The chest X-ray is one of the most commonly accessible radiological examinations for screening and diagnosis of many lung diseases. A tremendous number of X-ray imaging studies accompanied by radiological reports are accumulated and stored in many modern hospitals' Picture Archiving and Communication Systems (PACS). On the other side, it is still an open question how this type of hospital-size knowledge database containing invaluable imaging informatics (i.e., loosely labeled) can be used to facilitate the data-hungry deep learning paradigms in building truly large-scale high precision computer-aided diagnosis (CAD) systems.In this paper, we present a new chest X-ray database, namely "ChestX-ray8", which comprises 108,948 frontalview X-ray images of 32,717 unique patients with the textmined eight disease image labels (where each image can have multi-labels), from the associated radiological reports using natural language processing. Importantly, we demonstrate that these commonly occurring thoracic diseases can be detected and even spatially-located via a unified weaklysupervised multi-label image classification and disease localization framework, which is validated using our proposed dataset. Although the initial quantitative results are promising as reported, deep convolutional neural network based "reading chest X-rays" (i.e., recognizing and locating the common disease patterns trained with only image-level labels) remains a strenuous task for fully-automated high precision CAD systems.

Deep learning describes a class of machine learning algorithms that are capable of combining raw inputs into layers of intermediate features. These algorithms have recently shown impressive results across a variety of domains. Biology and medicine are data-rich disciplines, but the data are complex and often ill-understood. Hence, deep learning techniques may be particularly well suited to solve problems of these fields. We examine applications of deep learning to a variety of biomedical problems—patient classification, fundamental biological processes and treatment of patients—and discuss whether deep learning will be able to transform these tasks or if the biomedical sphere poses unique challenges. Following from an extensive literature review, we find that deep learning has yet to revolutionize biomedicine or definitively resolve any of the most pressing challenges in the field, but promising advances have been made on the prior state of the art. Even though improvements over previous baselines have been modest in general, the recent progress indicates that deep learning methods will provide valuable means for speeding up or aiding human investigation. Though progress has been made linking a specific neural network's prediction to input features, understanding how users should interpret these models to make testable hypotheses about the system under study remains an open challenge. Furthermore, the limited amount of labelled data for training presents problems in some domains, as do legal and privacy constraints on work with sensitive health records. Nonetheless, we foresee deep learning enabling changes at both bench and bedside with the potential to transform several areas of biology and medicine.

Chest X-rays are one of the most common radiological examinations in daily clinical routines. Reporting thorax diseases using chest X-rays is often an entry-level task for radiologist trainees. Yet, reading a chest X-ray image remains a challenging job for learning-oriented machine intelligence, due to (1) shortage of large-scale machinelearnable medical image datasets, and (2) lack of techniques that can mimic the high-level reasoning of human radiologists that requires years of knowledge accumulation and professional training. In this paper, we show the clinical free-text radiological reportscan be utilized as a priori knowledge for tackling these two key problems. We propose a novel Text-Image Embedding network (TieNet) for extracting the distinctive image and text representations. Multilevel attention models are integrated into an end-to-end trainable CNN-RNN architecture for highlighting the meaningful text words and image regions. We first apply TieNet to classify the chest X-rays by using both image features and text embeddings extracted from associated reports. The proposed auto-annotation framework achieves high accuracy (over 0.9 on average in AUCs) in assigning disease labels for our hand-label evaluation dataset. Furthermore, we transform the TieNet into a chest X-ray reporting system. It simulates the reporting process and can output disease classification and a preliminary report together. The classification results are significantly improved (6% increase on average in AUCs) compared to the state-of-the-art baseline on an unseen and hand-labeled dataset (OpenI).

Deep learning, which describes a class of machine learning algorithms, has recently showed impressive results across a variety of domains. Biology and medicine are data rich, but the data are complex and often ill-understood. Problems of this nature may be particularly well-suited to deep learning techniques. We examine applications of deep learning to a variety of biomedical problems—patient classification, fundamental biological processes, and treatment of patients—and discuss whether deep learning will transform these tasks or if the biomedical sphere poses unique challenges. We find that deep learning has yet to revolutionize or definitively resolve any of these problems, but promising advances have been made on the prior state of the art. Even when improvement over a previous baseline has been modest, we have seen signs that deep learning methods may speed or aid human investigation. More work is needed to address concerns related to interpretability and how to best model each problem. Furthermore, the limited amount of labeled data for training presents problems in some domains, as do legal and privacy constraints on work with sensitive health records. Nonetheless, we foresee deep learning powering changes at both bench and bedside with the potential to transform several areas of biology and medicine.

