Co-Principal Investigator: Elizabeth Cherry
Contact Information: Email: email@example.com; Phone: 607-253-3075
Sponsor: National Science Foundation (NSF)
Grant Number: CMMI-1028261
Title: Collaborative Research: CDI-TYPE II: Dynamics and Control of Cardiac Tissue
Annual Direct Cost: $213,796
Project Period: 09/15/10 – 08/31/14
DESCRIPTION (provided by applicant): Complex spatiotemporal dynamics underly many arrhythmic disorders of the heart - a complex biological system. However, despite decades of biomedical research and development of increasingly detailed computational models, the mechanisms that induce and sustain arrhythmias remain elusive. We propose to improve our fundamental understanding of these mechanisms and build on that understanding to develop low-energy approaches to suppress cardiac arrhythmias by revolutionizing the way in which numerical simulations are used. With the help of cutting-edge numerical algorithms we will compute a hierarchy of exact steady and time-periodic solutions of detailed ionic models of cardiac dynamics. These unstable solutions are hidden from view and describe recurrent
spatiotemporal patterns. Their determination for fully resolved cardiac tissue models is computationally extremely intensive, but once these solutions are obtained, they yield a radically new understanding of the spatiotemporally chaotic dynamics as a walk through a repertoire of corresponding recurrent patterns. This representation also allows development of nonlinear control of cardiac dynamics using electrical stimulation. Numerical component of the research program will be tightly integrated with experiments involving both cardiac tissue and cell cultures. The experiments will be used to both validate the proposed computational analysis and to test the control approach.
Intellectual Merit: This project proposes a radical and urgently needed paradigm shift from the computationally intensive direct numerical simulations to a description of cardiac dynamics in terms of a finite repertoire of spatiotemporal patterns. It addresses all key CDI challenges: (i) Understanding Complexity: development of reduced, but biologically realistic models of the heart; (ii) From Data to Knowledge: numerical/experimental data driven modeling; and (iii) Virtual Organizations: enhancing discovery and innovation by bringing together researchers from different institutions and fields; communicating, by means of novel visualizations, complex, high-dimensional numerical and experimental data to the broader, medically trained community.
Broader Impact: Cardiac arrhythmias are a major cause of mortality in the industrialized world, with attendant lowered life-expectancy and high socio-economic costs. Even an incremental reduction of arrhythmias by proposed control methodology would have a significant societal impact. Although the focus here is on cardiac dynamics, the methods developed will impact other fields dealing with high-dimensional complex systems that exhibit unstable recurrent patterns. Neural disorders (Parkinson), dynamics of fluids and plasmas, and climate studies offer some representative examples.
Our methods, results, and computer codes are, and will continue to be, disseminated through our TheVirtualHeart.org heart visualizations, ChaosBook.org webbook, and Channelflow.org public domain code and data repositories. Our team is cross-disciplinary (physical, biomedical, and computer sciences) and our complementary expertise provides unique opportunities for the training of graduate students and postdocs, including women and minorities, in experimental cardiology, high-dimensional complex systems, and novel equation-mining strategies that go beyond the current direct numerical simulations paradigm.