Multi-scale simulations of cardiac electrophysiology and mechanics using the University of Tokyo heart simulator

Abstract

The importance and need for an integrative mathematical modeling approach in the biological and medical fields is currently well recognized. Such an approach is crucial in understanding the complexity of hierarchical biological systems increasingly revealed by active researches in molecular and cellular biology. Particularly in cardiac functioning, modeling must cover such diverse phenomena as solid mechanics, fluid dynamics, electricity and biochemistry. Recent advancements in computational science and the development of high-performance computers have enabled the creation of multi-scale, multi-physics simulation heart models using the finite element method. Although whole heart or ventricular models of electrophysiology involving electro-mechanics with or without blood flow dynamics have been reported, to our knowledge no single model has yet succeeded in completely reproducing the behavior of the heart from the subcellular to whole organ levels. In this article, we present a brief methodology-focused review on some of the essential components for multi-scale, multi-physics heart modeling. A perspective of heart modeling in the era of high performance computing is also presented.

Integrated Heart—Coupling multiscale and multiphysics models for the simulation of the cardiac function

“…Several groups around the world [142,212,243,260] are using massively parallel computing and especially graphics processing units to speed up the computations in realistic heart geometries using highly-detailed physiological electrophysiology models, with the ultimate goal of providing near realtime simulations. Alternatively, other efforts point to reducing the complexity of the underlying cellular models [126].…”

“…A number of fully coupled electro-mechano-fluidic ventricle models [265,272] that incorporate highly detailed mechanical contraction models [186], crossbridge dynamics, and the interaction between the ventricles and the atria [243], have surfaced in recent years. While many of these "heart simulators" are constructed for the purposes of training cardiologists rather than performing clinically relevant studies, full-heart models are increasingly being targeted at patient-specific simulations by adding several degrees of personalization [170,228,250].…”

Taking Mathematics to Heart

“…Software development has also progressed quite rapidly in the last few years. As for today, the UT heart simulator from the group of T. Hisada (Tokyo University) [5] has provided perhaps the most comprehensive simulations of cardiac function.…”

Multi-scale Modeling of the Cardiovascular System: Disease Development, Progression, and Clinical Intervention

“…A major challenge is to develop methodologies and new approaches to integrate data in physiological networks to reveal emergent mechanisms of disease and to facilitate prediction and development of therapeutic interventions 2, 11, 76, 91, 103, 110, 136, 145 . No reasonable, efficient and cost-effective experimental or clinical strategy that can achieve these goals is currently available .…”