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The aim was to improve single-photon emission computed tomography (SPECT) quality for sparsely acquired 111In projections by adding deep learning generated synthetic intermediate projections (SIPs). Method: The recently constructed deep convolutional network for generating synthetic intermediate projections (CUSIP) was used for improving 20 sparsely acquired 111In-octreotide SPECTs. Reconstruction was performed with 120 (120P) or 30 (30P) projections, or 120 projections with 90 SIPs generated from 30 projections (30–120SIP). The SPECT reconstructions were performed with attenuation, scatter and collimator response corrections. Postfiltered 30P reconstructed SPECT was also analyzed. Image quality were quantitatively evaluated with root-mean-square error, peak signal-to-noise ratio and structural similarity index metrics. Result: The 30–120SIP reconstructed SPECT had statistically significant improved image quality parameters compared to 30P reconstructed SPECT with and without post filtering. The images visual appearance was similar to slightly filtered 120P SPECTs. Thereby, substantial acquisition time reduction with SIPs seems possible without image quality degradation.

In this study, we aim to compare the performance of systems and forensic facial comparison experts in terms of likelihood ratio computation to assess the potential of the machine to support the human expert in the courtroom. In forensics, transparency in the methods is essential. Consequently, state‐of‐the‐art free software was preferred over commercial software. Three different open‐source automated systems chosen for their availability and clarity were as follows: OpenFace, SeetaFace, and FaceNet; all three based on convolutional neural networks that return a distance (OpenFace, FaceNet) or similarity (SeetaFace). The returned distance or similarity is converted to a likelihood ratio using three different distribution fits: parametric fit Weibull distribution, nonparametric fit kernel density estimation, and isotonic regression with pool adjacent violators algorithm. The results show that with low‐quality frontal images, automated systems have better performance to detect nonmatches than investigators: 100% of precision and specificity in confusion matrix against 89% and 86% obtained by investigators, but with good quality images forensic experts have better results. The rank correlation between investigators and software is around 80%. We conclude that the software can assist in reporting officers as it can do faster and more reliable comparisons with full‐frontal images, which can help the forensic expert in casework.

Significance: Early detection of oral cancer is vital for high-risk patients, and machine learning-based automatic classification is ideal for disease screening. However, current datasets collected from high-risk populations are unbalanced and often have detrimental effects on the performance of classification. Aim: To reduce the class bias caused by data imbalance. Approach: We collected 3851 polarized white light cheek mucosa images using our customized oral cancer screening device. We use weight balancing, data augmentation, undersampling, focal loss, and ensemble methods to improve the neural network performance of oral cancer image classification with the imbalanced multi-class datasets captured from high-risk populations during oral cancer screening in low-resource settings. Results: By applying both data-level and algorithm-level approaches to the deep learning training process, the performance of the minority classes, which were difficult to distinguish at the beginning, has been improved. The accuracy of “premalignancy” class is also increased, which is ideal for screening applications. Conclusions: Experimental results show that the class bias induced by imbalanced oral cancer image datasets could be reduced using both data- and algorithm-level methods. Our study may provide an important basis for helping understand the influence of unbalanced datasets on oral cancer deep learning classifiers and how to mitigate.

Purpose: We propose a deep learning method for the automatic diagnosis of COVID-19 at patient presentation on chest radiography (CXR) images and investigates the role of standard and soft tissue CXR in this task. Approach: The dataset consisted of the first CXR exams of 9860 patients acquired within 2 days after their initial reverse transcription polymerase chain reaction tests for the SARS-CoV-2 virus, 1523 (15.5%) of whom tested positive and 8337 (84.5%) of whom tested negative for COVID-19. A sequential transfer learning strategy was employed to fine-tune a convolutional neural network in phases on increasingly specific and complex tasks. The COVID-19 positive/negative classification was performed on standard images, soft tissue images, and both combined via feature fusion. A U-Net variant was used to segment and crop the lung region from each image prior to performing classification. Classification performances were evaluated and compared on a held-out test set of 1972 patients using the area under the receiver operating characteristic curve (AUC) and the DeLong test. Results: Using full standard, cropped standard, cropped, soft tissue, and both types of cropped CXR yielded AUC values of 0.74 [0.70, 0.77], 0.76 [0.73, 0.79], 0.73 [0.70, 0.76], and 0.78 [0.74, 0.81], respectively. Using soft tissue images significantly underperformed standard images, and using both types of CXR failed to significantly outperform using standard images alone. Conclusions: The proposed method was able to automatically diagnose COVID-19 at patient presentation with promising performance, and the inclusion of soft tissue images did not result in a significant performance improvement.

Purpose: To detect and diagnose coronavirus disease 2019 (COVID-19) better and faster, separable VGG-ResNet (SVRNet) and separable VGG-DenseNet (SVDNet) models are proposed, and a detection system is designed, based on lung x-rays to diagnose whether patients are infected with COVID-19. Approach: Combining deep learning and transfer learning, 1560 lung x-ray images in the COVID-19 x-ray image database (COVID-19 Radiography Database) were used as the experimental data set, and the most representative image classification models, VGG16, ResNet50, InceptionV3, and Xception, were fine-tuned and trained. Then, two new models for lung x-ray detection, SVRNet and SVDNet, were proposed on this basis. Finally, 312 test set images (including 44 COVID-19 and 268 normal images) were used as input to evaluate the classification accuracy, sensitivity, and specificity of SVRNet and SVDNet models. Results: In the classification experiment of lung x-rays that tested positive and negative for COVID-19, the classification accuracy, sensitivity, and specificity of SVRNet and SVDNet are 99.13%, 99.14%, 99.12% and 99.37%, 99.43%, 99.31%, respectively. Compared with the VGG16 network, SVRNet and SVDNet increased by 3.07%, 2.84%, 3.31% and 3.31%, 3.13%, 3.50%, respectively. On the other hand, the parameters of SVRNet and SVDNet are 5.65 × 10 6 and 6.57 × 10 6 , respectively. These are 61.56% and 55.31% less than VGG16, respectively. Conclusions: The SVRNet and SVDNet models proposed greatly reduce the number of parameters, while improving the accuracy and increasing the operating speed, and can accurately and quickly detect lung x-rays containing COVID-19.

