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A New Advanced MRI Biomarker for Remyelinated Lesions in Multiple Sclerosis
Author(s) -
Rahmanzadeh Reza,
Galbusera Riccardo,
Lu PoJui,
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 ErnstWilhelm,
Leppert David,
Kuhle Jens,
Kappos Ludwig,
Brück Wolfgang,
Reich Daniel S.,
Stadelmann Christine,
Wang Yi,
Granziera Cristina
Publication year - 2022
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.26441
Subject(s) - medicine , multiple sclerosis , lesion , pathology , magnetic resonance imaging , quantitative susceptibility mapping , histopathology , white matter , myelin , nuclear medicine , radiology , central nervous system , psychiatry
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