Jingxi Li

Jingxi Li, Yi-Chun Hung, Onur Kulce et al.

Research on optical computing has recently attracted significant attention due to the transformative advances in machine learning. Among different approaches, diffractive optical networks composed of spatially-engineered transmissive surfaces have been demonstrated for all-optical statistical inference and performing arbitrary linear transformations using passive, free-space optical layers. Here, we introduce a polarization multiplexed diffractive processor to all-optically perform multiple, arbitrarily-selected linear transformations through a single diffractive network trained using deep learning. In this framework, an array of pre-selected linear polarizers is positioned between trainable transmissive diffractive materials that are isotropic, and different target linear transformations (complex-valued) are uniquely assigned to different combinations of input/output polarization states. The transmission layers of this polarization multiplexed diffractive network are trained and optimized via deep learning and error-backpropagation by using thousands of examples of the input/output fields corresponding to each one of the complex-valued linear transformations assigned to different input/output polarization combinations. Our results and analysis reveal that a single diffractive network can successfully approximate and all-optically implement a group of arbitrarily-selected target transformations with a negligible error when the number of trainable diffractive features/neurons (N) approaches N_p x N_i x N_o, where N_i and N_o represent the number of pixels at the input and output fields-of-view, respectively, and N_p refers to the number of unique linear transformations assigned to different input/output polarization combinations. This polarization-multiplexed all-optical diffractive processor can find various applications in optical computing and polarization-based machine vision tasks.

Jingxi Li, Tianyi Gan, Yifan Zhao et al.

A unidirectional imager would only permit image formation along one direction, from an input field-of-view (FOV) A to an output FOV B, and in the reverse path, the image formation would be blocked. Here, we report the first demonstration of unidirectional imagers, presenting polarization-insensitive and broadband unidirectional imaging based on successive diffractive layers that are linear and isotropic. These diffractive layers are optimized using deep learning and consist of hundreds of thousands of diffractive phase features, which collectively modulate the incoming fields and project an intensity image of the input onto an output FOV, while blocking the image formation in the reverse direction. After their deep learning-based training, the resulting diffractive layers are fabricated to form a unidirectional imager. As a reciprocal device, the diffractive unidirectional imager has asymmetric mode processing capabilities in the forward and backward directions, where the optical modes from B to A are selectively guided/scattered to miss the output FOV, whereas for the forward direction such modal losses are minimized, yielding an ideal imaging system between the input and output FOVs. Although trained using monochromatic illumination, the diffractive unidirectional imager maintains its functionality over a large spectral band and works under broadband illumination. We experimentally validated this unidirectional imager using terahertz radiation, very well matching our numerical results. Using the same deep learning-based design strategy, we also created a wavelength-selective unidirectional imager, where two unidirectional imaging operations, in reverse directions, are multiplexed through different illumination wavelengths. Diffractive unidirectional imaging using structured materials will have numerous applications in e.g., security, defense, telecommunications and privacy protection.

Cagatay Isil, Deniz Mengu, Yifan Zhao et al.

High-resolution synthesis/projection of images over a large field-of-view (FOV) is hindered by the restricted space-bandwidth-product (SBP) of wavefront modulators. We report a deep learning-enabled diffractive display design that is based on a jointly-trained pair of an electronic encoder and a diffractive optical decoder to synthesize/project super-resolved images using low-resolution wavefront modulators. The digital encoder, composed of a trained convolutional neural network (CNN), rapidly pre-processes the high-resolution images of interest so that their spatial information is encoded into low-resolution (LR) modulation patterns, projected via a low SBP wavefront modulator. The diffractive decoder processes this LR encoded information using thin transmissive layers that are structured using deep learning to all-optically synthesize and project super-resolved images at its output FOV. Our results indicate that this diffractive image display can achieve a super-resolution factor of ~4, demonstrating a ~16-fold increase in SBP. We also experimentally validate the success of this diffractive super-resolution display using 3D-printed diffractive decoders that operate at the THz spectrum. This diffractive image decoder can be scaled to operate at visible wavelengths and inspire the design of large FOV and high-resolution displays that are compact, low-power, and computationally efficient.

