Chronic lesion expansion as an imaging biomarker in multiple sclerosis

The pathophysiological processes that drive disability progression in multiple sclerosis (MS) are not adequately captured by clinically available imaging biomarkers. Slowly expanding lesions (SELs) are a novel magnetic resonance imaging (MRI) biomarker proposed to reflect histopathologically defined chronic active lesions, which are associated with disease progression. SELs are identified through complex MRI analysis pipelines that measure volume changes in chronic MS lesions across serial MRI scans. This review provides a comprehensive overview of SELs, covering their proposed histopathological correlates, associations with clinical outcomes and response to disease-modifying therapies (DMTs). A distinguishing aim of this review is to provide the reader with a clear understanding of different SEL analysis techniques, particularly the two most established automated approaches, including their respective strengths and limitations. Each technique is compatible with conventional clinical MRI sequences, making clinical translation feasible. Current DMTs have modest effects on SELs, paralleling their limited efficacy in progressive MS. SELs may become a key outcome measure in clinical trials of DMTs for progressive MS. However, further research is needed to ascertain the optimal parameters for identifying clinically meaningful chronic lesion expansion with each analysis technique, and to clarify which SEL measures are most strongly associated with disability progression.