Optoheart · All-optical framework for the correlative imaging of cardiac meso-scale cytoarchitecture and multi-scale electrical conduction

All-optical framework for the correlative imaging of cardiac meso-scale cytoarchitecture and multi-scale electrical conduction

Millions of people are affected by abnormal heartbeats, or arrhythmias. Advances in understanding the precise conditions which promote the formation of arrhythmias will be vital to develop treatment strategies. Cardiac muscle cells need to act synchronously to an initiating electrical impulse to allow blood to be efficiently pumped around the body with each beat. Importantly, cardiac electric conduction is a tissue level phenomenon based on current propagation across billions of cells whose electro-mechanical function of contraction is intricately intertwined with their structural arrangement. In pathological conditions prone to develop arrhythmias, changes in tissue structure (consider scars and electrically inert tissue) caused by the disease have dire implications on the healthy function of cardiac conduction. Light-sheet microscopy (LSM) has proven a useful tool in bioimaging to image whole organs with high frame rates at cellular resolution and, in combination with tissue clearing methods, is often employed to reconstruct the cyto-architecture over entire organs. Inherently to LSM, however, residual opaque objects, always present to some extent even in extremely well optically cleared samples, cause stripe artifacts, which, in the best case, severely affect image homogeneity and, in the worst case, completely obscure features of interest. Since whole organ datasets now routinely comprise several terabytes, automated tools to count, trace, or segment features of interest are needed to extract meaningful insights. It is therefore necessary to devise technical solutions to increase fidelity in imaging and relax computational demands on the algorithms used to turn data into knowledge. In this study, we will develop innovative microscopy technology to measure cardiac tissue structure over the whole intact mouse heart and create maps of non-conducting tissue in health and disease. These structural maps of conducting and non-conducting tissue will inform previously obtained measurements of cardiac electric activity and allow to relate cardiac function back to its structure. This will provide us with vital information not only for our understanding of fundamental heart electrophysiology which will be translated to new medical treatments to for cardiac arrhythmias.

Data: CORDIS, © European Union