Self-supervised denoising for multimodal structured illumination microscopy enables long-term super-resolution live-cell imaging
Xingye Chen, Chang Qiao, Tao Jiang, Jiahao Liu, Quan Meng, Yunmin Zeng, Haoyu Chen, Hui Qiao, Dong Li, Jiamin Wu
Abstract
Abstract Detection noise significantly degrades the quality of structured illumination microscopy (SIM) images, especially under low-light conditions. Although supervised learning based denoising methods have shown prominent advances in eliminating the noise-induced artifacts, the requirement of a large amount of high-quality training data severely limits their applications. Here we developed a pixel-realignment-based self-supervised denoising framework for SIM (PRS-SIM) that trains an SIM image denoiser with only noisy data and substantially removes the reconstruction artifacts. We demonstrated that PRS-SIM generates artifact-free images with 20-fold less fluorescence than ordinary imaging conditions while achieving comparable super-resolution capability to the ground truth (GT). Moreover, we developed an easy-to-use plugin that enables both training and implementation of PRS-SIM for multimodal SIM platforms including 2D/3D and linear/nonlinear SIM. With PRS-SIM, we achieved long-term super-resolution live-cell imaging of various vulnerable bioprocesses, revealing the clustered distribution of Clathrin-coated pits and detailed interaction dynamics of multiple organelles and the cytoskeleton.