Acknowledgements: NIH R01AG048769, RF1 AG053991, R01AG057705 and Leducq Foundation (16/CVD/05)
Author contributions:AT and HB conceived the study; AT and RE developed the rOMT algorithm and Lagrangian framework analysis; RE performed all rOMT processing; SN provided key suggestions for processing the Lagrangian analysis; HB performed all rOMT post-processing and designed figures with contributions from RE; HB performed kinetic analysis; SK, SS and XL performed all glymphatics experiments. SK executed all morphometric analysis including brain atlas segmentation; HL designed all pulse-sequences and other hardware for the MRI experiments and computational pipeline for the volumetric analysis. SS, FX, WVN performed the immunohistochemistry. SC performed qPCR analysis. YX performed the quantitative AQP4 analysis. HB, RE and AT wrote the manuscript. JW advised on the SHRSP animal model and cerebral small vessel disease. MN advised on the glymphatic system. All authors posed scientific questions, read and revised the manuscript. All authors edited and reviewed the paper.
AbstractThe presence of advection in neuropil is contested and solute transport is claimed to occur 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 glymphatic system (GS) transport revealed that solute speed was faster in cerebrospinal fluid (CSF) compared to grey and white matter. rOMT analysis also demonstrated 2-fold differences in regional particle speed within the brain parenchyma. Collectively, these results imply that advective transport dominates in CSF while diffusion and advection both contribute to transport in parenchyma. In rats with chronic hypertension, solute transport in perivascular spaces (PVS) and PVS-to-tissue transfer was slower compared to normotension. Thus, the analytical framework of rOMT provides novel insights in local variation and dynamics of GS transport that may have implications for neurodegenerative diseases.