@article {, title = {Control and anticontrol of chaos in fractional-order models of Diabetes, HIV, Dengue, Migraine, Parkinson{\textquoteright}s and Ebola virus diseases}, journal = {Chaos, Solitons \& Fractals}, volume = {153}, year = {2021}, month = {12/2021}, url = {https://scholar.google.com/citations?view_op=view_citation\&hl=en\&user=jKiNd-0AAAAJ\&sortby=pubdate\&citation_for_view=jKiNd-0AAAAJ:hCrLmN-GePgC}, author = {Manashita Borah and Debanita Das and Antara Gayan and Flavio Fenton and Elizabeth Cherry} } @article {, title = {Interactive 3D Human Heart Simulations on Segmented Human MRI Hearts}, year = {2021}, url = {https://www.cinc.org/2021/Program/accepted/261.pdf}, author = {John P. Berman and FLAVIO H. FENTON and ELIZABETH M. CHERRY and Tinen Iles and Paul A. Iaizzo and Abouzar Kaboudian} } @article {, title = {A Network-based Cardiac Electrophysiology Simulator with Realistic Signal Generation and Response to Pacing Maneuvers}, journal = {Computing in Cardiology}, year = {2021}, url = {https://www.cinc.org/2021/Program/accepted/294_Preprint.pdf}, author = {Shahriar Iravanian and Ilija Uzelac and Abouzar Kaboudian and Jonathan Langberg and Flavio Fenton} } @article {, title = {Optimizing low-energy anti-fibrillation pacing: Lessons from a cellular automaton model}, journal = {arXiv preprint arXiv:2109.10861}, year = {2021}, month = {09/2021}, url = {https://scholar.google.com/citations?view_op=view_citation\&hl=en\&user=jKiNd-0AAAAJ\&sortby=pubdate\&citation_for_view=jKiNd-0AAAAJ:FPJr55Dyh1AC}, author = {Noah DeTal and Flavio Fenton} } @article {, title = {Quantifying arrhythmic long QT effects of hydroxychloroquine and azithromycin with whole-heart optical mapping and simulations}, journal = {Heart Rhythm O2}, volume = {2}, year = {2021}, month = {08/2021}, url = {https://scholar.google.com/citations?view_op=view_citation\&hl=en\&user=jKiNd-0AAAAJ\&sortby=pubdate\&citation_for_view=jKiNd-0AAAAJ:Ug5p-4gJ2f0C}, author = {Ilija Uzelac and Abouzar Kaboudian and Shahriar Iravanian and Jimena G Siles-Paredes and James C Gumbart and Hiroshi Ashikaga and Neal Bhatia and Robert F Gilmour Jr and Elizabeth M Cherry and Flavio H Fenton} } @article {, title = {Terminating spiral waves with a single designed stimulus: Teleportation as the mechanism for defibrillation}, journal = {arXiv preprint arXiv:2109.10850}, year = {2021}, month = {09/2021}, url = {https://scholar.google.com/citations?view_op=view_citation\&hl=en\&user=jKiNd-0AAAAJ\&sortby=pubdate\&citation_for_view=jKiNd-0AAAAJ:ClCfbGk0d_YC}, author = {Noah DeTal and Abouzar Kaboudian and Flavio Fenton} } @article {, title = {Accelerating simulations of cardiac electrical dynamics through a multi-GPU platform and an optimized data structure}, journal = {Concurrency and Computation: Practice and Experience}, volume = {32}, year = {2020}, month = {03/2020}, url = {https://scholar.google.com/citations?view_op=view_citation\&hl=en\&user=jKiNd-0AAAAJ\&cstart=20\&pagesize=80\&sortby=pubdate\&citation_for_view=jKiNd-0AAAAJ:vDijr-p_gm4C}, author = {Eduardo C Vasconcellos and Esteban WG Clua and Flavio H Fenton and Marcelo Zamith} } @article {, title = {Data-Driven Uncertainty Quantification for Cardiac Electrophysiological Models: Impact of Physiological Variability on Action Potential and Spiral Wave Dynamics}, journal = {Frontiers in physiology}, volume = {11}, year = {2020}, month = {11/2020}, url = {https://scholar.google.com/citations?view_op=view_citation\&hl=en\&user=jKiNd-0AAAAJ\&sortby=pubdate\&citation_for_view=jKiNd-0AAAAJ:tuHXwOkdijsC}, author = {Pras Pathmanathan and Suran K Galappaththige and Jonathan M Cordeiro and Abouzar Kaboudian and Flavio H Fenton and Richard A Gray} } @article {, title = {Excitable dynamics in neural and cardiac systems}, journal = {Communications in Nonlinear Science and Numerical Simulation}, volume = {86}, year = {2020}, month = {07/2020}, url = {https://scholar.google.com/citations?view_op=view_citation\&hl=en\&user=jKiNd-0AAAAJ\&sortby=pubdate\&citation_for_view=jKiNd-0AAAAJ:hMsQuOkrut0C}, author = {Roberto Barrio and Stephen Coombes and Mathieu Desroches and Flavio Fenton and Stefan Luther and Esther Pueyo} } @article {, title = {Fatal arrhythmias: another reason why doctors remain cautious about chloroquine/hydroxychloroquine for treating COVID-19}, journal = {Heart Rhythm}, volume = {17}, year = {2020}, month = {09/2020}, url = {https://scholar.google.com/citations?view_op=view_citation\&hl=en\&user=jKiNd-0AAAAJ\&sortby=pubdate\&citation_for_view=jKiNd-0AAAAJ:tYavs44e6CUC}, author = {Ilija Uzelac and Shahriar Iravanian and Hiroshi Ashikaga and Neal K Bhatia and Conner Herndon and Abouzar Kaboudian and James C Gumbart and Elizabeth M Cherry and Flavio H Fenton} } @article {, title = {Swarm Model Checking on the GPU}, journal = {International Journal on Software Tools for Technology Transfer}, year = {2020}, author = {R. DeFrancisco and S. Cho and M. Ferdman and S. A. Smolka} } @article {, title = {Timed Automata Benchmark Description}, journal = {arXiv preprint arXiv:2005.13151}, year = {2020}, author = {Fontana, Peter and Cleaveland, Rance} } @conference {, title = {Towards Automated Comprehension and Alignment of Cardiac Models at the System Invariant Level}, booktitle = {CSBio{\textquoteright}20: Proceedings of the Eleventh International Conference on Computational Systems-Biology and Bioinformatics}, year = {2020}, author = {Huang, Samuel and Diep, Madeline and Jang, Kuk and Cherry, Elizabeth M and Fenton, Flavio H and Cleaveland, Rance and Lindvall, Mikael and Mangharam, Rahul and Porter, Adam} } @article {, title = {Large-scale interactive numerical experiments of chaos, solitons and fractals in real time via GPU in a web browser}, journal = {Chaos, Solitons \& Fractals}, volume = {121}, year = {2019}, pages = {6{\textendash}29}, doi = {10.1016/j.chaos.2019.01.005}, url = {https://doi.org/10.1016/j.chaos.2019.01.005}, author = {Abouzar Kaboudian and ELIZABETH M. CHERRY and FLAVIO H. FENTON} } @conference {, title = {Parallel Acceleration on Removal of Optical Mapping Baseline Wandering}, booktitle = {2019 Computing in Cardiology (CinC)}, year = {2019}, month = {09/2019}, publisher = {IEEE}, organization = {IEEE}, url = {https://scholar.google.com/citations?view_op=view_citation\&hl=en\&user=jKiNd-0AAAAJ\&cstart=20\&pagesize=80\&sortby=pubdate\&citation_for_view=jKiNd-0AAAAJ:L7CI7m0gUJcC}, author = {Ilija Uzelac and Shahriar Iravanian and Flavio H Fenton} } @article {, title = {Probabilistic reachability for multi-parameter bifurcation analysis of cardiac alternans}, journal = {Theoretical Computer Science}, volume = {765}, year = {2019}, pages = {158{\textendash}169}, author = {Islam, Md Ariful and Cleaveland, Rance and Fenton, Flavio H and Grosu, Radu and Jones, Paul L and Smolka, Scott A} } @article {, title = {Real-time interactive simulations of large-scale systems on personal computers and cell phones: Toward patient-specific heart modeling and other applications}, journal = {Science Advances}, volume = {5}, year = {2019}, pages = {eaav6019}, doi = {10.1126/sciadv.aav6019}, url = {https://doi.org/10.1126/sciadv.aav6019}, author = {Abouzar Kaboudian and ELIZABETH M. CHERRY and FLAVIO H. FENTON} } @article {, title = {Simulating waves, chaos and synchronization with a microcontroller}, journal = {Chaos: An Interdisciplinary Journal of Nonlinear Science}, volume = {29}, year = {2019}, month = {12/2019}, url = {https://scholar.google.com/citations?view_op=view_citation\&hl=en\&user=jKiNd-0AAAAJ\&cstart=20\&pagesize=80\&sortby=pubdate\&citation_for_view=jKiNd-0AAAAJ:BUYA1_V_uYcC}, author = {Andrea J Welsh and Cristian Delgado and Casey Lee-Trimble and Abouzar Kaboudian and Flavio H Fenton} } @article {, title = {Spatiotemporal correlation uncovers characteristic lengths in cardiac tissue}, journal = {Physical Review E}, volume = {100}, year = {2019}, doi = {10.1103/physreve.100.020201}, url = {https://doi.org/10.1103/physreve.100.020201}, author = {Alessandro Loppini and Alessio Gizzi and Christian Cherubini and ELIZABETH M. CHERRY and FLAVIO H. FENTON and Simonetta Filippi} } @conference {, title = {Bisimulation in Behavioral Dynamical Systems and Generalized Synchronization Trees}, booktitle = {2018 IEEE Conference on Decision and Control (CDC)}, year = {2018}, publisher = {IEEE}, organization = {IEEE}, author = {Ferlez, James and Cleaveland, Rance and Marcus, Steven I} } @article {, title = {Discordant Alternans as a Mechanism for Initiation of Ventricular Fibrillation In Vitro}, journal = {Journal of the American Heart Association}, volume = {7}, year = {2018}, month = {09}, abstract = {

