摘要:SummaryIn vivoquantitative assessment of structural and functional biomarkers is essential for characterizing the pathophysiology of congenital disorders. In this regard, fixed tissue analysis has offered revolutionary insights into the underlying cellular architecture. However, histological analysis faces major drawbacks with respect to lack of spatiotemporal sampling and tissue artifacts during sample preparation. This study demonstrates the potential of light sheet fluorescence microscopy (LSFM) as a non-invasive, 4D (3days + time) optical sectioning tool for revealing cardiac mechano-transduction in zebrafish. Furthermore, we have described the utility of a scale and size-invariant feature detector, for analyzing individual morphology of fused cardiomyocyte nuclei and characterizing zebrafish ventricular contractility.Graphical abstractDisplay OmittedHighlights•Cardiac defect genes in humans have corresponding zebrafish orthologs•Light sheet modality is very effective for non-invasive, 4D modeling of zebrafish•Hessian detector is robust to varying nuclei scales and geometric transformations•Watershed filter is effective for separating fused cellular volumesBiotechnology; Biological sciences research methodologies; Biology experimental methods; Computer science