Brain disconnectome mapping derived from white matter lesions and serum neurofilament light levels in multiple sclerosis: A longitudinal multicenter study.

Adult Biomarkers Brain / diagnostic imaging Female Humans Intermediate Filaments Male Multiple Sclerosis / diagnostic imaging Prospective Studies White Matter / diagnostic imaging
Disconnectome mapping Longitudinal Magnetic resonance imaging Multiple sclerosis Neurofilament

Journal

NeuroImage. Clinical
ISSN: 2213-1582
Titre abrégé: Neuroimage Clin
Pays: Netherlands
ID NLM: 101597070

Informations de publication

Date de publication:
2022
Historique:
received: 10 06 2022
revised: 21 06 2022
accepted: 22 06 2022
pubmed: 1 7 2022
medline: 25 8 2022
entrez: 30 6 2022
Statut: ppublish

Résumé

Connectivity-based approaches incorporating the distribution and magnitude of the extended brain network aberrations caused by lesions may offer higher sensitivity for axonal damage in patients with multiple sclerosis (MS) than conventional lesion characteristics. Using individual brain disconnectome mapping, we tested the longitudinal associations between putative imaging-based brain network aberrations and levels of serum neurofilament light chain (NfL) as a neuroaxonal injury biomarker. MS patients (n = 312, mean age 42.9 years, 71 % female) and healthy controls (HC) (n = 59, mean age 39.9 years, 78 % female) were prospectively enrolled at four European MS centres, and reassessed after two years (MS, n = 242; HC, n = 30). Post-processing of 3 Tesla (3 T) MRI data was performed at one centre using a harmonized pipeline, and disconnectome maps were calculated using BCBtoolkit based on individual lesion maps. Global disconnectivity (GD) was defined as the average disconnectome probability in each patient's white matter. Serum NfL concentrations were measured by single molecule array (Simoa). Robust linear mixed models (rLMM) with GD or T2-lesion volume (T2LV) as dependent variables, patient as a random factor, serum NfL, age, sex, timepoint for visit, diagnosis, treatment, and center as fixed factors were run. rLMM revealed significant associations between GD and serum NfL (t = 2.94, p = 0.003), age (t = 4.21, p = 2.5 × 10 In our prospective multi-site MS cohort, rLMMs demonstrated that the extent of global and regional brain disconnectivity is sensitive to a systemic biomarker of axonal damage, serum NfL, in patients with MS. These findings provide a neuroaxonal correlate of advanced disconnectome mapping and provide a platform for further investigations of the functional and potential clinical relevance of brain disconnectome mapping in patients with brain disorders.

Sections du résumé

BACKGROUND AND OBJECTIVES
Connectivity-based approaches incorporating the distribution and magnitude of the extended brain network aberrations caused by lesions may offer higher sensitivity for axonal damage in patients with multiple sclerosis (MS) than conventional lesion characteristics. Using individual brain disconnectome mapping, we tested the longitudinal associations between putative imaging-based brain network aberrations and levels of serum neurofilament light chain (NfL) as a neuroaxonal injury biomarker.
METHODS
MS patients (n = 312, mean age 42.9 years, 71 % female) and healthy controls (HC) (n = 59, mean age 39.9 years, 78 % female) were prospectively enrolled at four European MS centres, and reassessed after two years (MS, n = 242; HC, n = 30). Post-processing of 3 Tesla (3 T) MRI data was performed at one centre using a harmonized pipeline, and disconnectome maps were calculated using BCBtoolkit based on individual lesion maps. Global disconnectivity (GD) was defined as the average disconnectome probability in each patient's white matter. Serum NfL concentrations were measured by single molecule array (Simoa). Robust linear mixed models (rLMM) with GD or T2-lesion volume (T2LV) as dependent variables, patient as a random factor, serum NfL, age, sex, timepoint for visit, diagnosis, treatment, and center as fixed factors were run.
RESULTS
rLMM revealed significant associations between GD and serum NfL (t = 2.94, p = 0.003), age (t = 4.21, p = 2.5 × 10
DISCUSSION
In our prospective multi-site MS cohort, rLMMs demonstrated that the extent of global and regional brain disconnectivity is sensitive to a systemic biomarker of axonal damage, serum NfL, in patients with MS. These findings provide a neuroaxonal correlate of advanced disconnectome mapping and provide a platform for further investigations of the functional and potential clinical relevance of brain disconnectome mapping in patients with brain disorders.

Identifiants

DOI: 10.1016/j.nicl.2022.103099 PMID: 35772194 PMC: PMC9253471
pubmed: 35772194
pii: S2213-1582(22)00164-4
doi: 10.1016/j.nicl.2022.103099
pmc: PMC9253471
pii:
doi:

Substances chimiques

Biomarkers 0

Types de publication

Journal Article Multicenter Study Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

103099

Informations de copyright

Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.

