An Efficient Deep Neural Network to Classify Large 3D Images With Small Objects.

3D imaging enables accurate diagnosis by providing spatial information about organ anatomy. However, using 3D images to train AI models is computationally challenging because they consist of 10x or 100x more pixels than their 2D counterparts. To be trained with high-resolution 3D images, convolutional neural networks resort to downsampling them or projecting them to 2D. We propose an effective alternative, a neural network that enables efficient classification of full-resolution 3D medical images. Compared to off-the-shelf convolutional neural networks, our network, 3D Globally-Aware Multiple Instance Classifier (3D-GMIC), uses 77.98%-90.05% less GPU memory and 91.23%-96.02% less computation. While it is trained only with image-level labels, without segmentation labels, it explains its predictions by providing pixel-level saliency maps. On a dataset collected at NYU Langone Health, including 85,526 patients with full-field 2D mammography (FFDM), synthetic 2D mammography, and 3D mammography, 3D-GMIC achieves an AUC of 0.831 (95% CI: 0.769-0.887) in classifying breasts with malignant findings using 3D mammography. This is comparable to the performance of GMIC on FFDM (0.816, 95% CI: 0.737-0.878) and synthetic 2D (0.826, 95% CI: 0.754-0.884), which demonstrates that 3D-GMIC successfully classified large 3D images despite focusing computation on a smaller percentage of its input compared to GMIC. Therefore, 3D-GMIC identifies and utilizes extremely small regions of interest from 3D images consisting of hundreds of millions of pixels, dramatically reducing associated computational challenges. 3D-GMIC generalizes well to BCS-DBT, an external dataset from Duke University Hospital, achieving an AUC of 0.848 (95% CI: 0.798-0.896).

Improving Information Extraction from Pathology Reports using Named Entity Recognition.

Pathology reports are considered the gold standard in medical research due to their comprehensive and accurate diagnostic information. Natural language processing (NLP) techniques have been developed to automate information extraction from pathology reports. However, existing studies suffer from two significant limitations. First, they typically frame their tasks as report classification, which restricts the granularity of extracted information. Second, they often fail to generalize to unseen reports due to variations in language, negation, and human error. To overcome these challenges, we propose a BERT (bidirectional encoder representations from transformers) named entity recognition (NER) system to extract key diagnostic elements from pathology reports. We also introduce four data augmentation methods to improve the robustness of our model. Trained and evaluated on 1438 annotated breast pathology reports, acquired from a large medical center in the United States, our BERT model trained with data augmentation achieves an entity F1-score of 0.916 on an internal test set, surpassing the BERT baseline (0.843). We further assessed the model's generalizability using an external validation dataset from the United Arab Emirates, where our model maintained satisfactory performance (F1-score 0.860). Our findings demonstrate that our NER systems can effectively extract fine-grained information from widely diverse medical reports, offering the potential for large-scale information extraction in a wide range of medical and AI research. We publish our code at https://github.com/nyukat/pathology_extraction.

A Competition, Benchmark, Code, and Data for Using Artificial Intelligence to Detect Lesions in Digital Breast Tomosynthesis.

