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 singularities that are associated with three-dimensional scroll waves are considered to be the organizing centres of life-threatening cardiac arrhythmias. The mechanisms that underlie the onset, maintenance and control 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.

MH negatively affects diastolic function, which, however, is compensated for by decreased spontaneous HR. Positive inotropy and a decrease in whole body oxygen consumption warrant further studies addressing the potential benefit of MH on the acutely failing heart.

Optical mapping is a high-resolution fluorescence imaging technique, which provides highly detailed visualizations of the electrophysiological wave phenomena, which trigger the beating of the heart. Recent advancements in optical mapping have demonstrated that the technique can now be performed with moving and contracting hearts and that motion and motion artifacts, once a major limitation, can now be overcome by numerically tracking and stabilizing the heart's motion. As a result, the optical measurement of electrical activity can be obtained from the moving heart surface in a co-moving frame of reference and motion artifacts can be reduced substantially. The aim of this study is to assess and validate the performance of a 2D marker-free motion tracking algorithm, which tracks motion and non-rigid deformations in video images. Because the tracking algorithm does not require markers to be attached to the tissue, it is necessary to verify that it accurately tracks the displacements of the cardiac tissue surface, which not only contracts and deforms, but also fluoresces and exhibits spatio-temporal physiology-related intensity changes. We used computer simulations to generate synthetic optical mapping videos, which show the contracting and fluorescing ventricular heart surface. The synthetic data reproduces experimental data as closely as possible and shows electrical waves propagating across the deforming tissue surface, as seen during voltage-sensitive imaging. We then tested the motion tracking and motion-stabilization algorithm on the synthetic as well as on experimental data. The motion tracking and motion-stabilization algorithm decreases motion artifacts approximately by 80% and achieves sub-pixel precision when tracking motion of 1–10 pixels (in a video image with 100 by 100 pixels), effectively inhibiting motion such that little residual motion remains after tracking and motion-stabilization. To demonstrate the performance of the algorithm, we present optical maps with a substantial reduction in motion artifacts showing action potential waves propagating across the moving and strongly deforming ventricular heart surface. The tracking algorithm reliably tracks motion if the tissue surface is illuminated homogeneously and shows sufficient contrast or texture which can be tracked or if the contrast is artificially or numerically enhanced. In this study, we also show how a reduction in dissociation-related motion artifacts can be quantified and linked to tracking precision. Our results can be used to advance optical mapping techniques, enabling them to image contracting hearts, with the ultimate goal of studying the mutual coupling of electrical and mechanical phenomena in healthy and diseased hearts.

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Optical mapping is a widely used imaging technique for investigating cardiac electrophysiology in intact, Langendorff-perfused hearts. Mechanical contraction of cardiac tissue, however, may result in severe motion artifacts and significant distortion of the fluorescence signals. Therefore, pharmacological uncoupling is widely used to reduce tissue motion. Recently, various image processing algorithms have been proposed to reduce motion artifacts. We will review these technological developments. Furthermore, we will present a novel approach for the three-dimensional, marker-free reconstruction of contracting Langendorff-perfused intact hearts under physiological conditions. The algorithm allows disentangling the fluorescence signals (e.g. membrane voltage or intracellular calcium) from the mechanical motion (e.g. tissue strain). We will discuss the algorithms reconstruction accuracy, resolution, and robustness using experimental data from Langendorff-perfused rabbit hearts.

In excitable media, chaotic dynamics governed by spiral or scroll waves is often not persistent but transient. Using extensive simulations employing different mathematical models we identify a specific type-II supertransient by an exponential increase of transient lifetimes with the system size in 2D and an investigation of the dynamics (number and lifetime of spiral waves, Kaplan-Yorke dimension). In 3D, simulations exhibit an increase of transient lifetimes and filament lengths only above a critical thickness. Finally, potential implications for understanding cardiac arrhythmias are discussed.

The heart is an elastic excitable medium, in which mechanical contraction is triggered by nonlinear waves of electrical excitation, which diffuse rapidly through the heart tissue and subsequently activate the cardiac muscle cells to contract. These highly dynamic excitation wave phenomena have yet to be fully observed within the depths of the heart muscle, as imaging technology is unable to penetrate the tissue and provide panoramic, three-dimensional visualizations necessary for adequate study. As a result, the electrophysiological mechanisms that are associated with the onset and progression of severe heart rhythm disorders such as atrial or ventricular fibrillation remain insufficiently understood. Here, we present a novel synchronization-based data assimilation approach with which it is possible to reconstruct excitation wave dynamics within the volume of elastic excitable media by observing spatiotemporal deformation patterns, which occur in response to excitation. The mechanical data are assimilated in a numerical replication of the measured elastic excitable system, and within this replication, the data drive the intrinsic excitable dynamics, which then coevolve and correspond to a reconstruction of the original dynamics. We provide a numerical proof-of-principle and demonstrate the performance of the approach by recovering even complicated three-dimensional scroll wave patterns, including vortex filaments of electrical excitation from within a deformable bulk tissue with fiber anisotropy. In the future, the reconstruction approach could be combined with high-speed imaging of the heart’s mechanical contractions to estimate its electrophysiological activity for diagnostic purposes.

The control of spatiotemporal dynamics in biological systems is a fundamental problem in nonlinear sciences and has important applications in engineering and medicine. Optogenetic tools combined with advanced optical technologies provide unique opportunities to develop and validate novel approaches to control spatiotemporal complexity in neuronal and cardiac systems. Understanding of the mechanisms and instabilities underlying the onset, perpetuation, and control of cardiac arrhythmias will enable the development and translation of novel therapeutic approaches. Here we describe in detail the preparation and optical mapping of transgenic channelrhodopsin-2 (ChR2) mouse hearts, cardiac cell cultures, and the optical setup for photostimulation using digital light processing.