Foundation models in computational pathology promise to unlock the development of new clinical decision support systems and models for precision medicine. However, there is a mismatch between most clinical analysis, which is defined at the level of one or more whole slide images, and foundation models to date, which process the thousands of image tiles contained in a whole slide image separately. The requirement to train a network to aggregate information across a large number of tiles in multiple whole slide images limits these models' impact. In this work, we present a slide-level foundation model for H&E-stained histopathology, PRISM, that builds on Virchow tile embeddings and leverages clinical report text for pre-training. Using the tile embeddings, PRISM produces slide-level embeddings with the ability to generate clinical reports, resulting in several modes of use. Using text prompts, PRISM achieves zero-shot cancer detection and sub-typing performance approaching and surpassing that of a supervised aggregator model. Using the slide embeddings with linear classifiers, PRISM surpasses supervised aggregator models. Furthermore, we demonstrate that fine-tuning of the PRISM slide encoder yields label-efficient training for biomarker prediction, a task that typically suffers from low availability of training data; an aggregator initialized with PRISM and trained on as little as 10% of the training data can outperform a supervised baseline that uses all of the data.

The use of artificial intelligence to enable precision medicine and decision support systems through the analysis of pathology images has the potential to revolutionize the diagnosis and treatment of cancer. Such applications will depend on models' abilities to capture the diverse patterns observed in pathology images. To address this challenge, we present Virchow, a foundation model for computational pathology. Using self-supervised learning empowered by the DINOv2 algorithm, Virchow is a vision transformer model with 632 million parameters trained on 1.5 million hematoxylin and eosin stained whole slide images from diverse tissue and specimen types, which is orders of magnitude more data than previous works. The Virchow model enables the development of a pan-cancer detection system with 0.949 overall specimen-level AUC across 17 different cancer types, while also achieving 0.937 AUC on 7 rare cancer types. The Virchow model sets the state-of-the-art on the internal and external image tile level benchmarks and slide level biomarker prediction tasks. The gains in performance highlight the importance of training on massive pathology image datasets, suggesting scaling up the data and network architecture can improve the accuracy for many high-impact computational pathology applications where limited amounts of training data are available.

In unsupervised learning, dimensionality reduction is an important tool for data exploration and visualization. Because these aims are typically open-ended, it can be useful to frame the problem as looking for patterns that are enriched in one dataset relative to another. These pairs of datasets occur commonly, for instance a population of interest vs. control or signal vs. signal free recordings.However, there are few methods that work on sets of data as opposed to data points or sequences. Here, we present a probabilistic model for dimensionality reduction to discover signal that is enriched in the target dataset relative to the background dataset. The data in these sets do not need to be paired or grouped beyond set membership. By using a probabilistic model where some structure is shared amongst the two datasets and some is unique to the target dataset, we are able to recover interesting structure in the latent space of the target dataset. The method also has the advantages of a probabilistic model, namely that it allows for the incorporation of prior information, handles missing data, and can be generalized to different distributional assumptions. We describe several possible variations of the model and demonstrate the application of the technique to de-noising, feature selection, and subgroup discovery settings.