Gao, R. et al. Science 363, eaau8302 (2019).

Expansion microscopy (ExM) has made a splash in the imaging world by allowing super-resolution imaging with conventional microscopes. ExM enlarges and clears samples, and is compatible with multiple probes for imaging of diverse targets. Gao et al. have now combined ExM with lattice light-sheet microscopy (LLSM) for super-resolution structural imaging of the brain. LLSM allows for fast, high-resolution, volumetric imaging with relatively low light doses. With this combination, which they term ExLLSM, the researchers obtained detailed images of the cortical column of the mouse brain, as well as the entire Drosophila brain. The researchers also developed bespoke tools to handle the huge amount of generated image data and reconstruct final image volumes from as many as 25,000 tiled subvolumes in each of multiple colors.