Cagatay Isıl, Tianyi Gan, F. Onuralp Ardic et al.

Image denoising, one of the essential inverse problems, targets to remove noise/artifacts from input images. In general, digital image denoising algorithms, executed on computers, present latency due to several iterations implemented in, e.g., graphics processing units (GPUs). While deep learning-enabled methods can operate non-iteratively, they also introduce latency and impose a significant computational burden, leading to increased power consumption. Here, we introduce an analog diffractive image denoiser to all-optically and non-iteratively clean various forms of noise and artifacts from input images - implemented at the speed of light propagation within a thin diffractive visual processor. This all-optical image denoiser comprises passive transmissive layers optimized using deep learning to physically scatter the optical modes that represent various noise features, causing them to miss the output image Field-of-View (FoV) while retaining the object features of interest. Our results show that these diffractive denoisers can efficiently remove salt and pepper noise and image rendering-related spatial artifacts from input phase or intensity images while achieving an output power efficiency of ~30-40%. We experimentally demonstrated the effectiveness of this analog denoiser architecture using a 3D-printed diffractive visual processor operating at the terahertz spectrum. Owing to their speed, power-efficiency, and minimal computational overhead, all-optical diffractive denoisers can be transformative for various image display and projection systems, including, e.g., holographic displays.

Tairan Liu, Yuzhu Li, Hatice Ceylan Koydemir et al.

We present a rapid and stain-free quantitative viral plaque assay using lensfree holographic imaging and deep learning. This cost-effective, compact, and automated device significantly reduces the incubation time needed for traditional plaque assays while preserving their advantages over other virus quantification methods. This device captures ~0.32 Giga-pixel/hour phase information of the objects per test well, covering an area of ~30x30 mm^2, in a label-free manner, eliminating staining entirely. We demonstrated the success of this computational method using vesicular stomatitis virus (VSV), herpes simplex virus (HSV-1) and encephalomyocarditis virus (EMCV). Using a neural network, this stain-free device automatically detected the first cell lysing events due to the VSV viral replication as early as 5 hours after the incubation, and achieved >90% detection rate for the VSV plaque-forming units (PFUs) with 100% specificity in <20 hours, providing major time savings compared to the traditional plaque assays that take at least 48 hours. Similarly, this stain-free device reduced the needed incubation time by ~48 hours for HSV-1 and ~20 hours for EMCV, achieving >90% detection rate with 100% specificity. We also demonstrated that this data-driven plaque assay offers the capability of quantifying the infected area of the cell monolayer, performing automated counting and quantification of PFUs and virus-infected areas over a 10-fold larger dynamic range of virus concentration than standard viral plaque assays. This compact, low-cost, automated PFU quantification device can be broadly used in virology research, vaccine development, and clinical applications.

Che-Yung Shen, Jingxi Li, Deniz Mengu et al.

As a label-free imaging technique, quantitative phase imaging (QPI) provides optical path length information of transparent specimens for various applications in biology, materials science, and engineering. Multispectral QPI measures quantitative phase information across multiple spectral bands, permitting the examination of wavelength-specific phase and dispersion characteristics of samples. Here, we present the design of a diffractive processor that can all-optically perform multispectral quantitative phase imaging of transparent phase-only objects in a snapshot. Our design utilizes spatially engineered diffractive layers, optimized through deep learning, to encode the phase profile of the input object at a predetermined set of wavelengths into spatial intensity variations at the output plane, allowing multispectral QPI using a monochrome focal plane array. Through numerical simulations, we demonstrate diffractive multispectral processors to simultaneously perform quantitative phase imaging at 9 and 16 target spectral bands in the visible spectrum. These diffractive multispectral processors maintain uniform performance across all the wavelength channels, revealing a decent QPI performance at each target wavelength. The generalization of these diffractive processor designs is validated through numerical tests on unseen objects, including thin Pap smear images. Due to its all-optical processing capability using passive dielectric diffractive materials, this diffractive multispectral QPI processor offers a compact and power-efficient solution for high-throughput quantitative phase microscopy and spectroscopy. This framework can operate at different parts of the electromagnetic spectrum and be used for a wide range of phase imaging and sensing applications.