Importance: An accurate and robust artificial intelligence (AI) algorithm for detecting cancer in digital breast tomosynthesis (DBT) could significantly improve detection accuracy and reduce health care costs worldwide. Objectives: To make training and evaluation data for the development of AI algorithms for DBT analysis available, to develop well-defined benchmarks, and to create publicly available code for existing methods. Design, Setting, and Participants: This diagnostic study is based on a multi-institutional international grand challenge in which research teams developed algorithms to detect lesions in DBT. A data set of 22 032 reconstructed DBT volumes was made available to research teams. Phase 1, in which teams were provided 700 scans from the training set, 120 from the validation set, and 180 from the test set, took place from December 2020 to January 2021, and phase 2, in which teams were given the full data set, took place from May to July 2021. Main Outcomes and Measures: The overall performance was evaluated by mean sensitivity for biopsied lesions using only DBT volumes with biopsied lesions; ties were broken by including all DBT volumes. Results: A total of 8 teams participated in the challenge. The team with the highest mean sensitivity for biopsied lesions was the NYU B-Team, with 0.957 (95% CI, 0.924-0.984), and the second-place team, ZeDuS, had a mean sensitivity of 0.926 (95% CI, 0.881-0.964). When the results were aggregated, the mean sensitivity for all submitted algorithms was 0.879; for only those who participated in phase 2, it was 0.926. Conclusions and Relevance: In this diagnostic study, an international competition produced algorithms with high sensitivity for using AI to detect lesions on DBT images. A standardized performance benchmark for the detection task using publicly available clinical imaging data was released, with detailed descriptions and analyses of submitted algorithms accompanied by a public release of their predictions and code for selected methods. These resources will serve as a foundation for future research on computer-assisted diagnosis methods for DBT, significantly lowering the barrier of entry for new researchers.

Improving breast cancer diagnostics with deep learning for MRI.

Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) has a high sensitivity in detecting breast cancer but often leads to unnecessary biopsies and patient workup. We used a deep learning (DL) system to improve the overall accuracy of breast cancer diagnosis and personalize management of patients undergoing DCE-MRI. On the internal test set (n = 3936 exams), our system achieved an area under the receiver operating characteristic curve (AUROC) of 0.92 (95% CI: 0.92 to 0.93). In a retrospective reader study, there was no statistically significant difference (P = 0.19) between five board-certified breast radiologists and the DL system (mean ΔAUROC, +0.04 in favor of the DL system). Radiologists' performance improved when their predictions were averaged with DL's predictions [mean ΔAUPRC (area under the precision-recall curve), +0.07]. We demonstrated the generalizability of the DL system using multiple datasets from Poland and the United States. An additional reader study on a Polish dataset showed that the DL system was as robust to distribution shift as radiologists. In subgroup analysis, we observed consistent results across different cancer subtypes and patient demographics. Using decision curve analysis, we showed that the DL system can reduce unnecessary biopsies in the range of clinically relevant risk thresholds. This would lead to avoiding biopsies yielding benign results in up to 20% of all patients with BI-RADS category 4 lesions. Last, we performed an error analysis, investigating situations where DL predictions were mostly incorrect. This exploratory work creates a foundation for deployment and prospective analysis of DL-based models for breast MRI.

Differences between human and machine perception in medical diagnosis.

Deep neural networks (DNNs) show promise in image-based medical diagnosis, but cannot be fully trusted since they can fail for reasons unrelated to underlying pathology. Humans are less likely to make such superficial mistakes, since they use features that are grounded on medical science. It is therefore important to know whether DNNs use different features than humans. Towards this end, we propose a framework for comparing human and machine perception in medical diagnosis. We frame the comparison in terms of perturbation robustness, and mitigate Simpson's paradox by performing a subgroup analysis. The framework is demonstrated with a case study in breast cancer screening, where we separately analyze microcalcifications and soft tissue lesions. While it is inconclusive whether humans and DNNs use different features to detect microcalcifications, we find that for soft tissue lesions, DNNs rely on high frequency components ignored by radiologists. Moreover, these features are located outside of the region of the images found most suspicious by radiologists. This difference between humans and machines was only visible through subgroup analysis, which highlights the importance of incorporating medical domain knowledge into the comparison.

Reducing False-Positive Biopsies using Deep Neural Networks that Utilize both Local and Global Image Context of Screening Mammograms.

Breast cancer is the most common cancer in women, and hundreds of thousands of unnecessary biopsies are done around the world at a tremendous cost. It is crucial to reduce the rate of biopsies that turn out to be benign tissue. In this study, we build deep neural networks (DNNs) to classify biopsied lesions as being either malignant or benign, with the goal of using these networks as second readers serving radiologists to further reduce the number of false-positive findings. We enhance the performance of DNNs that are trained to learn from small image patches by integrating global context provided in the form of saliency maps learned from the entire image into their reasoning, similar to how radiologists consider global context when evaluating areas of interest. Our experiments are conducted on a dataset of 229,426 screening mammography examinations from 141,473 patients. We achieve an AUC of 0.8 on a test set consisting of 464 benign and 136 malignant lesions.

