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In Vivo Imaging of Cerebrospinal Fluid Transport through the Intact Mouse Skull using Fluorescence Macroscopy

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Deep Venous Perivascular Space Dysfunction Reflects Glymphatic Aging and Predicts Cognitive Vulnerability: In Vivo

Kemeng Zhang¹, Ying Zhou¹, Yifei Li¹

¹Department of Neurology, Second Affiliated Hospital of Zhejiang University, School of Medicine, State Key Laboratory of Transvascular Implantation Devices, Hangzhou, China.

Aging and Disease

|May 18, 2026

Summary

Impaired glymphatic clearance, linked to cognitive decline, was visualized in human perivascular spaces (PVS) using MRI. Venous PVS burden, not arterial PVS, correlated with lower cognitive scores, suggesting a therapeutic target.

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Area of Science:

Neuroscience
Radiology
Gerontology

Background:

Impaired glymphatic clearance is a key factor in cognitive decline.
Cerebrospinal fluid (CSF) flow models suggest influx via arterial PVS (aPVS) and efflux via venous PVS (vPVS), but human roles are unclear.

Purpose of the Study:

To visualize directional glymphatic flow in vivo using MRI.
To functionally classify human PVS as arterial or venous.
To determine the association between PVS type and cognitive function.

Main Methods:

91 patients received intrathecal gadodiamide with serial MRI scans.
Perivascular spaces (PVS) were classified as aPVS (early enhancement) or vPVS (delayed enhancement).
Cognitive function was assessed using the telephone Montreal Cognitive Assessment (T-MoCA).

Main Results:

Direct in vivo MRI evidence of glymphatic flow within human PVS was obtained.
A novel functional classification differentiated aPVS and vPVS.
Higher basal ganglia vPVS burden correlated with age, hypertension, and lower T-MoCA scores, independent of age and education.

Conclusions:

This study provides the first in vivo MRI evidence of human glymphatic flow within PVS.
A new method functionally classifies PVS, revealing distinct roles for aPVS and vPVS.
Venous PVS burden is a potential therapeutic target for cognitive impairment.