Deficient MWF mapping in multiple sclerosis using 3D whole-brain multi-component relaxation MRI.

Area of Science:

• Neuroimaging
• Radiology
• Neurology

Background:

• Multiple Sclerosis (MS) research needs advanced MRI to quantify disease burden beyond lesions.
• Myelin-selective MRI, measuring myelin water fraction (MWF), shows promise for assessing white matter (WM) myelination.
• Current MRI lacks sensitive markers for MS disability and disease progression.

Purpose of the Study:

• To apply multi-component Driven Equilibrium Single Pulse Observation of T1 and T2 (mcDESPOT), a novel myelin-selective MRI technique, in a clinical MS pilot trial.
• To assess mcDESPOT's capability in correlating imaging markers with disease severity and disability (Extended Disability Status Scale - EDSS).
• To derive and validate new quantitative measures of myelin deficiency in MS.

Main Methods:

• Utilized whole-brain, isotropically-resolved 3D mcDESPOT MRI to acquire myelin water fraction (MWF) maps.
• Registered 3D MWF maps to standard space for voxel-based analysis and image segmentation.
• Derived deficient MWF volume (DV) and deficient MWF volume fraction (DVF) in various white matter regions, including normal-appearing white matter (NAWM).

Main Results:

• Lesion burden did not correlate significantly with clinical MS disease activity (EDSS).
• DVF in NAWM showed a significant correlation with EDSS scores (R2=0.37; p<0.001).
• mcDESPOT-derived DVF differentiated clinically isolated syndrome patients from controls (p<0.001) and relapsing-remitting from secondary-progressive MS (p<0.05).

Conclusions:

• mcDESPOT-defined DVF in NAWM is a sensitive imaging marker for MS disability and disease activity.
• This technique can potentially detect early myelin loss and transitions to progressive MS.
• Global atrophy, whole-brain MWF, and WM atrophy are key predictors of clinical disability in MS.