Artificial intelligence system reduces false-positive findings in the interpretation of breast ultrasound exams.

Though consistently shown to detect mammographically occult cancers, breast ultrasound has been noted to have high false-positive rates. In this work, we present an AI system that achieves radiologist-level accuracy in identifying breast cancer in ultrasound images. Developed on 288,767 exams, consisting of 5,442,907 B-mode and Color Doppler images, the AI achieves an area under the receiver operating characteristic curve (AUROC) of 0.976 on a test set consisting of 44,755 exams. In a retrospective reader study, the AI achieves a higher AUROC than the average of ten board-certified breast radiologists (AUROC: 0.962 AI, 0.924 ± 0.02 radiologists). With the help of the AI, radiologists decrease their false positive rates by 37.3% and reduce requested biopsies by 27.8%, while maintaining the same level of sensitivity. This highlights the potential of AI in improving the accuracy, consistency, and efficiency of breast ultrasound diagnosis.

A convolutional neural network for common coordinate registration of high-resolution histology images.

MOTIVATION: Registration of histology images from multiple sources is a pressing problem in large-scale studies of spatial -omics data. Researchers often perform 'common coordinate registration', akin to segmentation, in which samples are partitioned based on tissue type to allow for quantitative comparison of similar regions across samples. Accuracy in such registration requires both high image resolution and global awareness, which mark a difficult balancing act for contemporary deep learning architectures. RESULTS: We present a novel convolutional neural network (CNN) architecture that combines (i) a local classification CNN that extracts features from image patches sampled sparsely across the tissue surface and (ii) a global segmentation CNN that operates on these extracted features. This hybrid network can be trained in an end-to-end manner, and we demonstrate its relative merits over competing approaches on a reference histology dataset as well as two published spatial transcriptomics datasets. We believe that this paradigm will greatly enhance our ability to process spatial -omics data, and has general purpose applications for the processing of high-resolution histology images on commercially available GPUs. AVAILABILITY AND IMPLEMENTATION: All code is publicly available at https://github.com/flatironinstitute/st_gridnet. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

An artificial intelligence system for predicting the deterioration of COVID-19 patients in the emergency department.

During the coronavirus disease 2019 (COVID-19) pandemic, rapid and accurate triage of patients at the emergency department is critical to inform decision-making. We propose a data-driven approach for automatic prediction of deterioration risk using a deep neural network that learns from chest X-ray images and a gradient boosting model that learns from routine clinical variables. Our AI prognosis system, trained using data from 3661 patients, achieves an area under the receiver operating characteristic curve (AUC) of 0.786 (95% CI: 0.745-0.830) when predicting deterioration within 96 hours. The deep neural network extracts informative areas of chest X-ray images to assist clinicians in interpreting the predictions and performs comparably to two radiologists in a reader study. In order to verify performance in a real clinical setting, we silently deployed a preliminary version of the deep neural network at New York University Langone Health during the first wave of the pandemic, which produced accurate predictions in real-time. In summary, our findings demonstrate the potential of the proposed system for assisting front-line physicians in the triage of COVID-19 patients.

COVID-19 Prognosis via Self-Supervised Representation Learning and Multi-Image Prediction.

