The correct interpretation of breast density is important in the assessment of breast cancer risk. AI has been shown capable of accurately predicting breast density, however, due to the differences in imaging characteristics across mammography systems, models built using data from one system do not generalize well to other systems. Though federated learning (FL) has emerged as a way to improve the generalizability of AI without the need to share data, the best way to preserve features from all training data during FL is an active area of research. To explore FL methodology, the breast density classification FL challenge was hosted in partnership with the American College of Radiology, Harvard Medical School's Mass General Brigham, University of Colorado, NVIDIA, and the National Institutes of Health National Cancer Institute. Challenge participants were able to submit docker containers capable of implementing FL on three simulated medical facilities, each containing a unique large mammography dataset. The breast density FL challenge ran from June 15 to September 5, 2022, attracting seven finalists from around the world. The winning FL submission reached a linear kappa score of 0.653 on the challenge test data and 0.413 on an external testing dataset, scoring comparably to a model trained on the same data in a central location.

Despite the intense attention and considerable investment into clinical machine learning research, relatively few applications have been deployed at a large-scale in a real-world clinical environment. While research is important in advancing the state-of-the-art, translation is equally important in bringing these techniques and technologies into a position to ultimately impact healthcare. We believe a lack of appreciation for several considerations are a major cause for this discrepancy between expectation and reality. To better characterize a holistic perspective among researchers and practitioners, we survey several practitioners with commercial experience in developing CML for clinical deployment. Using these insights, we identify several main categories of challenges in order to better design and develop clinical machine learning applications.

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.

Although machine learning (ML) has shown promise in numerous domains, there are concerns about generalizability to out-of-sample data. This is currently addressed by centrally sharing ample, and importantly diverse, data from multiple sites. However, such centralization is challenging to scale (or even not feasible) due to various limitations. Federated ML (FL) provides an alternative to train accurate and generalizable ML models, by only sharing numerical model updates. Here we present findings from the largest FL study to-date, involving data from 71 healthcare institutions across 6 continents, to generate an automatic tumor boundary detector for the rare disease of glioblastoma, utilizing the largest dataset of such patients ever used in the literature (25, 256 MRI scans from 6, 314 patients). We demonstrate a 33% improvement over a publicly trained model to delineate the surgically targetable tumor, and 23% improvement over the tumor's entire extent. We anticipate our study to: 1) enable more studies in healthcare informed by large and diverse data, ensuring meaningful results for rare diseases and underrepresented populations, 2) facilitate further quantitative analyses for glioblastoma via performance optimization of our consensus model for eventual public release, and 3) demonstrate the effectiveness of FL at such scale and task complexity as a paradigm shift for multi-site collaborations, alleviating the need for data sharing.

Model brittleness is a key concern when deploying deep learning models in real-world medical settings. A model that has high performance at one institution may suffer a significant decline in performance when tested at other institutions. While pooling datasets from multiple institutions and re-training may provide a straightforward solution, it is often infeasible and may compromise patient privacy. An alternative approach is to fine-tune the model on subsequent institutions after training on the original institution. Notably, this approach degrades model performance at the original institution, a phenomenon known as catastrophic forgetting. In this paper, we develop an approach to address catastrophic forgetting based on elastic weight consolidation combined with modulation of batch normalization statistics under two scenarios: first, for expanding the domain from one imaging system's data to another imaging system's, and second, for expanding the domain from a large multi-institutional dataset to another single institution dataset. We show that our approach outperforms several other state-of-the-art approaches and provide theoretical justification for the efficacy of batch normalization modulation. The results of this study are generally applicable to the deployment of any clinical deep learning model which requires domain expansion.