Frederick M. Howard

James M. Dolezal, Sara Kochanny, Emma Dyer et al.

Deep learning methods have emerged as powerful tools for analyzing histopathological images, but current methods are often specialized for specific domains and software environments, and few open-source options exist for deploying models in an interactive interface. Experimenting with different deep learning approaches typically requires switching software libraries and reprocessing data, reducing the feasibility and practicality of experimenting with new architectures. We developed a flexible deep learning library for histopathology called Slideflow, a package which supports a broad array of deep learning methods for digital pathology and includes a fast whole-slide interface for deploying trained models. Slideflow includes unique tools for whole-slide image data processing, efficient stain normalization and augmentation, weakly-supervised whole-slide classification, uncertainty quantification, feature generation, feature space analysis, and explainability. Whole-slide image processing is highly optimized, enabling whole-slide tile extraction at 40X magnification in 2.5 seconds per slide. The framework-agnostic data processing pipeline enables rapid experimentation with new methods built with either Tensorflow or PyTorch, and the graphical user interface supports real-time visualization of slides, predictions, heatmaps, and feature space characteristics on a variety of hardware devices, including ARM-based devices such as the Raspberry Pi.

James M. Dolezal, Rachelle Wolk, Hanna M. Hieromnimon et al.

Artificial intelligence methods including deep neural networks (DNN) can provide rapid molecular classification of tumors from routine histology with accuracy that matches or exceeds human pathologists. Discerning how neural networks make their predictions remains a significant challenge, but explainability tools help provide insights into what models have learned when corresponding histologic features are poorly defined. Here, we present a method for improving explainability of DNN models using synthetic histology generated by a conditional generative adversarial network (cGAN). We show that cGANs generate high-quality synthetic histology images that can be leveraged for explaining DNN models trained to classify molecularly-subtyped tumors, exposing histologic features associated with molecular state. Fine-tuning synthetic histology through class and layer blending illustrates nuanced morphologic differences between tumor subtypes. Finally, we demonstrate the use of synthetic histology for augmenting pathologist-in-training education, showing that these intuitive visualizations can reinforce and improve understanding of histologic manifestations of tumor biology.

Jan Witowski, Ken G. Zeng, Joseph Cappadona et al.

Treatment selection in breast cancer is guided by molecular subtypes and clinical characteristics. However, current tools including genomic assays lack the accuracy required for optimal clinical decision-making. We developed a novel artificial intelligence (AI)-based approach that integrates digital pathology images with clinical data, providing a more robust and effective method for predicting the risk of cancer recurrence in breast cancer patients. Specifically, we utilized a vision transformer pan-cancer foundation model trained with self-supervised learning to extract features from digitized H&E-stained slides. These features were integrated with clinical data to form a multi-modal AI test predicting cancer recurrence and death. The test was developed and evaluated using data from a total of 8,161 female breast cancer patients across 15 cohorts originating from seven countries. Of these, 3,502 patients from five cohorts were used exclusively for evaluation, while the remaining patients were used for training. Our test accurately predicted our primary endpoint, disease-free interval, in the five evaluation cohorts (C-index: 0.71 [0.68-0.75], HR: 3.63 [3.02-4.37, p<0.001]). In a direct comparison (n=858), the AI test was more accurate than Oncotype DX, the standard-of-care 21-gene assay, achieving a C-index of 0.67 [0.61-0.74] versus 0.61 [0.49-0.73], respectively. Additionally, the AI test added independent prognostic information to Oncotype DX in a multivariate analysis (HR: 3.11 [1.91-5.09, p<0.001)]). The test demonstrated robust accuracy across major molecular breast cancer subtypes, including TNBC (C-index: 0.71 [0.62-0.81], HR: 3.81 [2.35-6.17, p=0.02]), where no diagnostic tools are currently recommended by clinical guidelines. These results suggest that our AI test improves upon the accuracy of existing prognostic tests, while being applicable to a wider range of patients.