The rapid spread of COVID-19 cases in recent months has strained hospital resources, making rapid and accurate triage of patients presenting to emergency departments a necessity. Machine learning techniques using clinical data such as chest X-rays have been used to predict which patients are most at risk of deterioration. We consider the task of predicting two types of patient deterioration based on chest X-rays: adverse event deterioration (i.e., transfer to the intensive care unit, intubation, or mortality) and increased oxygen requirements beyond 6 L per day. Due to the relative scarcity of COVID-19 patient data, existing solutions leverage supervised pretraining on related non-COVID images, but this is limited by the differences between the pretraining data and the target COVID-19 patient data. In this paper, we use self-supervised learning based on the momentum contrast (MoCo) method in the pretraining phase to learn more general image representations to use for downstream tasks. We present three results. The first is deterioration prediction from a single image, where our model achieves an area under receiver operating characteristic curve (AUC) of 0.742 for predicting an adverse event within 96 hours (compared to 0.703 with supervised pretraining) and an AUC of 0.765 for predicting oxygen requirements greater than 6 L a day at 24 hours (compared to 0.749 with supervised pretraining). We then propose a new transformer-based architecture that can process sequences of multiple images for prediction and show that this model can achieve an improved AUC of 0.786 for predicting an adverse event at 96 hours and an AUC of 0.848 for predicting mortalities at 96 hours. A small pilot clinical study suggested that the prediction accuracy of our model is comparable to that of experienced radiologists analyzing the same information.

Weakly-supervised High-resolution Segmentation of Mammography Images for Breast Cancer Diagnosis.

In the last few years, deep learning classifiers have shown promising results in image-based medical diagnosis. However, interpreting the outputs of these models remains a challenge. In cancer diagnosis, interpretability can be achieved by localizing the region of the input image responsible for the output, i.e. the location of a lesion. Alternatively, segmentation or detection models can be trained with pixel-wise annotations indicating the locations of malignant lesions. Unfortunately, acquiring such labels is labor-intensive and requires medical expertise. To overcome this difficulty, weakly-supervised localization can be utilized. These methods allow neural network classifiers to output saliency maps highlighting the regions of the input most relevant to the classification task (e.g. malignant lesions in mammograms) using only image-level labels (e.g. whether the patient has cancer or not) during training. When applied to high-resolution images, existing methods produce low-resolution saliency maps. This is problematic in applications in which suspicious lesions are small in relation to the image size. In this work, we introduce a novel neural network architecture to perform weakly-supervised segmentation of high-resolution images. The proposed model selects regions of interest via coarse-level localization, and then performs fine-grained segmentation of those regions. We apply this model to breast cancer diagnosis with screening mammography, and validate it on a large clinically-realistic dataset. Measured by Dice similarity score, our approach outperforms existing methods by a large margin in terms of localization performance of benign and malignant lesions, relatively improving the performance by 39.6% and 20.0%, respectively. Code and the weights of some of the models are available at https://github.com/nyukat/GLAM.

An interpretable classifier for high-resolution breast cancer screening images utilizing weakly supervised localization.

Medical images differ from natural images in significantly higher resolutions and smaller regions of interest. Because of these differences, neural network architectures that work well for natural images might not be applicable to medical image analysis. In this work, we propose a novel neural network model to address these unique properties of medical images. This model first uses a low-capacity, yet memory-efficient, network on the whole image to identify the most informative regions. It then applies another higher-capacity network to collect details from chosen regions. Finally, it employs a fusion module that aggregates global and local information to make a prediction. While existing methods often require lesion segmentation during training, our model is trained with only image-level labels and can generate pixel-level saliency maps indicating possible malignant findings. We apply the model to screening mammography interpretation: predicting the presence or absence of benign and malignant lesions. On the NYU Breast Cancer Screening Dataset, our model outperforms (AUC = 0.93) ResNet-34 and Faster R-CNN in classifying breasts with malignant findings. On the CBIS-DDSM dataset, our model achieves performance (AUC = 0.858) on par with state-of-the-art approaches. Compared to ResNet-34, our model is 4.1x faster for inference while using 78.4% less GPU memory. Furthermore, we demonstrate, in a reader study, that our model surpasses radiologist-level AUC by a margin of 0.11.

An artificial intelligence system for predicting the deterioration of COVID-19 patients in the emergency department.

