Multi-spectral imaging, which simultaneously captures the spatial and spectral information of a scene, is widely used across diverse fields, including remote sensing, biomedical imaging, and agricultural monitoring. Here, we introduce a snapshot multi-spectral imaging approach employing a standard monochrome image sensor with no additional spectral filters or customized components. Our system leverages the inherent chromatic aberration of wavelength-dependent defocusing as a natural source of physical encoding of multi-spectral information; this encoded image information is rapidly decoded via a deep learning-based multi-spectral Fourier Imager Network (mFIN). We experimentally tested our method with six illumination bands and demonstrated an overall accuracy of 92.98% for predicting the illumination channels at the input and achieved a robust multi-spectral image reconstruction on various test objects. This deep learning-powered framework achieves high-quality multi-spectral image reconstruction using snapshot image acquisition with a monochrome image sensor and could be useful for applications in biomedicine, industrial quality control, and agriculture, among others.

Virtual staining of tissue offers a powerful tool for transforming label-free microscopy images of unstained tissue into equivalents of histochemically stained samples. This study presents a diffusion model-based super-resolution virtual staining approach utilizing a Brownian bridge process to enhance both the spatial resolution and fidelity of label-free virtual tissue staining, addressing the limitations of traditional deep learning-based methods. Our approach integrates novel sampling techniques into a diffusion model-based image inference process to significantly reduce the variance in the generated virtually stained images, resulting in more stable and accurate outputs. Blindly applied to lower-resolution auto-fluorescence images of label-free human lung tissue samples, the diffusion-based super-resolution virtual staining model consistently outperformed conventional approaches in resolution, structural similarity and perceptual accuracy, successfully achieving a super-resolution factor of 4-5x, increasing the output space-bandwidth product by 16-25-fold compared to the input label-free microscopy images. Diffusion-based super-resolved virtual tissue staining not only improves resolution and image quality but also enhances the reliability of virtual staining without traditional chemical staining, offering significant potential for clinical diagnostics.

Generative models cover various application areas, including image, video and music synthesis, natural language processing, and molecular design, among many others. As digital generative models become larger, scalable inference in a fast and energy-efficient manner becomes a challenge. Here, we present optical generative models inspired by diffusion models, where a shallow and fast digital encoder first maps random noise into phase patterns that serve as optical generative seeds for a desired data distribution; a jointly-trained free-space-based reconfigurable decoder all-optically processes these generative seeds to create novel images (never seen before) following the target data distribution. Except for the illumination power and the random seed generation through a shallow encoder, these optical generative models do not consume computing power during the synthesis of novel images. We report the optical generation of monochrome and multi-color novel images of handwritten digits, fashion products, butterflies, and human faces, following the data distributions of MNIST, Fashion MNIST, Butterflies-100, and Celeb-A datasets, respectively, achieving an overall performance comparable to digital neural network-based generative models. To experimentally demonstrate optical generative models, we used visible light to generate, in a snapshot, novel images of handwritten digits and fashion products. These optical generative models might pave the way for energy-efficient, scalable and rapid inference tasks, further exploiting the potentials of optics and photonics for artificial intelligence-generated content.

We developed a rapid scanning optical microscope, termed "BlurryScope", that leverages continuous image acquisition and deep learning to provide a cost-effective and compact solution for automated inspection and analysis of tissue sections. BlurryScope integrates specialized hardware with a neural network-based model to quickly process motion-blurred histological images and perform automated pathology classification. This device offers comparable speed to commercial digital pathology scanners, but at a significantly lower price point and smaller size/weight, making it ideal for fast triaging in small clinics, as well as for resourcelimited settings. To demonstrate the proof-of-concept of BlurryScope, we implemented automated classification of human epidermal growth factor receptor 2 (HER2) scores on immunohistochemically (IHC) stained breast tissue sections, achieving concordant results with those obtained from a high-end digital scanning microscope. We evaluated this approach by scanning HER2-stained tissue microarrays (TMAs) at a continuous speed of 5,000 µm/s, which introduces bidirectional motion blur artifacts. These compromised images were then used to train our network models. Using a test set of 284 unique patient cores, we achieved blind testing accuracies of 79.3% and 89.7% for 4-class (0, 1+, 2+, 3+) and 2-class (0/1+, 2+/3+) HER2 score classification, respectively. BlurryScope automates the entire workflow, from image scanning to stitching and cropping of regions of interest, as well as HER2 score classification. We believe BlurryScope has the potential to enhance the current pathology infrastructure in resource-scarce environments, save diagnostician time and bolster cancer identification and classification across various clinical environments.