Auteurs

Henning H Rise (HH)

NORMENT, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway; Department of Psychology, University of Oslo, Oslo, Norway.

Synne Brune (S)

Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Neurology, Oslo University Hospital, Oslo, Norway.

Claudia Chien (C)

Charité -Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin & Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Experimental and Clinical Research Center, Germany; Charité -Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, NeuroCure Clinical Research Center, Germany; Charité -Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Department for Psychiatry and Psychotherapy, Germany.

Tone Berge (T)

Department of Mechanical, Electronics and Chemical Engineering, Oslo Metropolitan University, Oslo, Norway; Department of Research, Innovation and Education, Oslo University Hospital, Oslo, Norway.

Steffan D Bos (SD)

Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Neurology, Oslo University Hospital, Oslo, Norway.

Magí Andorrà (M)

Institut d'Investigacions Biomèdiques August Pi Sunyer, Barcelona, Spain.

Irene Pulido Valdeolivas (IP)

Institut d'Investigacions Biomèdiques August Pi Sunyer, Barcelona, Spain.

Mona K Beyer (MK)

Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Division of Radiology and Nuclear Medicine, Oslo University Hospital, Oslo, Norway.

Piotr Sowa (P)

Division of Radiology and Nuclear Medicine, Oslo University Hospital, Oslo, Norway.

Michael Scheel (M)

Charité -Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, NeuroCure Clinical Research Center, Germany; Charité -Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Department of Neuroradiology, Germany.

Alexander U Brandt (AU)

Charité -Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin & Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Experimental and Clinical Research Center, Germany; Charité -Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, NeuroCure Clinical Research Center, Germany; Department of Neurology, University of California, Irvine, CA, USA.

Susanna Asseyer (S)

Charité -Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin & Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Experimental and Clinical Research Center, Germany.

Kaj Blennow (K)

Clinical Neurochemistry Laboratory, Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Mölndal, Sweden.

Mads L Pedersen (ML)

NORMENT, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway; Department of Psychology, University of Oslo, Oslo, Norway.

Henrik Zetterberg (H)

Clinical Neurochemistry Laboratory, Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Mölndal, Sweden; Department of Neurodegenerative Disease, Institute of Neurology, University College London, London, United Kingdom; UK Dementia Research Institute at UCL, London, United Kingdom.

Michel Thiebaut de Schotten (MT)

Brain Connectivity and Behaviour Laboratory, Sorbonne Universities, Paris, France; Groupe d'Imagerie Neurofonctionnelle, Institut des Maladies Neurodégénératives- UMR 5293, CNRS, CEA University of Bordeaux, Bordeaux, France.

Maria Cellerino (M)

Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, Genoa, Italy.

Antonio Uccelli (A)

Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, Genoa, Italy; IRCCS Ospedale Policlinico San Martino, Genoa, Italy.

Friedemann Paul (F)

Charité -Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin & Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Experimental and Clinical Research Center, Germany; Charité -Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, NeuroCure Clinical Research Center, Germany; IRCCS Ospedale Policlinico San Martino, Genoa, Italy.

Pablo Villoslada (P)

Institut d'Investigacions Biomèdiques August Pi Sunyer, Barcelona, Spain.

Hanne F Harbo (HF)

Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Neurology, Oslo University Hospital, Oslo, Norway.

Lars T Westlye (LT)

NORMENT, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway; Department of Psychology, University of Oslo, Oslo, Norway; KG Jebsen, Centre for Neurodevelopmental Disorders, University of Oslo, Oslo, Norway.

Einar A Høgestøl (EA)

Department of Psychology, University of Oslo, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Neurology, Oslo University Hospital, Oslo, Norway. Electronic address: einar.august@gmail.com.

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Classifications MeSH

questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Brain disconnectome mapping derived from white...
questionsmedicales.fr › Facteurs biologiques › Marqueurs biologiques › Brain disconnectome mapping derived from white...
questionsmedicales.fr › Système nerveux › Système nerveux central › Encéphale › Brain disconnectome mapping derived from white...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Brain disconnectome mapping derived from white...
questionsmedicales.fr › Cellules › Structures cellulaires › Espace intracellulaire › Cytoplasme › Structures cytoplasmiques › Cytosquelette › Filaments intermédiaires › Brain disconnectome mapping derived from white...
questionsmedicales.fr › Maladies du système immunitaire › Maladies auto-immunes › Maladies auto-immunes du système nerveux › Maladies démyélinisantes auto-immunes du SNC › Sclérose en plaques › Brain disconnectome mapping derived from white...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Caractéristiques des études épidémiologiques › Études épidémiologiques › Études de cohortes › Études prospectives › Brain disconnectome mapping derived from white...
questionsmedicales.fr › Système nerveux › Système nerveux central › Moelle spinale › Substance blanche › Brain disconnectome mapping derived from white...