Volume Tells: Dual Cycle-Consistent Diffusion for 3D Fluorescence Microscopy De-noising and Super-Resolution

3D fluorescence microscopy is essential for understanding fundamental life processes through long-term live-cell imaging. However, due to inherent issues in imaging principles, it faces significant challenges including spatially varying noise and anisotropic resolution, where the axial resolution lags behind the lateral resolution up to 4.5 times. Meanwhile, laser power is kept low to maintain cell viability, leading to inaccessible low-noise and high-resolution paired ground truth (GT). To tackle these limitations, a dual Cycle-consistent Diffusion is proposed to effectively mine intra-volume imaging priors within 3D cell volumes in an unsupervised manner, i.e., Volume Tells (VTCD), achieving de-noising and super-resolution (SR) simultaneously. Specifically, a spatially iso-distributed denoiser is designed to exploit the noise distribution consistency between adjacent low-noise and high-noise regions within the 3D cell volume, suppressing the spatially varying noise. Then, in light of the structural consistency of the cell volume, a cross-plane global-propagation SR module propagates high-resolution details from the XY plane into adjacent regions in the XZ and YZ planes, progressively enhancing resolution across the entire 3D cell volume. Experimental results on 10 in vivo cellular dataset demonstrate high improvements in both denoising and super-resolution, with axial resolution enhanced from ~ 430 nm to ~ 90 nm.