Assessing Glymphatic Flow Modulation by Vasopressin and Relcovaptan Using Glymph-FIT: a Novel Approach with DCE-MRI

Motivation: Glymphatic flow is vital for clearing brain waste, which has implications for neurodegenerative diseases. A precise fitting tool is needed to provide sensitive measures of flow with vasopressin receptor modulation, so we designed Glymp-FIT. Goal(s): To assess relcovaptan's impact on very slow glymphatic flow and validate Glymph-FIT, our custom-designed gamma PDF-based DCE-MRI model, for accurately capturing dynamic flow changes. Approach: Using Glymph-FIT, we visualized glymphatic flow following relcovaptan administration, obtaining detailed temporal and spatial measurements. Results: Findings indicate that relcovaptan, as an antagonist, unexpectedly increases glymphatic flow, comparable to arginine vasopressin (AVP), which promotes V1A, V1B, and V2, suggesting indirect receptor activation effects. Impact: This study introduces Glymph-FIT, a novel tool for accurately measuring very slow glymphatic flow dynamics. Findings suggest V1A antagonism with relcovaptan enhances glymphatic flow, potentially offering new therapeutic strategies to improve brain waste clearance and potentially mitigate neurodegenerative disease progression.