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

Accumulating preclinical evidence has highlighted the importance of cerebrospinal fluid (CSF) compartmentalization and transport. However, detailed structural characterization in humans remains challenging. This study utilized contrast-enhanced T2-fluid-attenuated inversion recovery imaging on 3-Tesla magnetic resonance imaging (MRI) in a cohort of 477 patients, primarily with reversible cerebral vasoconstriction syndrome (RCVS), to provide a noninvasive 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 < 0.0001). A dynamic MRI subgroup analysis further revealed that the periarterial tracer kinetics were nearly identical to those of these PVeS nodes. Notably, the nodal-non-nodal gradient of the tracer intensity was significantly amplified in participants exhibiting overt periarterial tracer leakage (p = 0.0006). Although we could not directly visualize the arteriovenous perivascular shunting demonstrated in animal models, our findings may be supportive of potential human periarterial and meningeal border pathways. By establishing a diseased model-based imaging framework to characterize these glymphatic microstructures noninvasively, our results offer a preliminary basis for understanding the perivascular CSF environment and a hypothesized periarterial and meningeal border pathways in living humans.