Multimodal high-resolution mapping of contracting intact Langendorff-perfused hearts

Abstract

The vital function of the heart during normal sinus rhythm relies on the spread of regular excitation waves within the cardiac muscle tissue, leading to an orderly contraction and efficient pumping action. These electrical action potential waves are theproduct of a dynamic interplay between complex molecular processes on the cellular level and the global structure of the heart, as well as the spatio-temporal activation patterns themselves. As each excitation wave leaves the tissue in its wake temporarily unexcitable, the available space for excitation spread is not only limited by the 3D geometrical shape of the muscle tissue itself, but also by the path of preceding waves. This gives rise to irregular and potentially life-threatening chaotic activation dynamics, once the regular pathways for sinus rhythm are disturbed, whether it be by pathologic structural changes like scar tissue, or by dynamic effects like conduction block and wavefront breakup due to spurious preceding wavelets. To better understand the processes associated with the different dynamical states underlying regular and arrhythmic activity in the healthy and diseased heart, it is important to advance experimental imaging methods towards complete and simultaneous capture of the key dynamical and structural properties of the whole heart at high spatial and temporal resolution. This work develops experimental and numerical tools to combine several non-invasive optical, electrical, and acoustical measurement techniques in a single ex-vivo experiment, in order to facilitate simultaneous, dense, and comprehensive multimodal measurement of structure, movement and electrical dynamics of a beating heart, on its surface and within. Based on a Langendorff-perfusion setup for isolated hearts, multiple calibrated cameras allow three-dimensional shape reconstruction and panoramic optical mapping of the electrical activity visible at the epicardial surface. Using the same cameras, the 3D movement of the contracting heart is tracked using a novel purely optical marker-less motion tracking algorithm designed to be applicable to 360 ° imaging. The obtained data is further used for estimation of the excitation light field in order to eliminate residual motion artifacts without the need for ratiometric imaging methods. Simultaneously, the motion within the bulk tissue is recorded using fast 4D ultrasound imaging, while multi-channel ECG recordings allow analysis of the bulk electrical activity. Additionally, the heart structure is reconstructed at high spatial resolution using a CT scanner. The rich multimodal data sets obtained with these methods allow for detailed studies of the interplay and interdependence of cardiac dynamics and structure on the whole organ, as well as development of novel therapeutic and diagnostic concepts.