Abstract To improve the performance of Intensive Care Units (ICUs), the field of bio-statistics has developed scores which try to predict the likelihood of negative outcomes. These help evaluate the effectiveness of treatments and clinical practice, and also help to identify patients with unexpected outcomes. However, they have been shown by several studies to offer sub-optimal performance. Alternatively, Deep Learning offers state of the art capabilities in certain prediction tasks and research suggests deep neural networks are able to outperform traditional techniques. Nevertheless, a main impediment for the adoption of Deep Learning in healthcare is its reduced interpretability, for in this field it is crucial to gain insight into the why of predictions, to assure that models are actually learning relevant features instead of spurious correlations. To address this, we propose a deep multi-scale convolutional architecture trained on the Medical Information Mart for Intensive Care III (MIMIC-III) for mortality prediction, and the use of concepts from coalitional game theory to construct visual explanations aimed to show how important these inputs are deemed by the network. Results show our model attains a ROC AUC of 0.8735 ( ± 0.0025) which is competitive with the state of the art of Deep Learning mortality models trained on MIMIC-III data, while remaining interpretable. Supporting code can be found at https: github.com williamcaicedo ISeeU .
Although the most natural application of Deep Learning algorithms to medical diagnosis is automated medical image diagnosis @cite_38 , the usage of Physiological Time Series (PTS) and Electronic Medical Record (EMR) data, is a more general source of data on which machine learning models can be trained. EMRs are very attractive as a potential data source since their use is widespread, which makes them abundant and accessible electronically. However, there are certain challenges associated with their “secondary use” in Machine Learning @cite_39 . Despite this, several works have reported the successful use of EMRs and PTS to train Machine Learning Deep Learning based models for diagnosis.
@cite_38 @cite_39
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Despite tremendous progress in computer vision, there has not been an attempt to apply machine learning on very large-scale medical image databases. We present an interleaved text image deep learning system to extract and mine the semantic interactions of radiology images and reports from a national research hospital's Picture Archiving and Communication System. With natural language processing, we mine a collection of ∼216K representative two-dimensional images selected by clinicians for diagnostic reference and match the images with their descriptions in an automated manner. We then employ a weakly supervised approach using all of our available data to build models for generating approximate interpretations of patient images. Finally, we demonstrate a more strictly supervised approach to detect the presence and absence of a number of frequent disease types, providing more specific interpretations of patient scans. A relatively small amount of data is used for this part, due to the challenge in gathering quality labels from large raw text data. Our work shows the feasibility of large-scale learning and prediction in electronic patient records available in most modern clinical institutions. It also demonstrates the trade-offs to consider in designing machine learning systems for analyzing large medical data. Background: Electronic medical records (EMRs) are revolutionizing health-related research. One key issue for study quality is the accurate identification of patients with the condition of interest. Information in EMRs can be entered as structured codes or unstructured free text. The majority of research studies have used only coded parts of EMRs for case-detection, which may bias findings, miss cases, and reduce study quality. This review examines whether incorporating information from text into case-detection algorithms can improve research quality. Methods: A systematic search returned 9659 papers, 67 of which reported on the extraction of information from free text of EMRs with the stated purpose of detecting cases of a named clinical condition. Methods for extracting information from text and the technical accuracy of case-detection algorithms were reviewed. Results: Studies mainly used US hospital-based EMRs, and extracted information from text for 41 conditions using keyword searches, rule-based algorithms, and machine learning methods. There was no clear difference in case-detection algorithm accuracy between rule-based and machine learning methods of extraction. Inclusion of information from text resulted in a significant improvement in algorithm sensitivity and area under the receiver operating characteristic in comparison to codes alone (median sensitivity 78 (codes + text) vs 62 (codes), P = .03; median area under the receiver operating characteristic 95 (codes + text) vs 88 (codes), P = .025). Conclusions: Text in EMRs is accessible, especially with open source information extraction algorithms, and significantly improves case detection when combined with codes. More harmonization of reporting within EMR studies is needed, particularly standardized reporting of algorithm accuracy metrics like positive predictive value (precision) and sensitivity (recall). Despite the recent advances in automatically describing image contents, their applications have been mostly limited to image caption datasets containing natural images (e.g., Flickr 30k, MSCOCO). In this paper, we present a deep learning model to efficiently detect a disease from an image and annotate its contexts (e.g., location, severity and the affected organs). We employ a publicly available radiology dataset of chest x-rays and their reports, and use its image annotations to mine disease names to train convolutional neural networks (CNNs). In doing so, we adopt various regularization techniques to circumvent