The past decade has witnessed transformative applications of deep learning in various computational imaging, sensing and microscopy tasks. Due to the supervised learning schemes employed, these methods mostly depend on large-scale, diverse, and labeled training data. The acquisition and preparation of such training image datasets are often laborious and costly, also leading to biased estimation and limited generalization to new sample types. Here, we report a self-supervised learning model, termed GedankenNet, that eliminates the need for labeled or experimental training data, and demonstrate its effectiveness and superior generalization on hologram reconstruction tasks. Without prior knowledge about the sample types to be imaged, the self-supervised learning model was trained using a physics-consistency loss and artificial random images that are synthetically generated without any experiments or resemblance to real-world samples. After its self-supervised training, GedankenNet successfully generalized to experimental holograms of various unseen biological samples, reconstructing the phase and amplitude images of different types of objects using experimentally acquired test holograms. Without access to experimental data or knowledge of real samples of interest or their spatial features, GedankenNet's self-supervised learning achieved complex-valued image reconstructions that are consistent with the Maxwell's equations, and its output inference and object solutions accurately represent the wave propagation in free-space. GedankenNet framework also exhibits resilience to random, unknown perturbations in the physical forward model, including changes in the hologram distances, pixel size and illumination wavelength. This self-supervised learning of image reconstruction tasks creates new opportunities for various inverse problems in holography, microscopy and computational imaging fields.

Uncertainty estimation is critical for numerous applications of deep neural networks and draws growing attention from researchers. Here, we demonstrate an uncertainty quantification approach for deep neural networks used in inverse problems based on cycle consistency. We build forward-backward cycles using the physical forward model available and a trained deep neural network solving the inverse problem at hand, and accordingly derive uncertainty estimators through regression analysis on the consistency of these forward-backward cycles. We theoretically analyze cycle consistency metrics and derive their relationship with respect to uncertainty, bias, and robustness of the neural network inference. To demonstrate the effectiveness of these cycle consistency-based uncertainty estimators, we classified corrupted and out-of-distribution input image data using some of the widely used image deblurring and super-resolution neural networks as testbeds. The blind testing of our method outperformed other models in identifying unseen input data corruption and distribution shifts. This work provides a simple-to-implement and rapid uncertainty quantification method that can be universally applied to various neural networks used for solving inverse problems.

The application of deep learning techniques has greatly enhanced holographic imaging capabilities, leading to improved phase recovery and image reconstruction. Here, we introduce a deep neural network termed enhanced Fourier Imager Network (eFIN) as a highly generalizable framework for hologram reconstruction with pixel super-resolution and image autofocusing. Through holographic microscopy experiments involving lung, prostate and salivary gland tissue sections and Papanicolau (Pap) smears, we demonstrate that eFIN has a superior image reconstruction quality and exhibits external generalization to new types of samples never seen during the training phase. This network achieves a wide autofocusing axial range of 0.35 mm, with the capability to accurately predict the hologram axial distances by physics-informed learning. eFIN enables 3x pixel super-resolution imaging and increases the space-bandwidth product of the reconstructed images by 9-fold with almost no performance loss, which allows for significant time savings in holographic imaging and data processing steps. Our results showcase the advancements of eFIN in pushing the boundaries of holographic imaging for various applications in e.g., quantitative phase imaging and label-free microscopy.