BeatBox - HPC Environment for Biophysically and Anatomically Realistic Cardiac Simulations

Lead Research Organisation: University of Exeter
Department Name: Engineering Computer Science and Maths

Abstract

Despite over a century's study, the trigger mechanisms of cardiac arrhythmias are poorly understood. Even modern experimental methods do not provide sufficient temporal and spacial resolution to trace the development of fibrillation in samples of cardiac tissue, not to mention the heart in vivo. Advances in human genetics provide information on the impact of certain genes on cellular activity, but do not explain the resultant mechanisms by which fibrillation arises. Thus, for some genetic cardiac diseases, the first presenting symptom is death.Computer simulations of electrical activity in cardiac tissue have already led to developments in our understanding of heart fibrillation and sudden cardiac death and their impact is expected to increase significantly as we approach the ultimate goal of whole-heart modelling. Modelling the propagation of Action Potential through cardiac tissue is computationally expensive due to the huge number of equations per cell and the vast spacial and temporal scales required. The complexity of the problem encompasses the description of ionic currents underlying excitation of a single cell through the inhomogeneity of the tissue to the complex geometry of the whole heart. The timely running of computational models of cardiac tissue is increasingly dependent on the effective use of High Performance Computing (HPC). Current state of the art cardiac simulation tools are limited either by the availability of modern, detailed models, or by their ease of use. The miscellany of current model implementations leads many researchers to develop their own ad-hoc software, preventing them from both utilising the power of HPC effectively, and from collaborating fluidly. It is, therefore, impeding scientific progress.The aim of this project is to develop an HPC environment for biophysically and anatomically realistic simualtion of cardiac activity, an adaptable and extensible framework with which High Performance Computing may be harnessed by researchers.

Planned Impact

The proposed project is fundamental research, and it is expected that its economic and public health impact will be not immediate, but via subsequent research, so immediate beneficiaries are most likely to be academic. The impact on wellbeing and economy of the UK will depend on the results that are yet to be obtained, both within this project and by subsequent research, and therefore by necessity are highly speculative. I. Specifically, we identify the following groups of immediate potential beneficiaries: - Researchers working in mathematical modelling of cardiac arrhythmias. Benefits: the new research software tool that we develop, which will complement the existing software; our results obtained with this software which will stimulate further research. - Cardiac electrophysiology: experimentalists studying re-entrant arrhythmia in cell cultures, tissues and animals. Benefits: predictions obtained by mathematical modelling using the software we develop, both by ourselves and by other researchers, which are testable experimentally and which are potentially relevant for biomedical applications. - Nonlinear science: researchers working in the theory and applications of excitable media and in the theory of other nonlinear self-organized dissipative structures. For this group, the benefits will be of a similar kind to the first group above. Excitable media in general, and spiral and scroll waves in particular, have been predicted and observed in a wide variety of spatially extended thermodynamically non-equilibrium systems of various physical, chemical and biological origin. The software we develop will be easily adaptable to those kinds of models, and most advantages provided by it will be relevant in those applications, too. - Applied mathematicians and software developers. This group are also likely beneficiaries, as the practical solutions we will develop may be applicable in other areas. For the groups above, the ways to ensure the delivery of benefits will be traditional, via providing free access to the software, advice on its use, and publishing research journals and relevant conferences. The associated time scales are minimal, as the benefits will start immediately upon publication and we choose journals that publish quickly. II. The impact on public health and wealth creation will be through long-term potential beneficiaries. Speculatively, if our study will lead to the expected improvements in efficiency of the resonant pacing as a tool for low-voltage defibrillation, or deeper understanding of the Sick Sinus Syndrome, such long-term beneficiaries would be: - companies that manufacture pacemakers, operating theatre and implantable defibrillators, who will be able to get new pacing protocols to improve efficiency or decrease harmful side-effects of the devices and widen their use; - pharmaceutical companies that manufature antiarrhythmic drugs, who will develop new classes of drugs based on the new understanding of the dynamics of cardiac arrhythmia; - clinicians and the NHS, who will have new more efficients methods of treatment of cardiac arrhythmia at their disposal, with fewer harmful side-effects, and lower treatmeant and care costs. - cardiac patients, whose life expectancy and quality of life will improve, - general public, through tax revenue of the industries involved, lower burden on NHS and prolongation of the active life of the ageing population. These benefits will be delivered indirectly via subsequent, more applicable research projects, both by other researchers and by ourselves, that will utilize the results of this project. The timescales here are hardly predictable but in any case it will be many years, as is usually the case with new medical treatments. There is a possibility that some of the results obtained with this project will be directly exploitable. In such cases, we will contact relevant University offices.

