Flow optimization of ventricular catheters for shear stress-induced death of astrocytes

Abstract

The ventricular catheter for treatment of hydrocephalus has a low lifespan due to obstruction by brain tissue. Multiple catheter designs have been proposed, but breakthroughs have not been made yet particularly due to the lack of understanding of the obstruction mechanisms that appear to be coupled with the fluid dynamics of ventricular catheters and cerebrospinal fluid (CSF). Recent studies have shown that glial tissue, which is mainly comprised of astrocytes, is the major contributor to obstruction. Impeding glial tissue formation should then be the foremost goal of the next-generation catheter, which leaves a crucial question that has not been answered yet: How does the fluid dynamics of ventricular catheters affect glial tissue formation? Answering this question, this thesis suggests a new design objective based on in vitro microfluidic experiments on astrocytes and proposes a novel design scheme developed on a lumped-element model describing the fluid dynamics of ventricular catheters. The thesis conducted long-term in vitro microfluidic culture of astrocytes and showed that fluid shear stress inhibits astrocytes from increasing confluency and reduces their viability. In light of the result, using Computational Fluid Dynamics (CFD) simulations, we showed that the conventional geometry of ventricular catheters is vulnerable to astrocytes ingrowth. To find improved catheter geometries, we performed a numerical optimization based on a lumped-element model. We validated the lumped-element model against CFD simulations also in good agreement with the direct flow visualization we performed in the actual catheters. Apart from flow analysis, CSF was investigated, determining its range of surface tension and showing it to be shear thinning at low shear rates. Finally, we propose a new design paradigm for more robust catheters for hydrocephalus patients.