Diffusivity in the core of chronic multiple sclerosis lesions.

Area of Science:

• Neuroimaging
• Biomarkers
• Multiple Sclerosis (MS)

Background:

• Diffusion tensor imaging (DTI) shows potential for tracking MS progression, neurodegeneration, and de/remyelination.
• Pathological substrates of DTI alterations in MS brain lesions are not fully understood.
• Proposed that increased axial diffusivity (AD) indicates extracellular space (ECS) expansion and tissue destruction, while normalized radial diffusivity (RD) reflects myelin loss.

Purpose of the Study:

• Isolate contributions of extracellular water and demyelination to DTI indices in chronic MS lesions.
• Utilize the optic radiation (OR) as a highly cohesive fiber tract for analysis.
• Develop a method to more accurately assess demyelination in MS.

Main Methods:

• Acquired pre- and post-gadolinium T1, T2, and DTI images from 75 RRMS patients and 25 controls.
• Used probabilistic tractography to identify the OR and segmented T2 lesions within it.
• Calculated AD and RD, normalized RD by estimated ECS, and simulated diffusion effects.

Main Results:

• Lesional eigenvalues in the OR were significantly higher than in normal-appearing white matter (NAWM) and controls.
• Estimated ECS volume correlated with T1 hypointensity, and normalized RD remained elevated but showed reduced variability.
• DTI data and simulations suggested anisotropic water diffusion in ECS and explained eigenvalue-anisotropy discrepancies.

Conclusions:

• Presents a novel technique for reliably quantifying neurodegeneration versus demyelination in MS OR lesions.
• Offers a simple, effective method for single-tract diffusion analysis in MS clinical trials.
• Relevant for evaluating pro-remyelinating and neuroprotective therapies in MS.