BACKGROUND: Multiple sclerosis (MS) slowly expanding lesions (SELs) are defined on magnetic resonance imaging (MRI) as contiguous regions of pre-existing focal non-contrast-enhancing T2 lesions with constant and concentric local expansion on conventional T1-weighted and T2-weighted images. SELs are associated with an increased risk of disability progression. METHODS: Myelin-related changes detected using myelin water fraction (MWF) and magnetisation transfer ratio (MTR) in SELs and T2 lesions were measured over 192 weeks in participants with relapsing MS. RESULTS: In participants with SELs (SEL+), SELs (MWF: 0.12 ± 0.03, MTR: 33.1 ± 3.6 pu) showed reduced myelin measures at baseline compared to T2 lesions (MWF: 0.13 ± 0.02, MTR: 35.1 ± 2.4 pu). In participants without SELs (SEL-), T2 lesions had higher myelin measures (MWF: 0.15 ± 0.02, MTR: 36.2 ± 2.0 pu) compared to T2 lesions in SEL+. Over 4 years, only SELs showed decreases in MWF (-11.4%). The percentage of abnormal voxels within normal-appearing white matter was higher in SEL+ and increased over time (SEL+ MWF Week 0: 0.56%, Week 192: 0.98%
SEL- MWF Week 0: 0.13%, Week 192: 0.25%). CONCLUSION: Our results indicate progressive focal and global demyelination in SEL+ participants and that the presence of SELs might be a biomarker for participants with ongoing diffuse or smouldering inflammation within the whole brain.