More challenging computational imaging applications, such as3D snapshot microscopywhichcompresses 3Dvolumes intosingle2Dimages, require ahighly non-local optical encoder. We show that existing deep network decoders have a locality bias which prevents the optimization of such highly non-local optical encoders. We address this with a decoder based on a shallow neural network architecture using global kernel Fourier convolutional neural networks (FourierNets).

Confocal fluorescence microscopy is one of the most accessible and widely used imaging techniques for the study of biological processes at the cellular and subcellular levels. Scanning confocal microscopy allows the capture of high-quality images from thick three-dimensional (3D) samples, yet suffers from well-known limitations such as photobleaching and phototoxicity of specimens caused by intense light exposure, which limits its use in some applications, especially for living cells. Cellular damage can be alleviated by changing imaging parameters to reduce light exposure, often at the expense of image quality.Machine/deep learning methods for single-image super-resolution (SISR) can be applied to restore image quality by upscaling lower-resolution (LR) images to produce high-resolution images (HR). These SISR methods have been successfully applied to photo-realistic images due partly to the abundance of publicly available datasets. In contrast, the lack of publicly available data partly limits their application and success in scanning confocal microscopy.In this paper, we introduce a large scanning confocal microscopy dataset named SR-CACO-2 that is comprised of low-and high-resolution image pairs marked for three different fluorescent markers. It allows to evaluate the performance of SISR methods on three different upscaling levels (X2, X4, X8).

Differentiable simulations of optical systems can be combined with deep learning-based reconstruction networks to enable high performance computational imaging via end-to-end (E2E) optimization of both the optical encoder and the deep decoder. This has enabled imaging applications such as 3D localization microscopy, depth estimation, and lensless photography via the optimization of local optical encoders. More challenging computational imaging applications, such as 3D snapshot microscopy which compresses 3D volumes into single 2D images, require a highly non-local optical encoder. We show that existing deep network decoders have a locality bias which prevents the optimization of such highly non-local optical encoders. We address this with a decoder based on a shallow neural network architecture using global kernel Fourier convolutional neural networks (FourierNets). We show that FourierNets surpass existing deep network based decoders at reconstructing photographs captured by the highly non-local DiffuserCam optical encoder. Further, we show that FourierNets enable E2E optimization of highly non-local optical encoders for 3D snapshot microscopy. By combining FourierNets with a large-scale multi-GPU differentiable optical simulation, we are able to optimize non-local optical encoders 170$\times$ to 7372$\times$ larger than prior state of the art, and demonstrate the potential for ROI-type specific optical encoding with a programmable microscope.

Accurate multi-slice reconstruction from limited measurement data is crucial to speed up the acquisition process in medical and scientific imaging. However, it remains challenging due to the ill-posed nature of the problem and the high computational and memory demands. We propose a framework that addresses these challenges by integrating partitioned diffusion priors with physics-based constraints. By doing so, we substantially reduce memory usage per GPU while preserving high reconstruction quality, outperforming both physics-only and full multi-slice reconstruction baselines for different modalities, namely Magnetic Resonance Imaging (MRI) and four-dimensional Scanning Transmission Electron Microscopy (4D-STEM). Additionally, we show that the proposed method improves in-distribution accuracy as well as strong generalization to out-of-distribution datasets.

Precise pose estimation of optical microrobots is essential for enabling high-precision object tracking and autonomous biological studies. However, current methods rely heavily on large, high-quality microscope image datasets, which are difficult and costly to acquire due to the complexity of microrobot fabrication and the labour-intensive labelling. Digital twin systems offer a promising path for sim-to-real data augmentation, yet existing techniques struggle to replicate complex optical microscopy phenomena, such as diffraction artifacts and depth-dependent imaging.This work proposes a novel physics-informed deep generative learning framework that, for the first time, integrates wave optics-based physical rendering and depth alignment into a generative adversarial network (GAN), to synthesise high-fidelity microscope images for microrobot pose estimation efficiently. Our method improves the structural similarity index (SSIM) by 35.6% compared to purely AI-driven methods, while maintaining real-time rendering speeds (0.022 s/frame).The pose estimator (CNN backbone) trained on our synthetic data achieves 93.9%/91.9% (pitch/roll) accuracy, just 5.0%/5.4% (pitch/roll) below that of an estimator trained exclusively on real data. Furthermore, our framework generalises to unseen poses, enabling data augmentation and robust pose estimation for novel microrobot configurations without additional training data.

Deep learning is transforming microscopy, yet models often fail when applied to images from new instruments or acquisition settings. Conventional adversarial domain adaptation (ADDA) retrains entire networks, often disrupting learned semantic representations. Here, we overturn this paradigm by showing that adapting only the earliest convolutional layers, while freezing deeper layers, yields reliable transfer. Building on this principle, we introduce Subnetwork Image Translation ADDA with automatic depth selection (SIT-ADDA-Auto), a self-configuring framework that integrates shallow-layer adversarial alignment with predictive uncertainty to automatically select adaptation depth without target labels. We demonstrate robustness via multi-metric evaluation, blinded expert assessment, and uncertainty-depth ablations. Across exposure and illumination shifts, cross-instrument transfer, and multiple stains, SIT-ADDA improves reconstruction and downstream segmentation over full-encoder adaptation and non-adversarial baselines, with reduced drift of semantic features. Our results provide a design rule for label-free adaptation in microscopy and a recipe for field settings; the code is publicly available.

Table 6 provides summary statistics of domain coverage.