Multiscale Image Analysis of Calcium Dynamics in Cardiac Myocytes

Cardiac myocytes are the muscle cells that build up heart tissue and provide the mechanical action to pump blood by synchronously contracting at every heartbeat. Heart muscle contraction is regulated by intracellular calcium concentration which exhibits a complex spatio-temporal dynamical behavior at the molecular, cellular and tissue levels. Details of such dynamical patterns are closely related to the mechanisms responsible for cardiovascular diseases, the single largest cause of death in the developed countries. The emerging field of translational cardiology focuses on the study of how such mechanisms connect and influence each other across spatial and temporal scales, eventually yielding to a certain clinical condition. To study such calcium dynamics in cardiac myocytes, we benefit from the recent advances in the field of experimental cell physiology. Fluorescence microscopy allows us to observe the distribution of calcium in the cell with a spatial resolution below one micron and a frame rate around one millisecond, thus providing a very accurate monitoring of calcium fluxes in the cell. The aim of the thesis summarized in this paper, was to develop image processing computational techniques for extracting quantitative data of physiological relevance from fluorescence confocal microscopy images at different scales. The two main subjects covered in the thesis were image segmentation and classification methods applied to fluorescence microscopy imaging of cardiac myocytes and calcium imaging. These methods were applied to a variety of problems involving different space and time scales, such as the localization of molecular receptors, the detection and characterization of spontaneous calcium-release events, and the propagation of calcium waves across a culture of cardiac cells. The following is a summary of the thesis as a consequence of having been awarded the 7th Justiniano Casas Award accessit by the Sociedad Espanola de Optica.