Yair Rivenson

Cagatay Isil, Hatice Ceylan Koydemir, Merve Eryilmaz et al.

Gram staining has been one of the most frequently used staining protocols in microbiology for over a century, utilized across various fields, including diagnostics, food safety, and environmental monitoring. Its manual procedures make it vulnerable to staining errors and artifacts due to, e.g., operator inexperience and chemical variations. Here, we introduce virtual Gram staining of label-free bacteria using a trained deep neural network that digitally transforms darkfield images of unstained bacteria into their Gram-stained equivalents matching brightfield image contrast. After a one-time training effort, the virtual Gram staining model processes an axial stack of darkfield microscopy images of label-free bacteria (never seen before) to rapidly generate Gram staining, bypassing several chemical steps involved in the conventional staining process. We demonstrated the success of the virtual Gram staining workflow on label-free bacteria samples containing Escherichia coli and Listeria innocua by quantifying the staining accuracy of the virtual Gram staining model and comparing the chromatic and morphological features of the virtually stained bacteria against their chemically stained counterparts. This virtual bacteria staining framework effectively bypasses the traditional Gram staining protocol and its challenges, including stain standardization, operator errors, and sensitivity to chemical variations.

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.

Onur Kulce, Deniz Mengu, Yair Rivenson et al.

We report the design of diffractive surfaces to all-optically perform arbitrary complex-valued linear transformations between an input (N_i) and output (N_o), where N_i and N_o represent the number of pixels at the input and output fields-of-view (FOVs), respectively. First, we consider a single diffractive surface and use a matrix pseudoinverse-based method to determine the complex-valued transmission coefficients of the diffractive features/neurons to all-optically perform a desired/target linear transformation. In addition to this data-free design approach, we also consider a deep learning-based design method to optimize the transmission coefficients of diffractive surfaces by using examples of input/output fields corresponding to the target transformation. We compared the all-optical transformation errors and diffraction efficiencies achieved using data-free designs as well as data-driven (deep learning-based) diffractive designs to all-optically perform (i) arbitrarily-chosen complex-valued transformations including unitary, nonunitary and noninvertible transforms, (ii) 2D discrete Fourier transformation, (iii) arbitrary 2D permutation operations, and (iv) high-pass filtered coherent imaging. Our analyses reveal that if the total number (N) of spatially-engineered diffractive features/neurons is N_i x N_o or larger, both design methods succeed in all-optical implementation of the target transformation, achieving negligible error. However, compared to data-free designs, deep learning-based diffractive designs are found to achieve significantly larger diffraction efficiencies for a given N and their all-optical transformations are more accurate for N < N_i x N_o. These conclusions are generally applicable to various optical processors that employ spatially-engineered diffractive surfaces.

Deniz Mengu, Muhammed Veli, Yair Rivenson et al.

Diffractive optical networks unify wave optics and deep learning to all-optically compute a given machine learning or computational imaging task as the light propagates from the input to the output plane. Here, we report the design of diffractive optical networks for the classification and reconstruction of spatially overlapping, phase-encoded objects. When two different phase-only objects spatially overlap, the individual object functions are perturbed since their phase patterns are summed up. The retrieval of the underlying phase images from solely the overlapping phase distribution presents a challenging problem, the solution of which is generally not unique. We show that through a task-specific training process, passive diffractive networks composed of successive transmissive layers can all-optically and simultaneously classify two different randomly-selected, spatially overlapping phase images at the input. After trained with ~550 million unique combinations of phase-encoded handwritten digits from the MNIST dataset, our blind testing results reveal that the diffractive network achieves an accuracy of >85.8% for all-optical classification of two overlapping phase images of new handwritten digits. In addition to all-optical classification of overlapping phase objects, we also demonstrate the reconstruction of these phase images based on a shallow electronic neural network that uses the highly compressed output of the diffractive network as its input (with e.g., ~20-65 times less number of pixels) to rapidly reconstruct both of the phase images, despite their spatial overlap and related phase ambiguity. The presented phase image classification and reconstruction framework might find applications in e.g., computational imaging, microscopy and quantitative phase imaging fields.