Coronavirus 2019 (SARS-CoV-2 or COVID-19) is an infectious disease affecting the respiratory system, which has caused a global pandemic and widespread morbidity and mortality in humans. It has mild to severe symptoms similar to those of severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), resulting in multiorgan damage.1 Currently, two tests are available for detection of COVID-19 in the affected patients: diagnostic tests (current infection) and antibody tests (past infection). Diagnostic tests, such as reverse transcription polymerase chain reaction (RT-PCR) and antigen tests, are used for rapid diagnosis of COVID-19. Since false positives (FPs) are more common in antigen tests, RT-PCR is used as the gold standard for diagnosis of the disease. RT-PCR tests require an intensive lab work to acquire the results,2 and the cost of the test is a major concern in many countries that have a private health system. Although the PCR and antigen test can now provide a rapid diagnosis, the assessment of the lungs using medical imaging will provide information on disease burden. Also, faster and earlier detection of COVID-19 would help in isolating the affected patients sooner to alleviate the disease spread. Chest radiography (CXR) and computed tomography (CT) images are the conventional medical imaging modalities used in lung disease diagnosis.3,4 Though CT images are extensively used in the COVID-19 diagnosis,5–7 cost8 and radiation exposure are major concerns. CXR are preferred over CT images as they have less exposure to radiation and extensively available.9 Hence, in this study, CXR images are used for automatic diagnosis of COVID-19. Deep learning techniques are widely used in various fields, such as computer vision, machine vision, and speech recognition, among which computer vision is one of the most popular fields in which promising results to have been obtained in image classification tasks.10–12 In medical image analysis, deep learning has been widely investigated for computer-aided diagnosis and treatment.13,14 Several state-of-art methods have been proposed for the diagnosis of COVID-19 using CXR images15–19 and CT images5,20,21 based on deep learning techniques. The transfer learning approaches based on deep learning have been preferred in detection of COVID-19 due to the limited available dataset. Several studies have been implemented for COVID-19 diagnosis using the pretrained model as a feature extractor by implementing transfer learning techniques.22–24 Table 1 summarizes recent studies describing methods developed for detecting COVID-19 from CXR images; the overall datasets used for training and testing the model, accuracy, and the sensitivity are provided. Ozturk et al.18 developed the DarkCovidNet model for the detection of COVID-19 using multiclass classification. The model was developed using end-to-end architecture without adding any feature extraction techniques. Sensitivity of 85.35% was achieved by the proposed model. Wang and Wong25 proposed COVID-Net, a deep convolutional neural network (DCNN) developed by adopting machine-driven design exploration strategy. A multiclass classification was performed using CXR images in identifying COVID-19 from normal and non-COVID disease (i.e., pneumonia). Both qualitative and quantitative analysis were performed to determine the success of the model. The developed model was able to achieve a sensitivity of 91% for detecting COVID-19. Panwar et al.26 introduced nCOVnet, an algorithm developed based on a transfer learning model for faster diagnosis of COVID-19 from CXR images. The proposed model is built using VGG 16 as the base model. The model was able to achieve 97.62% in detecting COVID-19. Sethy et al.23 described a comparative study on Xception, ResNet18, ResNet50, Resnet 101, Inceptionv3, Inceptionresnetv2, GoogleNet, Densenet201, VGG16, VGG19, and AlexNet using the deep features extracted from the CNN layers and fed to the SVM classifier for classification. ResNet50 performed better compared with other classification models on a binary classification between viral pneumonia and COVID-19 with a classification accuracy of 95.38%. Jain et al.27 utilized ResNet50 model that was used in stage-I network model for distinguishing viral (including COVID-19) from bacterial pneumonia and normal cases using CXR images. Based on the result obtained, ResNet101 was used in stage-II network model to classify COVID-19 from other viral pneumonia. The model achieved an accuracy of 97% in COVID-19 detection. Narin et al.28 proposed three CNNs for the detection of COVID-19 through CXR images. The pretrained models chosen for comparative study were ResNet50, InceptionV3, and Inception-ResNetV2. A binary classification was performed between normal and COVID-19. ResNet50 model outperformed all the other models with the highest classification accuracy of 98%. Ioannis et al.22 compared VGG 19, Mobile Net, Inception, Xception, and Inception ResNetv2 pretrained models for the automatic detection of COVID-19 using CXR images. They implemented multiclass classification among COVID-19, normal, and pneumonia. MobileNetV2 achieved highest sensitivity rate of 98.6%. Asnaoui et al.29 put forward a comparative study on the pretrained DCNN models, namely VGG16, VGG19, Inception-ResNetV2, InceptionV3, ResNet50, DenseNet201, and MobileNetV2 for the classification of CXR into normal, bacteria, and coronavirus (multiclass classification). Inception-ResNetV2 model provided a sensitivity rate of 92.11% in detecting coronavirus. Hemdan et al.30 proposed COVIDX-Net a deep learning framework based on seven DCNNs namely, VGG19, Xception, ResNetV2, InceptionV3, Inception-ResNetV2, DenseNet201, and MobileNetV2 for the diagnosis of COVID-19 using x-ray images. The VGG19 and DenseNet201 achieved an accuracy of 90% compared with other models with F1-score of 0.89 for normal and 0.91 for COVID-19. Table 1 Methods described for diagnosis of COVID-19 from CXR and CT images.

Significance: Oral cancer is among the most common cancers globally, especially in low- and middle-income countries. Early detection is the most effective way to reduce the mortality rate. Deep learning-based cancer image classification models usually need to be hosted on a computing server. However, internet connection is unreliable for screening in low-resource settings. Aim: To develop a mobile-based dual-mode image classification method and customized Android application for point-of-care oral cancer detection. Approach: The dataset used in our study was captured among 5025 patients with our customized dual-modality mobile oral screening devices. We trained an efficient network MobileNet with focal loss and converted the model into TensorFlow Lite format. The finalized lite format model is ∼16.3 MB and ideal for smartphone platform operation. We have developed an Android smartphone application in an easy-to-use format that implements the mobile-based dual-modality image classification approach to distinguish oral potentially malignant and malignant images from normal/benign images. Results: We investigated the accuracy and running speed on a cost-effective smartphone computing platform. It takes ∼300 ms to process one image pair with the Moto G5 Android smartphone. We tested the proposed method on a standalone dataset and achieved 81% accuracy for distinguishing normal/benign lesions from clinically suspicious lesions, using a gold standard of clinical impression based on the review of images by oral specialists. Conclusions: Our study demonstrates the effectiveness of a mobile-based approach for oral cancer screening in low-resource settings.

