Incorporating the image formation process into deep learning improves network performance

We present Richardson–Lucy network (RLN), a fast and lightweight deep learning method for three-dimensional fluorescence microscopy deconvolution. RLN combines the traditional Richardson–Lucy iteration with a fully convolutional network structure, establishing a connection to the image formation process and thereby improving network performance. Containing only roughly 16,000 parameters, RLN enables four- to 50-fold faster processing than purely data-driven networks with many more parameters. By visual and quantitative analysis, we show that RLN provides better deconvolution, better generalizability and fewer artifacts than other networks, especially along the axial dimension. RLN outperforms classic Richardson–Lucy deconvolution on volumes contaminated with severe out of focus fluorescence or noise and provides four- to sixfold faster reconstructions of large, cleared-tissue datasets than classic multi-view pipelines. We demonstrate RLN’s performance on cells, tissues and embryos imaged with widefield-, light-sheet-, confocal- and super-resolution microscopy. Richardson–Lucy Network (RLN) combines the traditional Richardson–Lucy iteration with deep learning for improved deconvolution. RLN is more generalizable, offers fewer artifacts and requires less computing time than alternative approaches.