title: Program Code Generator for Cardiac Electrophysiology Simulation with Automatic PDE Boundary Condition Handling.
abstract: Clinical and experimental studies involving human hearts can have certain limitations. Methods such as computer simulations can be an important alternative or supplemental tool. Physiological simulation at the tissue or organ level typically involves the handling of partial differential equations (PDEs). Boundary conditions and distributed parameters, such as those used in pharmacokinetics simulation, add to the complexity of the PDE solution. These factors can tailor PDE solutions and their corresponding program code to specific problems. Boundary condition and parameter changes in the customized code are usually prone to errors and time-consuming. We propose a general approach for handling PDEs and boundary conditions in computational models using a replacement scheme for discretization. This study is an extension of a program generator that we introduced in a previous publication. The program generator can generate code for multi-cell simulations of cardiac electrophysiology. Improvements to the system allow it to handle simultaneous equations in the biological function model as well as implicit PDE numerical schemes. The replacement scheme involves substituting all partial differential terms with numerical solution equations. Once the model and boundary equations are discretized with the numerical solution scheme, instances of the equations are generated to undergo dependency analysis. The result of the dependency analysis is then used to generate the program code. The resulting program code are in Java or C programming language. To validate the automatic handling of boundary conditions in the program code generator, we generated simulation code using the FHN, Luo-Rudy 1, and Hund-Rudy cell models and run cell-to-cell coupling and action potential propagation simulations. One of the simulations is based on a published experiment and simulation results are compared with the experimental data. We conclude that the proposed program code generator can be used to generate code for physiological simulations and provides a tool for studying cardiac electrophysiology.
authors.affiliation: Department of Bioinformatics, College of Life Sciences, Ritsumeikan University, Shiga, Japan.
authors.forename: Florencio Rusty
authors.initials: FR
authors.lastname: Punzalan
authors.affiliation: Department of Computer Science, College of Information Science and Engineering, Ritsumeikan University, Shiga, Japan.
authors.forename: Yoshitoshi
authors.initials: Y
authors.lastname: Kunieda
authors.affiliation: Department of Bioinformatics, College of Life Sciences, Ritsumeikan University, Shiga, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Amano
mesh_terms: D000465:Algorithms; D054849:Cardiac Electrophysiology / Q000379:methods*; D003198:Computer Simulation; D006801:Humans; D008564:Membrane Potentials / Q000502:physiology; D008962:Models, Theoretical; D009716:Numerical Analysis, Computer-Assisted; D013997:Time Factors