Background2Background: a self-supervised background removal framework for high dimensional microscopy

Classifiers based on Deep Neural Networks exhibit strong performance across domains, yet can fail catastrophically if they rely on spurious correlations, i.e., features that are predictive of the target label in the training data but are not causally linked and thus fail to generalize. For the vision domain, many such spurious correlations manifest themselves within the background of the image, where only the foreground is predictive of the class label. In this paper, we introduce Automated Background Swapping (AutoBackSwap) to reduce the reliance of classifiers on such spurious backgrounds. AutoBackSwap uses a secondary network to disentangle the foreground and background, followed by infilling to synthesize complete backgrounds, and finally combines different foregrounds and inpainted backgrounds to augment the training data. We find that patch-wise labeling of just a few hundred samples suffices to train the secondary network and automatically augment the full training dataset on challenging image classification tasks. In contrast to many previous methods, AutoBackSwap proves very effective even if there is not a single sample in the training data breaking the spurious correlation. Across a range of image classification tasks with spurious backgrounds, AutoBackSwap consistently outperforms prior methods.

Fluorescence microscopy images are degraded by noise and diffraction-induced blur, which compromise structural fidelity and limit quantitative analysis. Supervised deep learning methods achieve impressive restoration performance but require large-scale paired datasets that are difficult to obtain in practice. To address this issue, we propose SDIP, a zero-shot deep image prior (DIP) framework that sequentially performs denoising and deconvolution without external training data. An aSeqDIP-based module first suppresses noise while preserving fine structures through sequential autoencoding regularization. In the deconvolution stage, a wavelet-based background correction step is incorporated before the proposed RLG-DIP module performs artifact-reduced deconvolution. RLG-DIP uses the Richardson-Lucy deconvolution result as a physically consistent guidance prior, integrating the imaging model with the implicit prior of DIP to stabilize the ill-posed deconvolution process. Experiments on the BioSR dataset across multiple cellular structures demonstrate that SDIP improves both signal-to-noise ratio and resolution, achieving superior visual quality and improved quantitative performance on most evaluated structures. The proposed framework may also provide useful insights for designing physically guided DIP methods for other inverse problems.

Image Scanning Microscopy (ISM) is a fluorescence imaging technique that combines detector-array acquisition and computational reconstruction to achieve the theoretical resolution of an ideal confocal microscope, i.e., one operating with an infinitesimally small pinhole, while maintaining high signal-to-noise ratio. Among the reconstruction methods for obtaining the super-resolved image, multi-image deconvolution (MID) and its extension aimed at preserving the optical sectioning capability of confocal microscopy, known as super-resolution sectioning ISM (s$^2$ISM), are among the most widely used approaches. Both methods rely on Richardson--Lucy-type iterative schemes, whose semi-convergent behavior requires early stopping and often leads to noise amplification and reconstruction artifacts. In this work, we introduce a self-tuning explicit regularization framework for both MID and s$^2$ISM reconstruction. Within a Bayesian maximum a posteriori formulation, we combine a multi-frame Poisson data fidelity term with explicit regularization, considering $\ell_1$ and smoothed total variation penalties as representative examples. We further develop an automatic and ground-truth-free strategy for regularization parameter selection by adapting the residual whiteness principle to the multi-frame Poisson setting and introducing a spectral high-pass extension tailored to s$^2$ISM. The resulting framework enables stable reconstructions without empirical stopping rules. To demonstrate the proposed framework, we consider first-order optimization schemes based on proximal gradient and mirror descent methods with adaptive backtracking strategies. Experiments on simulated and real fluorescence ISM datasets demonstrate improved reconstruction stability and image quality with respect to unregularized approaches, while enabling robust super-resolution and optical sectioning in low-photon conditions.