the large normal-vs-diseased cases bias. Recurrent neural networks (RNNs) are then trained to describe the contexts of a detected disease, based on the deep CNN features. Moreover, we introduce a novel approach to use the weights of the already trained pair of CNN RNN on the domain-specific image text dataset, to infer the joint image text contexts for composite image labeling. Significantly improved image annotation results are demonstrated using the recurrent neural cascade model by taking the joint image text contexts into account. Deep learning is considered as a popular and powerful method in pattern recognition and classification. However, there are not many deep structured applications used in medical imaging diagnosis area, because large dataset is not always available for medical images. In this study we tested the feasibility of using deep learning algorithms for lung cancer diagnosis with the cases from Lung Image Database Consortium (LIDC) database. The nodules on each computed tomography (CT) slice were segmented according to marks provided by the radiologists. After down sampling and rotating we acquired 174412 samples with 52 by 52 pixel each and the corresponding truth files. Three deep learning algorithms were designed and implemented, including Convolutional Neural Network (CNN), Deep Belief Networks (DBNs), Stacked Denoising Autoencoder (SDAE). To compare the performance of deep learning algorithms with traditional computer aided diagnosis (CADx) system, we designed a scheme with 28 image features and support vector machine. The accuracies of CNN, DBNs, and SDAE are 0.7976, 0.8119, and 0.7929, respectively; the accuracy of our designed traditional CADx is 0.7940, which is slightly lower than CNN and DBNs. We also noticed that the mislabeled nodules using DBNs are 4 larger than using traditional CADx, this might be resulting from down sampling process lost some size information of the nodules. The rapid growth of Electronic Health Records (EHRs), as well as the accompanied opportunities in Data-Driven Healthcare (DDH), has been attracting widespread interests and attentions. Recent progress in the design and applications of deep learning methods has shown promising results and is forcing massive changes in healthcare academia and industry, but most of these methods rely on massive labeled data. In this work, we propose a general deep learning framework which is able to boost risk prediction performance with limited EHR data. Our model takes a modified generative adversarial network namely ehrGAN, which can provide plausible labeled EHR data by mimicking real patient records, to augment the training dataset in a semi-supervised learning manner. We use this generative model together with a convolutional neural network (CNN) based prediction model to improve the onset prediction performance. Experiments on two real healthcare datasets demonstrate that our proposed framework produces realistic data samples and achieves significant improvements on classification tasks with the generated data over several stat-of-the-art baselines. To realize the full potential of deep learning for medical imaging, large annotated datasets are required for training. Such datasets are difficult to acquire due to privacy issues, lack of experts available for annotation, underrepresentation of rare conditions, and poor standardization. The lack of annotated data has been addressed in conventional vision applications using synthetic images refined via unsupervised adversarial training to look like real images. However, this approach is difficult to extend to general medical imaging because of the complex and diverse set of features found in real human tissues. We propose a novel framework that uses a reverse flow, where adversarial training is used to make real medical images more like synthetic images, and clinically-relevant features are preserved via self-regularization. These domain-adapted synthetic-like images can then be accurately interpreted by networks trained on large datasets of synthetic medical images. We implement this approach on the notoriously difficult task of depth-estimation from monocular endoscopy which has a variety of applications in colonoscopy, robotic surgery, and invasive endoscopic procedures. We train a depth estimator on a large data set of synthetic images generated using an accurate forward model of an endoscope and an anatomically-realistic colon. Our analysis demonstrates that the structural similarity of endoscopy depth estimation in a real pig colon predicted from a network trained solely on synthetic data improved by 78.7 by using reverse domain adaptation. Importance Application of deep learning algorithms to whole-slide pathology images can potentially improve diagnostic accuracy and efficiency. Objective Assess the performance of automated deep learning algorithms at detecting metastases in hematoxylin and eosin–stained tissue sections of lymph nodes of women with breast cancer and compare it with pathologists’ diagnoses in a diagnostic setting. Design, Setting, and Participants Researcher challenge competition (CAMELYON16) to develop automated solutions for detecting lymph node metastases (November 2015-November 2016). A training data set of whole-slide images from 2 centers in the Netherlands with (n = 110) and without (n = 160) nodal metastases verified by immunohistochemical staining were provided to challenge participants to build algorithms. Algorithm performance was evaluated in an independent test set of 129 whole-slide images (49 with and 80 without metastases). The same test set of corresponding glass slides was also evaluated by a panel of 11 pathologists with time constraint (WTC) from the Netherlands to ascertain likelihood of nodal metastases for each slide in a flexible 2-hour session, simulating routine pathology workflow, and by 1 pathologist without time constraint (WOTC). Exposures Deep learning algorithms submitted as part of a challenge competition or pathologist interpretation. Main Outcomes and Measures The