Abstract P1180: Multi-scale Imaging And Analysis To Elucidate Cardiac Structure And Contractile Function

Abstract

Heart failure remains the leading cause of mortality worldwide, largely due to the lack of regenerative capacity of mature cardiomyocytes. The advanced understanding of cardiac architecture and function is critical to uncover the underlying mechanism of cardiac morphogenesis and the remodeling process in response to myocardial infarction. Recent progress has demonstrated that zebrafish and neonatal mice have the capacity to restore cardiac function following the injury, laying the foundation to investigate the cues to structural and functional abnormalities. For this reason, we have developed a light-sheet fluorescence microscope along with the tailored computational methods to investigate the 3-dimensional (3D) architecture of the intact mouse heart, and 4D (3D spatial + 1D temporal) cardiac contractility in zebrafish larvae. This method provides us ~ 2 um isotropic spatial resolution across the atria and ventricles with minimal photo-damage and maximal penetration depth. In combination with established tissue clearing methods, we are able to investigate myocardial trabeculation and compaction in mouse hearts within the 2-minute laser scanning. To unravel the contractile dysfunction following the anticancer therapy, we have coupled our imaging system with retrospective synchronization algorithm for the 4D reconstruction of myocardial deformation from end-systole to end-diastole in zebrafish hearts. To further interpret the deluge of 3D and 4D images, we have also developed a machine learning-based platform for interactive image analysis. Collectively, our multi-scale imaging strategy provides an entry point to assess micro-architecture and cardiac contractile function in the entire heart without physical slicing, holding the great potential to uncover the process of cardiac morphogenesis and regeneration.