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.

Keywords: Oxygen extraction fraction; QSM + qBOLD; multiple sclerosis; quantitative blood oxygen level dependent; quantitative susceptibility mapping; remyelination.

Figure 1.

Examples of one Gd-enhanced lesion (circled in red) in T1w + Gd, T2-FLAIR, MWF, and OEF image from a MS subject.

Figure 2.

Boxplots of lesion OEF and MWF measurements at baseline, 3 months, and 12 months. Significant increase in OEF and MWF from baseline to 3 months and baseline to 12 months (p < 0.05) were observed. The red line, blue box, black whisker, and red cross indicate median value, interquartile range, the range extending to 1.5 of the interquartile range, and outlier beyond the whisker range. Asterisk (*) indicates the significance difference (p < 0.05, linear mixed-effect model).

Figure 3.

Scatter plots of lesion OEF and MWF changes from baseline to 3 months and from 3 months to 12 months. ΔMWF shows a significant positive association with ΔOEF from baseline to 3 months. Each dot indicates each lesion, and each color indicates different subjects. Asterisk (*) indicates the significance difference (p < 0.05, linear mixed-effect model).