Beatbox - a computer simulation environment for computational biology of the heart

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 offer increasingly detailed insight into these phenomena, providing a view of cellular-level activity on the scale of a whole tissue wall. Already, advances in this field have 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 dependant on the effective use of High Performance Computing (HPC), i.e. systems with parallel processors. Current state of the art cardiac simulation tools are limited either by the availability of modern, detailed models, or by their hardware portability or 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, arguably, impeding scientific progress. This paper presents a roadmap for the development of Beatbox, a computer simulation environment for computational biology of the heart—an adaptable and extensible framework with which High Performance Computing may be harnessed by researchers

Role of a habitat's air humidity in Covid-19 mortality

This is the author accepted manuscript. The final version is available from Elsevier via the DOI in this recordAvailability of supporting data: The datasets used and/or analysed in this paper are available from the websites.Transient local over-dry environment might be a contributor and an explanation for the observed asynchronous local rises in Covid-19 mortality. We propose that a habitat's air humidity negatively correlate with Covid-19 morbidity and mortality, and support this hypothesis on the example of publicly available data from German federal states

Orbital movement of spiral waves

Spiral waves in active media react to small perturbations as particle-like objects. Here we apply the asymptotic theory to the interaction of spiral waves with a localized inhomogeneity, which leads to a novel prediction: drift of the spiral rotation centre along circular orbits around the inhomogeneity. The stationary orbits have alternating stability and fixed radii, determined by the properties of the bulk medium and the type of inhomogeneity, while the drift speed along an orbit depends on the strength of the inhomogeneity. Direct simulations confirm the validity and robustness of the theoretical predictions and show that these unexpected effects should be observable in experiment

Cardiac re-entry dynamics & self-termination in DT-MRI based model of Human Foetal Heart

The effect of heart geometry and anisotropy on cardiac re-entry dynamics and self-termination is studied here in anatomically realistic computer simulations of human foetal heart. 20 weeks of gestational age human foetal heart isotropic and anisotropic anatomy models from diffusion tensor MRI data sets are used in the computer simulations. The fibre orientation angles of the heart were obtained from the DT-MRI primary eigenvalues. In a spatially homogeneous electrophysiological mono domain model with the DT-MRI based heart geometries, we initiate simplified Fitz-Hugh-Nagumo kinetics cardiac re-entry at a prescribed location in a 2D slice, and in the full 3D anatomy model. In a slice of the heart, the MRI based fibre anisotropy changes the re-entry dynamics from pinned to anatomical re-entry. In the full 3D MRI based model, the foetal heart fibre anisotropy changes the re-entry dynamics from a persistent re-entry to the re-entry self-termination

Filament Tension and Phase Locking of Meandering Scroll Waves

Meandering spiral waves are often observed in excitable media such as the Belousov-Zhabotinsky reaction and cardiac tissue. We derive a theory for drift dynamics of meandering rotors in general reaction-diffusion systems and apply it to two types of external disturbances: an external field and curvature-induced drift in three dimensions. We find two distinct regimes: with small filament curvature, meandering scroll waves exhibit filament tension, whose sign determines the stability and drift direction. In the regimes of strong external fields or meandering motion close to resonance, however, phase locking of the meander pattern is predicted and observed

Filament tension and phase-locked drift of meandering scroll waves

This paper was subsequently published in Physical Review Letters vol. 119, article 258101 (DOI: http://hdl.handle.net/10871/31612). The author accepted manuscript of the published article is in ORE: http://hdl.handle.net/10871/31612Rotating scroll waves are self-organising patterns which are found in many oscillating or excitable systems. Here we show that quasi-periodic (meandering) scroll waves, which include the rotors that organise cardiac arrhythmias, exhibit filament tension when averaged over the meander cycle. With strong filament curvature or medium thickness gradients, however, scroll wave dynamics are governed by phase-locked drift instead of filament tension. Our results are validated in computational models of cycloidal meander and a cardiac tissue model with linear core.This paper was subsequently published in Physical Review Letters, vol. 119, article 258101 (DOI: 10.1103/PhysRevLett.119.258101). The accepted version is in ORE at http://hdl.handle.net/10871/3161

