Patterning Chronic Active Demyelination in Slowly Expanding/Evolving White Matter MS Lesions

Area of Science:

• Neuroimaging
• Neurology
• Radiology

Background:

• Slowly expanding/evolving lesions in MS may contribute to progressive disability.
• Conventional MRI may not fully capture the dynamic changes within these lesions.

Purpose of the Study:

• To evaluate longitudinal changes in myelin and axonal tissue integrity within white matter slowly expanding/evolving lesions.
• To utilize magnetization transfer ratio (MTR) and diffusion tensor imaging (DTI) radial diffusivity to assess these changes.

Main Methods:

• Analysis of the SYNERGY Phase 2 clinical trial dataset (NCT01864148) including 299 patients with relapsing-remitting and secondary-progressive MS.
• Longitudinal MRI assessment using T1-weighted, T2-weighted, MTR, and DTI at baseline up to week 72.
• Comparison of slowly expanding/evolving lesions with non-slowly expanding/evolving lesions.

Main Results:

• Slowly expanding/evolving lesions exhibited lower normalized MTR and greater DTI radial diffusivity compared to non-slowly expanding/evolving lesions in both RRMS and SPMS patients.
• Longitudinal analysis revealed a decrease in normalized MTR and an increase in DTI radial diffusivity in slowly expanding/evolving lesions over time.
• These changes were significant (P < .001) and positively correlated between lesion types.

Conclusions:

• Longitudinal changes in MTR and DTI radial diffusivity within slowly expanding/evolving lesions are consistent with progressive demyelination.
• These findings support the concept of 'smoldering' white matter MS plaques as a driver of tissue loss and disability accumulation.
• Advanced MRI techniques provide insights into the pathological processes occurring in MS lesions over time.