Background-{\textemdash}Ventricular tachyarrhythmias are often preceded by short sequences of premature ventricular complexes. In a previous study, a restitution-based computational model predicted which sequences of stimulated premature complexes were most likely to induce ventricular fibrillation in canines in vivo. However, the underlying mechanism, based on discordant-alternans dynamics, could not be verified in that study. The current study seeks to elucidate the mechanism by determining whether the spatiotemporal evolution of action potentials and initiation of ventricular fibrillation in in vitro experiments are consistent with model predictions.

Methods and Results-{\textemdash}Optical mapping voltage signals from canine right-ventricular tissue (n=9) were obtained simultaneously from the entire epicardium and endocardium during and after premature stimulus sequences. Model predictions of action potential propagation along a 1-dimensional cable were developed using action potential duration versus diastolic interval data. The model predicted sign-change patterns in action potential duration and diastolic interval spatial gradients with posterior probabilities of 91.1\%, and 82.1\%, respectively. The model predicted conduction block with 64\% sensitivity and 100\% specificity. A generalized estimating equation logistic-regression approach showed that model-prediction effects were significant for both conduction block (P\<191015, coefficient 44.36) and sustained ventricular fibrillation (P=0.0046, coefficient, 1.63) events.

Conclusions-{\textemdash}The observed sign-change patterns favored discordant alternans, and the model successfully identified sequences of premature stimuli that induced conduction block. This suggests that the relatively simple discordant-alternans-based process that led to block in the model may often be responsible for ventricular fibrillation onset when preceded by premature beats. These observations may aid in developing improved methods for anticipating block and ventricular fibrillation. (J Am Heart Assoc. 2018;7:e007898. DOI: 10.1161/JAHA.117.007898.)

