Three-Dimensional Lesion Phenotyping and Physiologic Characterization Inform Remyelination Ability in Multiple...

Area of Science:

• Neuroimaging
• Biomarkers
• Multiple Sclerosis Pathophysiology

Background:

• Current multiple sclerosis (MS) management relies on 2D MRI, which inadequately captures lesion complexity.
• 2D MRI fails to assess lesion metabolic alterations and remyelination potential.
• A novel 3D lesion phenotyping approach is needed to understand MS lesion characteristics.

Purpose of the Study:

• To investigate physiologic profiles within and around MS lesions using 3D phenotyping.
• To correlate these physiologic profiles with lesion phenotypes (shape, texture).
• To identify potential noninvasive biomarkers for MS lesion characterization.

Main Methods:

• 3D segmentation of MS lesions from 3T T2-FLAIR images.
• Calibrated fMRI to measure cerebral blood flow (CBF), BOLD signal, and CMRO2.
• Calculation of BOLD slope and white matter integrity using diffusion kurtosis imaging.

Main Results:

• Identified BOLD slope as a noninvasive biomarker for lesion metabolic activity.
• Metabolically active lesions (positive BOLD slope) exhibited higher CMRO2 and CBF.
• Active lesions with intact white matter showed symmetrical shapes and complex textures.

Conclusions:

• 3D lesion phenotyping and metabolic signatures offer insights into lesion activity, age, and reactivation risk.
• This approach can inform clinical management and disease surveillance in MS.
• Findings provide a platform for evaluating myelin repair therapeutics.