presence of specific metastatic foci and the absence vs presence of lymph node metastasis in a slide or image using receiver operating characteristic curve analysis. The 11 pathologists participating in the simulation exercise rated their diagnostic confidence as definitely normal, probably normal, equivocal, probably tumor, or definitely tumor. Results The area under the receiver operating characteristic curve (AUC) for the algorithms ranged from 0.556 to 0.994. The top-performing algorithm achieved a lesion-level, true-positive fraction comparable with that of the pathologist WOTC (72.4 [95 CI, 64.3 -80.4 ]) at a mean of 0.0125 false-positives per normal whole-slide image. For the whole-slide image classification task, the best algorithm (AUC, 0.994 [95 CI, 0.983-0.999]) performed significantly better than the pathologists WTC in a diagnostic simulation (mean AUC, 0.810 [range, 0.738-0.884]; P Conclusions and Relevance In the setting of a challenge competition, some deep learning algorithms achieved better diagnostic performance than a panel of 11 pathologists participating in a simulation exercise designed to mimic routine pathology workflow; algorithm performance was comparable with an expert pathologist interpreting whole-slide images without time constraints. Whether this approach has clinical utility will require evaluation in a clinical setting. One of the biggest issues facing the use of machine learning in medical imaging is the lack of availability of large, labelled datasets. The annotation of medical images is not only expensive and time consuming but also highly dependent on the availability of expert observers. The limited amount of training data can inhibit the performance of supervised machine learning algorithms which often need very large quantities of data on which to train to avoid overfitting. So far, much effort has been directed at extracting as much information as possible from what data is available. Generative Adversarial Networks (GANs) offer a novel way to unlock additional information from a dataset by generating synthetic samples with the appearance of real images. This paper demonstrates the feasibility of introducing GAN derived synthetic data to the training datasets in two brain segmentation tasks, leading to improvements in Dice Similarity Coefficient (DSC) of between 1 and 5 percentage points under different conditions, with the strongest effects seen fewer than ten training image stacks are available. The widespread availability of electronic health records (EHRs) promises to usher in the era of personalized medicine. However, the problem of extracting useful clinical representations from longitudinal EHR data remains challenging. In this paper, we explore deep neural network models with learned medical feature embedding to deal with the problems of high dimensionality and temporality. Specifically, we use a multi-layer convolutional neural network (CNN) to parameterize the model and is thus able to capture complex non-linear longitudinal evolution of EHRs. Our model can effectively capture local short temporal dependency in EHRs, which is beneficial for risk prediction. To account for high dimensionality, we use the embedding medical features in the CNN model which hold the natural medical concepts. Our initial experiments produce promising results and demonstrate the effectiveness of both the medical feature embedding and the proposed convolutional neural network in risk prediction on cohorts of congestive heart failure and diabetes patients compared with several strong baselines. Learning representative computational models from medical imaging data requires large training data sets. Often, voxel-level annotation is unfeasible for sufficient amounts of data. An alternative to manual annotation, is to use the enormous amount of knowledge encoded in imaging data and corresponding reports generated during clinical routine. Weakly supervised learning approaches can link volume-level labels to image content but suffer from the typical label distributions in medical imaging data where only a small part consists of clinically relevant abnormal structures. In this paper we propose to use a semantic representation of clinical reports as a learning target that is predicted from imaging data by a convolutional neural network. We demonstrate how we can learn accurate voxel-level classifiers based on weak volume-level semantic descriptions on a set of 157 optical coherence tomography (OCT) volumes. We specifically show how semantic information increases classification accuracy for intraretinal cystoid fluid (IRC), subretinal fluid (SRF) and normal retinal tissue, and how the learning algorithm links semantic concepts to image content and geometry. Exponential growth in Electronic Healthcare Records (EHR) has resulted in new opportunities and urgent needs for discovery of meaningful data-driven representations and patterns of diseases in Computational Phenotyping research. Deep Learning models have shown superior performance for robust prediction in computational phenotyping tasks, but suffer from the issue of model interpretability which is crucial for clinicians involved in decision-making. In this paper, we introduce a novel knowledge-distillation approach called Interpretable Mimic Learning, to learn interpretable phenotype features for making robust prediction while mimicking the performance of deep learning models. Our framework uses Gradient Boosting Trees to learn interpretable features from deep learning models such as Stacked Denoising Autoencoder and Long Short-Term Memory. Exhaustive experiments on a real-world clinical time-series dataset show that our method obtains similar or better performance than the deep learning models, and it provides interpretable phenotypes for clinical decision making. This review covers computer-assisted analysis of images in the field of medical imaging. Recent advances in machine learning, especially with regard to deep learning, are helping to identify, classify, and quantify patterns in medical