Do enlarged white matter perivascular spaces reflect brain clearance dysfunction? Insights from intrathecal contrast-enhanced MRI

TL;DR

This study uses MRI to investigate if enlarged white matter perivascular spaces are linked to brain clearance dysfunction by tracking contrast agent movement.

Contribution

The study provides new insights into the dynamics of CSF exchange with perivascular spaces in different brain regions.

Findings

Perivascular spaces in both white matter and basal ganglia showed CSF exchange after intrathecal contrast injection.

Basal ganglia perivascular spaces enhanced more rapidly and intensely compared to white matter ones.

The delayed and reduced enhancement in white matter perivascular spaces questions their use as markers of clearance dysfunction.

Abstract

Visible perivascular spaces of cerebral white matter at magnetic resonance imaging (MRI) were in several studies proposed to be an integral part of brain-wide perivascular clearance pathways, and their enlargement could therefore serve as markers of perivascular clearance dysfunction. We studied whether MRI-visible perivascular spaces in subcortical white matter communicate with subarachnoid cerebrospinal fluid (CSF).

MRI-visible perivascular spaces of the basal ganglia served as controls. Intrathecal 0.5 mmol gadobutrol was utilized as CSF tracer, and T1-weighted MRI was performed before, and at multiple time points after (3, 6, 24 and 48 h) injection. Perivascular spaces with diameter ≥ 2 mm were included in the analysis, and a circular region of interest was placed manually within one perivascular space and in adjacent brain parenchyma of each region.

The study included 27 symptomatic individuals undergoing clinical work-up of various CSF circulation disorders, but in whom no treatable condition was found. Perivascular spaces of both white matter and basal ganglia enhanced with intrathecal gadobutrol, confirming CSF exchange with perivascular spaces. While perivascular spaces of basal ganglia enhanced most with peak at 6 h (233.2% [34.9 to 431.5%]) (p < 0.01), coinciding with peak enhancement in subarachnoid CSF, perivascular spaces of white matter enhanced less and more slowly with peak at 48 h (159.1% [37.9 to 280.3%]) (p < 0.01).

The various degrees of CSF exchange with MRI-visible subcortical perivascular spaces suggest these may be dilated for different reasons, therefore questioning their validity as markers of perivascular clearance function.

The online version contains supplementary material available at 10.1007/s00234-025-03877-7.

Figures