Deep learning-enabled efficient image restoration for 3D microscopy of turbid biological specimens

Though three-dimensional (3D) fluorescence microscopy has been an essential tool for modern life science research, the light scattering by biological specimens fundamentally prevents its more widespread applications in live imaging. We hereby report a deep-learning approach, termed ScatNet, that enables reversion of 3D fluorescence microscopy from high-resolution targets to low-quality, light-scattered measurements, thereby allowing restoration for a blurred and light-scattered 3D image of deep tissue. Our approach can computationally extend the imaging depth for current 3D fluorescence microscopes, without the addition of complicated optics. Combining ScatNet approach with cutting-edge light-sheet fluorescence microscopy (LSFM), we demonstrate the image restoration of cell nuclei in the deep layer of live Drosophilamelanogaster embryos at single-cell resolution. Applying our approach to two-photon excitation microscopy, we could improve the signal-to-noise ratio (SNR) and resolution of neurons in mouse brain beyond the photon ballistic region.