Meningeal lymphatic architecture and drainage dynamics surrounding the human middle meningeal artery

The anatomical basis of cerebrospinal and interstitial fluid clearance along the human ventral meninges remains poorly defined. Here, we present the in vivo and ex vivo evidence of a distinct CSF-ISF drainage compartment surrounding the middle meningeal artery (MMA) in humans. In five healthy participants, dynamic contrast-enhanced MRI revealed delayed signal enhancement along the MMA-peripheral region, peaking at 90 min, substantially later than adjacent vascular and lymphatic structures, consistent with slower, nonvascular clearance dynamics. To validate these findings, we performed the high-resolution spatial mapping of the dorsal and ventral dura using immunofluorescence and imaging mass cytometry, identifying PROX1+, PDPN+, and LYVE1+ lymphatic-like structures that are aligned along the MMA. These findings define a previously unrecognized outflow zone in the human ventral dura and support the presence of organized meningeal lymphatic architecture beyond dorsal compartments. This integrated human framework motivates future mechanistic studies into the role of ventral lymphatics in brain fluid clearance and neuroimmune regulation.