images. At the core of these advances is the ability to exploit hierarchical feature representations learned solely from data, instead of features designed by hand according to domain-specific knowledge. Deep learning is rapidly becoming the state of the art, leading to enhanced performance in various medical applications. We introduce the fundamentals of deep learning methods and review their successes in image registration, detection of anatomical and cellular structures, tissue segmentation, computer-aided disease diagnosis and prognosis, and so on. We conclude by discussing research issues and suggesting future directions for further improvement. Over past several years, machine learning, or more generally artificial intelligence, has generated overwhelming research interest and attracted unprecedented public attention. As tomographic imaging researchers, we share the excitement from our imaging perspective [item 1) in the Appendix], and organized this special issue dedicated to the theme of “Machine learning for image reconstruction.” This special issue is a sister issue of the special issue published in May 2016 of this journal with the theme “Deep learning in medical imaging” [item 2) in the Appendix]. While the previous special issue targeted medical image processing analysis, this special issue focuses on data-driven tomographic reconstruction. These two special issues are highly complementary, since image reconstruction and image analysis are two of the main pillars for medical imaging. Together we cover the whole workflow of medical imaging: from tomographic raw data features to reconstructed images and then extracted diagnostic features readings. The use of machine learning (ML) has been increasing rapidly in the medical imaging field, including computer-aided diagnosis (CAD), radiomics, and medical image analysis. Recently, an ML area called deep learning emerged in the computer vision field and became very popular in many fields. It started from an event in late 2012, when a deep-learning approach based on a convolutional neural network (CNN) won an overwhelming victory in the best-known worldwide computer vision competition, ImageNet Classification. Since then, researchers in virtually all fields, including medical imaging, have started actively participating in the explosively growing field of deep learning. In this paper, the area of deep learning in medical imaging is overviewed, including (1) what was changed in machine learning before and after the introduction of deep learning, (2) what is the source of the power of deep learning, (3) two major deep-learning models: a massive-training artificial neural network (MTANN) and a convolutional neural network (CNN), (4) similarities and differences between the two models, and (5) their applications to medical imaging. This review shows that ML with feature input (or feature-based ML) was dominant before the introduction of deep learning, and that the major and essential difference between ML before and after deep learning is the learning of image data directly without object segmentation or feature extraction; thus, it is the source of the power of deep learning, although the depth of the model is an important attribute. The class of ML with image input (or image-based ML) including deep learning has a long history, but recently gained popularity due to the use of the new terminology, deep learning. There are two major models in this class of ML in medical imaging, MTANN and CNN, which have similarities as well as several differences. In our experience, MTANNs were substantially more efficient in their development, had a higher performance, and required a lesser number of training cases than did CNNs. “Deep learning”, or ML with image input, in medical imaging is an explosively growing, promising field. It is expected that ML with image input will be the mainstream area in the field of medical imaging in the next few decades. Abstract The purpose of this research was to implement a deep learning network to overcome two of the major bottlenecks in improved image reconstruction for clinical positron emission tomography (PET). These are the lack of an automated means for the optimization of advanced image reconstruction algorithms, and the computational expense associated with these state-of-the art methods. We thus present a novel end-to-end PET image reconstruction technique, called DeepPET, based on a deep convolutional encoder–decoder network, which takes PET sinogram data as input and directly and quickly outputs high quality, quantitative PET images. Using simulated data derived from a whole-body digital phantom, we randomly sampled the configurable parameters to generate realistic images, which were each augmented to a total of more than 291,000 reference images. Realistic PET acquisitions of these images were simulated, resulting in noisy sinogram data, used for training, validation, and testing the DeepPET network. We demonstrated that DeepPET generates higher quality images compared to conventional techniques, in terms of relative root mean squared error (11 53 lower than ordered subset expectation maximization (OSEM) filtered back-projection (FBP), structural similarity index (1 11 higher than OSEM FBP), and peak signal-to-noise ratio (1.1 3.8 dB higher than OSEM FBP). In addition, we show that DeepPET reconstructs images 108 and 3 times faster than OSEM and FBP, respectively. Finally, DeepPET was successfully applied to real clinical data. This study shows that an end-to-end encoder–decoder network can produce high quality PET images at a fraction of the time compared to conventional methods. Deep learning algorithms require large amounts of labeled data which is difficult to attain for medical imaging. Even if a particular dataset is accessible, a learned classifier struggles to maintain the same level of performance on a different medical imaging dataset from a new or never-seen data source domain. Utilizing generative adversarial networks in a semi-supervised learning architecture, we address