Yijie Zhang, Tairan Liu, Manmohan Singh et al.

Optical Coherence Tomography (OCT) is a widely used non-invasive biomedical imaging modality that can rapidly provide volumetric images of samples. Here, we present a deep learning-based image reconstruction framework that can generate swept-source OCT (SS-OCT) images using undersampled spectral data, without any spatial aliasing artifacts. This neural network-based image reconstruction does not require any hardware changes to the optical set-up and can be easily integrated with existing swept-source or spectral domain OCT systems to reduce the amount of raw spectral data to be acquired. To show the efficacy of this framework, we trained and blindly tested a deep neural network using mouse embryo samples imaged by an SS-OCT system. Using 2-fold undersampled spectral data (i.e., 640 spectral points per A-line), the trained neural network can blindly reconstruct 512 A-lines in ~6.73 ms using a desktop computer, removing spatial aliasing artifacts due to spectral undersampling, also presenting a very good match to the images of the same samples, reconstructed using the full spectral OCT data (i.e., 1280 spectral points per A-line). We also successfully demonstrate that this framework can be further extended to process 3x undersampled spectral data per A-line, with some performance degradation in the reconstructed image quality compared to 2x spectral undersampling. This deep learning-enabled image reconstruction approach can be broadly used in various forms of spectral domain OCT systems, helping to increase their imaging speed without sacrificing image resolution and signal-to-noise ratio.

Calvin Brown, Artem Goncharov, Zachary Ballard et al.

Conventional spectrometers are limited by trade-offs set by size, cost, signal-to-noise ratio (SNR), and spectral resolution. Here, we demonstrate a deep learning-based spectral reconstruction framework, using a compact and low-cost on-chip sensing scheme that is not constrained by the design trade-offs inherent to grating-based spectroscopy. The system employs a plasmonic spectral encoder chip containing 252 different tiles of nanohole arrays fabricated using a scalable and low-cost imprint lithography method, where each tile has a unique geometry and, thus, a unique optical transmission spectrum. The illumination spectrum of interest directly impinges upon the plasmonic encoder, and a CMOS image sensor captures the transmitted light, without any lenses, gratings, or other optical components in between, making the entire hardware highly compact, light-weight and field-portable. A trained neural network then reconstructs the unknown spectrum using the transmitted intensity information from the spectral encoder in a feed-forward and non-iterative manner. Benefiting from the parallelization of neural networks, the average inference time per spectrum is ~28 microseconds, which is orders of magnitude faster compared to other computational spectroscopy approaches. When blindly tested on unseen new spectra (N = 14,648) with varying complexity, our deep-learning based system identified 96.86% of the spectral peaks with an average peak localization error, bandwidth error, and height error of 0.19 nm, 0.18 nm, and 7.60%, respectively. This system is also highly tolerant to fabrication defects that may arise during the imprint lithography process, which further makes it ideal for applications that demand cost-effective, field-portable and sensitive high-resolution spectroscopy tools.

Kevin de Haan, Yijie Zhang, Jonathan E. Zuckerman et al.

Pathology is practiced by visual inspection of histochemically stained slides. Most commonly, the hematoxylin and eosin (H&E) stain is used in the diagnostic workflow and it is the gold standard for cancer diagnosis. However, in many cases, especially for non-neoplastic diseases, additional "special stains" are used to provide different levels of contrast and color to tissue components and allow pathologists to get a clearer diagnostic picture. In this study, we demonstrate the utility of supervised learning-based computational stain transformation from H&E to different special stains (Masson's Trichrome, periodic acid-Schiff and Jones silver stain) using tissue sections from kidney needle core biopsies. Based on evaluation by three renal pathologists, followed by adjudication by a fourth renal pathologist, we show that the generation of virtual special stains from existing H&E images improves the diagnosis in several non-neoplastic kidney diseases sampled from 58 unique subjects. A second study performed by three pathologists found that the quality of the special stains generated by the stain transformation network was statistically equivalent to those generated through standard histochemical staining. As the transformation of H&E images into special stains can be achieved within 1 min or less per patient core specimen slide, this stain-to-stain transformation framework can improve the quality of the preliminary diagnosis when additional special stains are needed, along with significant savings in time and cost, reducing the burden on healthcare system and patients.