}, keywords = {alternans, arrhythmia (mechanisms), computer-based model, electrophysiology, ventricular fibrillation}, doi = {10.1161/JAHA.117.007898}, author = {Munoz, Laura and R. M. Gelzer, Anna and Fenton, Flavio and Qian, Wei and Lin, WeiYe and F. Gilmour, Robert and F. Otani, Niels} } @article {, title = {Electromechanical vortex filaments during cardiac fibrillation}, journal = {Nature}, volume = {555}, year = {2018}, pages = {667+}, abstract = {

The self-organized dynamics of vortex-like rotating waves, which are also known as scroll waves, are the basis of the formation of complex spatiotemporal patterns in many excitable chemical and biological systems. In the heart, filament-like phase singularities5,6\ that are associated with three-dimensional scroll waves7\ are considered to be the organizing centres of life-threatening cardiac arrhythmias. The mechanisms that underlie the onset, maintenance and control14,15,16\ of electromechanical turbulence in the heart are inherently three-dimensional phenomena. However, it has not previously been possible to visualize the three-dimensional spatiotemporal dynamics of scroll waves inside cardiac tissues. Here we show that three-dimensional mechanical scroll waves and filament-like phase singularities can be observed deep inside the contracting heart wall using high-resolution four-dimensional ultrasound-based strain imaging. We found that mechanical phase singularities co-exist with electrical phase singularities during cardiac fibrillation. We investigated the dynamics of electrical and mechanical phase singularities by simultaneously measuring the membrane potential, intracellular calcium concentration and mechanical contractions of the heart. We show that cardiac fibrillation can be characterized using the three-dimensional spatiotemporal dynamics of mechanical phase singularities, which arise inside the fibrillating contracting ventricular wall. We demonstrate that electrical and mechanical phase singularities show complex interactions and we characterize their dynamics in terms of trajectories, topological charge and lifetime. We anticipate that our findings will provide novel perspectives for non-invasive diagnostic imaging and therapeutic applications.

}, doi = {https://doi.org/10.1038/nature26001}, author = {Jan Christoph and M. Chebbok and Carl Richter and Johannes Schr{\"o}der-Schetelig and Philip Bittihn and Seth Stein and Ilija Uzelac and FLAVIO H. FENTON and Gerd Hasenfuss and Robert F. Gilmour and Stefan Luther} } @article {, title = {Probabilistic reachability for multi-parameter bifurcation analysis of cardiac alternans}, journal = {Theoretical Computer Science}, year = {2018}, month = {02/2018}, abstract = {

Using a probabilistic reachability-based approach, we present a multi-parameter bifurcation analysis of electrical alternans in the two-current Mitchell{\textendash}Schaeffer (MS) cardiac-cell model. Electrical alternans is a phenomenon characterized by a variation in successive Action Potential Durations generated by a cardiac cell or tissue. Alternans are known to initiate re-entrant waves and are an important physiological indicator of an impending life-threatening arrhythmia such as ventricular fibrillation. The multi-parameter bifurcation analysis we perform identifies a bifurcation hypersurface in the MS model parameter space, such that a small perturbation to this region results in a transition from highly likely alternans to highly likely non-alternans behavior. Our approach to this problem rests on encoding alternans-like behavior in the MS model as a five-mode, multinomial hybrid automaton. To perform multi-parameter bifurcation analysis of cardiac alternans, we first treat the parameters in question as bounded random variables. We then apply a sophisticated guided-search-based probabilistic reachability analysis to compute a bounded bifurcation region (possibly very tight) that contains the bifurcation hypersurface (BH). Our probabilistic reachability analysis uses a technique that combines a δ-decision procedure with statistical tests. In the process of computing the bifurcation region, we further partition the parameter space into two more regions such that any valuation chosen from one of the regions will either produce alternans or non-alternans behavior with a probability greater than a user-defined threshold.

