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Aydogan Ozcan

Publications and source records attributed to Aydogan Ozcan.

At least 145 records · Page 8Linked to original sources
arXiv2019

Automated screening of sickle cells using a smartphone-based microscope and deep learning

Sickle cell disease (SCD) is a major public health priority throughout much of the world, affecting millions of people. In many regions, particularly those in resource-limited settings, SCD is not consistently diagnosed. In Africa, where the majority of SCD patients reside, more than 50% of the 0.2-0.3 million children born with SCD each year will die from it; many of these deaths are in fact preventable with correct diagnosis and treatment. Here we present a deep learning framework which can perform automatic screening of sickle cells in blood smears using a smartphone microscope. This framework uses two distinct, complementary deep neural networks. The first neural network enhances and standardizes the blood smear images captured by the smartphone microscope, spatially and spectrally matching the image quality of a laboratory-grade benchtop microscope. The second network acts on the output of the first image enhancement neural network and is used to perform the semantic segmentation between healthy and sickle cells within a blood smear. These segmented images are then used to rapidly determine the SCD diagnosis per patient. We blindly tested this mobile sickle cell detection method using blood smears from 96 unique patients (including 32 SCD patients) that were imaged by our smartphone microscope, and achieved ~98% accuracy, with an area-under-the-curve (AUC) of 0.998. With its high accuracy, this mobile and cost-effective method has the potential to be used as a screening tool for SCD and other blood cell disorders in resource-limited settings.

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arXiv2019

Three-dimensional virtual refocusing of fluorescence microscopy images using deep learning

Three-dimensional (3D) fluorescence microscopy in general requires axial scanning to capture images of a sample at different planes. Here we demonstrate that a deep convolutional neural network can be trained to virtually refocus a 2D fluorescence image onto user-defined 3D surfaces within the sample volume. With this data-driven computational microscopy framework, we imaged the neuron activity of a Caenorhabditis elegans worm in 3D using a time-sequence of fluorescence images acquired at a single focal plane, digitally increasing the depth-of-field of the microscope by 20-fold without any axial scanning, additional hardware, or a trade-off of imaging resolution or speed. Furthermore, we demonstrate that this learning-based approach can correct for sample drift, tilt, and other image aberrations, all digitally performed after the acquisition of a single fluorescence image. This unique framework also cross-connects different imaging modalities to each other, enabling 3D refocusing of a single wide-field fluorescence image to match confocal microscopy images acquired at different sample planes. This deep learning-based 3D image refocusing method might be transformative for imaging and tracking of 3D biological samples, especially over extended periods of time, mitigating photo-toxicity, sample drift, aberration and defocusing related challenges associated with standard 3D fluorescence microscopy techniques.

cs.CV↗
arXiv2019

Design of Task-Specific Optical Systems Using Broadband Diffractive Neural Networks

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.

cs.NE↗
arXiv2019

Deep learning-based color holographic microscopy

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.

eess.IV↗
arXiv2019

Class-specific Differential Detection in Diffractive Optical Neural Networks Improves Inference Accuracy

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.

cs.NE↗
arXiv2019

Analysis of Diffractive Optical Neural Networks and Their Integration with Electronic Neural Networks

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.

cs.NE↗
arXiv2019

Resolution enhancement in scanning electron microscopy using deep learning

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.

cs.CV↗
arXiv2018

Deep learning enables high-throughput analysis of particle-aggregation-based bio-sensors imaged using holography

Aggregation-based assays, using micro- and nano-particles have been widely accepted as an efficient and cost-effective bio-sensing tool, particularly in microbiology, where particle clustering events are used as a metric to infer the presence of a specific target analyte and quantify its concentration. Here, we present a sensitive and automated readout method for aggregation-based assays using a wide-field lens-free on-chip microscope, with the ability to rapidly analyze and quantify microscopic particle aggregation events in 3D, using deep learning-based holographic image reconstruction. In this method, the computation time for hologram reconstruction and particle autofocusing steps remains constant, regardless of the number of particles/clusters within the 3D sample volume, which provides a major throughput advantage, brought by deep learning-based image reconstruction. As a proof of concept, we demonstrate rapid detection of herpes simplex virus (HSV) by monitoring the clustering of antibody-coated micro-particles, achieving a detection limit of ~5 viral copies per micro-liter (i.e., ~25 copies per test).