Onur Kulce, Deniz Mengu, Yair Rivenson et al.

Precise engineering of materials and surfaces has been at the heart of some of the recent advances in optics and photonics. These advances around the engineering of materials with new functionalities have also opened up exciting avenues for designing trainable surfaces that can perform computation and machine learning tasks through light-matter interaction and diffraction. Here, we analyze the information processing capacity of coherent optical networks formed by diffractive surfaces that are trained to perform an all-optical computational task between a given input and output field-of-view. We show that the dimensionality of the all-optical solution space covering the complex-valued transformations between the input and output fields-of-view is linearly proportional to the number of diffractive surfaces within the optical network, up to a limit that is dictated by the extent of the input and output fields-of-view. Deeper diffractive networks that are composed of larger numbers of trainable surfaces can cover a higher dimensional subspace of the complex-valued linear transformations between a larger input field-of-view and a larger output field-of-view, and exhibit depth advantages in terms of their statistical inference, learning and generalization capabilities for different image classification tasks, when compared with a single trainable diffractive surface. These analyses and conclusions are broadly applicable to various forms of diffractive surfaces, including e.g., plasmonic and/or dielectric-based metasurfaces and flat optics that can be used to form all-optical processors.

Tairan Liu, Kevin de Haan, Bijie Bai et al.

Polarized light microscopy provides high contrast to birefringent specimen and is widely used as a diagnostic tool in pathology. However, polarization microscopy systems typically operate by analyzing images collected from two or more light paths in different states of polarization, which lead to relatively complex optical designs, high system costs or experienced technicians being required. Here, we present a deep learning-based holographic polarization microscope that is capable of obtaining quantitative birefringence retardance and orientation information of specimen from a phase recovered hologram, while only requiring the addition of one polarizer/analyzer pair to an existing holographic imaging system. Using a deep neural network, the reconstructed holographic images from a single state of polarization can be transformed into images equivalent to those captured using a single-shot computational polarized light microscope (SCPLM). Our analysis shows that a trained deep neural network can extract the birefringence information using both the sample specific morphological features as well as the holographic amplitude and phase distribution. To demonstrate the efficacy of this method, we tested it by imaging various birefringent samples including e.g., monosodium urate (MSU) and triamcinolone acetonide (TCA) crystals. Our method achieves similar results to SCPLM both qualitatively and quantitatively, and due to its simpler optical design and significantly larger field-of-view, this method has the potential to expand the access to polarization microscopy and its use for medical diagnosis in resource limited settings.

Deniz Mengu, Yifan Zhao, Nezih T. Yardimci et al.

As an optical machine learning framework, Diffractive Deep Neural Networks (D2NN) take advantage of data-driven training methods used in deep learning to devise light-matter interaction in 3D for performing a desired statistical inference task. Multi-layer optical object recognition platforms designed with this diffractive framework have been shown to generalize to unseen image data achieving e.g., >98% blind inference accuracy for hand-written digit classification. The multi-layer structure of diffractive networks offers significant advantages in terms of their diffraction efficiency, inference capability and optical signal contrast. However, the use of multiple diffractive layers also brings practical challenges for the fabrication and alignment of these diffractive systems for accurate optical inference. Here, we introduce and experimentally demonstrate a new training scheme that significantly increases the robustness of diffractive networks against 3D misalignments and fabrication tolerances in the physical implementation of a trained diffractive network. By modeling the undesired layer-to-layer misalignments in 3D as continuous random variables in the optical forward model, diffractive networks are trained to maintain their inference accuracy over a large range of misalignments; we term this diffractive network design as vaccinated D2NN (v-D2NN). We further extend this vaccination strategy to the training of diffractive networks that use differential detectors at the output plane as well as to jointly-trained hybrid (optical-electronic) networks to reveal that all of these diffractive designs improve their resilience to misalignments by taking into account possible 3D fabrication variations and displacements during their training phase.

