A comprehensive framework for evaluation of high pacing frequency and arrhythmic optical mapping signals

Introduction: High pacing frequency or irregular activity due to arrhythmia produces complex optical mapping signals and challenges for processing. The objective is to establish an automated activation time-based analytical framework applicable to optical mapping images of complex electrical behavior.Methods: Optical mapping signals with varying complexity from sheep (N = 7) ventricular preparations were examined. Windows of activation centered on each action potential upstroke were derived using Hilbert transform phase. Upstroke morphology was evaluated for potential multiple activation components and peaks of upstroke signal derivatives defined activation time. Spatially and temporally clustered activation time points were grouped in to wave fronts for individual processing. Each activation time point was evaluated for corresponding repolarization times. Each wave front was subsequently classified based on repetitive or non-repetitive events. Wave fronts were evaluated for activation time minima defining sites of wave front origin. A visualization tool was further developed to probe dynamically the ensemble activation sequence.Results: Our framework facilitated activation time mapping during complex dynamic events including transitions to rotor-like reentry and ventricular fibrillation. We showed that using fixed AT windows to extract AT maps can impair interpretation of the activation sequence. However, the phase windowing of action potential upstrokes enabled accurate recapitulation of repetitive behavior, providing spatially coherent activation patterns. We further demonstrate that grouping the spatio-temporal distribution of AT points in to coherent wave fronts, facilitated interpretation of isolated conduction events, such as conduction slowing, and to derive dynamic changes in repolarization properties. Focal origins precisely detected sites of stimulation origin and breakthrough for individual wave fronts. Furthermore, a visualization tool to dynamically probe activation time windows during reentry revealed a critical single static line of conduction slowing associated with the rotation core.Conclusion: This comprehensive analytical framework enables detailed quantitative assessment and visualization of complex electrical behavior

Dynamics of cardiac re-entry in micro-CT and serial histological sections based models of mammalian hearts

Cardiac re-entry regime of self-organised abnormal synchronisation underlie dangerous arrhythmias and fatal fibrillation. Recent advances in the theory of dissipative vortices, experimental studies, and anatomically realistic computer simulations, elucidated the role of cardiac re-entry interaction with fine anatomical features in the heart, and anatomy induced drift. The fact that anatomy and structural anisotropy of the heart is consistent within a species suggested its possible functional effect on spontaneous drift of cardiac re-entry. A comparative study of the anatomy induced drift could be used in order to predict evolution of atrial arrhythmia, and improve low-voltage defibrillation protocols and ablation strategies. Here, in micro-CT based model of rat pulmonary vein wall, and in sheep atria models based on high resolution serial histological sections, we demonstrate effects of heart geometry and anisotropy on cardiac re-entry anatomy induced drift, its pinning to fluctuations of thickness in the layer. The data sets of sheep atria and rat pulmonary vein wall are incorporated into the BeatBox High Performance Computing simulation environment. Re-entry is initiated at prescribed locations in the spatially homogeneous mono-domain models of cardiac tissue. Excitation is described by FitzHugh-Nagumo kinetics. In the in-silico models, isotropic and anisotropic conduction show specific anatomy effects and the interplay between anatomy and anisotropy of the heart. The main objectives are to demonstrate the functional role of the species hearts geometry and anisotropy on cardiac re-entry anatomy induced drift. In case of the rat pulmonary vein wall with ~90 degree transmural fibre rotation, it is shown that the joint effect of the PV wall geometry and anisotropy turns a plane excitation wave into a re-entry pinned to a small fluctuation of thickness in the wall

A comprehensive framework for evaluation of high pacing frequency and arrhythmic optical mapping signals

Introduction: High pacing frequency or irregular activity due to arrhythmia produces complex optical mapping signals and challenges for processing. The objective is to establish an automated activation time-based analytical framework applicable to optical mapping images of complex electrical behavior. Methods: Optical mapping signals with varying complexity from sheep (N = 7) ventricular preparations were examined. Windows of activation centered on each action potential upstroke were derived using Hilbert transform phase. Upstroke morphology was evaluated for potential multiple activation components and peaks of upstroke signal derivatives defined activation time. Spatially and temporally clustered activation time points were grouped in to wave fronts for individual processing. Each activation time point was evaluated for corresponding repolarization times. Each wave front was subsequently classified based on repetitive or non-repetitive events. Wave fronts were evaluated for activation time minima defining sites of wave front origin. A visualization tool was further developed to probe dynamically the ensemble activation sequence. Results: Our framework facilitated activation time mapping during complex dynamic events including transitions to rotor-like reentry and ventricular fibrillation. We showed that using fixed AT windows to extract AT maps can impair interpretation of the activation sequence. However, the phase windowing of action potential upstrokes enabled accurate recapitulation of repetitive behavior, providing spatially coherent activation patterns. We further demonstrate that grouping the spatio-temporal distribution of AT points in to coherent wave fronts, facilitated interpretation of isolated conduction events, such as conduction slowing, and to derive dynamic changes in repolarization properties. Focal origins precisely detected sites of stimulation origin and breakthrough for individual wave fronts. Furthermore, a visualization tool to dynamically probe activation time windows during reentry revealed a critical single static line of conduction slowing associated with the rotation core. Conclusion: This comprehensive analytical framework enables detailed quantitative assessment and visualization of complex electrical behavior