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arXiv2018

Deep learning-based super-resolution in coherent imaging systems

We present a deep learning framework based on a generative adversarial network (GAN) to perform super-resolution in coherent imaging systems. We demonstrate that this framework can enhance the resolution of both pixel size-limited and diffraction-limited coherent imaging systems. We experimentally validated the capabilities of this deep learning-based coherent imaging approach by super-resolving complex images acquired using a lensfree on-chip holographic microscope, the resolution of which was pixel size-limited. Using the same GAN-based approach, we also improved the resolution of a lens-based holographic imaging system that was limited in resolution by the numerical aperture of its objective lens. This deep learning-based super-resolution framework can be broadly applied to enhance the space-bandwidth product of coherent imaging systems using image data and convolutional neural networks, and provides a rapid, non-iterative method for solving inverse image reconstruction or enhancement problems in optics.

cs.CV↗
arXiv2018

Response to Comment on "All-optical machine learning using diffractive deep neural networks"

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.

cs.NE↗
arXiv2018

Accurate color imaging of pathology slides using holography and absorbance spectrum estimation of histochemical stains

Holographic microscopy presents challenges for color reproduction due to the usage of narrow-band illumination sources, which especially impacts the imaging of stained pathology slides for clinical diagnoses. Here, an accurate color holographic microscopy framework using absorbance spectrum estimation is presented. This method uses multispectral holographic images acquired and reconstructed at a small number (e.g., three to six) of wavelengths, estimates the absorbance spectrum of the sample, and projects it onto a color tristimulus. Using this method, the wavelength selection is optimized to holographically image 25 pathology slide samples with different tissue and stain combinations to significantly reduce color errors in the final reconstructed images. The results can be used as a practical guide for various imaging applications and, in particular, to correct color distortions in holographic imaging of pathology samples spanning different dyes and tissue types.

physics.med-ph↗
arXiv2018

All-Optical Machine Learning Using Diffractive Deep Neural Networks

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.

cs.NE↗
arXiv2018

PhaseStain: Digital staining of label-free quantitative phase microscopy images using deep learning

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.

eess.IV↗
arXiv2018

Toward a Thinking Microscope: Deep Learning in Optical Microscopy and Image Reconstruction

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.

cs.LG↗
arXiv2018

Deep learning-based virtual histology staining using auto-fluorescence of label-free tissue

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.

cs.CV↗
arXiv2018

Extended depth-of-field in holographic image reconstruction using deep learning based auto-focusing and phase-recovery

Holography encodes the three dimensional (3D) information of a sample in the form of an intensity-only recording. However, to decode the original sample image from its hologram(s), auto-focusing and phase-recovery are needed, which are in general cumbersome and time-consuming to digitally perform. Here we demonstrate a convolutional neural network (CNN) based approach that simultaneously performs auto-focusing and phase-recovery to significantly extend the depth-of-field (DOF) in holographic image reconstruction. For this, a CNN is trained by using pairs of randomly de-focused back-propagated holograms and their corresponding in-focus phase-recovered images. After this training phase, the CNN takes a single back-propagated hologram of a 3D sample as input to rapidly achieve phase-recovery and reconstruct an in focus image of the sample over a significantly extended DOF. This deep learning based DOF extension method is non-iterative, and significantly improves the algorithm time-complexity of holographic image reconstruction from O(nm) to O(1), where n refers to the number of individual object points or particles within the sample volume, and m represents the focusing search space within which each object point or particle needs to be individually focused. These results highlight some of the unique opportunities created by data-enabled statistical image reconstruction methods powered by machine learning, and we believe that the presented approach can be broadly applicable to computationally extend the DOF of other imaging modalities.

cs.CV↗
arXiv2018

High-throughput screening of encapsulated islets using wide-field lens-free on-chip imaging

Islet microencapsulation is a promising solution to diabetes treatment, but its quality control based on manual microscopic inspection is extremely low-throughput, highly variable and laborious. This study presents a high-throughput islet-encapsulation quality screening system based on lens-free on-chip imaging with a wide field-of-view of 18.15 cm^2, which is more than 100 times larger than that of a lens-based optical microscope, enabling it to image and analyze ~8,000 microcapsules in a single frame. Custom-written image reconstruction and processing software provides the user with clinically important information, such as microcapsule count, size, intactness, and information on whether each capsule contains an islet. This high-throughput and cost-effective platform can be useful for researchers to develop better encapsulation protocols as well as perform quality control prior to transplantation.

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