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.

Hongda Wang, Hatice Ceylan Koydemir, Yunzhe Qiu et al.

We present a computational live bacteria detection system that periodically captures coherent microscopy images of bacterial growth inside a 60 mm diameter agar-plate and analyzes these time-lapsed holograms using deep neural networks for rapid detection of bacterial growth and classification of the corresponding species. The performance of our system was demonstrated by rapid detection of Escherichia coli and total coliform bacteria (i.e., Klebsiella aerogenes and Klebsiella pneumoniae subsp. pneumoniae) in water samples. These results were confirmed against gold-standard culture-based results, shortening the detection time of bacterial growth by >12 h as compared to the Environmental Protection Agency (EPA)-approved analytical methods. Our experiments further confirmed that this method successfully detects 90% of bacterial colonies within 7-10 h (and >95% within 12 h) with a precision of 99.2-100%, and correctly identifies their species in 7.6-12 h with 80% accuracy. Using pre-incubation of samples in growth media, our system achieved a limit of detection (LOD) of ~1 colony forming unit (CFU)/L within 9 h of total test time. This computational bacteria detection and classification platform is highly cost-effective (~$0.6 per test) and high-throughput with a scanning speed of 24 cm2/min over the entire plate surface, making it highly suitable for integration with the existing analytical methods currently used for bacteria detection on agar plates. Powered by deep learning, this automated and cost-effective live bacteria detection platform can be transformative for a wide range of applications in microbiology by significantly reducing the detection time, also automating the identification of colonies, without labeling or the need for an expert.

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.

Yi Luo, Deniz Mengu, Nezih T. Yardimci et al.

We report a broadband diffractive optical neural network design that simultaneously processes a continuum of wavelengths generated by a temporally-incoherent broadband source to all-optically perform a specific task learned using deep learning. We experimentally validated the success of this broadband diffractive neural network architecture by designing, fabricating and testing seven different multi-layer, diffractive optical systems that transform the optical wavefront generated by a broadband THz pulse to realize (1) a series of tunable, single passband as well as dual passband spectral filters, and (2) spatially-controlled wavelength de-multiplexing. Merging the native or engineered dispersion of various material systems with a deep learning-based design strategy, broadband diffractive neural networks help us engineer light-matter interaction in 3D, diverging from intuitive and analytical design methods to create task-specific optical components that can all-optically perform deterministic tasks or statistical inference for optical machine learning.

Tairan Liu, Zhensong Wei, Yair Rivenson et al.

We report a framework based on a generative adversarial network (GAN) that performs high-fidelity color image reconstruction using a single hologram of a sample that is illuminated simultaneously by light at three different wavelengths. The trained network learns to eliminate missing-phase-related artifacts, and generates an accurate color transformation for the reconstructed image. Our framework is experimentally demonstrated using lung and prostate tissue sections that are labeled with different histological stains. This framework is envisaged to be applicable to point-of-care histopathology, and presents a significant improvement in the throughput of coherent microscopy systems given that only a single hologram of the specimen is required for accurate color imaging.

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.

Kevin de Haan, Zachary S. Ballard, Yair Rivenson et al.

We report resolution enhancement in scanning electron microscopy (SEM) images using a generative adversarial network. We demonstrate the veracity of this deep learning-based super-resolution technique by inferring unresolved features in low-resolution SEM images and comparing them with the accurately co-registered high-resolution SEM images of the same samples. Through spatial frequency analysis, we also report that our method generates images with frequency spectra matching higher resolution SEM images of the same fields-of-view. By using this technique, higher resolution SEM images can be taken faster, while also reducing both electron charging and damage to the samples.

