Rapid 3D imaging of entire organs and organisms at cellular resolution is a recurring challenge in life science. This paper reports on a computational light-sheet microscopy able to achieve minute-timescale high-resolution mapping of entire macro-scale organs. By combining dual-side confocally-scanned Bessel light-sheet illumination with a content-aware compressed sensing (CACS) computation pipeline, the approach yields 3D images with high, isotropic spatial resolution and rapid acquisition. The authors demonstrate imaging of whole mouse brain, gastrocnemius, and tibialis muscles at a throughput of 5–10 min per sample and subcellular resolution of ~1.5 µm. Various system-level cellular analyses, such as mapping cell populations and tracing neurons, are readily accomplished.