Yuzhu Li, Nir Pillar, Jingxi Li et al.

Histological examination is a crucial step in an autopsy; however, the traditional histochemical staining of post-mortem samples faces multiple challenges, including the inferior staining quality due to autolysis caused by delayed fixation of cadaver tissue, as well as the resource-intensive nature of chemical staining procedures covering large tissue areas, which demand substantial labor, cost, and time. These challenges can become more pronounced during global health crises when the availability of histopathology services is limited, resulting in further delays in tissue fixation and more severe staining artifacts. Here, we report the first demonstration of virtual staining of autopsy tissue and show that a trained neural network can rapidly transform autofluorescence images of label-free autopsy tissue sections into brightfield equivalent images that match hematoxylin and eosin (H&E) stained versions of the same samples, eliminating autolysis-induced severe staining artifacts inherent in traditional histochemical staining of autopsied tissue. Our virtual H&E model was trained using >0.7 TB of image data and a data-efficient collaboration scheme that integrates the virtual staining network with an image registration network. The trained model effectively accentuated nuclear, cytoplasmic and extracellular features in new autopsy tissue samples that experienced severe autolysis, such as COVID-19 samples never seen before, where the traditional histochemical staining failed to provide consistent staining quality. This virtual autopsy staining technique can also be extended to necrotic tissue, and can rapidly and cost-effectively generate artifact-free H&E stains despite severe autolysis and cell death, also reducing labor, cost and infrastructure requirements associated with the standard histochemical staining.

Che-Yung Shen, Jingxi Li, Tianyi Gan et al.

Optical phase conjugation (OPC) is a nonlinear technique used for counteracting wavefront distortions, with various applications ranging from imaging to beam focusing. Here, we present the design of a diffractive wavefront processor to approximate all-optical phase conjugation operation for input fields with phase aberrations. Leveraging deep learning, a set of passive diffractive layers was optimized to all-optically process an arbitrary phase-aberrated coherent field from an input aperture, producing an output field with a phase distribution that is the conjugate of the input wave. We experimentally validated the efficacy of this wavefront processor by 3D fabricating diffractive layers trained using deep learning and performing OPC on phase distortions never seen by the diffractive processor during its training. Employing terahertz radiation, our physical diffractive processor successfully performed the OPC task through a shallow spatially-engineered volume that axially spans tens of wavelengths. In addition to this transmissive OPC configuration, we also created a diffractive phase-conjugate mirror by combining deep learning-optimized diffractive layers with a standard mirror. Given its compact, passive and scalable nature, our diffractive wavefront processor can be used for diverse OPC-related applications, e.g., turbidity suppression and aberration correction, and is also adaptable to different parts of the electromagnetic spectrum, especially those where cost-effective wavefront engineering solutions do not exist.

Che-Yung Shen, Jingxi Li, Tianyi Gan et al.

Quantitative phase imaging (QPI) is a label-free technique that provides optical path length information for transparent specimens, finding utility in biology, materials science, and engineering. Here, we present quantitative phase imaging of a 3D stack of phase-only objects using a wavelength-multiplexed diffractive optical processor. Utilizing multiple spatially engineered diffractive layers trained through deep learning, this diffractive processor can transform the phase distributions of multiple 2D objects at various axial positions into intensity patterns, each encoded at a unique wavelength channel. These wavelength-multiplexed patterns are projected onto a single field-of-view (FOV) at the output plane of the diffractive processor, enabling the capture of quantitative phase distributions of input objects located at different axial planes using an intensity-only image sensor. Based on numerical simulations, we show that our diffractive processor could simultaneously achieve all-optical quantitative phase imaging across several distinct axial planes at the input by scanning the illumination wavelength. A proof-of-concept experiment with a 3D-fabricated diffractive processor further validated our approach, showcasing successful imaging of two distinct phase objects at different axial positions by scanning the illumination wavelength in the terahertz spectrum. Diffractive network-based multiplane QPI designs can open up new avenues for compact on-chip phase imaging and sensing devices.

