Multiphasic transport in the human cranial dura: how meningeal lymphatic vessels drive waste clearance from brain cerebrospinal fluid

The discovery of meningeal lymphatic vessels (mLVs) has reshaped our understanding of brain waste clearance, positioning them as a very important clearance route. However, quantifying the precise hydrodynamics and solute transport mechanisms within the human dura mater in vivo remains highly challenging due to the multiscale nature of cranial fluid dynamics and imaging resolution limits. We integrated patient-specific intrathecal contrast-enhanced MRI (gMRI) data from a single healthy subject with a novel anatomical segmentation of the cranial dura mater. By employing a hierarchy of inverse mathematical and micro-mechanical models, we estimated previously inaccessible physiological transport parameters. To ensure parameter identifiability, we deliberately modeled a scenario where the meningeal lymphatic vessels act as the sole fluid efflux route, thereby establishing an upper limit for their clearance capacity. These baseline estimates subsequently informed a spatially distributed, double-porosity 3D computational model of the human dura to simulate the fluid dynamics of cranial clearance. Our analysis suggests that purely diffusive macroscopic models fail to replicate in vivo tracer distribution. Conversely, a dual-porosity advection-diffusion framework successfully captures the tissue kinetics. The transport within the mLV compartment is characterized by highly convective clearance (with \(Pe > 1\) ), with macroscopic fluid velocities and effective lymphatic diffusion coefficients yielding an upper-bound advective capacity theoretically sufficient to clear the total albumin content in the Cerebrospinal Fluid (CSF). Based on our findings on a single subject (Gonzo) solute clearance within the human cranial dura mater emerges as multiphasic, advection-dominated process. Rather than relying on passive Fickian diffusion, molecules appear to be actively and rapidly cleared through the meningeal lymphatic network via convective mechanisms. While our assumption of exclusively mLV-driven clearance provides a theoretical upper limit for their capacity, this hierarchical modeling approach successfully bridges clinical imaging and microscopic fluid dynamics, offering quantitative insights into the primary mechanical drivers of dural fluid clearance.