Optimal Mass Transport with Lagrangian Workflow Reveals Advective and Diffusion Driven Solute Transport in the Glymphatic System

• Published in: Scientific reports 2020-02, Vol.10 (1), p.1990-1990, Article 1990
• Main Authors: Koundal, Sunil, Elkin, Rena, Nadeem, Saad, Xue, Yuechuan, Constantinou, Stefan, Sanggaard, Simon, Liu, Xiaodan, Monte, Brittany, Xu, Feng, Van Nostrand, William, Nedergaard, Maiken, Lee, Hedok, Wardlaw, Joanna, Benveniste, Helene, Tannenbaum, Allen
• Format: Article
• Language: English
• Subjects: 59/57; 631/378; 631/378/1689/1283; Advection; Animals; Brain research; Cerebral Small Vessel Diseases - diagnosis; Cerebral Small Vessel Diseases - pathology; Cerebrospinal fluid; Cerebrospinal Fluid - metabolism; Computer science; Diffusion; Disease; Disease Models, Animal; Extracellular Fluid - metabolism; Female; Glymphatic System - diagnostic imaging; Glymphatic System - metabolism; Glymphatic System - pathology; Humanities and Social Sciences; Humans; Hydrodynamics; Hypotheses; Magnetic Resonance Imaging; Male; Mass transport; Models, Neurological; multidisciplinary; Neurodegeneration; Neurodegenerative diseases; Neuropil; Neuropil - metabolism; Parenchyma; Rats; Science; Science (multidisciplinary); Simulation; Solute transport; Solutes; Substantia alba; Vascular diseases
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-020-59045-9

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.