Fibre-specific white matter changes in multiple sclerosis patients with optic neuritis

Area of Science:

• Neuroimaging
• Neuroscience
• Radiology

Background:

• Irreversible disability in multiple sclerosis (MS) is primarily driven by axonal degeneration.
• Early detection of axonal degeneration is crucial for predicting clinical disability and treatment efficacy in MS.
• Existing methods for assessing white matter pathology in MS can be confounded by inflammation, demyelination, and oedema.

Purpose of the Study:

• To investigate a novel method for measuring axonal degeneration in MS using high angular resolution diffusion magnetic resonance imaging.
• To develop and validate axonal markers, specifically fibre density and cross-section, using fixel-based analysis (FBA).
• To assess the sensitivity and specificity of FBA in detecting early axonal changes in MS patients with optic neuritis.

Main Methods:

• Acquisition of diffusion-weighted imaging datasets from 17 MS patients with optic neuritis and 14 healthy controls using a 3T scanner.
• Application of advanced acquisition and modelling techniques for improved axonal sensitivity and specificity.
• Fixel-based analysis (FBA) to estimate fibre density and fibre cross-section (fixels) in white matter tracts.

Main Results:

• Fibre density demonstrated comparable sensitivity to standard diffusion tensor imaging (DTI) parameters for detecting white matter pathology in MS.
• Fibre density was not affected by crossing axonal fibres, unlike standard DTI metrics.
• Whole-brain FBA revealed significant reductions in fibre density and fibre cross-section in the inferior fronto-occipital fasciculus (including optic radiations) of MS patients compared to controls.

Conclusions:

• Fixel-based analysis (FBA) is a sensitive method for detecting early axonal degeneration in MS, specifically in the optic radiations.
• The identified reductions in fibre density and cross-section in MS patients suggest early axonal loss and white matter atrophy.
• Fibre-specific markers derived from FBA hold promise for monitoring axonal injury and evaluating therapeutic interventions in early-stage MS.