Oral cancer is one of the most common cancers worldwide, with high mortality rates. According to the International Agency for Research on Cancer, there were an estimated 377,000 new cases of lip and oral cavity cancers in 2020, with nearly 177,000 deaths worldwide.1 Despite advances in oncology therapy, mortality rates for oral cancer remain high over the past few decades. A majority of oral cancer patients do not have access to timely, quality diagnosis, and treatment, especially in rural areas, resulting in poor survival rates. The overall 5-year survival rate of diagnosed oral cancer patients is around 50% and has varied by race and area,2 whereas survival rates as high as 65% have been reported in developed countries; in some rural areas, they can be as low as 15% depending on the affected part of the oral cavity. The 2020 Cancer Statistics Report from India estimated that 66.6% of patients suffering from head and neck cancer were diagnosed at the locally advanced stage.3 In short, patient survival rates and prognosis are severely compromised when oral cancer patients are diagnosed at more advanced stages4,5 so that enhancing early diagnosis could mean a significant rise in positive survival outcomes.6,7 As oral squamous cell carcinoma (OSCC) accounts for ∼90% of all oral cancer,8,9 these two terms tend to be used interchangeably. OSCC, which originates as an epithelial dysplasia (from a histopathologic perspective), generally develops from precursor lesions termed as oral potentially malignant disorders (OPMDs).10,11 Nevertheless, it is not inevitable that all OPMDs, even the most commonly encountered such as oral lichen planus, leukoplakia, and erythroplakia,11 result in the subsequent development of malignancies.10,12 Diagnosing OPMDs as definable diseases is also challenging due to the numerous varieties, various forms, and overlapping features. However, studies10,13,14 have found that when an OPMD changes to a nonhomogeneous presentation, it is more likely to be considered as an adverse progression, in other words, nonhomogeneous lesions have a greater risk of malignant transformation as against homogeneous lesions. Hence, compared with defined diagnosis, distinguishing the potential malignant characteristics of OPMD is a greater concern. In summary, an ideal clinical prediction method should be employed to diagnose OSCC early and in particular to assess malignancy at the OPMD stage. Currently, conventional oral examination (COE) consisting of visual and tactile assessment (followed by tissue biopsy if there are any suspicious findings) is the most routine procedure in the management of oral cancer and precursor disease. However, one limitation for COE is that several features of oral cancer may appear benign and even mimic aphthous ulcers, and they are too clinically heterogeneous and subtle for general dentists to distinguish. Second, because of its invasive nature and sampling bias that can lead to underdiagnosis or misdiagnosis, biopsy is often not ideal as a screening tool.15 Furthermore, although specialists can recognize most of the characteristics that differentiate benign and cancerous lesions, the number of specialists and health resources are limited and concentrated across regions, causing a large part of the oral cancer burden to fall on low-resource communities. Therefore, the idea of establishing a cost-effective screening strategy as an adjunctive aid to the current procedures is gaining widespread popularity.16 Recently, deep learning techniques have exhibited a comparative advantage over feature-based methods in medical image analysis. A variety of studies17,18 showed that deep learning algorithms are able to surpass the performance of human experts in many disease recognition scenarios. In oral cancer diagnosis, deep learning methods also showed promising results for automatic analysis of pathology, confocal laser endomicroscopy (CLE) images, and fluorescence images. For example, Kumar et al.19 proposed a two-stage method that used a segmentation network and a random forest tree classifier to identify different stages of oral cancer in histological images. Aubreville et al.20 tested the deep convolutional neural network for OSCC diagnosis on CLE images, and the results showed that it outperformed the feature-based classification methods. Song et al.21,22 developed mobile connected devices to acquire fluorescence oral images and used them to identify oral disease. However, these methods all require expensive devices or a specifically designed screening platform, which are not accessible to everyone. In other words, patients are still required to go a professional clinic to receive disease diagnosis. With the rapid development of both imaging and sensing technologies in camera systems, the ubiquity of smartphones is equipped with higher quality, low-noise, and faster camera modules. Smartphone-based white light inspection methods23–25 are good solutions for acquiring oral images. Camalan et al.23 used a CNN-based network for classifying white light images as normal or suspicious; however, the patient sample is very limited: with only 54 cases. To build a reliable system, Welikala et al.24 collected more clinically labeled data for network training and evaluation, achieving a sensitivity of 52.13% and a specificity of 49.11% on multiclass classification task. However, we found that the clinical imaging capturing from hand-held smartphone cameras may exhibit a large variability, leading to poor diagnostic performance of the detection algorithm. For example, from a computer vision point of view, the shape and size of imaging lesions depend on the fields-of-view and focal distance, respectively. Unfortunately, a limited amount of research focuses on this problem. To address these challenges, we aim to explore reliable and robust smartphone-based white light image approaches, including an image-capturing method, resampling method, and high performance of CNN model, for oral disease recognition. Our main contributions are summarized as follows. 1. We propose a simple yet effective image-capturing method for consistent lesion position and focal distance over different images. The method allows direct focus on discriminative parts for disease recognition, without utilizing any region proposal methods,24,25 or relying on bounding box annotation24 by oral specialists. 2. We present a resampling method to alleviate the effect of image variability that introduced by the hand-held smartphone camera; at the same time, it can remedy the class imbalance problem. 3. We use one of the latest proposed convolutional neural networks (HRNet) for oral disease classification and achieve better results than common classification models. Analysis of the model’s performance on our collected images shows that common imaging pattern on a smartphone is a valuable approach for the early diagnosis. 2. Materials and Methods 2.1. Image-Capturing Method The focal length of the main camera in a smartphone is commonly short, for example, the iPhone 12 has a wide-angle (only 26 mm) camera. The focal length number tells us how much of the scene is captured in the picture, and the lower the number is, the wider the view is. Since most lesions are relatively small, we cannot capture the photograph where the lesion occupies most areas of the image. This means that the captured image may have many irrelevant backgrounds. In addition, even with the same lesion, the size of the imaging lesion may vary with different distances between the camera and lesion or using different cameras with different focal lengths. Thus these would introduce the large variability to the system’s performance going forward, and we need to find a method to reduce this considerable variability. Although identifying oral disease is very difficult for the nonmedical expert, locating the position of oral lesions is relatively easy because the visual appearance of normal and diseased tissue is significantly different. We use the camera grid to assist in locating the lesion in the center of image and to keep each area of lesion in the images neither too small nor too big. Thus it is possible to use the fixed region of interest (ROI) method to crop the discriminative parts and filter the irrelevant backgrounds, without utilizing any region proposal methods or relying on any manually cropped methods. This particular positioning of the main object in an image is helpful to improve the performance of CNN for image recognition. We use the native phone’s camera app to capture the oral cavity image. As shown in Fig. 1, the camera grid helps us to see if the lesion is properly placed at the center for optimal balance in the shot. The operation can be easily done by a person using a hand-held smartphone camera. The basic steps are as follows. Open in a separate window Fig. 1 Illustration of data acquisition. The aspect ratio is set 4:3; the image shows a lesion at the center of the region.

Significance: Speckle noise is an inherent limitation of optical coherence tomography (OCT) images that makes clinical interpretation challenging. The recent emergence of deep learning could offer a reliable method to reduce noise in OCT images. Aim: We sought to investigate the use of deep features (VGG) to limit the effect of blurriness and increase perceptual sharpness and to evaluate its impact on the performance of OCT image denoising (DnCNN). Approach: Fifty-one macula-centered OCT pairs were used in training of the network. Another set of 20 OCT pair was used for testing. The DnCNN model was cascaded with a VGG network that acted as a perceptual loss function instead of the traditional losses of L1 and L2. The VGG network remains fixed during the training process. We focused on the individual layers of the VGG-16 network to decipher the contribution of each distinctive layer as a loss function to produce denoised OCT images that were perceptually sharp and that preserved the faint features (retinal layer boundaries) essential for interpretation. The peak signal-to-noise ratio (PSNR), edge-preserving index, and no-reference image sharpness/blurriness [perceptual sharpness index (PSI), just noticeable blur (JNB), and spectral and spatial sharpness measure (S3)] metrics were used to compare deep feature losses with the traditional losses. Results: The deep feature loss produced images with high perceptual sharpness measures at the cost of less smoothness (PSNR) in OCT images. The deep feature loss outperformed the traditional losses (L1 and L2) for all of the evaluation metrics except for PSNR. The PSI, S3, and JNB estimates of deep feature loss performance were 0.31, 0.30, and 16.53, respectively. For L1 and L2 losses performance, the PSI, S3, and JNB were 0.21 and 0.21, 0.17 and 0.16, and 14.46 and 14.34, respectively. Conclusions: We demonstrate the potential of deep feature loss in denoising OCT images. Our preliminary findings suggest research directions for further investigation.

Significance: In general, image reconstruction methods used in diffuse optical tomography (DOT) are based on diffusion approximation, and they consider the breast tissue as a homogenous, semi-infinite medium. However, the semi-infinite medium assumption used in DOT reconstruction is not valid when the chest wall is underneath the breast tissue. Aim: We aim to reduce the chest wall’s effect on the estimated average optical properties of breast tissue and obtain accurate forward model for DOT reconstruction. Approach: We propose a deep learning-based neural network approach where a convolution neural network (CNN) is trained to simultaneously obtain accurate optical property values for both the breast tissue and the chest wall. Results: The CNN model shows great promise in reducing errors in estimating the optical properties of the breast tissue in the presence of a shallow chest wall. For patient data, the CNN model predicted the breast tissue optical absorption coefficient, which was independent of chest wall depth. Conclusions: Our proposed method can be readily used in DOT and diffuse spectroscopy measurements to improve the accuracy of estimated tissue optical properties.

