A New Advanced MRI Biomarker for Remyelinated Lesions in Multiple Sclerosis

Reza Rahmanzadeh, Riccardo Galbusera, Po Jui Lu, Erik Bahn, Matthias Weigel, Muhamed Barakovic, Jonas Franz, Thanh D. Nguyen, Pascal Spincemaille, Simona Schiavi, Alessandro Daducci, Francesco La Rosa, Martina Absinta, Pascal Sati, Meritxell Bach Cuadra, Ernst Wilhelm Radue, David Leppert, Jens Kuhle, Ludwig Kappos, Wolfgang BrückDaniel S. Reich, Christine Stadelmann, Yi Wang, Cristina Granziera

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)486-502
Number of pages17
JournalAnnals of neurology
Volume92
Issue number3
DOIs
StatePublished - Sep 2022

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology

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