Removing Biases from Molecular Representations via Information Maximization.

High-throughput drug screening -- using cell imaging or gene expression measurements as readouts of drug effect -- is a critical tool in biotechnology to assess and understand the relationship between the chemical structure and biological activity of a drug. Since large-scale screens have to be divided into multiple experiments, a key difficulty is dealing with batch effects, which can introduce systematic errors and non-biological associations in the data. We propose InfoCORE, an Information maximization approach for COnfounder REmoval, to effectively deal with batch effects and obtain refined molecular representations. InfoCORE establishes a variational lower bound on the conditional mutual information of the latent representations given a batch identifier. It adaptively reweighs samples to equalize their implied batch distribution. Extensive experiments on drug screening data reveal InfoCORE's superior performance in a multitude of tasks including molecular property prediction and molecule-phenotype retrieval. Additionally, we show results for how InfoCORE offers a versatile framework and resolves general distribution shifts and issues of data fairness by minimizing correlation with spurious features or removing sensitive attributes. The code is available at https://github.com/uhlerlab/InfoCORE.

Collaborative Privacy-preserving Approaches for Distributed Deep Learning Using Multi-Institutional Data.

Deep learning (DL) algorithms have shown remarkable potential in automating various tasks in medical imaging and radiologic reporting. However, models trained on low quantities of data or only using data from a single institution often are not generalizable to other institutions, which may have different patient demographics or data acquisition characteristics. Therefore, training DL algorithms using data from multiple institutions is crucial to improving the robustness and generalizability of clinically useful DL models. In the context of medical data, simply pooling data from each institution to a central location to train a model poses several issues such as increased risk to patient privacy, increased costs for data storage and transfer, and regulatory challenges. These challenges of centrally hosting data have motivated the development of distributed machine learning techniques and frameworks for collaborative learning that facilitate the training of DL models without the need to explicitly share private medical data. The authors describe several popular methods for collaborative training and review the main considerations for deploying these models. They also highlight publicly available software frameworks for federated learning and showcase several real-world examples of collaborative learning. The authors conclude by discussing some key challenges and future research directions for distributed DL. They aim to introduce clinicians to the benefits, limitations, and risks of using distributed DL for the development of medical artificial intelligence algorithms. ©RSNA, 2023 Quiz questions for this article are available in the supplemental material.

Multi-population generalizability of a deep learning-based chest radiograph severity score for COVID-19.

To tune and test the generalizability of a deep learning-based model for assessment of COVID-19 lung disease severity on chest radiographs (CXRs) from different patient populations. A published convolutional Siamese neural network-based model previously trained on hospitalized patients with COVID-19 was tuned using 250 outpatient CXRs. This model produces a quantitative measure of COVID-19 lung disease severity (pulmonary x-ray severity (PXS) score). The model was evaluated on CXRs from 4 test sets, including 3 from the United States (patients hospitalized at an academic medical center (N = 154), patients hospitalized at a community hospital (N = 113), and outpatients (N = 108)) and 1 from Brazil (patients at an academic medical center emergency department (N = 303)). Radiologists from both countries independently assigned reference standard CXR severity scores, which were correlated with the PXS scores as a measure of model performance (Pearson R). The Uniform Manifold Approximation and Projection (UMAP) technique was used to visualize the neural network results. Tuning the deep learning model with outpatient data showed high model performance in 2 United States hospitalized patient datasets (R = 0.88 and R = 0.90, compared to baseline R = 0.86). Model performance was similar, though slightly lower, when tested on the United States outpatient and Brazil emergency department datasets (R = 0.86 and R = 0.85, respectively). UMAP showed that the model learned disease severity information that generalized across test sets. A deep learning model that extracts a COVID-19 severity score on CXRs showed generalizable performance across multiple populations from 2 continents, including outpatients and hospitalized patients.

QU-BraTS: MICCAI BraTS 2020 Challenge on Quantifying Uncertainty in Brain Tumor Segmentation - Analysis of Ranking Scores and Benchmarking Results.