Filament Tension and Phase Locking of Meandering Scroll Waves

This is the author accepted manuscript. The final version is available from American Physical Society via the DOI in this recordThe version of this paper which was originally published at arXiv.org is in ORE: http://hdl.handle.net/10871/25921Meandering spiral waves are often observed in excitable media such as the Belousov-Zhabotinsky reaction and cardiac tissue. We derive a theory for drift dynamics of meandering rotors in general reaction-diffusion systems and apply it to two types of external disturbances: an external field and curvature-induced drift in three dimensions. We find two distinct regimes: with small filament curvature, meandering scroll waves exhibit filament tension, whose sign determines the stability and drift direction. In the regimes of strong external fields or meandering motion close to resonance, however, phase locking of the meander pattern is predicted and observed.H. D. was funded by FWO-Flanders during part of this work. The computational resources (Stevin Supercomputer Infrastructure) and services used in this work were provided by the VSC (Flemish Supercomputer Center), funded by Ghent University, FWO and the Flemish Government–department EWI. I. V. B. and V. N. B. gratefully acknowledge EPSRC (UK) support via Grant No. EP/D074789/1. I. V. B. acknowledges EPSRC (UK) support via Grant No. EP/P008690/1. V. N. B. acknowledges EPSRC (UK) current support via Grant No. EP/N014391/1 (UK)

A response function framework for the dynamics of meandering or large-core spiral waves and modulated traveling waves

This is the author accepted manuscript. The final version is available from the American Physical Society via the DOI in this record.In many oscillatory or excitable systems, dynamical patterns emerge which are stationary or periodic in a moving frame of reference. Examples include traveling waves or spiral waves in chemical systems or cardiac tissue. We present a unified theoretical framework for the drift of such patterns under small external perturbations, in terms of overlap integrals between the perturbation and the adjoint critical eigenfunctions of the linearised operator (i.e. ‘response functions’). For spiral waves, the finite radius of the spiral tip trajectory as well as spiral wave meander are taken into account. Different coordinates systems can be chosen, depending on whether one wants to predict the motion of the spiral wave tip, the time-averaged tip path, or the center of the meander flower. The framework is applied to analyse the drift of a meandering spiral wave in a constant external field in different regimes.Engineering and Physical Sciences Research Council (EPSRC

Evolution of spiral and scroll waves of excitation in a mathematical model of ischaemic border zone

Abnormal electrical activity from the boundaries of ischemic cardiac tissue is recognized as one of the major causes in generation of ischemia-reperfusion arrhythmias. Here we present theoretical analysis of the waves of electrical activity that can rise on the boundary of cardiac cell network upon its recovery from ischaemia-like conditions. The main factors included in our analysis are macroscopic gradients of the cell-to-cell coupling and cell excitability and microscopic heterogeneity of individual cells. The interplay between these factors allows one to explain how spirals form, drift together with the moving boundary, get transiently pinned to local inhomogeneities, and finally penetrate into the bulk of the well-coupled tissue where they reach macroscopic scale. The asymptotic theory of the drift of spiral and scroll waves based on response functions provides explanation of the drifts involved in this mechanism, with the exception of effects due to the discreteness of cardiac tissue. In particular, this asymptotic theory allows an extrapolation of 2D events into 3D, which has shown that cells within the border zone can give rise to 3D analogues of spirals, the scroll waves. When and if such scroll waves escape into a better coupled tissue, they are likely to collapse due to the positive filament tension. However, our simulations have shown that such collapse of newly generated scrolls is not inevitable and that under certain conditions filament tension becomes negative, leading to scroll filaments to expand and multiply leading to a fibrillation-like state within small areas of cardiac tissue.Comment: 26 pages, 13 figures, appendix and 2 movies, as accepted to PLoS ONE 2011/08/0

Analytical, Optimal, and Sparse Optimal Control of Traveling Wave Solutions to Reaction-Diffusion Systems

This work deals with the position control of selected patterns in reaction-diffusion systems. Exemplarily, the Schl\"{o}gl and FitzHugh-Nagumo model are discussed using three different approaches. First, an analytical solution is proposed. Second, the standard optimal control procedure is applied. The third approach extends standard optimal control to so-called sparse optimal control that results in very localized control signals and allows the analysis of second order optimality conditions.Comment: 22 pages, 3 figures, 2 table