Publications

10 25 50

Related Projects

Project Reference Relationship Related To Start End Award Value
EP/I029664/1 01/09/2011 31/07/2012 £217,270
EP/I029664/2 Transfer EP/I029664/1 01/08/2012 31/08/2013 £130,041
 
Description - Beatbox has been transferred from an in-house tool into a publicly available software distributed freely under GNU license, with auto-configuration infrastructure to be easily adaptable for new architecture, detailed user manual, automatic tests, and example scripts illustrating its use.

- New technical features have been incorporated into the software: new solvers (multigrid elliptic solver for the bidomain model, alternating-direction timestepper for the diffusion); several new local kinetics/cardiac excitation kinetics models, both from CELLML and implemented from scratch or based on author code; examples of new anatomical models (human atrium, rabbit heart), including those that originate from MRI datasets, and new output and postprocessing facilities.

- A workshop for the current and prospective users of Beatbox has been held, with presentations explaining principles and software solutions befhind it, as well as hands-in tutorials.

- The software has been used in ongoing research which resulted in a number of journal publications and conference presentations. Some of the research results would be difficult or impossible to obtain with other existing software, for instance, arrythmogenic effect of nontrivial spatio-temporal changes of cardiac tissue properties (reperfusion arrhythmias) and complex behaviour of scroll waves in realistic atrial geomery subject to feedback-controlled low-voltage stimulation.
Exploitation Route The software is usable by pharmaceutical and biomedical industries, say for "in silico" testing of new drugs or ICDs. It is also usable for education purposes, say by students of electrophysiology, both within and outside academia. Finally, some of the programming solutions are usable in software technology. The software is distributed freely under GNU license through author's website.

The research results are disseminated in the usual way, through open publications, conference presentations and personal contacts of the authors.
Sectors Digital/Communication/Information Technologies (including Software),Education,Pharmaceuticals and Medical Biotechnology

URL http://empslocal.ex.ac.uk/people/staff/vnb262/projects/BeatBox/
 
Description EPSRC Centre for Predictive Modelling in Healthcare
Amount £2,008,955 (GBP)
Funding ID EP/N014391/1 
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Academic/University
Country United Kingdom
Start 01/2016 
End 12/2019
 
Description EPSRC Overseas Travel grant EP/P008690/1 "Research Collaboration Visit to the Auckland Bioengineering Institute, New Zealand."
Amount £15,890 (GBP)
Funding ID EP/P008690/1 
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Academic/University
Country United Kingdom
Start 08/2016 
End 11/2016
 
Description EPSRC POEMS Network Travel grant
Amount £750 (GBP)
Organisation University of Sheffield 
Sector Academic/University
Country United Kingdom
Start 08/2016 
End 09/2016
 
Description EPCC 
Organisation University of Edinburgh
Country United Kingdom 
Sector Academic/University 
PI Contribution Joint research and joint research outputs
Collaborator Contribution Joint research and joint research outputs
Impact Software 1. BeatBox software http://empslocal.ex.ac.uk/people/staff/vnb262/software/BeatBox/ Publications 1. S. Kharche, A. Jackson, I. V. Biktasheva and V. N. Biktashev, "Simulation of Low Energy Defibrillation Using a Novel Cardiac Simulation Environment, Beatbox", Digital Research 2012, September 10-12, Oxford, UK. Workshop 1. BeatBox users workshop took place in Manchester on June 24-25, 2013. See the Workshop materials http://wiener.ex.ac.uk/~vadim/projects/BeatBox/workshop/ Scalability studies 1. The presentation at the users' workshop (PDF, 1.2M) http://wiener.ex.ac.uk/~vadim/projects/BeatBox/workshop/beatbox-scalability-profiling.pdf 2. A more recent study http://empslocal.ex.ac.uk/people/staff/vnb262/projects/BeatBox/scalability/index.html
Start Year 2010
 
Description EPSRC POEMS Network Travel grant, University of Sheffield, UK 
Organisation University of Sheffield
Department Faculty of Engineering
Country United Kingdom 
Sector Academic/University 
PI Contribution Research visit to the Auckland Bioengineering Institute, University of Auckland, August- September 2016.
Collaborator Contribution £750 towards the cost of Research visit to the Auckland Bioengineering Institute, University of Auckland, August- September 2016.
Impact Research visit to the Auckland Bioengineering Institute, University of Auckland, August- September 2016.
Start Year 2016
 
