@inproceedings{3dffa78e0fb44bf2831fae1d16d9c5bd,
title = "Bifurcation analysis of cardiac alternans using δ-decidability",
abstract = "We present a bifurcation analysis of electrical alternans in the two-current Mitchell-Schaeffer (MS) cardiac-cell model using the theory of δ-decidability over the reals. Electrical alternans is a phenomenon characterized by a variation in the successive Action Potential Durations (APDs) generated by a single 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 bifurcation analysis we perform determines, for each control parameter τ of the MS model, the bifurcation point in the range of τ such that a small perturbation to this value results in a transition from alternans to non-alternans behavior. To the best of our knowledge, our analysis represents the first formal verification of non-trivial dynamics in a numerical cardiac-cell model. Our approach to this problem rests on encoding alternans-like behavior in the MS model as a 11-mode, multinomial hybrid automaton (HA). For each model parameter, we then apply a sophisticated, guided-searchbased reachability analysis to this HA to estimate parameter ranges for both alternans and non-alternans behavior. The bifurcation point separates these two ranges, but with an uncertainty region due to the underlying δ-decision procedure. This uncertainty region, however, can be reduced by decreasing δ at the expense of increasing the model exploration time. Experimental results are provided that highlight the effectiveness of this method.",
author = "Islam, {Md Ariful} and Greg Byrne and Soonho Kong and Clarke, {Edmund M.} and Rance Cleaveland and Fenton, {Flavio H.} and Radu Grosu and Jones, {Paul L.} and Smolka, {Scott A.}",
note = "Publisher Copyright: {\textcopyright} Springer International Publishing AG 2016.; 14th Conference on Computational Methods in Systems Biology, CMSB 2016 ; Conference date: 21-09-2016 Through 23-09-2016",
year = "2016",
doi = "10.1007/978-3-319-45177-0_9",
language = "English",
isbn = "9783319451763",
series = "Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics)",
publisher = "Springer-Verlag",
pages = "132--146",
editor = "Nicola Paoletti and Ezio Bartocci and Pietro Lio",
booktitle = "Computational Methods in Systems Biology - 14th International Conference, CMSB 2016, Proceedings",
}