A New Advanced MRI Biomarker for Remyelinated Lesions in Multiple Sclerosis. Issue 3 (13th July 2022)

• Record Type: Journal Article
• Authors: Rahmanzadeh, Reza; Galbusera, Riccardo; Lu, Po‐Jui; Bahn, Erik; Weigel, Matthias; Barakovic, Muhamed; Franz, Jonas; Nguyen, Thanh D.; Spincemaille, Pascal; Schiavi, Simona; Daducci, Alessandro; La Rosa, Francesco; Absinta, Martina; Sati, Pascal; Bach Cuadra, Meritxell; Radue, Ernst‐Wilhelm; Leppert, David; Kuhle, Jens; Kappos, Ludwig; Brück, Wolfgang; Reich, Daniel S.; Stadelmann, Christine; Wang, Yi; Granziera, Cristina
• Is Part Of: Annals of neurology. Volume 92:Issue 3(2022)
• Page Start: 486
• Page End: 502
• Publication Date: 2022-07-13
• Subjects: Neurology -- Periodicals; Pediatric neurology -- Periodicals; Nervous system -- Surgery -- Periodicals; 616.8
• DOI: 10.1002/ana.26441
• Languages: English
• ISSNs: 0364-5134

Abstract

Abstract : Objectives: Neuropathological studies have shown that multiple sclerosis (MS) lesions are heterogeneous in terms of myelin/axon damage and repair as well as iron content. However, it remains a challenge to identify specific chronic lesion types, especially remyelinated lesions, in vivo in patients with MS. Methods: We performed 3 studies: (1) a cross‐sectional study in a prospective cohort of 115 patients with MS and 76 healthy controls, who underwent 3 T magnetic resonance imaging (MRI) for quantitative susceptibility mapping (QSM), myelin water fraction (MWF), and neurite density index (NDI) maps. White matter (WM) lesions in QSM were classified into 5 QSM lesion types (iso‐intense, hypo‐intense, hyperintense, lesions with hypo‐intense rims, and lesions with paramagnetic rim legions [PRLs]); (2) a longitudinal study of 40 patients with MS to study the evolution of lesions over 2 years; (3) a postmortem histopathology‐QSM validation study in 3 brains of patients with MS to assess the accuracy of QSM classification to identify neuropathological lesion types in 63 WM lesions. Results: At baseline, hypo‐ and isointense lesions showed higher mean MWF and NDI values compared to other QSM lesion types ( p < 0.0001). Further, at 2‐year follow‐up, hypo‐/iso‐intense lesions showed an increase in MWF. Postmortem analyses revealed that QSM highly accurately identifies (1) fully remyelinated areas as hypo‐/iso‐intense (sensitivity = 88.89% and specificity = 100%), (2) chronic inactive lesions as hyperintense (sensitivity = 71.43% and specificity = 92.00%), and (3) chronic active/smoldering lesions as PRLs (sensitivity = 92.86% and specificity = 86.36%). Interpretation: These results provide the first evidence that it is possible to distinguish chronic MS lesions in a clinical setting, hereby supporting with new biomarkers to develop and assess remyelinating treatments. ANN NEUROL 2022;92:486–502