SignificanceAutomated understanding of human embryonic stem cell (hESC) videos is essential for the quantified analysis and classification of various states of hESCs and their health for diverse applications in regenerative medicine.AimThis paper aims to develop an ensemble method and bagging of deep learning classifiers as a model for hESC classification on a video dataset collected using a phase contrast microscope.ApproachThe paper describes a deep learning-based random network (RandNet) with an autoencoded feature extractor for the classification of hESCs into six different classes, namely, (1)cell clusters, (2)debris, (3)unattached cells, (4)attached cells, (5)dynamically blebbing cells, and (6)apoptotically blebbing cells. The approach uses unlabeled data to pre-train the autoencoder network and fine-tunes it using the available annotated data.ResultsThe proposed approach achieves a classification accuracy of 97.23 ± 0.94 % and outperforms the state-of-the-art methods. Additionally, the approach has a very low training cost compared with the other deep-learning-based approaches, and it can be used as a tool for annotating new videos, saving enormous hours of manual labor.ConclusionsRandNet is an efficient and effective method that uses a combination of subnetworks trained using both labeled and unlabeled data to classify hESC images.

Significance: Digital holographic microscopy (DHM) is a promising technique for the study of semitransparent biological specimen such as red blood cells (RBCs). It is important and meaningful to detect and count biological cells at the single cell level in biomedical images for biomarker discovery and disease diagnostics. However, the biological cell analysis based on phase information of images is inefficient due to the complexity of numerical phase reconstruction algorithm applied to raw hologram images. New cell study methods based on diffraction pattern directly are desirable. Aim: Deep fully convolutional networks (FCNs) were developed on raw hologram images directly for high-throughput label-free cell detection and counting to assist the biological cell analysis in the future. Approach: The raw diffraction patterns of RBCs were recorded by use of DHM. Ground-truth mask images were labeled based on phase images reconstructed from RBC holograms using numerical reconstruction algorithm. A deep FCN, which is UNet, was trained on the diffraction pattern images to achieve the label-free cell detection and counting. Results: The implemented deep FCNs provide a promising way to high-throughput and label-free counting of RBCs with a counting accuracy of 99% at a throughput rate of greater than 288 cells per second and 200 μm×200 μm field of view at the single cell level. Compared to convolutional neural networks, the FCNs can get much better results in terms of accuracy and throughput rate. Conclusions: High-throughput label-free cell detection and counting were successfully achieved from diffraction patterns with deep FCNs. It is a promising approach for biological specimen analysis based on raw hologram directly.

Significance: Physiological parameters extracted from diffuse reflectance spectroscopy (DRS) provide clinicians quantitative information about tissue that helps aid in diagnosis. There is a great need for an accurate and cost-effective method for extracting parameters from DRS measurements. Aim: The aim is to explore the accuracy and speed of physiological parameter extraction using machine learning models compared to that of the widely used Monte Carlo lookup table (MCLUT) inverse model. Approach: Diffuse reflectance spectra were simulated using a light transport model based on Monte Carlo simulations and weighted to six wavelengths. Deep learning (DL), random forest (RF), gradient boosting machine (GBM), and generalized linear model (GLM) machine learning models were built using a training set of 10,000 spectra from the simulated data. The MCLUT and machine learning models were used to predict physiological parameters from a separate test set of 30,000 simulated spectra. Mean absolute errors were calculated to evaluate the accuracy and compare it among MCLUT and machine learning models. In addition, the computational time to predict parameters from the test set was recorded to compare the speed among MCLUT and machine learning models. Results: The DL, RF, GBM, and GLM models all had significantly lower errors than the MCLUT inverse method for six wavelengths. The DL model proved to have the lowest errors, with all absolute percent errors under 10%. The DL model had much faster runtimes than the MCLUT. Conclusions: Machine learning is promising for extracting physiological parameters from six-wavelength DRS data, with both lower errors and a faster runtime than the widely used MCLUT model.

Significance: Colorectal cancer incidence has decreased largely due to detection and removal of polyps. Computer-aided diagnosis development may improve on polyp detection and discrimination. Aim: To advance detection and discrimination using currently available commercial colonoscopy systems, we developed a deep neural network (DNN) separating the color channels from images acquired under narrow-band imaging (NBI) and white-light endoscopy (WLE). Approach: Images of normal colon mucosa and polyps from colonoscopies were studied. Each color image was extracted based on the color channel: red/green/blue. A multilayer DNN was trained using one-channel, two-channel, and full-color images. The trained DNN was then tested for performance in detection of polyps. Results: The DNN performed better using full-colored NBI over WLE images in the detection of polyps. Furthermore, the DNN performed better using the two-channel red + green images when compared to full-color WLE images. Conclusions: The separation of color channels from full-color NBI and WLE images taken from commercially available colonoscopes may improve the ability of the DNN to detect and discriminate polyps. Further studies are needed to better determine the color channels and combination of channels to include and exclude in DNN development for clinical use.

Funder: Cantab Capital Institute for the Mathematics of Information, Funder: Alan Turing Institute; doi: https://doi.org/10.13039/100012338, In recent years the use of convolutional layers to encode an inductive bias (translational equivariance) in neural networks has proven to be a very fruitful idea. The successes of this approach have motivated a line of research into incorporating other symmetries into deep learning methods, in the form of group equivariant convolutional neural networks. Much of this work has been focused on roto-translational symmetry of R d , but other examples are the scaling symmetry of R d and rotational symmetry of the sphere. In this work, we demonstrate that group equivariant convolutional operations can naturally be incorporated into learned reconstruction methods for inverse problems that are motivated by the variational regularisation approach. Indeed, if the regularisation functional is invariant under a group symmetry, the corresponding proximal operator will satisfy an equivariance property with respect to the same group symmetry. As a result of this observation, we design learned iterative methods in which the proximal operators are modelled as group equivariant convolutional neural networks. We use roto-translationally equivariant operations in the proposed methodology and apply it to the problems of low-dose computerised tomography reconstruction and subsampled magnetic resonance imaging reconstruction. The proposed methodology is demonstrated to improve the reconstruction quality of a learned reconstruction method with a little extra computational cost at training time but without any extra cost at test time.

Purpose: Given the recent COVID-19 pandemic and its stress on global medical resources, presented here is the development of a machine intelligent method for thoracic computed tomography (CT) to inform management of patients on steroid treatment. Approach: Transfer learning has demonstrated strong performance when applied to medical imaging, particularly when only limited data are available. A cascaded transfer learning approach extracted quantitative features from thoracic CT sections using a fine-tuned VGG19 network. The extracted slice features were axially pooled to provide a CT-scan-level representation of thoracic characteristics and a support vector machine was trained to distinguish between patients who required steroid administration and those who did not, with performance evaluated through receiver operating characteristic (ROC) curve analysis. Least-squares fitting was used to assess temporal trends using the transfer learning approach, providing a preliminary method for monitoring disease progression. Results: In the task of identifying patients who should receive steroid treatments, this approach yielded an area under the ROC curve of 0.85±0.10 and demonstrated significant separation between patients who received steroids and those who did not. Furthermore, temporal trend analysis of the prediction score matched expected progression during hospitalization for both groups, with separation at early timepoints prior to convergence near the end of the duration of hospitalization. Conclusions: The proposed cascade deep learning method has strong clinical potential for informing clinical decision-making and monitoring patient treatment.

