage in multiple sclerosis (MS) is crucial for improving patient outcomes.
• Diffusion MRI tractography is a key tool for analyzing WM microstructure, but is limited by false positives.
• Novel techniques are needed to enhance the specificity and clinical utility of WM analysis in MS.

Purpose of the Study:

• To investigate microstructural changes in WM tracts of MS patients using advanced diffusion MRI techniques.
• To compare the sensitivity of the intracellular compartment (IC) measure derived from COMMIT against fractional anisotropy (FA) for detecting WM abnormalities in MS.

Main Methods:

• Employed the Convex Optimization Modeling for Microstructure Informed Tractography (COMMIT) technique on multishell diffusion MRI data.
• Analyzed data from 40 healthy controls (HCs) and 40 MS patients.
• Segmented WM tracts and quantitatively analyzed IC and FA values, applying threshold-free cluster enhancement (TFCE) correction.

Main Results:

• MS patients exhibited significantly decreased IC values across a widespread pattern of WM voxels compared to HCs (p < 0.05, TFCE corrected).
• Reductions in FA were also observed in MS patients compared to HCs (p < 0.05, TFCE corrected).
• A significant overlap (76.72%) was found between voxels with reduced IC and reduced FA, with lower IC values explaining FA reductions.

Conclusions:

• Lower intracellular compartment (IC) values are a significant indicator of microstructural damage in the white matter of MS patients.
• The COMMIT technique and its derived IC measure show potential as a more sensitive biomarker for detecting WM abnormalities in MS than fractional anisotropy (FA).
• These findings may enhance the clinical feasibility and specificity of diffusion MRI-based assessments in multiple sclerosis.