Remyelination and its association with increased oxygen extraction fraction in acute multiple sclerosis lesions

Area of Science:

• Neuroimaging
• Neuroinflammation
• Neurodegeneration

Background:

• Multiple Sclerosis (MS) is a demyelinating disease characterized by inflammatory lesions in the central nervous system.
• Understanding the dynamic processes of lesion evolution, including demyelination and remyelination, is crucial for therapeutic development.
• Oxygen extraction fraction (OEF) and myelin water fraction (MWF) are key biomarkers for assessing tissue oxygen metabolism and myelin integrity, respectively.

Purpose of the Study:

• To investigate the longitudinal relationship between changes in oxygen extraction fraction (OEF) and myelin water fraction (MWF) in acute multiple sclerosis (MS) lesions.
• To explore the potential of a novel integrative MRI model (QQ) for quantifying OEF and its association with remyelination processes.
• To determine if early increases in OEF reflect the metabolic demands associated with remyelination in MS lesions.

Main Methods:

• Longitudinal MRI scans were performed on 22 MS patients with 68 new gadolinium-enhancing lesions at baseline, 3 months, and 12 months.
• Oxygen extraction fraction (OEF) was quantified using the QQ model, integrating quantitative susceptibility mapping (QSM) and quantitative blood oxygen level-dependent (qBOLD).
• Myelin content was measured by myelin water fraction (MWF) using FAST-T2 imaging, and a linear mixed-effect model analyzed longitudinal changes and associations.

Main Results:

• Both OEF and MWF significantly increased from baseline to 3 months (p < 0.05), indicating early changes in oxygen metabolism and myelin content.
• OEF and MWF levels remained stable between 3 months and 12 months, suggesting a stabilization phase after initial lesion activity.
• A significant positive association was found between changes in OEF and MWF from baseline to 3 months (β = 0.0768, p = 0.007), linking increased OEF to myelin repair.

Conclusions:

• The early increase in OEF in acute MS lesions appears to be associated with the metabolic demands of the remyelination process.
• The QQ model demonstrates potential for enhancing the understanding of oxygen metabolism mechanisms underlying remyelination in MS.
• These findings provide novel insights into the dynamic interplay between metabolic changes and myelin repair in the context of MS lesion evolution.