Significance: Photoacoustic (PA) imaging can provide structural, functional, and molecular information for preclinical and clinical studies. For PA imaging (PAI), non-ideal signal detection deteriorates image quality, and quantitative PAI (QPAI) remains challenging due to the unknown light fluence spectra in deep tissue. In recent years, deep learning (DL) has shown outstanding performance when implemented in PAI, with applications in image reconstruction, quantification, and understanding. Aim: We provide (i) a comprehensive overview of the DL techniques that have been applied in PAI, (ii) references for designing DL models for various PAI tasks, and (iii) a summary of the future challenges and opportunities. Approach: Papers published before November 2020 in the area of applying DL in PAI were reviewed. We categorized them into three types: image understanding, reconstruction of the initial pressure distribution, and QPAI. Results: When applied in PAI, DL can effectively process images, improve reconstruction quality, fuse information, and assist quantitative analysis. Conclusion: DL has become a powerful tool in PAI. With the development of DL theory and technology, it will continue to boost the performance and facilitate the clinical translation of PAI.

Significance: Label-free quantitative phase imaging is a promising technique for the automatic detection of abnormal red blood cells (RBCs) in real time. Although deep-learning techniques can accurately detect abnormal RBCs from quantitative phase images efficiently, their applications in diagnostic testing are limited by the lack of transparency. More interpretable results such as morphological and biochemical characteristics of individual RBCs are highly desirable. Aim: An end-to-end deep-learning model was developed to efficiently discriminate thalassemic RBCs (tRBCs) from healthy RBCs (hRBCs) in quantitative phase images and segment RBCs for single-cell characterization. Approach: Two-dimensional quantitative phase images of hRBCs and tRBCs were acquired using digital holographic microscopy. A mask region-based convolutional neural network (Mask R-CNN) model was trained to discriminate tRBCs and segment individual RBCs. Characterization of tRBCs was achieved utilizing SHapley Additive exPlanation analysis and canonical correlation analysis on automatically segmented RBC phase images. Results: The implemented model achieved 97.8% accuracy in detecting tRBCs. Phase-shift statistics showed the highest influence on the correct classification of tRBCs. Associations between the phase-shift features and three-dimensional morphological features were revealed. Conclusions: The implemented Mask R-CNN model accurately identified tRBCs and segmented RBCs to provide single-RBC characterization, which has the potential to aid clinical decision-making.

Reducing the bit-depth is an effective approach to lower the cost of optical coherence tomography (OCT) systems and increase the transmission efficiency in data acquisition and telemedicine. However, a low bit-depth will lead to the degeneration of the detection sensitivity thus reduce the signal-to-noise ratio (SNR) of OCT images. In this paper, we propose to use deep learning for the reconstruction of the high SNR OCT images from the low bit-depth acquisition. Its feasibility was preliminarily evaluated by applying the proposed method to the quantized $3\sim8$-bit data from native 12-bit interference fringes. We employed a pixel-to-pixel generative adversarial network architecture in the low to high bit-depth OCT image transition. Retinal OCT data of a healthy subject from a homemade spectral-domain OCT system was used in the study. Extensively qualitative and quantitative results show this deep-learning-based approach could significantly improve the SNR of the low bit-depth OCT images especially at the choroidal region. Superior similarity and SNR between the reconstructed images and the original 12-bit OCT images could be derived when the bit-depth $\geq 5$. This work demonstrates the proper integration of OCT and deep learning could benefit the development of healthcare in low-resource settings., Comment: submitted

Purpose: Hippocampus contouring for radiotherapy planning is performed on MR image data due to poor anatomical visibility on computed tomography (CT) data. Deep learning methods for direct CT hippocampus auto-segmentation exist, but use MR-based training contours. We investigate if these can be replaced by CT-based contours without loss in segmentation performance. This would remove the MR not only from inference but also from training. Approach: The hippocampus was contoured by medical experts on MR and CT data of 45 patients. Convolutional neural networks (CNNs) for hippocampus segmentation on CT were trained on CT-based or propagated MR-based contours. In both cases, their predictions were evaluated against the MR-based contours considered as the ground truth. Performance was measured using several metrics, including Dice score, surface distances, and contour Dice score. Bayesian dropout was used to estimate model uncertainty. Results: CNNs trained on propagated MR contours (median Dice 0.67) significantly outperform those trained on CT contours (0.59) and also experts contouring manually on CT (0.59). Differences between the latter two are not significant. Training on MR contours results in lower model uncertainty than training on CT contours. All contouring methods (manual or CNN) on CT perform significantly worse than a CNN segmenting the hippocampus directly on MR (median Dice 0.76). Additional data augmentation by rigid transformations improves the quantitative results but the difference remains significant. Conclusions: CT-based training contours for CT hippocampus segmentation cannot replace propagated MR-based contours without significant loss in performance. However, if MR-based contours are used, the resulting segmentations outperform experts in contouring the hippocampus on CT.

Significance: Melanoma is a deadly cancer that physicians struggle to diagnose early because they lack the knowledge to differentiate benign from malignant lesions. Deep machine learning approaches to image analysis offer promise but lack the transparency to be widely adopted as stand-alone diagnostics. Aim: We aimed to create a transparent machine learning technology (i.e., not deep learning) to discriminate melanomas from nevi in dermoscopy images and an interface for sensory cue integration. Approach: Imaging biomarker cues (IBCs) fed ensemble machine learning classifier (Eclass) training while raw images fed deep learning classifier training. We compared the areas under the diagnostic receiver operator curves. Results: Our interpretable machine learning algorithm outperformed the leading deep-learning approach 75% of the time. The user interface displayed only the diagnostic imaging biomarkers as IBCs. Conclusions: From a translational perspective, Eclass is better than convolutional machine learning diagnosis in that physicians can embrace it faster than black box outputs. Imaging biomarkers cues may be used during sensory cue integration in clinical screening. Our method may be applied to other image-based diagnostic analyses, including pathology and radiology.

Purpose: Deep learning (DL) algorithms have shown promising results for brain tumor segmentation in MRI. However, validation is required prior to routine clinical use. We report the first randomized and blinded comparison of DL and trained technician segmentations. Approach: We compiled a multi-institutional database of 741 pretreatment MRI exams. Each contained a postcontrast T1-weighted exam, a T2-weighted fluid-attenuated inversion recovery exam, and at least one technician-derived tumor segmentation. The database included 729 unique patients (470 males and 259 females). Of these exams, 641 were used for training the DL system, and 100 were reserved for testing. We developed a platform to enable qualitative, blinded, controlled assessment of lesion segmentations made by technicians and the DL method. On this platform, 20 neuroradiologists performed 400 side-by-side comparisons of segmentations on 100 test cases. They scored each segmentation between 0 (poor) and 10 (perfect). Agreement between segmentations from technicians and the DL method was also evaluated quantitatively using the Dice coefficient, which produces values between 0 (no overlap) and 1 (perfect overlap). Results: The neuroradiologists gave technician and DL segmentations mean scores of 6.97 and 7.31, respectively (p

Significance: Researchers have made great progress in single-image super-resolution (SISR) using deep convolutional neural networks. However, in the field of leukocyte imaging, the performance of existing SISR methods is still limited as it fails to thoroughly explore the geometry and structural consistency of leukocytes. The inaccurate super-resolution (SR) results will hinder the pathological study of leukocytes, since the structure and cell lineage determine the types of leukocyte and will significantly affect the subsequent inspection. Aim: We propose a deep network that takes full use of the geometry prior and structural consistency of the leukocyte images. We establish and annotate a leukocyte dataset, which contains five main types of leukocytes (basophil, eosinophil, monocyte, lymphocyte, and neutrophil), for learning the structure and geometry information. Approach: Our model is composed of two modules: prior network and SR network. The prior network estimates the parsing map of the low-resolution (LR) image, and then the SR network takes both the estimated parsing map and LR image as input to predict the final high-resolution image. Result: Experiments show that the geometry prior and structural consistency in use obviously improves the SR performance of leukocyte images, enhancing the peak-signal-to-noise ratio (PSNR) by about 0.4 dB in our benchmark. Conclusion: As proved by our leukocyte SR benchmark, the proposed method significantly outperforms state-of-the-art SR methods. Our method not only improves the PSNR and structural similarity indices, but also accurately preserves the structural details of leukocytes. The proposed method is believed to have potential use in the wide-field cell prescreening by simply using a low-power objective.