Yichen Wu, Yilin Luo, Gunvant Chaudhari et al.

Deep learning brings bright-field microscopy contrast to holographic images of a sample volume, bridging the volumetric imaging capability of holography with the speckle- and artifact-free image contrast of bright-field incoherent microscopy.

Deniz Mengu, Yi Luo, Yair Rivenson et al.

In their Comment, Wei et al. (arXiv:1809.08360v1 [cs.LG]) claim that our original interpretation of Diffractive Deep Neural Networks (D2NN) represent a mischaracterization of the system due to linearity and passivity. In this Response, we detail how this mischaracterization claim is unwarranted and oblivious to several sections detailed in our original manuscript (Science, DOI: 10.1126/science.aat8084) that specifically introduced and discussed optical nonlinearities and reconfigurability of D2NNs, as part of our proposed framework to enhance its performance. To further refute the mischaracterization claim of Wei et al., we, once again, demonstrate the depth feature of optical D2NNs by showing that multiple diffractive layers operating collectively within a D2NN present additional degrees-of-freedom compared to a single diffractive layer to achieve better classification accuracy, as well as improved output signal contrast and diffraction efficiency as the number of diffractive layers increase, showing the deepness of a D2NN, and its inherent depth advantage for improved performance. In summary, the Comment by Wei et al. does not provide an amendment to the original teachings of our original manuscript, and all of our results, core conclusions and methodology of research reported in Science (DOI: 10.1126/science.aat8084) remain entirely valid.

Deniz Mengu, Yi Luo, Yair Rivenson et al.

Optical machine learning offers advantages in terms of power efficiency, scalability and computation speed. Recently, an optical machine learning method based on Diffractive Deep Neural Networks (D2NNs) has been introduced to execute a function as the input light diffracts through passive layers, designed by deep learning using a computer. Here we introduce improvements to D2NNs by changing the training loss function and reducing the impact of vanishing gradients in the error back-propagation step. Using five phase-only diffractive layers, we numerically achieved a classification accuracy of 97.18% and 89.13% for optical recognition of handwritten digits and fashion products, respectively; using both phase and amplitude modulation (complex-valued) at each layer, our inference performance improved to 97.81% and 89.32%, respectively. Furthermore, we report the integration of D2NNs with electronic neural networks to create hybrid-classifiers that significantly reduce the number of input pixels into an electronic network using an ultra-compact front-end D2NN with a layer-to-layer distance of a few wavelengths, also reducing the complexity of the successive electronic network. Using a 5-layer phase-only D2NN jointly-optimized with a single fully-connected electronic layer, we achieved a classification accuracy of 98.71% and 90.04% for the recognition of handwritten digits and fashion products, respectively. Moreover, the input to the electronic network was compressed by >7.8 times down to 10x10 pixels. Beyond creating low-power and high-frame rate machine learning platforms, D2NN-based hybrid neural networks will find applications in smart optical imager and sensor design.

Yair Rivenson, Tairan Liu, Zhensong Wei et al.

Using a deep neural network, we demonstrate a digital staining technique, which we term PhaseStain, to transform quantitative phase images (QPI) of labelfree tissue sections into images that are equivalent to brightfield microscopy images of the same samples that are histochemically stained. Through pairs of image data (QPI and the corresponding brightfield images, acquired after staining) we train a generative adversarial network (GAN) and demonstrate the effectiveness of this virtual staining approach using sections of human skin, kidney and liver tissue, matching the brightfield microscopy images of the same samples stained with Hematoxylin and Eosin, Jones' stain, and Masson's trichrome stain, respectively. This digital staining framework might further strengthen various uses of labelfree QPI techniques in pathology applications and biomedical research in general, by eliminating the need for chemical staining, reducing sample preparation related costs and saving time. Our results provide a powerful example of some of the unique opportunities created by data driven image transformations enabled by deep learning.