}, keywords = {Bifurcation analysis, Cardiac alternans, Cardiac modeling, Formal methods, Hybrid systems, Probabilistic reachability}, issn = {0304-3975}, doi = {https://doi.org/10.1016/j.tcs.2018.02.005}, url = {http://www.sciencedirect.com/science/article/pii/S0304397518300823}, author = {Md. Ariful Islam and Rance Cleaveland and FLAVIO H. FENTON and Radu Grosu and Paul L. Jones and Scott A. Smolka} } @conference {, title = {Bisimulation and Hennessy-Milner Logic for Generalized Synchronization Trees}, booktitle = {Proceedings Combined 24th International Workshop on Expressiveness in Concurrency and 14th Workshop on Structural Operational Semantics and 14th Workshop on Structural Operational Semantics, {EXPRESS/SOS} 2017, Berlin, Germany, 4th September 2017.}, year = {2017}, doi = {10.4204/EPTCS.255.3}, url = {https://doi.org/10.4204/EPTCS.255.3}, author = {James Ferlez and Rance Cleaveland and Steven I. Marcus} } @article {, title = {Corrections to "A Menagerie of Timed Automata"}, journal = {ACM Comput. Surv.}, volume = {50}, year = {2017}, pages = {42:1{\textendash}42:8}, keywords = {Timed automata, timed transition systems, transition systems}, issn = {0360-0300}, doi = {10.1145/3078809}, url = {http://doi.acm.org/10.1145/3078809}, author = {Keiren, Jeroen J. A. and Fontana, Peter and Cleaveland, Rance} } @conference {, title = {Data assimilation for cardiac electrical dynamics}, booktitle = {Proceedings of the 5th {International} {Conference} on {Computational} and {Mathematical} {Biomedical} {Engineering}}, year = {2017}, address = {Pittsburgh, PA}, abstract = {

New insights into the mechanisms underlying cardiac arrhythmias may be possible from a greater understanding of variables unobserved in experimental settings. When experimental observations are sparse, data assimilation can be effective at recovering a more complete system state estimate. We have recently shown using synthetic observations of one- and three-dimensional cardiac tissue that data assimilation can be used to recover state variables observed sparsely in space and time or unobserved. Here we extend these findings to show that data assimilation remains effective in reconstructing cardiac states with underlying system spatial heterogeneity and in the presence of significant model error.

}, author = {Cherry, E. M. and Cairns, D. I. and Holt, N. and LaVigne, N. S. and Fenton, F. H. and Hoffman, M. J.}, editor = {Nithiarasu, P. and Robertson, A. M.} } @article {, title = {Dynamics of a human spiral wave}, journal = {Phys. Today}, volume = {70}, year = {2017}, month = {02/2017}, url = {https://scholar.google.com/citations?view_op=view_citation\&hl=en\&user=jKiNd-0AAAAJ\&cstart=20\&pagesize=80\&citation_for_view=jKiNd-0AAAAJ:BrmTIyaxlBUC}, author = {Andrea J Welsh and Edwin F Greco and Flavio H Fenton} } @article {, title = {Efficient parameterization of cardiac action potential models using a genetic algorithm}, journal = {Chaos: An Interdisciplinary Journal of Nonlinear Science}, volume = {27}, year = {2017}, pages = {093922}, abstract = {

Finding appropriate values for parameters in mathematical models of cardiac cells is a challenging task. Here, we show that it is possible to obtain good parameterizations in as little as 30{\textendash}40 s when as many as 27 parameters are fit simultaneously using a genetic algorithm and two flexible phenomenological models of cardiac action potentials. We demonstrate how our implementation works by considering cases of {\textquotedblleft}model recovery{\textquotedblright} in which we attempt to find parameter values that match model-derived action potential data from several cycle lengths. We assess performance by evaluating the parameter values obtained, action potentials at fit and non-fit cycle lengths, and bifurcation plots for fidelity to the truth as well as consistency across different runs of the algorithm. We also fit the models to action potentials recorded experimentally using microelectrodes and analyze performance. We find that our implementation can efficiently obtain model parameterizations that are in good agreement with the dynamics exhibited by the underlying systems that are included in the fitting process. However, the parameter values obtained in good parameterizations can exhibit a significant amount of variability, raising issues of parameter identifiability and sensitivity. Along similar lines, we also find that the two models differ in terms of the ease of obtaining parameterizations that reproduce model dynamics accurately, most likely reflecting different levels of parameter identifiability for the two models.

