Facilitating arrhythmia simulation: the method of quantitative cellular automata modeling and parallel running

BackgroundMany arrhythmias are triggered by abnormal electrical activity at the ionic channel and cell level, and then evolve spatio-temporally within the heart. To understand arrhythmias better and to diagnose them more precisely by their ECG waveforms, a whole-heart model is required to explore the association between the massively parallel activities at the channel/cell level and the integrative electrophysiological phenomena at organ level.MethodsWe have developed a method to build large-scale electrophysiological models by using extended cellular automata, and to run such models on a cluster of shared memory machines. We describe here the method, including the extension of a language-based cellular automaton to implement quantitative computing, the building of a whole-heart model with Visible Human Project data, the parallelization of the model on a cluster of shared memory computers with OpenMP and MPI hybrid programming, and a simulation algorithm that links cellular activity with the ECG.ResultsWe demonstrate that electrical activities at channel, cell, and organ levels can be traced and captured conveniently in our extended cellular automaton system. Examples of some ECG waveforms simulated with a 2-D slice are given to support the ECG simulation algorithm. A performance evaluation of the 3-D model on a four-node cluster is also given.ConclusionsQuantitative multicellular modeling with extended cellular automata is a highly efficient and widely applicable method to weave experimental data at different levels into computational models. This process can be used to investigate complex and collective biological activities that can be described neither by their governing differentiation equations nor by discrete parallel computation. Transparent cluster computing is a convenient and effective method to make time-consuming simulation feasible. Arrhythmias, as a typical case, can be effectively simulated with the methods described.

[1]  P. Savard,et al.  Forward problem of electrocardiography: construction of human torso models and field calculations using finite element method , 1994, Medical and Biological Engineering and Computing.

[2]  Stephen Wolfram,et al.  Cellular automata as models of complexity , 1984, Nature.

[3]  A. Noma,et al.  Reconstruction of sino-atrial node pacemaker potential based on the voltage clamp experiments. , 1980, The Japanese journal of physiology.

[4]  M Delmar,et al.  Ionic Mechanisms of Electrotonic Inhibition and Concealed Conduction in Rabbit Atrioventricular Nodal Myocytes , 1993, Circulation.

[5]  C. Luo,et al.  A dynamic model of the cardiac ventricular action potential. I. Simulations of ionic currents and concentration changes. , 1994, Circulation research.

[6]  C S Henriquez,et al.  Influence of dynamic gap junction resistance on impulse propagation in ventricular myocardium: a computer simulation study. , 2001, Biophysical journal.

[7]  J. Dana Eckart Cellang 2.0: language reference manual , 1992, SIGP.

[8]  P Siregar,et al.  A cellular automata model of the heart and its coupling with a qualitative model. , 1996, Computers and biomedical research, an international journal.

[9]  Michael J. Ackerman,et al.  The Visible Human Project™: A Resource for Anatomical Visualization , 1998, MedInfo.

[10]  G. Huiskamp,et al.  Simulation of depolarization in a membrane-equations-based model of the anisotropic ventricle , 1998, IEEE Transactions on Biomedical Engineering.

[11]  J. Zhang,et al.  Reconstruction of Cardiac Ventricular Geometry and Fiber Orientation Using Magnetic Resonance Imaging , 2000, Annals of Biomedical Engineering.

[12]  Jack Dongarra,et al.  MPI: The Complete Reference , 1996 .

[13]  R M Gulrajani,et al.  The inverse problem in electrocardiography: solutions in terms of equivalent sources. , 1988, Critical reviews in biomedical engineering.

[14]  A L Bardou,et al.  Modeling of cardiac electrophysiological mechanisms: from action potential genesis to its propagation in myocardium. , 1996, Critical reviews in biomedical engineering.

[15]  Hao Zhu,et al.  Asynchronous adaptive time step in quantitative cellular automata modeling , 2004, BMC Bioinformatics.

[16]  O P Gandhi,et al.  Power deposition in the head and neck of an anatomically based human body model for plane wave exposures. , 1998, Physics in medicine and biology.

[17]  J. Clark,et al.  Mathematical model of an adult human atrial cell: the role of K+ currents in repolarization. , 1998, Circulation research.

[18]  R J Cohen,et al.  Cellular automata models for reentrant arrhythmias. , 1990, Journal of electrocardiology.

