RT Journal Article SR Electronic T1 Three-dimensional residual channel attention networks denoise and sharpen fluorescence microscopy image volumes JF bioRxiv FD Cold Spring Harbor Laboratory SP 2020.08.27.270439 DO 10.1101/2020.08.27.270439 A1 Jiji Chen A1 Hideki Sasaki A1 Hoyin Lai A1 Yijun Su A1 Jiamin Liu A1 Yicong Wu A1 Alexander Zhovmer A1 Christian A. Combs A1 Ivan Rey-Suarez A1 Hungyu Chang A1 Chi Chou Huang A1 Xuesong Li A1 Min Guo A1 Srineil Nizambad A1 Arpita Upadhyaya A1 Shih-Jong J. Lee A1 Luciano A.G. Lucas A1 Hari Shroff YR 2020 UL http://biorxiv.org/content/early/2020/08/28/2020.08.27.270439.abstract AB We demonstrate residual channel attention networks (RCAN) for restoring and enhancing volumetric time-lapse (4D) fluorescence microscopy data. First, we modify RCAN to handle image volumes, showing that our network enables denoising competitive with three other state-of-the-art neural networks. We use RCAN to restore noisy 4D super-resolution data, enabling image capture over tens of thousands of images (thousands of volumes) without apparent photobleaching. Second, using simulations we show that RCAN enables class-leading resolution enhancement, superior to other networks. Third, we exploit RCAN for denoising and resolution improvement in confocal microscopy, enabling ∼2.5-fold lateral resolution enhancement using stimulated emission depletion (STED) microscopy ground truth. Fourth, we develop methods to improve spatial resolution in structured illumination microscopy using expansion microscopy ground truth, achieving improvements of ∼1.4-fold laterally and ∼3.4-fold axially. Finally, we characterize the limits of denoising and resolution enhancement, suggesting practical benchmarks for evaluating and further enhancing network performance.Competing Interest StatementH.Sasaki, H.L., H.C., C.C.H., S-J J.L., L.A.G.L. are employees of DRVISION, LLC, a machine vision company. They have developed Aivia (a commercial software platform) that offers the 3D RCAN developed here.