}, issn = {1054-1500}, doi = {10.1063/1.5000354}, url = {http://aip.scitation.org/doi/10.1063/1.5000354}, author = {Cairns, Darby I. and Fenton, Flavio H. and Cherry, E. M.} } @article {, title = {Mechanism for amplitude alternans in electrocardiograms and the initiation of spatiotemporal chaos}, journal = {Physical Review Letters}, volume = {118}, year = {2017}, pages = {168101}, abstract = {

It is widely believed that one major life-threatening transition to chaotic fibrillation occurs via spiral-wave breakup that is preceded by spatiotemporal dispersion of refractoriness due to alternations in the duration of the cardiac action potential (AP). However, recent clinical and experimental evidence suggests that other characteristics of the AP may contribute to, and perhaps drive, this dangerous dynamical instability. To identify the relative roles of AP characteristics, we performed experiments in rabbit hearts under conditions to minimize AP duration dynamics which unmasked pronounced AP amplitude alternans just before the onset of fibrillation. We used a simplified ionic cell model to derive a return map and a stability condition that elucidates a novel underlying mechanism for AP alternans and spiral breakup. We found that inactivation of the sodium current is key to developing amplitude alternans and is directly connected to conduction block and initiation of arrhythmias. Simulations in 2D where AP amplitude alternation led to turbulence confirm our hypothesis.

}, author = {Chen, Diandian Diana and Gray, Richard A and Uzelac, Ilija and Herndon, Conner and Fenton, Flavio H} } @article {, title = {A Menagerie of Timed Automata (vol 50, 42, 2017)}, journal = {ACM COMPUTING SURVEYS}, volume = {50}, year = {2017}, author = {Keiren, Jeroen JA and Fontana, Peter and Cleaveland, Rance} } @article {, title = {Simultaneous Quantification of Spatially Discordant Alternans in Voltage and Intracellular Calcium in Langendorff-Perfused Rabbit Hearts and Inconsistencies with Models of Cardiac Action Potentials and Ca Transients}, journal = {Frontiers in Physiology}, volume = {8}, year = {2017}, doi = {10.3389/fphys.2017.00819}, url = {https://doi.org/10.3389/fphys.2017.00819}, author = {Ilija Uzelac and Yanyan C. Ji and Daniel Hornung and Johannes Schr{\"o}der-Scheteling and Stefan Luther and Richard A. Gray and ELIZABETH M. CHERRY and FLAVIO H. FENTON} } @conference {, title = {Bifurcation Analysis of Cardiac Alternans Using δ -Decidability.}, booktitle = {CMSB}, year = {2016}, publisher = {Springer}, organization = {Springer}, keywords = {dblp}, isbn = {978-3-319-45176-3}, url = {http://dblp.uni-trier.de/db/conf/cmsb/cmsb2016.html$\#$IslamBKCCFGJS16}, author = {Islam, Md. Ariful and Byrne, Greg and Kong, Soonho and Clarke, Edmund M. and Cleaveland, Rance and Fenton, Flavio H. and Grosu, Radu and Jones, Paul L. and Smolka, Scott A.}, editor = {Bartocci, Ezio and Li{\`o}, Pietro and Paoletti, Nicola} } @article {, title = {SHARP BOUNDARY ELECTROCARDIAC SIMULATIONS}, year = {2016}, address = {Stony Brook}, abstract = {

We present a sharp boundary electrocardiac simulation model based on the finite volume embedded boundary method for the solution of voltage dynamics in irregular domains with anisotropy and a high degree of anatomical detail. This method is second order accurate uniformly up to boundaries and is able to resolve small features without the use of fine meshes. This capability is necessary to enable the repeated simulations required for future verification and validation and uncertainty quantification studies of defibrillation, where fine-scale heterogeneities, such as those formed by small blood vessels, play an important role and require resolution.

}, keywords = {cardiac electrophysiology, embedded boundary method, tensor diffusion}, doi = {10.1137/15M1019283}, author = {SHUAI XUE and HYUNKYUNG LIM and JAMES GLIMM and FLAVIO H. FENTON and ELIZABETH M. CHERRY} } @article {, title = {Model-Order Reduction of Ion Channel Dynamics Using Approximate Bisimulation}, journal = {Theoretical Computer Science}, volume = {599C}, year = {2015}, month = {09/2015}, chapter = {34}, author = {Md. A. Islam and A. Murthy and E. Bartocci and E. M. Cherry and F. H. Fenton and J. Glimm and S. A. Smolka and R. Grosu} }