DeepFilters: Scattering-Aware Pupil Engineering with Learned Digital Filter Reconstruction for Extended Depth of Field Microscopy

Extended depth of field microscopy encodes axial information into a single acquisition through engineered point spread functions, but conventional and deep optics approaches are subject to degradation in scattering tissue. We introduce DeepFilters, a scattering-aware deep optics framework that jointly optimizes a parameterized pupil filter and a digital-filter-based reconstruction network through a calibrated differentiable forward model to achieve broad generalization without retraining. Incorporating empirical scattering kernels, physics-guided regularization, and a hybrid genetic-gradient initialization strategy, DeepFilters extends the PSF from 16 micron to >400 micron in clear media and enables signal recovery beyond 120 micron deep in biological tissues, validated across fixed brain slices and sea urchin embryos.

Whitened Score Diffusion: A Structured Prior for Imaging Inverse Problems

Conventional score-based diffusion models (DMs) may struggle with anisotropic Gaussian diffusion processes due to the required inversion of covariance matrices in the denoising score matching training objective \cite{vincent_connection_2011}. We propose Whitened Score (WS) diffusion models, a novel SDE-based framework that learns the Whitened Score function instead of the standard score. This approach circumvents covariance inversion, extending score-based DMs by enabling stable training of DMs on arbitrary Gaussian forward noising processes. WS DMs establish equivalence with FM for arbitrary Gaussian noise, allow for tailored spectral inductive biases, and provide strong Bayesian priors for imaging inverse problems with structured noise. We experiment with a variety of computational imaging tasks using the CIFAR and CelebA ($64\times64$) datasets and demonstrate that WS diffusion priors trained on anisotropic Gaussian noising processes consistently outperform conventional diffusion priors based on isotropic Gaussian noise.

Robust single-shot 3D fluorescence imaging in scattering media with a simulator-trained neural network

Imaging through scattering is a pervasive and difficult problem in many biological applications. The high background and the exponentially attenuated target signals due to scattering fundamentally limits the imaging depth of fluorescence microscopy. Light-field systems are favorable for high-speed volumetric imaging, but the 2D-to-3D reconstruction is fundamentally ill-posed and scattering exacerbates the condition of the inverse problem. Here, we develop a scattering simulator that models low-contrast target signals buried in heterogeneous strong background. We then train a deep neural network solely on synthetic data to descatter and reconstruct a 3D volume from a single-shot light-field measurement with low signal-to-background ratio (SBR). We apply this network to our previously developed Computational Miniature Mesoscope and demonstrate the robustness of our deep learning algorithm on a 75 micron thick fixed mouse brain section and on bulk scattering phantoms with different scattering conditions. The network can robustly reconstruct emitters in 3D with a 2D measurement of SBR as low as 1.05 and as deep as a scattering length. We analyze fundamental tradeoffs based on network design factors and out-of-distribution data that affect the deep learning model's generalizability to real experimental data. Broadly, we believe that our simulator-based deep learning approach can be applied to a wide range of imaging through scattering techniques where experimental paired training data is lacking.