Purpose: In assessing the severity of age-related macular degeneration (AMD), the Age-Related Eye Disease Study (AREDS) Simplified Severity Scale predicts the risk of progression to late AMD. However, its manual use requires the time-consuming participation of expert practitioners. Although several automated deep learning systems have been developed for classifying color fundus photographs (CFP) of individual eyes by AREDS severity score, none to date has used a patient-based scoring system that uses images from both eyes to assign a severity score.Design: DeepSeeNet, a deep learning model, was developed to classify patients automatically by the AREDS Simplified Severity Scale (score 0-5) using bilateral CFP.Participants: DeepSeeNet was trained on 58,402 and tested on 900 images from the longitudinal follow-up of 4,549 participants from AREDS. Gold standard labels were obtained using reading center grades.Methods: DeepSeeNet simulates the human grading process by first detecting individual AMD risk factors (drusen size, pigmentary abnormalities) for each eye and then calculating a patient-based AMD severity score using the AREDS Simplified Severity Scale. Main Outcome Measures: Overall accuracy, specificity, sensitivity, Cohen's kappa, and area under the curve (AUC). The performance of DeepSeeNet was compared with that of retinal specialists. Results: DeepSeeNet performed better on patient-based classification (accuracy = 0.671; kappa = 0.558) than retinal specialists (accuracy = 0.599; kappa = 0.467) with high AUC in the detection of large drusen (0.94), pigmentary abnormalities (0.93), and late AMD (0.97). DeepSeeNet also outperformed retinal specialists in the detection of large drusen (accuracy 0.742 vs. 0.696; kappa 0.601 vs. 0.517) and pigmentary abnormalities (accuracy 0.890 vs. 0.813; kappa 0.723 vs. 0.535) but showed lower performance in the detection of late AMD (accuracy 0.967 vs. 0.973; kappa 0.663 vs. 0.754). Conclusions: By simulating the human grading process, DeepSeeNet demonstrated high accuracy with increased transparency in the automated assignment of individual patients to AMD risk categories based on the AREDS Simplified Severity Scale. These results highlight the potential of deep learning to assist and enhance clinical decision-making in patients with AMD, such as early AMD detection and risk prediction for developing late AMD. DeepSeeNet is publicly available on https://github.com/ncbi-nlp/ DeepSeeNet.

A vast amount of scientific information is encoded in natural language text, and the quantity of such text has become so great that it is no longer economically feasible to have a human as the first step in the search process. Natural language processing and text mining tools have become essential to facilitate the search for and extraction of information from text. This has led to vigorous research efforts to create useful tools and to create humanly labeled text corpora, which can be used to improve such tools. To encourage combining these efforts into larger, more powerful and more capable systems, a common interchange format to represent, store and exchange the data in a simple manner between different language processing systems and text mining tools is highly desirable. Here we propose a simple extensible mark-up language format to share text documents and annotations. The proposed annotation approach allows a large number of different annotations to be represented including sentences, tokens, parts of speech, named entities such as genes or diseases and relationships between named entities. In addition, we provide simple code to hold this data, read it from and write it back to extensible mark-up language files and perform some sample processing. We also describe completed as well as ongoing work to apply the approach in several directions. Code and data are available at http://bioc.sourceforge.net/.Database URL: http://bioc.sourceforge.net/

When reading medical images such as a computed tomography (CT) scan, radiologists generally search across the image to find lesions, characterize and measure them, and then describe them in the radiological report. To automate this process, we propose a multitask universal lesion analysis network (MULAN) for joint detection, tagging, and segmentation of lesions in a variety of body parts, which greatly extends existing work of single-task lesion analysis on specific body parts. MULAN is based on an improved Mask R-CNN framework with three head branches and a 3D feature fusion strategy. It achieves the state-ofthe-art accuracy in the detection and tagging tasks on the DeepLesion dataset, which contains 32K lesions in the whole body. We also analyze the relationship between the three tasks and show that tag predictions can improve detection accuracy via a score refinement layer.

Manually curating chemicals, diseases and their relationships is significantly important to biomedical research, but it is plagued by its high cost and the rapid growth of the biomedical literature. In recent years, there has been a growing interest in developing computational approaches for automatic chemical-disease relation (CDR) extraction. Despite these attempts, the lack of a comprehensive benchmarking dataset has limited the comparison of different techniques in order to assess and advance the current state-of-the-art. To this end, we organized a challenge task through BioCreative V to automatically extract CDRs from the literature. We designed two challenge tasks: disease named entity recognition (DNER) and chemical-induced disease (CID) relation extraction. To assist system development and assessment, we created a large annotated text corpus that consisted of human annotations of chemicals, diseases and their interactions from 1500 PubMed articles. 34 teams worldwide participated in the CDR task: 16 (DNER) and 18 (CID). The best systems achieved an F-score of 86.46% for the DNER task—a result that approaches the human inter-annotator agreement (0.8875)—and an F-score of 57.03% for the CID task, the highest results ever reported for such tasks. When combining team results via machine learning, the ensemble system was able to further improve over the best team results by achieving 88.89% and 62.80% in F-score for the DNER and CID task, respectively. Additionally, another novel aspect of our evaluation is to test each participating system’s ability to return real-time results: the average response time for each team’s DNER and CID web service systems were 5.6 and 9.3 s, respectively. Most teams used hybrid systems for their submissions based on machining learning. Given the level of participation and results, we found our task to be successful in engaging the text-mining research community, producing a large annotated corpus and improving the results of automatic disease recognition and CDR extraction.Database URL: http://www.biocreative.org/tasks/biocreative-v/track-3-cdr/