An automated approach to analyze microstructural remodeling from confocal microscopies of ventricular myocytes from diseased hearts

Abstract

Various types of heart disease are associated with structural remodeling of cardiac cells. In this work, we present a software framework for automated analyses of structures and protein distributions involved in excitation-contraction coupling in cardiac muscle cells (myocytes). The software framework was designed for processing sets of three-dimensional image stacks, which were created by fluorescent labeling and scanning confocal microscopy of ventricular myocytes from a rabbit infarction model. Design of the software framework reflected the large data volume of image stacks and their large number by selection of efficient and automated methods of digital image processing. Specifically, we selected methods with small user interaction and automated parameter identification by analysis of image stacks. We applied the software framework to exemplary data yielding quantitative information on the arrangement of cell membrane (sarcolemma), the density of ryanodine receptor clusters and their distance to the sarcolemma. We suggest that the presented software framework can be used to automatically quantify various aspects of cellular remodeling, which will provide insights in basic mechanisms of heart diseases and their modeling using computational approaches. Further applications of the developed approaches include clinical cardiological diagnosis and therapy planning.