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

Abstract

The study investigates the relationship between longitudinal changes in oxygen extraction fraction (OEF) and remyelination in acute multiple sclerosis (MS) lesions. Twenty-two MS patients with 68 new gadolinium-enhancing lesions underwent MRI scans at baseline, 3 months, and 12 months. OEF was quantified using QQ, an integrative model combining quantitative susceptibility mapping (QSM) and quantitative blood oxygen level-dependent (qBOLD), while myelin content was measured by myelin water fraction using FAST-T2 imaging. A linear mixed-effect model assessed longitudinal changes in OEF and MWF and their associations. Both OEF and MWF significantly increased from baseline to 3 months (OEF: 20.1% ± 8.6%–25.0% ± 6.0%, p < 0.05 and MWF: 7.6% ± 2.5%–8.4% ± 2.8%, p < 0.05) but remained stable between 3 months and 12 months. A significant positive association was observed between changes in OEF and MWF from baseline to 3 months ( $\beta$  = 0.0768, p = 0.007). These findings suggest that early increase in OEF may reflect the metabolic demands of remyelination in acute MS lesions. This study highlights QQ’s potential to enhance our understanding of oxygen metabolism-related mechanism underlying remyelination.