Ocular Solute Movement Direction and Intracranial Clearance via Vitreous Gadolinium-based Contrast Agent MR Imaging: Potential as a Novel Biomarker for Glymphatic Dysfunction.

Abstract

Purpose: The ocular and brain glymphatic systems may share common physiological pathways. We hypothesized that the anteroposterior movement of gadolinium-based contrast agent (GBCA) that has leaked into the vitreous could serve as a biomarker for brain glymphatic function. This study aimed to retrospectively investigate the association between the intravitreal GBCA distribution on MRI and recently proposed imaging markers of impaired brain waste clearance.

Methods: We analyzed 156 eyes from 78 adult participants who underwent 3T MRI 4 hr after standard-dose GBCA administration. On 3D-real IR images, we calculated a "contrast shift index" (the signal difference between anterior and posterior vitreous volumes of interest: VOIa-VOIp) to quantify the anteroposterior GBCA distribution. The primary outcome was a composite endpoint of positivity for either putative meningeal lymphatics at the posterior sigmoid sinus (PML-PSS) or enhanced basal ganglia perivascular spaces (PVS-BG). Multivariable logistic regression with cluster-robust inference was used to assess predictors, including the contrast shift index, mean vitreous contrast distribution, age, sex, and axial length of the eye.

Results: A positive contrast shift index, indicating preferential anterior GBCA distribution, was significantly and independently associated with the composite outcome of impaired brain clearance (P = 0.006). Age (P <0.001) and male sex (P = 0.009) were also independent predictors. A predictive model incorporating these factors demonstrated high discrimination, with an area under the receiver operating characteristic curve (AUC) of 0.872. Axial length of the eye and mean vitreous contrast distribution were not significant independent predictors.

Conclusion: The anteroposterior distribution of GBCA in the vitreous is a novel, non-invasive imaging biomarker associated with impaired brain clearance function. This "contrast shift index" may reflect systemic glymphatic dysregulation common to both the eye and brain, offering a new avenue for assessing neurodegenerative risk.