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Quantifying Remyelination Using χ-Separation in White Matter and Cortical Multiple Sclerosis Lesions
Jannis Müller1, Po-Jui Lu1, Alessandro Cagol1
1From the Translational Imaging in Neurology (ThINk) Basel (J.M., P.-J.L., A.C., E.R., M.O.-P., X.C., C.T., M.B., R.G., M.W., S.A.S., L.K., C.G.), Department of Biomedical Engineering, Faculty of Medicine, and Neurologic Clinic and Policlinic, MS Center and Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB) (J.M., P.-J.L., A.C., E.R., M.O.-P., X.C., C.T., M.B., R.G., M.W., L.K., J.K., C.G.), University Hospital Basel and University of Basel, Switzerland; Department of Health Sciences (A.C.), University of Genova, Italy; Laboratory for Imaging Science and Technology (H.-G.S., J.L.), Department of Electrical and Computer Engineering, Seoul National University, South Korea; Division of Radiological Physics (M.W.), Department of Radiology, University Hospital Basel; Department of Clinical Research (S.A.S.), Clinical Trial Unit, University Hospital Basel, Switzerland; and Department of Radiology (Y.W., T.D.N., P.S.), Weill Medical College of Cornell University, New York, NY.
Younger multiple sclerosis (MS) patients with lower disability show greater myelin repair capacity. This remyelination positively correlated with improved clinical outcomes over two years.
Area of Science:
- Neuroimaging
- Biophysics
- Neuroimmunology
Background:
- Myelin and iron are crucial for remyelination in multiple sclerosis (MS) lesions.
- Assessing myelin and iron contributions is vital for understanding MS progression and repair.
- Novel biophysical modeling offers new insights into tissue composition.
Purpose of the Study:
- To investigate myelin and iron levels in MS lesions and normal-appearing brain tissue using a novel biophysical model.
- To explore the relationship between myelin/iron levels and clinical outcomes in MS patients.
- To assess the capacity for remyelination in different MS phenotypes and patient demographics.
Main Methods:
- A prospective cohort study of MS patients and healthy controls using multiecho MRI (T2*- and T2-weighted sequences).
- Application of the χ-separation model to estimate myelin- and iron-sensitive susceptibility maps.
- Segmentation of white matter lesions (WMLs), cortical lesions (CLs), and normal-appearing white matter (NAWM).
- Statistical analyses included cross-sectional and longitudinal comparisons, and linear regression models for clinical outcome associations.
Main Results:
- White matter lesions (WMLs) showed significantly lower myelin and iron concentrations compared to normal-appearing white matter (NAWM) at baseline.
- Both myelin and iron levels increased in WMLs over a 2-year follow-up period, indicating remyelination.
- Younger age, lower disability (Expanded Disability Status Scale [EDSS]), and relapsing-remitting MS (RRMS) phenotype were associated with greater remyelination.
- Increased myelin content correlated with clinical improvement in EDSS scores.
Conclusions:
- The χ-separation model effectively quantifies myelin and iron in MS brain tissue.
- Younger RRMS patients with lower disability demonstrate a higher capacity for remyelination.
- Remyelination capacity is linked to clinical disability improvement over time in MS patients.
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