Jingtian Hu, Kun Liao, Niyazi Ulas Dinc et al.

Phase imaging is widely used in biomedical imaging, sensing, and material characterization, among other fields. However, direct imaging of phase objects with subwavelength resolution remains a challenge. Here, we demonstrate subwavelength imaging of phase and amplitude objects based on all-optical diffractive encoding and decoding. To resolve subwavelength features of an object, the diffractive imager uses a thin, high-index solid-immersion layer to transmit high-frequency information of the object to a spatially-optimized diffractive encoder, which converts/encodes high-frequency information of the input into low-frequency spatial modes for transmission through air. The subsequent diffractive decoder layers (in air) are jointly designed with the encoder using deep-learning-based optimization, and communicate with the encoder layer to create magnified images of input objects at its output, revealing subwavelength features that would otherwise be washed away due to diffraction limit. We demonstrate that this all-optical collaboration between a diffractive solid-immersion encoder and the following decoder layers in air can resolve subwavelength phase and amplitude features of input objects in a highly compact design. To experimentally demonstrate its proof-of-concept, we used terahertz radiation and developed a fabrication method for creating monolithic multi-layer diffractive processors. Through these monolithically fabricated diffractive encoder-decoder pairs, we demonstrated phase-to-intensity transformations and all-optically reconstructed subwavelength phase features of input objects by directly transforming them into magnified intensity features at the output. This solid-immersion-based diffractive imager, with its compact and cost-effective design, can find wide-ranging applications in bioimaging, endoscopy, sensing and materials characterization.

Danny Barash, Emilie Manning, Aidan Van Vleck et al.

Noninvasive optical imaging modalities can probe patient's tissue in 3D and over time generate gigabytes of clinically relevant data per sample. There is a need for AI models to analyze this data and assist clinical workflow. The lack of expert labelers and the large dataset required (>100,000 images) for model training and tuning are the main hurdles in creating foundation models. In this paper we introduce FoundationShift, a method to apply any AI model from computational pathology without retraining. We show our method is more accurate than state of the art models (SAM, MedSAM, SAM-Med2D, CellProfiler, Hover-Net, PLIP, UNI and ChatGPT), with multiple imaging modalities (OCT and RCM). This is achieved without the need for model retraining or fine-tuning. Applying our method to noninvasive in vivo images could enable physicians to readily incorporate optical imaging modalities into their clinical practice, providing real time tissue analysis and improving patient care.

Bijie Bai, Hongda Wang, Yuzhu Li et al.

The immunohistochemical (IHC) staining of the human epidermal growth factor receptor 2 (HER2) biomarker is widely practiced in breast tissue analysis, preclinical studies and diagnostic decisions, guiding cancer treatment and investigation of pathogenesis. HER2 staining demands laborious tissue treatment and chemical processing performed by a histotechnologist, which typically takes one day to prepare in a laboratory, increasing analysis time and associated costs. Here, we describe a deep learning-based virtual HER2 IHC staining method using a conditional generative adversarial network that is trained to rapidly transform autofluorescence microscopic images of unlabeled/label-free breast tissue sections into bright-field equivalent microscopic images, matching the standard HER2 IHC staining that is chemically performed on the same tissue sections. The efficacy of this virtual HER2 staining framework was demonstrated by quantitative analysis, in which three board-certified breast pathologists blindly graded the HER2 scores of virtually stained and immunohistochemically stained HER2 whole slide images (WSIs) to reveal that the HER2 scores determined by inspecting virtual IHC images are as accurate as their immunohistochemically stained counterparts. A second quantitative blinded study performed by the same diagnosticians further revealed that the virtually stained HER2 images exhibit a comparable staining quality in the level of nuclear detail, membrane clearness, and absence of staining artifacts with respect to their immunohistochemically stained counterparts. This virtual HER2 staining framework bypasses the costly, laborious, and time-consuming IHC staining procedures in laboratory, and can be extended to other types of biomarkers to accelerate the IHC tissue staining used in life sciences and biomedical workflow.

Jingxi Li, Deniz Mengu, Nezih T. Yardimci et al.