Description Exeter 
Organisation University of Exeter
Country United Kingdom 
Sector Academic/University 
PI Contribution joint research, participation in and organisation of mini symposia, joint funding applications
Collaborator Contribution joint research, participation in and organisation of mini symposia, joint funding applications
Impact Grant applications 1. EPSRC Grant application EP/L005387/1 "Meander and drift of spiral and scroll waves", 2013. 2. EPSRC project EP/K038915/1"BeatBox - HPC Environment for Biophysically and Anatomically Realistic Cardiac Simulations", 2010. 3. BBSRC grant application "BB/L018349/1 "HPC simulation environment for high-resolution intracellular Ca dynamics", 2013. Papers I. V. Biktasheva, H. Dierckx, and V. N. Biktashev, "Drift of scroll waves in thin layers caused by thickness features", submitted to Phys Rev Lett, 2014. arXiv:1408.3654 [nlin.PS] 2. Sanjay R. Kharche, Irina V. Biktasheva, Gunnar Seemann, Henggui Zhang, and Vadim N. Biktashev, "Anatomy Induced Drift of Spiral Waves in the Human Atrium", submitted to BMRI, 2014. 3. Vadim N. Biktashev, Irina V. Biktasheva, "Dynamics of filaments of scroll waves", in Engineering of Chemical Complexity II, eds. A.S.Mikhailov and G.Ertl, pp 221-238, World Scientific, Singapore, 2014. arXiv:1403.6654v1 [nlin.PS] 4. S.R. Kharche, I.V. Biktasheva, H.G. Zhang, and V.N. Biktashev, "Simulating the Role of Anisotropy in Human Atrial Cardioversion", The 35th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC'13), Osaka, Japan, IEEE Engineering in Medicine and Biology Society, pp 6838-41, 2013. 5. S.R. Kharche, J. Beling, I.V. Biktasheva, H.G. Zhang, and V.N. Biktashev, "Simulating Cell Apoptosis Induced Sinus Node Dysfunction", The 35th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC'13), Osaka, Japan, IEEE Engineering in Medicine and Biology Society, pp 6842-5, 2013. 6. S.R. Kharche, T. Stary, I.V. Biktasheva, H. Zhang, and V.N. Biktashev, "Computer simulation of the role of fibre orientation in cardioversion of chronic atrial fibrillation", Journal of Electrocardiology 46(4), e6-e7I, 2013. 7. I.V. Biktasheva, N A. Sarvazyan, and V.N. Biktashev, "Dynamics of Scroll Waves of Excitation in a Mathematical Model of Ischaemic Border Zone" , COMPUTING IN CARDIOLOGY, 39:445-448, 2012. 8. S. Kharche, I. Biktasheva, G. Seemann, H. Zhang, and V. Biktashev, "Cardioversion Using Feedback Stimuli in Human Atria" , COMPUTING IN CARDIOLOGY, 39:133-136, 2012. Conference/Minisymposia 1. Mini symposium "Dynamics of Spiral Waves - Parts I and II", SIAM CONFERENCE ON APPLICATIONS OF DYNAMICAL SYSTEMS 2013 (DS13), Snow Bird, Utah, USA. 2. Minisymposium "Dynamics of Spiral and Scroll Waves in Cardiac Tissue", SIAM CONFERENCE ON Nonlinear Waves and Coherent Structures 2014 (DS14), Cambridge, UK.
Start Year 2012
 
Description Manchester 
Organisation University of Manchester
Department School of Physics and Astronomy Manchester
Country United Kingdom 
Sector Academic/University 
PI Contribution Joint research and joint research outputs, collaboration on Beabox project
Collaborator Contribution Joint research and joint research outputs, collaboration on Beabox project
Impact Software 1. BeatBox - HPC Environment for Biophysically and Anatomically Realistic Cardiac Simulations Publications 1. S.R. Kharche, T. Stary, I. V. Biktasheva, A. J. Workman, A. C.Rankin, A. V. Holden and H. Zhang, "Computer Simulation of the Anti-arrhythmic Effects of Chronic ß-blocker Treatment on Human Atrial Electrophysiology", submitted to Europace journal. Presentations 1. S. Kharche, I. Biktasheva, G. Seemann, H.G. Zhang, V. Biktashev, "Cardioversion Using Feedback Stimuli in Human Atria", CMMB meeting "Multiscale Modelling in Medicine and Biology", September 3-5, 2012, Nottinham, UK 2. S. Kharche, I. Biktasheva, G. Seemann, H. Zhang, and V. Biktashev, "Cardioversion Using Feedback Stimuli in Human Atria", 39th Annual Conference on Computing in Cardiology, , September 9-12, 2012, Krakow, Poland; Computing in Cardiology 39:133-136, 2012. 3. S. Kharche, I. Biktasheva, G. Seemann, H. Zhang, V. Biktashev "Low Energy Cardioversion Using Feedback Stimuli in Human Atria", Multiscale Modelling in Medicine and Biology: 3-5 September 2012, Centre for Mathematical Medicine and Biology, University of Nottingham. 4. S. R. Kharche, T. Stary, I. V. Biktasheva, H. Zhang and V. N. Biktashev, "The role of fibre orientation in cardioversion of chronic atrial fibrillation: a simulation study", Proc 37th IUPS (2013) 5. S. R. Kharche1, T. Stary, I. V. Biktasheva, H. Zhang and V. Biktashev, "Simulating cell apoptosis induced sinus node dysfunction", Proc 37th IUPS (2013) 6. S. R. Kharche, T. Stary, I. V. Biktasheva, A. J. Workman, A. C. Rankin, A. V. Holden and H. Zhang, "Effects of human atrial ionic remodelling by ß-blocker therapy on mechanisms of atrial fibrillation: a computer simulation" Journal of Electrocardiology, Volume 46, Issue 4 , Page e6, July 2013 7. S. R. Kharche, T. Stary, I. V. Biktasheva, H. Zhang, V. N. Biktashev "Computer simulation of the role of fibre orientation in cardioversion of chronic atrial fibrillation" Journal of Electrocardiology, Volume 46, Issue 4 , Pages e6-e7, July 2013 Workshop 1. BeatBox users workshop took place in Manchester on June 24-25, 2013. See the Workshop materials at http://wiener.ex.ac.uk/~vadim/projects/BeatBox/workshop/ Scalability studies 1. The presentation at the users' workshop (PDF, 1.2M) http://wiener.ex.ac.uk/~vadim/projects/BeatBox/workshop/beatbox-scalability-profiling.pdf 2. A more recent study http://empslocal.ex.ac.uk/people/staff/vnb262/projects/BeatBox/scalability/index.html
 