Significance: Automatic and accurate classification of three-dimensional (3-D) retinal optical coherence tomography (OCT) images is essential for assisting ophthalmologist in the diagnosis and grading of macular diseases. Therefore, more effective OCT volume classification for automatic recognition of macular diseases is needed. Aim: For OCT volumes in which only OCT volume-level labels are known, OCT volume classifiers based on its global feature and deep learning are designed, validated, and compared with other methods. Approach: We present a general framework to classify OCT volume for automatic recognizing macular diseases. The architecture of the framework consists of three modules: B-scan feature extractor, two-dimensional (2-D) feature map generation, and volume-level classifier. Our architecture could address OCT volume classification using two 2-D image machine learning classification algorithms. Specifically, a convolutional neural network (CNN) model is trained and used as a B-scan feature extractor to construct a 2-D feature map of an OCT volume and volume-level classifiers such as support vector machine and CNN with/without attention mechanism for 2-D feature maps are described. Results: Our proposed methods are validated on the publicly available Duke dataset, which consists of 269 intermediate age-related macular degeneration (AMD) volumes and 115 normal volumes. Fivefold cross-validation was done, and average accuracy, sensitivity, and specificity of 98.17%, 99.26%, and 95.65%, respectively, are achieved. The experiments show that our methods outperform the state-of-the-art methods. Our methods are also validated on our private clinical OCT volume dataset, consisting of 448 AMD volumes and 462 diabetic macular edema volumes. Conclusions: We present a general framework of OCT volume classification based on its 2-D feature map and CNN with attention mechanism and describe its implementation schemes. Our proposed methods could classify OCT volumes automatically and effectively with high accuracy, and they are a potential practical tool for screening of ophthalmic diseases from OCT volume.

Significance: Detection and characterization of coronary atherosclerotic plaques often need reviews of a large number of optical coherence tomography (OCT) imaging slices to make a clinical decision. However, it is a challenge to manually review all the slices and consider the interrelationship between adjacent slices. Approach: Inspired by the recent success of deep convolutional network on the classification of medical images, we proposed a ResNet-3D network for classification of coronary plaque calcification in OCT pullbacks. The ResNet-3D network was initialized with a trained ResNet-50 network and a three-dimensional convolution filter filled with zeros padding and non-zeros padding with a convolutional filter. To retrain ResNet-50, we used a dataset of ∼4860 OCT images, derived by 18 entire pullbacks from different patients. In addition, we investigated a two-phase training method to address the data imbalance. For an improved performance, we evaluated different input sizes for the ResNet-3D network, such as 3, 5, and 7 OCT slices. Furthermore, we integrated all ResNet-3D results by majority voting. Results: A comparative analysis proved the effectiveness of the proposed ResNet-3D networks against ResNet-2D network in the OCT dataset. The classification performance (F1-scores=94% for non-zeros padding and F1-score=96% for zeros padding) demonstrated the potential of convolutional neural networks (CNNs) in classifying plaque calcification. Conclusions: This work may provide a foundation for further work in extending the CNN to voxel segmentation, which may lead to a supportive diagnostic tool for assessment of coronary plaque vulnerability.

Significance: Two-dimensional (2-D) fully convolutional neural networks have been shown capable of producing maps of sO2 from 2-D simulated images of simple tissue models. However, their potential to produce accurate estimates in vivo is uncertain as they are limited by the 2-D nature of the training data when the problem is inherently three-dimensional (3-D), and they have not been tested with realistic images. Aim: To demonstrate the capability of deep neural networks to process whole 3-D images and output 3-D maps of vascular sO2 from realistic tissue models/images. Approach: Two separate fully convolutional neural networks were trained to produce 3-D maps of vascular blood oxygen saturation and vessel positions from multiwavelength simulated images of tissue models. Results: The mean of the absolute difference between the true mean vessel sO2 and the network output for 40 examples was 4.4% and the standard deviation was 4.5%. Conclusions: 3-D fully convolutional networks were shown capable of producing accurate sO2 maps using the full extent of spatial information contained within 3-D images generated under conditions mimicking real imaging scenarios. We demonstrate that networks can cope with some of the confounding effects present in real images such as limited-view artifacts and have the potential to produce accurate estimates in vivo.

Purpose: Deep learning has achieved major breakthroughs during the past decade in almost every field. There are plenty of publicly available algorithms, each designed to address a different task of computer vision in general. However, most of these algorithms cannot be directly applied to images in the medical domain. Herein, we are focused on the required preprocessing steps that should be applied to medical images prior to deep neural networks. Approach: To be able to employ the publicly available algorithms for clinical purposes, we must make a meaningful pixel/voxel representation from medical images which facilitates the learning process. Based on the ultimate goal expected from an algorithm (classification, detection, or segmentation), one may infer the required pre-processing steps that can ideally improve the performance of that algorithm. Required pre-processing steps for computed tomography (CT) and magnetic resonance (MR) images in their correct order are discussed in detail. We further supported our discussion by relevant experiments to investigate the efficiency of the listed preprocessing steps. Results: Our experiments confirmed how using appropriate image pre-processing in the right order can improve the performance of deep neural networks in terms of better classification and segmentation. Conclusions: This work investigates the appropriate pre-processing steps for CT and MR images of prostate cancer patients, supported by several experiments that can be useful for educating those new to the field (https://github.com/NIH-MIP/Radiology_Image_Preprocessing_for_Deep_Learning).

Significance: Spatial frequency-domain imaging (SFDI) is a powerful technique for mapping tissue oxygen saturation over a wide field of view. However, current SFDI methods either require a sequence of several images with different illumination patterns or, in the case of single-snapshot optical properties (SSOP), introduce artifacts and sacrifice accuracy. Aim: We introduce OxyGAN, a data-driven, content-aware method to estimate tissue oxygenation directly from single structured-light images. Approach: OxyGAN is an end-to-end approach that uses supervised generative adversarial networks. Conventional SFDI is used to obtain ground truth tissue oxygenation maps for ex vivo human esophagi, in vivo hands and feet, and an in vivo pig colon sample under 659- and 851-nm sinusoidal illumination. We benchmark OxyGAN by comparing it with SSOP and a two-step hybrid technique that uses a previously developed deep learning model to predict optical properties followed by a physical model to calculate tissue oxygenation. Results: When tested on human feet, cross-validated OxyGAN maps tissue oxygenation with an accuracy of 96.5%. When applied to sample types not included in the training set, such as human hands and pig colon, OxyGAN achieves a 93% accuracy, demonstrating robustness to various tissue types. On average, OxyGAN outperforms SSOP and a hybrid model in estimating tissue oxygenation by 24.9% and 24.7%, respectively. Finally, we optimize OxyGAN inference so that oxygenation maps are computed ∼10 times faster than previous work, enabling video-rate, 25-Hz imaging. Conclusions: Due to its rapid acquisition and processing speed, OxyGAN has the potential to enable real-time, high-fidelity tissue oxygenation mapping that may be useful for many clinical applications.

