Multimodal MRI in Multiple Sclerosis

National Institute Of Neurological Disorders And Stroke

Investigators

Linked publications, trials & patents

Abstract

In Fiscal Year 2025, we continued to pursue our Specific Aims: to study the pathophysiology of MS through neuroimaging, to study the biology of inflammatory demyelination in a translationally relevant primate model of MS, and to develop markers, and design and conduct clinical trials, for treating chronic inflammation and promoting tissue protection and remyelination in MS. We have seen significant progress toward accomplishing all these Aims, with several achievements detailed here. For Aim 1, we made substantial advances in understanding MS pathophysiology through neuroimaging. We achieved a major milestone with the incorporation of the central vein sign (CVS) into the McDonald Criteria for MS diagnosis (Amin et al. 2025), representing a significant step toward clinical implementation of this biomarker. Our multicenter validation studies demonstrated that automated CVS detection performs as well as manual assessment (Manning et al. 2025), with excellent reliability across sites (Martin et al. 2025). We further confirmed that CVS has superior diagnostic performance compared to oligoclonal bands (Toljan et al. 2025), reinforcing its clinical utility. Building on our work with chronically inflamed lesions, we validated multicenter automated detection of paramagnetic rim lesions (PRL) (Chen et al. 2025) and demonstrated their high specificity for MS in real-world clinical data (Hemond et al. 2025). We showed that PRL formation can be predicted by initial gadolinium-enhancing lesion diameter (Al Gburi et al. 2025), providing insights into lesion evolution mechanisms. We continued advancing brain imaging technology, demonstrating that brain age modeling can be significantly improved for individuals with MS using advanced techniques (La Rosa et al. 2025). Our cognitive assessment work revealed that the written symbol digit modalities test is sensitive to both cognitive and motor disability (Greenwald et al. 2025a), with differential validity across test modalities (Greenwald et al. 2025b). We contributed to work describing novel T2 contrast analysis at 7T MRI (Wang et al. 2025) and improved techniques for harmonizing brain volume measurements across sites (Lu et al. 2025). With the North American Imaging in Multiple Sclerosis Cooperative (NAIMS), we published a comprehensive consensus statement on the use of 7T MRI in MS (Harrison et al. 2025), establishing guidelines for this advanced technology. Our exploration of ultra-low-field portable MRI systems showed substantial progress, with high-field-blinded assessments demonstrating clinical utility (Okar et al. 2025) and successful application to progressive multifocal leukoencephalopathy (Okar et al. 2025). We also developed generative adversarial networks to synthesize high-quality 3T images from 64-mT low-field MRI (Lucas et al. 2025), potentially democratizing neuroimaging access. For Aim 2, we achieved a landmark publication in Science with our 4D marmoset brain map that reveals MRI and molecular signatures for the onset of MS-like lesions (Lin et al. 2025). This comprehensive spatiotemporal atlas represents years of work integrating single-cell and spatial transcriptomics with advanced neuroimaging. We also characterized TSPO expression patterns in marmoset experimental autoimmune encephalomyelitis (Falk et al. 2025), providing insights into neuroinflammation imaging markers. Our collaborative work identified significant oligodendrocyte progenitor and microglial cell death as a feature of remyelination following experimental demyelination (Gaitsch et al. 2025). We also contributed to understanding how myeloid lineage C3, a component of the complement system, induces reactive gliosis and neuronal stress during CNS inflammation (Garton et al. 2025), revealing new therapeutic targets. Under Aim 3, we made significant strides in clinical translation. We contributed to major clinical trials, including the tolebrutinib study in non-relapsing secondary progressive MS published in the New England Journal of Medicine (Fox et al. 2025), representing a potential breakthrough in progressive MS treatment. We also reported 2-year safety and efficacy outcomes from the tolebrutinib phase 2b extension study (Oh et al. 2025). We reviewed comprehensive imaging outcome measures for phase 2 trials targeting compartmentalized inflammation (Gaitán et al. 2025), advancing trial methodology. Our review of novel human iPSC models highlighted new approaches for studying neuroinflammation in neurodegenerative disease, with potential therapeutic applications (Summers et al. 2025). We continued collaborative work across neurological diseases, contributing to studies of HTLV-1 associated myelopathy/tropical spastic paraparesis (Stack et al. 2025) and genetic susceptibility research in MS (Pagalilauan et al. 2025). Our systematic review and meta-analysis examined factors governing successful animal-to-human translation in MS drug development (Berg et al. 2025), with important implications for translational research, and we advanced methodological approaches with new tools for automated experimental parameter extraction (Zurrer et al. 2025).