Combined [¹¹C]PBR28 PET and Quantitative T1 Mapping Reveal Choroid Plexus Alterations in Multiple Sclerosis

Background The choroid plexus (CP), central to cerebrospinal fluid (CSF) regulation and immune cell trafficking, has been implicated in multiple sclerosis (MS).

We investigated TSPO-PET standardized uptake value ratio (SUVR) in the CP, with relation to T□ relaxation times and CP volume using 7T MRI.

Quantitative T1 (qT1) maps were obtained from 38 MS participants and 21 healthy controls (HCs) using 7T MRI. Within 4 weeks, PET imaging was conducted with [¹¹C]PBR28 to measure SUVR in the CP. Group differences and associations in CP SUVR, qT1, and CP volume were assessed.

CP SUVR, CP qT1, and head□size-corrected CP volumes were higher in MS than HCs (p<0.05). CP volume associated strongly with CP qT1 (r=0.52, p<0.05). In MS, CP SUVR inversely correlated with qT1 (ρ= –0.45, p<0.05). No significant associations were observed with disability scores, white□matter lesion burden and cortical lesion counts.

Our findings support elevated microglial/macrophage activation in CP alongside structural alterations. CP volume emerges as a complementary MRI marker of inflammation rather than a direct surrogate for TSPO-PET tracer uptake. The inverse CP SUVR–qT□ relationship in MS suggests that chronic extracellular expansion can accelerate tracer washout. Competing Interest Statement SS, RT, SB, AK, RA, PRN, GRWM and DAR have nothing to disclose. DLA reports consulting fees from Biogen, Biohaven, BMS, Eli Lilly, EMD Serono, Find Therapeutics, Frequency Therapeutics, GSK, Idorsia Pharmaceuticals, Kiniksa Pharmaceuticals, Merck, Novartis, Race to Erase MS, Roche, Sanofi-Aventis, Shionogi, and Xfacto Communications; as well as an equity interest in NeuroRx. SN has received research funding from the Canadian Institutes of Health Research, the National Institutes of Health, the Myelin Repair Foundation, Immunotec, and F. Hoffman LaRoche; he has been a consultant for Sana Biotech and is a part-time employee of NeuroRx Research, a Clario Company. Funding Statement This study was supported in part by the United States Department of Defense, Multiple Sclerosis Research Program, Investigator–Initiated Research Award (Award No. W81XWH19-1-0486) (DAR). SS thanks the Fonds de Recherche Québec – Santé for personal support (scholarship). RT was supported by the Canada Graduate Scholarships Doctoral Award (CGS–D). 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: McGill University Health Centre Research Ethics Board 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 Data availability statement 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 to qualified investigators on reasonable request.