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Physics-Driven Zero-Shot Reconstruction of Isotropic 3D Fluorescence Microscopy under Undersampled Acquisition

Preprint Created on 16 Jun 2026 bioRxiv

Three-dimensional (3D) imaging represents the development of next generation of fluorescence microscopy. However, routine axial down-sampling makes isotropic resolution unrealistic. Here, we propose DeepUI, a physical zero-shot framework designed to achieve isotropic 3D fluorescence images from a low axial sampling rate. DeepUI fully leverages the intrinsic characteristics of 3D images through physics-guided degradation, which incorporates spatial-frequency joint learning to generate a scaled optical transfer function, combined with noise degradation and an up-sampling branch. Typically requiring just 5 minutes for training and 0.5 minutes for high-throughput and fast prediction, we demonstrate the superior performance of DeepUI to get isotropic results, and the exclusivity to axial down-sampling conditions, even in more challenging conditions, including defocused background, noise, and resolution blur.

Cao, R., Jin, T., Xin, F., Hou, Y., Fu, Y., Jin, B., Li, L., Gao, S., Wang, H., Li, Y., Saimi, D., Ren, W., Wang, W., Xin, G., Yuan, K., Chen, Z., Su, X., Kim, D., Li, M., Xi, P.

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