Volumetric denoising enables high-throughput volume electron microscopy and efficient downstream analysis.

Volume electron microscopy (VEM) enables nanometer-resolution three-dimensional (3D) visualization of biological specimens via serial sectioning and imaging. Owing to limitations of downstream analysis, VEM datasets are often acquired at slow speeds and high resolutions, thereby limiting achievable imaging throughput. By systematically searching for optimal VEM acquisition conditions, we find that sufficient spatial resolution effectively counteracts high image noise in preserving 3D structural information. To further verify that denoising is more effective in restoring volumetric datasets than axial interpolation, we compared machine learning-based methods, including a newly developed 3D context-based denoising model, through various tasks on VEM datasets acquired simultaneously. Our volumetric approach not only outperforms other baseline methods in faithful feature recovery but also facilitates robust serial block-face cutting down to 20 nm by allowing fast imaging. This work provides both an optimized acquisition strategy and volumetric denoising methods as actionable guidelines for maximizing VEM throughput.