both problems of labeled data scarcity and data domain overfitting. For cardiac abnormality classification in chest X-rays, we demonstrate that an order of magnitude less data is required with semi-supervised learning generative adversarial networks than with conventional supervised learning convolutional neural networks. In addition, we demonstrate its robustness across different datasets for similar classification tasks. Predictive modeling with electronic health record (EHR) data is anticipated to drive personalized medicine and improve healthcare quality. Constructing predictive statistical models typically requires extraction of curated predictor variables from normalized EHR data, a labor-intensive process that discards the vast majority of information in each patient’s record. We propose a representation of patients’ entire raw EHR records based on the Fast Healthcare Interoperability Resources (FHIR) format. We demonstrate that deep learning methods using this representation are capable of accurately predicting multiple medical events from multiple centers without site-specific data harmonization. We validated our approach using de-identified EHR data from two US academic medical centers with 216,221 adult patients hospitalized for at least 24 h. In the sequential format we propose, this volume of EHR data unrolled into a total of 46,864,534,945 data points, including clinical notes. Deep learning models achieved high accuracy for tasks such as predicting: in-hospital mortality (area under the receiver operator curve [AUROC] across sites 0.93–0.94), 30-day unplanned readmission (AUROC 0.75–0.76), prolonged length of stay (AUROC 0.85–0.86), and all of a patient’s final discharge diagnoses (frequency-weighted AUROC 0.90). These models outperformed traditional, clinically-used predictive models in all cases. We believe that this approach can be used to create accurate and scalable predictions for a variety of clinical scenarios. In a case study of a particular prediction, we demonstrate that neural networks can be used to identify relevant information from the patient’s chart. The use of deep learning for medical imaging has seen tremendous growth in the research community. One reason for the slow uptake of these systems in the clinical setting is that they are complex, opaque and tend to fail silently. Outside of the medical imaging domain, the machine learning community has recently proposed several techniques for quantifying model uncertainty (i.e. a model knowing when it has failed). This is important in practical settings, as we can refer such cases to manual inspection or correction by humans. In this paper, we aim to bring these recent results on estimating uncertainty to bear on two important outputs in deep learning-based segmentation. The first is producing spatial uncertainty maps, from which a clinician can observe where and why a system thinks it is failing. The second is quantifying an image-level prediction of failure, which is useful for isolating specific cases and removing them from automated pipelines. We also show that reasoning about spatial uncertainty, the first output, is a useful intermediate representation for generating segmentation quality predictions, the second output. We propose a two-stage architecture for producing these measures of uncertainty, which can accommodate any deep learning-based medical segmentation pipeline. Abstract Deep learning methods, and in particular convolutional neural networks (CNNs), have led to an enormous breakthrough in a wide range of computer vision tasks, primarily by using large-scale annotated datasets. However, obtaining such datasets in the medical domain remains a challenge. In this paper, we present methods for generating synthetic medical images using recently presented deep learning Generative Adversarial Networks (GANs). Furthermore, we show that generated medical images can be used for synthetic data augmentation, and improve the performance of CNN for medical image classification. Our novel method is demonstrated on a limited dataset of computed tomography (CT) images of 182 liver lesions (53 cysts, 64 metastases and 65 hemangiomas). We first exploit GAN architectures for synthesizing high quality liver lesion ROIs. Then we present a novel scheme for liver lesion classification using CNN. Finally, we train the CNN using classic data augmentation and our synthetic data augmentation and compare performance. In addition, we explore the quality of our synthesized examples using visualization and expert assessment. The classification performance using only classic data augmentation yielded 78.6 sensitivity and 88.4 specificity. By adding the synthetic data augmentation the results increased to 85.7 sensitivity and 92.4 specificity. We believe that this approach to synthetic data augmentation can generalize to other medical classification applications and thus support radiologists’ efforts to improve diagnosis. The 2010 i2b2 VA Workshop on Natural Language Processing Challenges for Clinical Records presented three tasks: a concept extraction task focused on the extraction of medical concepts from patient reports; an assertion classification task focused on assigning assertion types for medical problem concepts; and a relation classification task focused on assigning relation types that hold between medical problems, tests, and treatments. i2b2 and the VA provided an annotated reference standard corpus for the three tasks. Using this reference standard, 22 systems were developed for concept extraction, 21 for assertion classification, and 16 for relation classification. @PARASPLIT These systems showed that machine learning approaches could be augmented with rule-based systems to determine concepts, assertions, and relations. Depending on the task, the rule-based systems can either provide input for machine learning or post-process the output of machine learning. Ensembles of classifiers, information from unlabeled data, and external knowledge sources can help when the training data are inadequate.