In order to work and travel safely during the outbreak of COVID-19, a method of security detection based on deep learning is proposed by using machine vision instead of manual monitoring. To detect the illegal behaviors of workers without masks in workplaces and densely populated areas, an improved convolutional neural network VGG-19 algorithm is proposed under the framework of tensorflow, and more than 3000 images are collected for model training and testing. Using VGG-19 network model, three FC layers are optimized into one flat layer and two FC layers with reduced parameters. The softmax classification layer of the original model is replaced by a 2-label softmax classifier. The experimental results show that the precision of the model is 97.62% and the recall is 96.31%. The precision of identifying the workers without masks is 96.82%, the recall is 94.07%, and the data set provided has a high precision. For the future social health and safety to provide favorable test data.

Biomedical photoacoustic tomography, which can provide high resolution 3D soft tissue images based on the optical absorption, has advanced to the stage at which translation from the laboratory to clinical settings is becoming possible. The need for rapid image formation and the practical restrictions on data acquisition that arise from the constraints of a clinical workflow are presenting new image reconstruction challenges. There are many classical approaches to image reconstruction, but ameliorating the effects of incomplete or imperfect data through the incorporation of accurate priors is challenging and leads to slow algorithms. Recently, the application of Deep Learning, or deep neural networks, to this problem has received a great deal of attention. This paper reviews the literature on learned image reconstruction, summarising the current trends, and explains how these new approaches fit within, and to some extent have arisen from, a framework that encompasses classical reconstruction methods. In particular, it shows how these new techniques can be understood from a Bayesian perspective, providing useful insights. The paper also provides a concise tutorial demonstration of three prototypical approaches to learned image reconstruction. The code and data sets for these demonstrations are available to researchers. It is anticipated that it is in in vivo applications - where data may be sparse, fast imaging critical and priors difficult to construct by hand - that Deep Learning will have the most impact. With this in mind, the paper concludes with some indications of possible future research directions.

Purpose: Prostate cancer primarily arises from the glandular epithelium. Histomophometric techniques have been used to assess the glandular epithelium in automated detection and classification pipelines; however, they are often rigid in their implementation, and their performance suffers on large datasets where variation in staining, imaging, and preparation is difficult to control. The purpose of this study is to quantify performance of a pixelwise segmentation algorithm that was trained using different combinations of weak and strong stroma, epithelium, and lumen labels in a prostate histology dataset. Approach: We have combined weakly labeled datasets generated using simple morphometric techniques and high-quality labeled datasets from human observers in prostate biopsy cores to train a convolutional neural network for use in whole mount prostate labeling pipelines. With trained networks, we characterize pixelwise segmentation of stromal, epithelium, and lumen (SEL) regions on both biopsy core and whole-mount H&E-stained tissue. Results: We provide evidence that by simply training a deep learning algorithm on weakly labeled data generated from rigid morphometric methods, we can improve the robustness of classification over the morphometric methods used to train the classifier. Conclusions: We show that not only does our approach of combining weak and strong labels for training the CNN improve qualitative SEL labeling within tissue but also the deep learning generated labels are superior for cancer classification in a higher-order algorithm over the morphometrically derived labels it was trained on.

Non-contact vital sign monitoring enables the estimation of vital signs, such as heart rate, respiratory rate and oxygen saturation (SpO2), by measuring subtle color changes on the skin surface using a video camera. For patients in a hospital ward, the main challenges in the development of continuous and robust non-contact monitoring techniques are the identification of time periods and the segmentation of skin regions of interest (ROIs) from which vital signs can be estimated. We propose a deep learning framework to tackle these challenges. Approach: This paper presents two convolutional neural network (CNN) models. The first network was designed for detecting the presence of a patient and segmenting the patient’s skin area. The second network combined the output from the first network with optical flow for identifying time periods of clinical intervention so that these periods can be excluded from the estimation of vital signs. Both networks were trained using video recordings from a clinical study involving 15 pre-term infants conducted in the high dependency area of the neonatal intensive care unit (NICU) of the John Radcliffe Hospital in Oxford, UK. Main results: Our proposed methods achieved an accuracy of 98.8% for patient detection, a mean intersection-over-union (IOU) score of 88.6% for skin segmentation and an accuracy of 94.5% for clinical intervention detection using two-fold cross validation. Our deep learning models produced accurate results and were robust to different skin tones, changes in light conditions, pose variations and different clinical interventions by medical staff and family visitors. Significance: Our approach allows cardio-respiratory signals to be continuously derived from the patient’s skin during which the patient is present and no clinical intervention is undertaken.

Fluorescence microscopy plays a vital role in understanding the subcellular structures of living cells. However, it requires considerable effort in sample preparation related to chemical fixation, staining, cost, and time. To reduce those factors, we present a virtual fluorescence staining method based on deep neural networks (VirFluoNet) to transform fluorescence images of molecular labels into other molecular fluorescence labels in the same field-of-view. To achieve this goal, we develop and train a conditional generative adversarial network (cGAN) to perform digital fluorescence imaging demonstrated on human osteosarcoma U2OS cell fluorescence images captured under Cell Painting staining protocol. A detailed comparative analysis is also conducted on the performance of the cGAN network between predicting fluorescence channels based on phase contrast or based on another fluorescence channel using human breast cancer MDA-MB-231 cell line as a test case. In addition, we implement a deep learning model to perform autofocusing on another human U2OS fluorescence dataset as a preprocessing step to defocus an out-focus channel in U2OS dataset. A quantitative index of image prediction error is introduced based on signal pixel-wise spatial and intensity differences with ground truth to evaluate the performance of prediction to high-complex and throughput fluorescence. This index provides a rational way to perform image segmentation on error signals and to understand the likelihood of mis-interpreting biology from the predicted image. In total, these findings contribute to the utility of deep learning image regression for fluorescence microscopy datasets of biological cells, balanced against savings of cost, time, and experimental effort. Furthermore, the approach introduced here holds promise for modeling the internal relationships between organelles and biomolecules within living cells., 20 pages, 9 figures

Quasi-static ultrasound elastography (USE) is an imaging modality that measures deformation (i.e. strain) of tissue in response to an applied mechanical force. In USE, the strain modulus is traditionally obtained by deriving the displacement field estimated between a pair of radio-frequency data. In this work we propose a recurrent network architecture with convolutional long-short-term memory decoder blocks to improve displacement estimation and spatio-temporal continuity between time series ultrasound frames. The network is trained in an unsupervised way, by optimising a similarity metric between the reference and compressed image. Our training loss is also composed of a regularisation term that preserves displacement continuity by directly optimising the strain smoothness, and a temporal continuity term that enforces consistency between successive strain predictions. In addition, we propose an open-access in vivo database for quasi-static USE, which consists of radio-frequency data sequences captured on the arm of a human volunteer. Our results from numerical simulation and in vivo data suggest that our recurrent neural network can account for larger deformations, as compared with two other feed-forward neural networks. In all experiments, our recurrent network outperformed the state-of-the-art for both learning-based and optimisation-based methods, in terms of elastographic signal-to-noise ratio, strain consistency, and image similarity. Finally, our open-source code provides a 3D-slicer visualisation module that can be used to process ultrasound RF frames in real-time, at a rate of up to 20 frames per second, using a standard GPU.