Description Research Collaboration Visit to the Auckland Bioengineering Institute, New Zealand. 
Organisation University of Auckland
Department Auckland Bioengineering Institute (ABI)
Country New Zealand 
Sector Academic/University 
PI Contribution Research Collaboration Visit to the Auckland Bioengineering Institute, New Zealand.
Collaborator Contribution host for Research Collaboration Visit to the Auckland Bioengineering Institute, New Zealand.
Impact Invited Lecture "Wave-particle duality of dissipative vortices and implications for cardiology" (Video http://www.abi.auckland.ac.nz/en/about/events/2016/wave-particle-duality-of-dissipative-vortices-and-implications-f.html) , in Auckland Bioengineering Institute seminar series , 30 August 2016, University of Auckland, New Zealand.
Start Year 2016
 
Title BeatBox - HPC Environment for Biophysically and Anatomically Realistic Cardiac Simulations 
Description BeatBox is a unified cardiac simulation environment that can be used to perform biophysically and anatomically realistic cardiac simulations. BeatBox provides: A script interpreter to allow flexibility in setting up numerical experiments, thus eliminating the requirement to manipulate low level code and lengthy recompilations each time the simulation schedule is altered or a new simulation is constructed; Serial and parallel (MPI) simulations; A collection of ODE solvers (Euler, RK4); A collection of finite differences PDE solvers for isotropic and anisotropic tissue models on regular and irregular boundary domains; A major selection of CellML cardiac models and other excitable media models; Multiscale tissue modelling: 0-dimensional individual cell simulation, 1-dimensional fibre, 2-dimensional sheet and 3-dimensional slab of tissue, up to anatomically realistic whole heart simulations using the provided tissue model repository. Run time measurements including tip tracing, filament tracing, ECG, samples of any variables; Extensibility: You can easily plug in your own solvers as well as cell kinetics models and tissue models (e.g. MRI finite difference meshes) into BeatBox's highly structured code. BeatBox is free software and is distributed under version 3 (or later) of the GNU public licence. 
Type Of Technology Software 
Year Produced 2013 
Open Source License? Yes  
Impact "Study the Impact of the Current Rectangular Pulses at a ten Tusscher-Panfilov Model of Human Ventricular Myocyte", Boris B. Gorbunov, in preparation for Journal of Physics D - Applied Physics 
URL https://github.com/beatbox-heart
 
Description Lecture "Wave-particle duality of dissipative vortices and implications for cardiology", in Auckland Bioengineering Institute seminar series , 30 August 2016, University of Auckland, New Zealand. 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact Invited Lecture "Wave-particle duality of dissipative vortices and implications for cardiology" (Video http://www.abi.auckland.ac.nz/en/about/events/2016/wave-particle-duality-of-dissipative-vortices-and-implications-f.html) ,
in Auckland Bioengineering Institute seminar series , 30 August 2016, University of Auckland, New Zealand.
Year(s) Of Engagement Activity 2016
URL http://www.abi.auckland.ac.nz/en/about/events/2016/wave-particle-duality-of-dissipative-vortices-and...