Evidence of early microstructural white matter abnormalities in multiple sclerosis from multi-shell diffusion MRI.

Area of Science:

• Neuroimaging
• Neurology
• Biomedical Engineering

Background:

• Multiple sclerosis (MS) causes irreversible white matter (WM) damage, leading to long-term disability.
• Current imaging techniques struggle to detect early-stage microstructural WM changes in MS.
• Axonal loss is a key factor in MS-related disability.

Purpose of the Study:

• To assess microstructural WM abnormalities in early-stage MS using advanced diffusion MRI.
• To evaluate the sensitivity of the restricted signal fraction (FR) from the Composite Hindered and Restricted Model of Diffusion (CHARMED) in detecting early MS-related axonal changes.
• To compare the diagnostic performance of FR with conventional Diffusion Tensor Imaging (DTI) metrics.

Main Methods:

• Ultra-high gradient strength multi-shell diffusion MRI was employed.
• The CHARMED model was used to estimate the restricted signal fraction (FR), reflecting axonal volume.
• 22 early MS patients and 15 healthy controls were scanned, with analysis in WM lesions and normal-appearing white matter (NAWM).

Main Results:

• A significant reduction in FR was observed in WM lesions and widespread in NAWM of MS patients compared to controls.
• These FR changes in NAWM were not influenced by proximity to lesions or ventricles.
• Conventional DTI parameters showed no significant differences between groups; FR outperformed DTI in distinguishing lesions from NAWM.

Conclusions:

• Widespread microstructural changes, indicative of axonal damage, are present in NAWM in early MS.
• These early pathological changes are detectable with multi-shell diffusion MRI (CHARMED model) but not conventional DTI.
• Advanced diffusion imaging offers superior sensitivity for characterizing axonal microstructure in early MS, aiding in early diagnosis and understanding disease progression.