[19]  S. Rush,et al.  A Practical Algorithm for Solving Dynamic Membrane Equations , 1978, IEEE Transactions on Biomedical Engineering.

[20]  Rohit Chandra,et al.  Parallel programming in openMP , 2000 .

[21]  G. Gintant,et al.  Heterogeneity within the ventricular wall. Electrophysiology and pharmacology of epicardial, endocardial, and M cells. , 1991, Circulation research.

[22]  P S Chen,et al.  Effects of myocardial fiber orientation on the electrical induction of ventricular fibrillation. , 1993, The American journal of physiology.

[23]  JoAnn E. Manson,et al.  Prospective Study of Sudden Cardiac Death Among Women in the United States , 2003, Circulation.

[24]  Cristopher Moore,et al.  New constructions in cellular automata , 2003 .

[25]  William M. Smith,et al.  Distributed computing for membrane-based modeling of action potential propagation , 2000, IEEE Transactions on Biomedical Engineering.

[26]  D. Durrer,et al.  Total Excitation of the Isolated Human Heart , 1970, Circulation.

[27]  G B Ermentrout,et al.  Cellular automata approaches to biological modeling. , 1993, Journal of theoretical biology.

[28]  G Plank,et al.  Computational tools for modeling electrical activity in cardiac tissue. , 2003, Journal of electrocardiology.

[29]  H. Frederick Nijhout,et al.  Pattern Formation In The Physical And Biological Sciences , 1997 .

[30]  C. H. Barbosa Simulation of a plane wavefront propagating in cardiac tissue using a cellular automata model. , 2003, Physics in medicine and biology.

[31]  F. Cappuccio,et al.  Variant of SCN5A Sodium Channel Implicated in Risk of Cardiac Arrhythmia , 2002, Science.

[32]  R Vogel,et al.  Mathematical model of vertebrate gap junctions derived from electrical measurements on homotypic and heterotypic channels , 1998, The Journal of physiology.

[33]  P Wach,et al.  The antiarrhythmic effect of verapamil on atrioventricular re-entry in the Wolff-Parkinson-White syndrome: a computer model study. , 1996, International journal of bio-medical computing.

[34]  Yongmin Kim,et al.  On the contribution of volume currents to the total magnetic field resulting from the heart excitation process: a simulation study , 1996, IEEE Transactions on Biomedical Engineering.

[35]  C. Luo,et al.  A model of the ventricular cardiac action potential. Depolarization, repolarization, and their interaction. , 1991, Circulation research.

[36]  Lorraine G. Olson,et al.  A new method for incorporating weighted temporal and spatial smoothing in the inverse problem of electrocardiography , 2002, IEEE Transactions on Biomedical Engineering.

[37]  A. McCulloch,et al.  Nonuniform Muscle Fiber Orientation Causes Spiral Wave Drift in a Finite Element Model of Cardiac Action Potential Propagation , 1994, Journal of cardiovascular electrophysiology.

[38]  D. Noble,et al.  Reconstruction of the electrical activity of cardiac Purkinje fibres. , 1975, The Journal of physiology.

[39]  Y Rudy,et al.  Electrophysiologic effects of acute myocardial ischemia. A mechanistic investigation of action potential conduction and conduction failure. , 1997, Circulation research.

[40]  N V Thakor,et al.  Electrophysiologic models of heart cells and cell networks. , 1998, IEEE engineering in medicine and biology magazine : the quarterly magazine of the Engineering in Medicine & Biology Society.

[41]  J. Jalife,et al.  Cardiac Electrophysiology: From Cell to Bedside , 1990 .

[42]  E. Johnson,et al.  Fast sodium current in cardiac muscle. A quantitative description. , 1980, Biophysical journal.

[43]  H. Gutowitz Cellular automata: theory and experiment : proceedings of a workshop , 1991 .

[44]  M. Burgess,et al.  Computer simulations of three-dimensional propagation in ventricular myocardium. Effects of intramural fiber rotation and inhomogeneous conductivity on epicardial activation. , 1993, Circulation research.

[45]  Karl A. Tomlinson,et al.  Cardiac Microstructure: Implications for Electrical Propagation and Defibrillation in the Heart , 2002, Circulation research.