Multiscale parareal algorithm for long-time mesoscopic simulations of microvascular blood flow in zebrafish

Abstract

Various biological processes such as transport of oxygen and nutrients, thrombus formation, vascular angiogenesis and remodeling are related to cellular/subcellular level biological processes, where mesoscopic simulations resolving detailed cell dynamics provide a key to understanding and identifying the cellular basis of disease. However, the intrinsic stochastic effects can play an important role in mesoscopic processes, while the time step allowed in a mesoscopic simulation is restricted by rapid cellular/subcellular dynamic processes. These challenges significantly limit the timescale that can be reached by mesoscopic simulations even with high-performance computing. To break this bottleneck and achieve a biologically meaningful timescale, we propose a multiscale parareal algorithm in which a continuum-based solver supervises a mesoscopic simulation in the time-domain. Using an iterative prediction-correction strategy, the parallel-in-time mesoscopic simulation supervised by its continuum-based counterpart can converge fast. The effectiveness of the proposed method is first verified in a time-dependent flow with a sinusoidal flowrate through a Y-shaped bifurcation channel. The results show that the supervised mesoscopic simulations of both Newtonian fluids and non-Newtonian bloods converge to reference solutions after a few iterations. Physical quantities of interest including velocity, wall shear stress and flowrate are computed to compare against those of reference solutions, showing a less than 1% relative error on flowrate in the Newtonian flow and a less than 3% relative error in the non-Newtonian blood flow. The proposed method is then applied to a large-scale mesoscopic simulation of microvessel blood flow in a zebrafish hindbrain for temporal acceleration. The three-dimensional geometry of the vasculature is constructed directly from the images of live zebrafish under a confocal microscope, resulting in a complex vascular network with 95 branches and 57 bifurcations. The time-dependent blood flow from heartbeats in this realistic vascular network of zebrafish hindbrain is simulated using dissipative particle dynamics as the mesoscopic model, which is supervised by a one-dimensional blood flow model (continuum-based model) in multiple temporal sub-domains. The computational analysis shows that the resulting microvessel blood flow converges to the reference solution after only two iterations. The proposed method is suitable for long-time mesoscopic simulations with complex fluids and geometries. It can be readily combined with classical spatial decomposition for further acceleration.