LAUSR

OBJECTIVE Choroid plexus (CP) is a key regulator in cerebrospinal fluid production, but its contribution to glymphatic clearance function and association with white matter hyperintensity (WMH) remains unclear. METHODS This retrospective study included two prospective 3.0-T MRI cohorts. In Cohort 1, patients with indications for lumbar puncture underwent 3D-T1 before and at 39 hours after intrathecal administration of contrast agent (Glymphatic MRI). In Cohort 2, WMH patients were enrolled from CIRCLE study and had a median follow-up time of 1.4 years. WMH and CP of the lateral ventricles were automatically segmented on T2 FLAIR and 3D-T1, respectively. CP volume was expressed as a ratio to intracranial volume. Glymphatic clearance was measured as signal percentage change from baseline to 39 hours at eight brain locations based on Glymphatic MRI in the first cohort, or as non-invasive diffusion tensor image analysis along the perivascular space (DTI-ALPS) index based on DTI in the second cohort. RESULTS In Cohort 1, 52 patients were included. Higher CP volume was correlated with slower glymphatic clearance rate in all brain locations. In Cohort 2, 197 patients were included. Baseline CP volume was positively associated with WMH volume and its growth. Furthermore, DTI-ALPS index partially mediated the association of CP with both WMH load and growth. INTERPRETATIONS Enlarged CP volume could be an indicator for larger growth of WMH, potentially involving impaired glymphatic clearance function. The exploration of CP may provide a novel perspective to clarify the mechanism of WMH pathogenesis, as well as other glymphatic-related disorders. This article is protected by copyright. All rights reserved.