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A New Advanced MRI Biomarker for Remyelinated Lesions in Multiple Sclerosis.
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.
Afiliación
  • Rahmanzadeh R; Neurology Clinic and Policlinic, Departments of Medicine, Clinical Research and Biomedical Engineering, University Hospital Basel and University of Basel, Basel, Switzerland.
  • Galbusera R; Translational Imaging in Neurology (ThINk) Basel, Department of Biomedical Engineering, University Hospital Basel and University of Basel, Basel, Switzerland.
  • Lu PJ; Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), University Hospital Basel and University of Basel, Basel, Switzerland.
  • Bahn E; Neurology Clinic and Policlinic, Departments of Medicine, Clinical Research and Biomedical Engineering, University Hospital Basel and University of Basel, Basel, Switzerland.
  • Weigel M; Translational Imaging in Neurology (ThINk) Basel, Department of Biomedical Engineering, University Hospital Basel and University of Basel, Basel, Switzerland.
  • Barakovic M; Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), University Hospital Basel and University of Basel, Basel, Switzerland.
  • Franz J; Neurology Clinic and Policlinic, Departments of Medicine, Clinical Research and Biomedical Engineering, University Hospital Basel and University of Basel, Basel, Switzerland.
  • Nguyen TD; Translational Imaging in Neurology (ThINk) Basel, Department of Biomedical Engineering, University Hospital Basel and University of Basel, Basel, Switzerland.
  • Spincemaille P; Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), University Hospital Basel and University of Basel, Basel, Switzerland.
  • Schiavi S; Institute of Neuropathology, University Medical Center, Göttingen, Germany.
  • Daducci A; Neurology Clinic and Policlinic, Departments of Medicine, Clinical Research and Biomedical Engineering, University Hospital Basel and University of Basel, Basel, Switzerland.
  • La Rosa F; Translational Imaging in Neurology (ThINk) Basel, Department of Biomedical Engineering, University Hospital Basel and University of Basel, Basel, Switzerland.
  • Absinta M; Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), University Hospital Basel and University of Basel, Basel, Switzerland.
  • Sati P; Division of Radiological Physics, Department of Radiology, University Hospital Basel, Basel, Switzerland.
  • Bach Cuadra M; Neurology Clinic and Policlinic, Departments of Medicine, Clinical Research and Biomedical Engineering, University Hospital Basel and University of Basel, Basel, Switzerland.
  • Radue EW; Translational Imaging in Neurology (ThINk) Basel, Department of Biomedical Engineering, University Hospital Basel and University of Basel, Basel, Switzerland.
  • Leppert D; Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), University Hospital Basel and University of Basel, Basel, Switzerland.
  • Kuhle J; Institute of Neuropathology, University Medical Center, Göttingen, Germany.
  • Kappos L; Max Planck Institute for Experimental Medicine, Göttingen, Germany.
  • Brück W; Campus Institute for Dynamics of Biological Networks, University of Göttingen, Göttingen, Germany.
  • Reich DS; Department of Radiology, Weill Cornell Medical College, New York, NY.
  • Stadelmann C; Department of Radiology, Weill Cornell Medical College, New York, NY.
  • Wang Y; Department of Computer Science, University of Verona, Verona, Italy.
  • Granziera C; Department of Computer Science, University of Verona, Verona, Italy.
Ann Neurol ; 92(3): 486-502, 2022 09.
Article en En | MEDLINE | ID: mdl-35713309
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;92486-502.
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Esclerosis Múltiple Tipo de estudio: Observational_studies / Prevalence_studies / Risk_factors_studies Límite: Humans Idioma: En Revista: Ann Neurol Año: 2022 Tipo del documento: Article País de afiliación: Suiza
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Esclerosis Múltiple Tipo de estudio: Observational_studies / Prevalence_studies / Risk_factors_studies Límite: Humans Idioma: En Revista: Ann Neurol Año: 2022 Tipo del documento: Article País de afiliación: Suiza