Yair Rivenson, Aydogan Ozcan

We discuss recently emerging applications of the state-of-art deep learning methods on optical microscopy and microscopic image reconstruction, which enable new transformations among different modes and modalities of microscopic imaging, driven entirely by image data. We believe that deep learning will fundamentally change both the hardware and image reconstruction methods used in optical microscopy in a holistic manner.

Xing Lin, Yair Rivenson, Nezih T. Yardimci et al.

We introduce an all-optical Diffractive Deep Neural Network (D2NN) architecture that can learn to implement various functions after deep learning-based design of passive diffractive layers that work collectively. We experimentally demonstrated the success of this framework by creating 3D-printed D2NNs that learned to implement handwritten digit classification and the function of an imaging lens at terahertz spectrum. With the existing plethora of 3D-printing and other lithographic fabrication methods as well as spatial-light-modulators, this all-optical deep learning framework can perform, at the speed of light, various complex functions that computer-based neural networks can implement, and will find applications in all-optical image analysis, feature detection and object classification, also enabling new camera designs and optical components that can learn to perform unique tasks using D2NNs.

Yair Rivenson, Hongda Wang, Zhensong Wei et al.

Histological analysis of tissue samples is one of the most widely used methods for disease diagnosis. After taking a sample from a patient, it goes through a lengthy and laborious preparation, which stains the tissue to visualize different histological features under a microscope. Here, we demonstrate a label-free approach to create a virtually-stained microscopic image using a single wide-field auto-fluorescence image of an unlabeled tissue sample, bypassing the standard histochemical staining process, saving time and cost. This method is based on deep learning, and uses a convolutional neural network trained using a generative adversarial network model to transform an auto-fluorescence image of an unlabeled tissue section into an image that is equivalent to the bright-field image of the stained-version of the same sample. We validated this method by successfully creating virtually-stained microscopic images of human tissue samples, including sections of salivary gland, thyroid, kidney, liver and lung tissue, also covering three different stains. This label-free virtual-staining method eliminates cumbersome and costly histochemical staining procedures, and would significantly simplify tissue preparation in pathology and histology fields.

Yair Rivenson, Zoltan Gorocs, Harun Gunaydin et al.

We demonstrate that a deep neural network can significantly improve optical microscopy, enhancing its spatial resolution over a large field-of-view and depth-of-field. After its training, the only input to this network is an image acquired using a regular optical microscope, without any changes to its design. We blindly tested this deep learning approach using various tissue samples that are imaged with low-resolution and wide-field systems, where the network rapidly outputs an image with remarkably better resolution, matching the performance of higher numerical aperture lenses, also significantly surpassing their limited field-of-view and depth-of-field. These results are transformative for various fields that use microscopy tools, including e.g., life sciences, where optical microscopy is considered as one of the most widely used and deployed techniques. Beyond such applications, our presented approach is broadly applicable to other imaging modalities, also spanning different parts of the electromagnetic spectrum, and can be used to design computational imagers that get better and better as they continue to image specimen and establish new transformations among different modes of imaging.

Yair Rivenson, Yibo Zhang, Harun Gunaydin et al.

Phase recovery from intensity-only measurements forms the heart of coherent imaging techniques and holography. Here we demonstrate that a neural network can learn to perform phase recovery and holographic image reconstruction after appropriate training. This deep learning-based approach provides an entirely new framework to conduct holographic imaging by rapidly eliminating twin-image and self-interference related spatial artifacts. Compared to existing approaches, this neural network based method is significantly faster to compute, and reconstructs improved phase and amplitude images of the objects using only one hologram, i.e., requires less number of measurements in addition to being computationally faster. We validated this method by reconstructing phase and amplitude images of various samples, including blood and Pap smears, and tissue sections. These results are broadly applicable to any phase recovery problem, and highlight that through machine learning challenging problems in imaging science can be overcome, providing new avenues to design powerful computational imaging systems.