Mapping human glymphatic compartments and putative meningeal border pathways in diseased models

Abstract Accumulating preclinical evidence has highlighted the importance of CSF compartmentalization and transport. However, detailed structural characterization in humans remains challenging. This study utilized contrast-enhanced T2 fluid-attenuated inversion recovery imaging on a 3 T MRI machine in a cohort of 477 patients, primarily with reversible cerebral vasoconstriction syndrome, to provide a non-invasive in vivo diseased model to delineate distinct subarachnoid compartmentalization and potential leptomeningeal arteriovenous perivascular shunting. We characterized a homogeneous CSF milieu within the ensheathed periarterial glymphatic space. This environment, structurally defined by the perivascular membrane, exhibited uniform tracer intensities across both proximal and distal arterial segments (P = 0.118) on both static and dynamic models, opposed to the heterogeneous CSF appearance observed outside the perivascular membrane. We also observed nodal tracer enrichment in specific locations of the leptomeningeal perivenous space (PVeS) across initial and follow-up MRI. Furthermore, the periarterial tracer enrichment intensities matched those in these nodal portions of the PVeS but significantly exceeded those in the non-nodal portions (P By establishing a diseased model-based imaging framework to characterize these glymphatic microstructures non-invasively, our results offer a preliminary basis for understanding the perivascular CSF environment and hypothesized periarterial and meningeal border pathways in living humans.