Deep learning (DL) models have provided state-of-the-art performance in various medical imaging benchmarking challenges, including the Brain Tumor Segmentation (BraTS) challenges. However, the task of focal pathology multi-compartment segmentation (e.g., tumor and lesion sub-regions) is particularly challenging, and potential errors hinder translating DL models into clinical workflows. Quantifying the reliability of DL model predictions in the form of uncertainties could enable clinical review of the most uncertain regions, thereby building trust and paving the way toward clinical translation. Several uncertainty estimation methods have recently been introduced for DL medical image segmentation tasks. Developing scores to evaluate and compare the performance of uncertainty measures will assist the end-user in making more informed decisions. In this study, we explore and evaluate a score developed during the BraTS 2019 and BraTS 2020 task on uncertainty quantification (QU-BraTS) and designed to assess and rank uncertainty estimates for brain tumor multi-compartment segmentation. This score (1) rewards uncertainty estimates that produce high confidence in correct assertions and those that assign low confidence levels at incorrect assertions, and (2) penalizes uncertainty measures that lead to a higher percentage of under-confident correct assertions. We further benchmark the segmentation uncertainties generated by 14 independent participating teams of QU-BraTS 2020, all of which also participated in the main BraTS segmentation task. Overall, our findings confirm the importance and complementary value that uncertainty estimates provide to segmentation algorithms, highlighting the need for uncertainty quantification in medical image analyses. Finally, in favor of transparency and reproducibility, our evaluation code is made publicly available at https://github.com/RagMeh11/QU-BraTS.

Assessing the Trustworthiness of Saliency Maps for Localizing Abnormalities in Medical Imaging.

PURPOSE: To evaluate the trustworthiness of saliency maps for abnormality localization in medical imaging. MATERIALS AND METHODS: Using two large publicly available radiology datasets (Society for Imaging Informatics in Medicine-American College of Radiology Pneumothorax Segmentation dataset and Radiological Society of North America Pneumonia Detection Challenge dataset), the performance of eight commonly used saliency map techniques were quantified in regard to (a) localization utility (segmentation and detection), (b) sensitivity to model weight randomization, (c) repeatability, and (d) reproducibility. Their performances versus baseline methods and localization network architectures were compared, using area under the precision-recall curve (AUPRC) and structural similarity index measure (SSIM) as metrics. RESULTS: All eight saliency map techniques failed at least one of the criteria and were inferior in performance compared with localization networks. For pneumothorax segmentation, the AUPRC ranged from 0.024 to 0.224, while a U-Net achieved a significantly superior AUPRC of 0.404 (P < .005). For pneumonia detection, the AUPRC ranged from 0.160 to 0.519, while a RetinaNet achieved a significantly superior AUPRC of 0.596 (P <.005). Five and two saliency methods (of eight) failed the model randomization test on the segmentation and detection datasets, respectively, suggesting that these methods are not sensitive to changes in model parameters. The repeatability and reproducibility of the majority of the saliency methods were worse than localization networks for both the segmentation and detection datasets. CONCLUSION: The use of saliency maps in the high-risk domain of medical imaging warrants additional scrutiny and recommend that detection or segmentation models be used if localization is the desired output of the network.Keywords: Technology Assessment, Technical Aspects, Feature Detection, Convolutional Neural Network (CNN) Supplemental material is available for this article. © RSNA, 2021.

Improvement and Multi-Population Generalizability of a Deep Learning-Based Chest Radiograph Severity Score for COVID-19.

PURPOSE: To improve and test the generalizability of a deep learning-based model for assessment of COVID-19 lung disease severity on chest radiographs (CXRs) from different patient populations. MATERIALS AND METHODS: A published convolutional Siamese neural network-based model previously trained on hospitalized patients with COVID-19 was tuned using 250 outpatient CXRs. This model produces a quantitative measure of COVID-19 lung disease severity (pulmonary x-ray severity (PXS) score). The model was evaluated on CXRs from four test sets, including 3 from the United States (patients hospitalized at an academic medical center (N=154), patients hospitalized at a community hospital (N=113), and outpatients (N=108)) and 1 from Brazil (patients at an academic medical center emergency department (N=303)). Radiologists from both countries independently assigned reference standard CXR severity scores, which were correlated with the PXS scores as a measure of model performance (Pearson r). The Uniform Manifold Approximation and Projection (UMAP) technique was used to visualize the neural network results. RESULTS: Tuning the deep learning model with outpatient data improved model performance in two United States hospitalized patient datasets (r=0.88 and r=0.90, compared to baseline r=0.86). Model performance was similar, though slightly lower, when tested on the United States outpatient and Brazil emergency department datasets (r=0.86 and r=0.85, respectively). UMAP showed that the model learned disease severity information that generalized across test sets. CONCLUSIONS: Performance of a deep learning-based model that extracts a COVID-19 severity score on CXRs improved using training data from a different patient cohort (outpatient versus hospitalized) and generalized across multiple populations.