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

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.

Automated summary

The study highlights the importance of mesoscopic simulations in understanding the cellular basis of diseases. A multiscale parareal algorithm is proposed to accelerate mesoscopic simulations in the time domain, demonstrating its effectiveness through case studies.