Abstract
Introduction:
Improved understanding of multiple sclerosis (MS) symptomatology, disease mechanisms, and clinical effectiveness can be achieved by investigating microstructural damage. The aim was to gain deeper insights into changes in white matter (WM) tracts in MS patients.
Methods:
Diffusion magnetic resonance imaging-based tractography was utilized to segment WM tracts into regions of interest for further quantitative analysis. However, tractography is susceptible to false-positive findings, reducing its specificity and clinical feasibility. To address these limitations, the Convex Optimization Modeling for Microstructure Informed Tractography (COMMIT) technique was used. COMMIT was used to derive measures of intracellular compartment (IC) and isotropic compartments from multishell diffusion data of 40 healthy controls (HCs) and 40 MS patients.
Results:
The analysis revealed a widespread pattern of significantly decreased IC values in MS patients compared with HCs across 61,581 voxels (p FWE < 0.05, threshold-free cluster enhancement [TFCE] corrected). Similar WM structures studied using the fractional anisotropy (FA) value also showed a reduction in FA among MS patients compared with HCs across 57,304 voxels (p FWE < 0.05, TFCE corrected). Out of the 61,581 voxels exhibiting lower IC, a substantial overlap of 47,251 voxels (76.72%) also demonstrated lower FA in MS patients compared with HCs.
Discussion:
The data suggested that lower IC values contributed to the explanation of FA reductions. In addition, IC showed promising potential for evaluating microstructural abnormalities in WM in MS, potentially being more sensitive than the frequently used FA value.
Impact statement
In the last decade, numerous neuroimaging studies have shown that multiple sclerosis (MS) promotes changes in structural connectivity. Advanced techniques for identifying the origin and location of white matter (WM) abnormalities might result from integrating diffusion magnetic resonance imaging measures with connectivity-based evaluation and new image analysis methods. In this study, the Convex Optimization Modeling for Microstructure Informed Tractography (COMMIT) framework with the ball-and-sticks forward model was used to eliminate false-positive brain connections. Then we applied a whole-brain and regional tract-based spatial statistical analysis approach to test its potential in detecting microstructural alterations in isotropic compartment and intracellular compartment signal fraction maps produced from the COMMIT global fitting between healthy controls (HCs) and MS patients utilizing multishell diffusion data.
The analysis revealed a widespread pattern of significantly decreased IC values in MS patients compared with HCs. Similar WM structures studied using the fractional anisotropy value also showed a substantial trend toward statistical significance.
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