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A quantitative measure of choroid plexus contrast enhancement strongly relates to markers of diffuse brain tissue injury in multiple sclerosis

Senthil, S. V.; Tagge, I.; Fetco, D.; Hsieh, C.-H.; Assemlal, H.-E.; Karimaghaloo, Z.; Fetco, E.; Moore, G. R. W.; Arnold, D. L.; Rudko, D. A.; Narayanan, S.

2025-03-27 neurology
10.1101/2025.03.26.25324694 medRxiv
Show abstract

ObjectiveRecent 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). Methods34 MS participants underwent 7T MRI including MP2RAGE-based qT1 mapping pre- and post-contrast, and FLAIR acquisitions. "Delta T1" ({Delta}T1) 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 {Delta}T1 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{Delta}T1 of ChP was significantly associated with pre-Gd qT1 of NAWM ({beta} =0.20, R2 = 0.54, p<0.001) and GM ({beta} = 0.32, R2 = 0.62, p<0.001). No significant associations were found between ChP {Delta}T1 and WML volume (p = 0.3) or WML qT1 (p = 0.05). InterpretationThe 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.

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