During the coronavirus disease 2019 (COVID-19) pandemic, rapid and accurate triage of patients at the emergency department is critical to inform decision-making. We propose a data-driven approach for automatic prediction of deterioration risk using a deep neural network that learns from chest X-ray images and a gradient boosting model that learns from routine clinical variables. Our AI prognosis system, trained using data from 3,661 patients, achieves an area under the receiver operating characteristic curve (AUC) of 0.786 (95% CI: 0.745-0.830) when predicting deterioration within 96 hours. The deep neural network extracts informative areas of chest X-ray images to assist clinicians in interpreting the predictions and performs comparably to two radiologists in a reader study. In order to verify performance in a real clinical setting, we silently deployed a preliminary version of the deep neural network at New York University Langone Health during the first wave of the pandemic, which produced accurate predictions in real-time. In summary, our findings demonstrate the potential of the proposed system for assisting front-line physicians in the triage of COVID-19 patients.

Prediction of Total Knee Replacement and Diagnosis of Osteoarthritis by Using Deep Learning on Knee Radiographs: Data from the Osteoarthritis Initiative.

Background The methods for assessing knee osteoarthritis (OA) do not provide enough comprehensive information to make robust and accurate outcome predictions. Purpose To develop a deep learning (DL) prediction model for risk of OA progression by using knee radiographs in patients who underwent total knee replacement (TKR) and matched control patients who did not undergo TKR. Materials and Methods In this retrospective analysis that used data from the OA Initiative, a DL model on knee radiographs was developed to predict both the likelihood of a patient undergoing TKR within 9 years and Kellgren-Lawrence (KL) grade. Study participants included a case-control matched subcohort between 45 and 79 years. Patients were matched to control patients according to age, sex, ethnicity, and body mass index. The proposed model used a transfer learning approach based on the ResNet34 architecture with sevenfold nested cross-validation. Receiver operating characteristic curve analysis and conditional logistic regression assessed model performance for predicting probability and risk of TKR compared with clinical observations and two binary outcome prediction models on the basis of radiographic readings: KL grade and OA Research Society International (OARSI) grade. Results Evaluated were 728 participants including 324 patients (mean age, 64 years ± 8 [standard deviation]; 222 women) and 324 control patients (mean age, 64 years ± 8; 222 women). The prediction model based on DL achieved an area under the receiver operating characteristic curve (AUC) of 0.87 (95% confidence interval [CI]: 0.85, 0.90), outperforming a baseline prediction model by using KL grade with an AUC of 0.74 (95% CI: 0.71, 0.77; P < .001). The risk for TKR increased with probability that a person will undergo TKR from the DL model (odds ratio [OR], 7.7; 95% CI: 2.3, 25; P < .001), KL grade (OR, 1.92; 95% CI: 1.17, 3.13; P = .009), and OARSI grade (OR, 1.20; 95% CI: 0.41, 3.50; P = .73). Conclusion The proposed deep learning model better predicted risk of total knee replacement in osteoarthritis than did binary outcome models by using standard grading systems. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Richardson in this issue.

fastMRI: A Publicly Available Raw k-Space and DICOM Dataset of Knee Images for Accelerated MR Image Reconstruction Using Machine Learning.

A publicly available dataset containing k-space data as well as Digital Imaging and Communications in Medicine image data of knee images for accelerated MR image reconstruction using machine learning is presented.

Artificial Intelligence Explained for Nonexperts.

Artificial intelligence (AI) has made stunning progress in the last decade, made possible largely due to the advances in training deep neural networks with large data sets. Many of these solutions, initially developed for natural images, speech, or text, are now becoming successful in medical imaging. In this article we briefly summarize in an accessible way the current state of the field of AI. Furthermore, we highlight the most promising approaches and describe the current challenges that will need to be solved to enable broad deployment of AI in clinical practice.

Improving the Ability of Deep Neural Networks to Use Information from Multiple Views in Breast Cancer Screening.

