Abstract
The glymphatic system (GS) hypothesis states that advective driven cerebrospinal fluid (CSF) influx from the perivascular spaces into the interstitial fluid space rapidly transport solutes and clear waste from brain. However, the presence of advection in neuropil is contested and solutes are claimed to be transported by diffusion only. To address this controversy, we implemented a regularized version of the optimal mass transport (rOMT) problem, wherein the advection/diffusion equation is the only a priori assumption required. rOMT analysis with a Lagrangian perspective of GS transport revealed that solute speed was faster in CSF compared to grey and white matter. Further, rOMT analysis also demonstrated 2-fold differences in regional solute speed within the brain. Collectively, these results imply that advective transport dominates in CSF while diffusion and advection both contribute to GS transport in parenchyma. In a rat model of cerebral small vessel disease (cSVD), solute transport in the perivascular spaces (PVS) and PVS-to-tissue transfer was slower compared to normal rats. Thus, the analytical framework of rOMT provides novel insights in the local dynamics of GS transport that may have implications for neurodegenerative diseases. Future studies should apply the rOMT analysis approach to confirm GS transport reductions in humans with cSVD.
Highlights
The glymphatic system (GS) hypothesis states that advective driven cerebrospinal fluid (CSF) influx from the perivascular spaces into the interstitial fluid space rapidly transport solutes and clear waste from brain
We highlight that the Lagrangian formulation was used to construct dynamic ‘pathlines’ for visualizing GS transport flows in one comprehensive figure, derived from the regularized version of the optimal mass transport (rOMT) returned velocity field and interpolated images (Methods and Fig. 1)
We refer to the extraction and visualization of the Lagrangian representation of Glymphatic Dynamics as our GLaD framework (Fig. 1). rOMT as well as GLaD analysis was performed on dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) images taken over the 120 min interval starting at the time of peak signal (Fig. 1a)
Summary
The glymphatic system (GS) hypothesis states that advective driven cerebrospinal fluid (CSF) influx from the perivascular spaces into the interstitial fluid space rapidly transport solutes and clear waste from brain. ROMT analysis demonstrated 2-fold differences in regional solute speed within the brain These results imply that advective transport dominates in CSF while diffusion and advection both contribute to GS transport in parenchyma. Given initial and final mass distributions, OMT provides a powerful dynamic computational fluid formulation that gives an optimal interpolation path of minimal energy among all possible interpolations that preserve mass[37]. In this way, OMT can be formulated as a variational problem based on the principle of least action.
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