Gaining knowledge and actionable insights from complex, high-dimensional and heterogeneous biomedical data remains a key challenge in transforming health care. Various types of data have been emerging in modern biomedical research, including electronic health records, imaging, -omics, sensor data and text, which are complex, heterogeneous, poorly annotated and generally unstructured. Traditional data mining and statistical learning approaches typically need to first perform feature engineering to obtain effective and more robust features from those data, and then build prediction or clustering models on top of them. There are lots of challenges on both steps in a scenario of complicated data and lacking of sufficient domain knowledge. The latest advances in deep learning technologies provide new effective paradigms to obtain end-to-end learning models from complex data. In this article, we review the recent literature on applying deep learning technologies to advance the health care domain. Based on the analyzed work, we suggest that deep learning approaches could be the vehicle for translating big biomedical data into improved human health. However, we also note limitations and needs for improved methods development and applications, especially in terms of ease-of-understanding for domain experts and citizen scientists. We discuss such challenges and suggest developing holistic and meaningful interpretable architectures to bridge deep learning models and human interpretability.

In the context of epilepsy monitoring, electroencephalography (EEG) remains the modality of choice. Functional near-infrared spectroscopy (fNIRS) is a relatively innovative modality that cannot only characterize hemodynamic profiles of seizures but also allow for long-term recordings. We employ deep learning methods to investigate the benefits of integrating fNIRS measures for seizure detection. We designed a deep recurrent neural network with long short-term memory units and subsequently validated it using the CHBMIT scalp EEG database—a compendium of 896 h of surface EEG seizure recordings. After validating our network using EEG, fNIRS, and multimodal data comprising a corpus of 89 seizures from 40 refractory epileptic patients was used as model input to evaluate the integration of fNIRS measures. Following heuristic hyperparameter optimization, multimodal EEG-fNIRS data provide superior performance metrics (sensitivity and specificity of 89.7% and 95.5%, respectively) in a seizure detection task, with low generalization errors and loss. False detection rates are generally low, with 11.8% and 5.6% for EEG and multimodal data, respectively. Employing multimodal neuroimaging, particularly EEG-fNIRS, in epileptic patients, can enhance seizure detection performance. Furthermore, the neural network model proposed and characterized herein offers a promising framework for future multimodal investigations in seizure detection and prediction.

The scientific, clinical, and pedagogical significance of devising methodologies to train nonprofessional subjects to recognize diagnostic visual patterns in medical images has been broadly recognized. However, systematic approaches to doing so remain poorly established. Using mammography as an exemplar case, we use a series of experiments to demonstrate that deep learning (DL) techniques can, in principle, be used to train naïve subjects to reliably detect certain diagnostic visual patterns of cancer in medical images. In the main experiment, subjects were required to learn to detect statistical visual patterns diagnostic of cancer in mammograms using only the mammograms and feedback provided following the subjects’ response. We found not only that the subjects learned to perform the task at statistically significant levels, but also that their eye movements related to image scrutiny changed in a learning-dependent fashion. Two additional, smaller exploratory experiments suggested that allowing subjects to re-examine the mammogram in light of various items of diagnostic information may help further improve DL of the diagnostic patterns. Finally, a fourth small, exploratory experiment suggested that the image information learned was similar across subjects. Together, these results prove the principle that DL methodologies can be used to train nonprofessional subjects to reliably perform those aspects of medical image perception tasks that depend on visual pattern recognition expertise.

Major calcifications are of great concern when performing percutaneous coronary interventions because they inhibit proper stent deployment. We created a comprehensive software to segment calcifications in intravascular optical coherence tomography (IVOCT) images and to calculate their impact using the stent-deployment calcification score, as reported by Fujino et al. We segmented the vascular lumen and calcifications using the pretrained SegNet, convolutional neural network, which was refined for our task. We cleaned segmentation results using conditional random field processing. We evaluated the method on manually annotated IVOCT volumes of interest (VOIs) without lesions and with calcifications, lipidous, or mixed lesions. The dataset included 48 VOIs taken from 34 clinical pullbacks, giving a total of 2640 in vivo images. Annotations were determined from consensus between two expert analysts. Keeping VOIs intact, we performed 10-fold cross-validation over all data. Following segmentation noise cleaning, we obtained sensitivities of 0.85 ± 0.04, 0.99 ± 0.01, and 0.97 ± 0.01 for calcified, lumen, and other tissue classes, respectively. From segmented regions, we automatically determined calcification depth, angle, and thickness attributes. Bland–Altman analysis suggested strong correlation between manually and automatically obtained lumen and calcification attributes. Agreement between manually and automatically obtained stent-deployment calcification scores was good (four of five lesions gave exact agreement). Results are encouraging and suggest our classification approach could be applied clinically for assessment and treatment planning of coronary calcification lesions.

Spectral-domain optical coherence tomography (SDOCT) is a noncontact and noninvasive imaging technology offering three-dimensional (3-D), objective, and quantitative assessment of optic nerve head (ONH) in human eyes in vivo. The image quality of SDOCT scans is crucial for an accurate and reliable interpretation of ONH structure and for further detection of diseases. Traditionally, signal strength (SS) is used as an index to include or exclude SDOCT scans for further analysis. However, it is insufficient to assess other image quality issues such as off-centration, out of registration, missing data, motion artifacts, mirror artifacts, or blurriness, which require specialized knowledge in SDOCT for such assessment. We proposed a deep learning system (DLS) as an automated tool for filtering out ungradable SDOCT volumes. In total, 5599 SDOCT ONH volumes were collected for training (80%) and primary validation (20%). Other 711 and 298 volumes from two independent datasets, respectively, were used for external validation. An SDOCT volume was labeled as ungradable when SS was 5 or when any artifacts influenced the measurement circle or > 25 % of the peripheral area. Artifacts included (1) off-centration, (2) out of registration, (3) missing signal, (4) motion artifacts, (5) mirror artifacts, and (6) blurriness. An SDOCT volume was labeled as gradable when SS was ≥ 5 , and there was an absence of any artifacts or artifacts only influenced 25 % peripheral area but not the retinal nerve fiber layer calculation circle. We developed and validated a 3-D DLS based on squeeze-and-excitation ResNeXt blocks and experimented with different training strategies. The area under the receiver operating characteristic curve (AUC), sensitivity, specificity, and accuracy were calculated to evaluate the performance. Heatmaps were generated by gradient-weighted class activation map. Our findings show that the presented DLS achieved a good performance in both primary and external validations, which could potentially increase the efficiency and accuracy of SDOCT volumetric scans quality control by filtering out ungradable ones automatically.

The segmentation of organs at risk is a crucial and time-consuming step in radiotherapy planning. Good automatic methods can significantly reduce the time clinicians have to spend on this task. Due to its variability in shape and low contrast to surrounding structures, segmenting the parotid gland is challenging. Motivated by the recent success of deep learning, we study the use of two-dimensional (2-D), 2-D ensemble, and three-dimensional (3-D) U-Nets for segmentation. The mean Dice similarity to ground truth is ∼0.83 for all three models. A patch-based approach for class balancing seems promising for false-positive reduction. The 2-D ensemble and 3-D U-Net are applied to the test data of the 2015 MICCAI challenge on head and neck autosegmentation. Both deep learning methods generalize well onto independent data (Dice 0.865 and 0.88) and are superior to a selection of model- and atlas-based methods with respect to the Dice coefficient. Since appropriate reference annotations are essential for training but often difficult and expensive to obtain, it is important to know how many samples are needed for training. We evaluate the performance after training with different-sized training sets and observe no significant increase in the Dice coefficient for more than 250 training cases.