3D engineering of matter has opened up new avenues for designing systems that can perform various computational tasks through light-matter interaction. Here, we demonstrate the design of optical networks in the form of multiple diffractive layers that are trained using deep learning to transform and encode the spatial information of objects into the power spectrum of the diffracted light, which are used to perform optical classification of objects with a single-pixel spectroscopic detector. Using a time-domain spectroscopy setup with a plasmonic nanoantenna-based detector, we experimentally validated this machine vision framework at terahertz spectrum to optically classify the images of handwritten digits by detecting the spectral power of the diffracted light at ten distinct wavelengths, each representing one class/digit. We also report the coupling of this spectral encoding achieved through a diffractive optical network with a shallow electronic neural network, separately trained to reconstruct the images of handwritten digits based on solely the spectral information encoded in these ten distinct wavelengths within the diffracted light. These reconstructed images demonstrate task-specific image decompression and can also be cycled back as new inputs to the same diffractive network to improve its optical object classification. This unique machine vision framework merges the power of deep learning with the spatial and spectral processing capabilities of diffractive networks, and can also be extended to other spectral-domain measurement systems to enable new 3D imaging and sensing modalities integrated with spectrally encoded classification tasks performed through diffractive optical networks.

Yijie Zhang, Kevin de Haan, Yair Rivenson et al.

Histological staining is a vital step used to diagnose various diseases and has been used for more than a century to provide contrast to tissue sections, rendering the tissue constituents visible for microscopic analysis by medical experts. However, this process is time-consuming, labor-intensive, expensive and destructive to the specimen. Recently, the ability to virtually-stain unlabeled tissue sections, entirely avoiding the histochemical staining step, has been demonstrated using tissue-stain specific deep neural networks. Here, we present a new deep learning-based framework which generates virtually-stained images using label-free tissue, where different stains are merged following a micro-structure map defined by the user. This approach uses a single deep neural network that receives two different sources of information at its input: (1) autofluorescence images of the label-free tissue sample, and (2) a digital staining matrix which represents the desired microscopic map of different stains to be virtually generated at the same tissue section. This digital staining matrix is also used to virtually blend existing stains, digitally synthesizing new histological stains. We trained and blindly tested this virtual-staining network using unlabeled kidney tissue sections to generate micro-structured combinations of Hematoxylin and Eosin (H&E), Jones silver stain, and Masson's Trichrome stain. Using a single network, this approach multiplexes virtual staining of label-free tissue with multiple types of stains and paves the way for synthesizing new digital histological stains that can be created on the same tissue cross-section, which is currently not feasible with standard histochemical staining methods.

Jingxi Li, Deniz Mengu, Yi Luo et al.

Diffractive deep neural networks have been introduced earlier as an optical machine learning framework that uses task-specific diffractive surfaces designed by deep learning to all-optically perform inference, achieving promising performance for object classification and imaging. Here we demonstrate systematic improvements in diffractive optical neural networks based on a differential measurement technique that mitigates the non-negativity constraint of light intensity. In this scheme, each class is assigned to a separate pair of photodetectors, behind a diffractive network, and the class inference is made by maximizing the normalized signal difference between the detector pairs. Moreover, by utilizing the inherent parallelization capability of optical systems, we reduced the signal coupling between the positive and negative detectors of each class by dividing their optical path into two jointly-trained diffractive neural networks that work in parallel. We further made use of this parallelization approach, and divided individual classes among multiple jointly-trained differential diffractive neural networks. Using this class-specific differential detection in jointly-optimized diffractive networks, our simulations achieved testing accuracies of 98.52%, 91.48% and 50.82% for MNIST, Fashion-MNIST and grayscale CIFAR-10 datasets, respectively. Similar to ensemble methods practiced in machine learning, we also independently-optimized multiple differential diffractive networks that optically project their light onto a common detector plane, and achieved testing accuracies of 98.59%, 91.06% and 51.44% for MNIST, Fashion-MNIST and grayscale CIFAR-10, respectively. Through these systematic advances in designing diffractive neural networks, the reported classification accuracies set the state-of-the-art for an all-optical neural network design.