In breast cancer screening, radiologists make the diagnosis based on images that are taken from two angles. Inspired by this, we seek to improve the performance of deep neural networks applied to this task by encouraging the model to use information from both views of the breast. First, we took a closer look at the training process and observed an imbalance between learning from the two views. In particular, we observed that layers processing one of the views have parameters with larger gradients in magnitude, and contribute more to the overall loss reduction. Next, we tested several methods targeted at utilizing both views more equally in training. We found that using the same weights to process both views, or using modality dropout, leads to a boost in performance. Looking forward, our results indicate improving learning dynamics as a promising avenue for improving utilization of multiple views in deep neural networks for medical diagnosis.

Deep Neural Networks Improve Radiologists' Performance in Breast Cancer Screening.

We present a deep convolutional neural network for breast cancer screening exam classification, trained, and evaluated on over 200000 exams (over 1000000 images). Our network achieves an AUC of 0.895 in predicting the presence of cancer in the breast, when tested on the screening population. We attribute the high accuracy to a few technical advances. 1) Our network's novel two-stage architecture and training procedure, which allows us to use a high-capacity patch-level network to learn from pixel-level labels alongside a network learning from macroscopic breast-level labels. 2) A custom ResNet-based network used as a building block of our model, whose balance of depth and width is optimized for high-resolution medical images. 3) Pretraining the network on screening BI-RADS classification, a related task with more noisy labels. 4) Combining multiple input views in an optimal way among a number of possible choices. To validate our model, we conducted a reader study with 14 readers, each reading 720 screening mammogram exams, and show that our model is as accurate as experienced radiologists when presented with the same data. We also show that a hybrid model, averaging the probability of malignancy predicted by a radiologist with a prediction of our neural network, is more accurate than either of the two separately. To further understand our results, we conduct a thorough analysis of our network's performance on different subpopulations of the screening population, the model's design, training procedure, errors, and properties of its internal representations. Our best models are publicly available at https://github.com/nyukat/breast_cancer_classifier.

Machine learning in breast MRI.

Machine-learning techniques have led to remarkable advances in data extraction and analysis of medical imaging. Applications of machine learning to breast MRI continue to expand rapidly as increasingly accurate 3D breast and lesion segmentation allows the combination of radiologist-level interpretation (eg, BI-RADS lexicon), data from advanced multiparametric imaging techniques, and patient-level data such as genetic risk markers. Advances in breast MRI feature extraction have led to rapid dataset analysis, which offers promise in large pooled multiinstitutional data analysis. The object of this review is to provide an overview of machine-learning and deep-learning techniques for breast MRI, including supervised and unsupervised methods, anatomic breast segmentation, and lesion segmentation. Finally, it explores the role of machine learning, current limitations, and future applications to texture analysis, radiomics, and radiogenomics. Level of Evidence: 3 Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2019. J. Magn. Reson. Imaging 2020;52:998-1018.

Artificial Intelligence for Mammography and Digital Breast Tomosynthesis: Current Concepts and Future Perspectives.

Although computer-aided diagnosis (CAD) is widely used in mammography, conventional CAD programs that use prompts to indicate potential cancers on the mammograms have not led to an improvement in diagnostic accuracy. Because of the advances in machine learning, especially with use of deep (multilayered) convolutional neural networks, artificial intelligence has undergone a transformation that has improved the quality of the predictions of the models. Recently, such deep learning algorithms have been applied to mammography and digital breast tomosynthesis (DBT). In this review, the authors explain how deep learning works in the context of mammography and DBT and define the important technical challenges. Subsequently, they discuss the current status and future perspectives of artificial intelligence-based clinical applications for mammography, DBT, and radiomics. Available algorithms are advanced and approach the performance of radiologists-especially for cancer detection and risk prediction at mammography. However, clinical validation is largely lacking, and it is not clear how the power of deep learning should be used to optimize practice. Further development of deep learning models is necessary for DBT, and this requires collection of larger databases. It is expected that deep learning will eventually have an important role in DBT, including the generation of synthetic images.