A Quantitative Measure of Choroid Plexus Contrast Enhancement Strongly Relates to Markers of Diffuse Brain Tissue Injury in Multiple Sclerosis

Abstract: Objective: Recent studies suggest that disruptions of the blood –cerebrospinal fluid barrier within the choroid plexus (ChP) may contribute to MS pathogenesis. We investigated the relationship between a quantitative marker of ChP enhancement and markers of focal and diffuse brain tissue injury in multiple sclerosis (MS). Methods: 34 MS participants underwent 7T MRI including MP2RAGE-based qT1 mapping pre – and post contrast, and FLAIR acquisitions. Delta T1 (ΔT1) maps were calculated by subtraction of post –contrast from co-registered pre-contrast qT1 maps. ChP, white matter lesions (WML), normal–appearing white matter (NAWM) and grey matter (GM) were segmented. Linear regression analyses were conducted between mean ΔT1 values of ChP and (1) WML volume, (2) pre–Gd mean qT1 of WML, (3) pre–Gd mean qT1 of NAWM, and (4) pre–Gd mean qT1 of GM. Results: ΔT1 of ChP was significantly associated with pre–Gd qT1 of NAWM ( β=0.20 , R2 = 0.54, p<0.001) and GM (β = 0.32, R2 = 0.62, p<0.001). No significant associations were found between ChP ΔT1 and WML volume (p = 0.3) or WML qT1 (p = 0.05). Interpretation: The strong associations we observed between the degree of ChP contrast enhancement and markers of diffuse brain tissue injury, combined with a lack of a relationship with lesion volume or qT1 within lesions, support the hypothesis that entry of toxic factors into the CSF via the ChP may constitute an additional mechanism of brain tissue injury distinct from the classic lesion-based pathology of MS. ### Competing Interest Statement S.S., I.T., D.F., C.H.H., H.E.A., E.F., Z.K., D.A.R., G.R.W.M., S.N. have nothing to report. D.L.A. received partial funding for data acquisition from Novartis Canada. ### Funding Statement This study was supported in part by the Canadian Institutes of Health Research, grant #153005 (SN), the United States Department of Defense, Multiple Sclerosis Research Program, Investigator–Initiated Research Award (Award No. W81XWH19–1–0486) (DAR) and an Investigator–Initiated award from Novartis Canada (DLA). SS thanks the Fonds de Recherche Québec – Santé for personal support (scholarship). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The Research Ethics Board of the Montreal Neurological Institute-Hospital gave ethical approval for this work. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes The data that support the findings of this study are not publicly available due to concerns surrounding patient confidentiality but are available from the corresponding author on reasonable request.