Rise, Henning H;
Brune, Synne;
Chien, Claudia;
Berge, Tone;
Bos, Steffan D;
Andorrà, Magí;
Valdeolivas, Irene Pulido;
... Høgestøl, Einar A; + view all
(2022)
Brain disconnectome mapping derived from white matter lesions and serum neurofilament light levels in multiple sclerosis: A longitudinal multicenter study.
NeuroImage: Clinical
, 35
, Article 103099. 10.1016/j.nicl.2022.103099.
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Abstract
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 × 10-5), and longitudinal changes in NfL (t = -2.29, p = 0.02), but not for sex (t = 0.63, p = 0.53) or treatments (t = 0.80-0.83, p = 0.41-0.42). Voxel-wise analyses revealed significant associations between dysconnectivity in cerebellar and brainstem regions and serum NfL (t = 7.03, p < 0.001). 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.
| Type: | Article |
|---|---|
| Title: | Brain disconnectome mapping derived from white matter lesions and serum neurofilament light levels in multiple sclerosis: A longitudinal multicenter study |
| Location: | Netherlands |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.nicl.2022.103099 |
| Publisher version: | https://doi.org/10.1016/j.nicl.2022.103099 |
| Language: | English |
| Additional information: | © 2022 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
| Keywords: | Disconnectome mapping, Longitudinal, Magnetic resonance imaging, Multiple sclerosis, Neurofilament |
| UCL classification: | UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10151924 |
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