Deep-learning super-resolution light-sheet add-on microscopy (Deep-SLAM) for easy isotropic volumetric imaging of large biological specimens

Isotropic 3D histological imaging of large biological specimens is highly desired but remains highly challenging to current fluorescence microscopy technique. Here we present a new method, termed deep-learning super-resolution light-sheet add-on microscopy (Deep-SLAM), to enable fast, isotropic light-sheet fluorescence imaging on a conventional wide-field microscope. After integrating a minimized add-on device that transforms an inverted microscope into a 3D light-sheet microscope, we further integrate a deep neural network (DNN) procedure to quickly restore the ambiguous z-reconstructed planes that suffer from still insufficient axial resolution of light-sheet illumination, thereby achieving isotropic 3D imaging of thick biological specimens at single-cell resolution. We apply this easy and cost-effective Deep-SLAM approach to the anatomical imaging of single neurons in a meso-scale mouse brain, demonstrating its potential for readily converting commonly-used commercialized 2D microscopes to high-throughput 3D imaging, which is previously exclusive for high-end microscopy implementations.