Virchow2: Scaling Self-Supervised Mixed Magnification Models in Pathology

Foundation models are rapidly being developed for computational pathology applications. However, it remains an open question which factors are most important for downstream performance with data scale and diversity, model size, and training algorithm all playing a role. In this work, we propose algorithmic modifications, tailored for pathology, and we present the result of scaling both data and model size, surpassing previous studies in both dimensions. We introduce two new models: Virchow2, a 632 million parameter vision transformer, and Virchow2G, a 1.9 billion parameter vision transformer, each trained with 3.1 million histopathology whole slide images, with diverse tissues, originating institutions, and stains. We achieve state of the art performance on 12 tile-level tasks, as compared to the top performing competing models. Our results suggest that data diversity and domain-specific methods can outperform models that only scale in the number of parameters, but, on average, performance benefits from the combination of domain-specific methods, data scale, and model scale.

Virchow 2: Scaling Self-Supervised Mixed Magnification Models in Pathology

Foundation models are rapidly being developed for computational pathology applications. However, it remains an open question which factors are most important for downstream performance with data scale and diversity, model size, and training algorithm all playing a role. In this work, we present the result of scaling both data and model size, surpassing previous studies in both dimensions, and introduce two new models: Virchow 2, a 632M parameter vision transformer, and Virchow 2G, a 1.85B parameter vision transformer, each trained with 3.1M histopathology whole slide images. To support this scale, we propose domain-inspired adaptations to the DINOv2 training algorithm, which is quickly becoming the default method in self-supervised learning for computational pathology. We achieve state of the art performance on twelve tile-level tasks, as compared to the top performing competing models. Our results suggest that data diversity and domain-specific training can outperform models that only scale in the number of parameters, but, on average, performance benefits from domain-tailoring, data scale, and model scale.

PRISM: A Multi-Modal Generative Foundation Model for Slide-Level Histopathology

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.

Adapting Self-Supervised Learning for Computational Pathology

Self-supervised learning (SSL) has emerged as a key technique for training networks that can generalize well to diverse tasks without task-specific supervision. This property makes SSL desirable for computational pathology, the study of digitized images of tissues, as there are many target applications and often limited labeled training samples. However, SSL algorithms and models have been primarily developed in the field of natural images and whether their performance can be improved by adaptation to particular domains remains an open question. In this work, we present an investigation of modifications to SSL for pathology data, specifically focusing on the DINOv2 algorithm. We propose alternative augmentations, regularization functions, and position encodings motivated by the characteristics of pathology images. We evaluate the impact of these changes on several benchmarks to demonstrate the value of tailored approaches.

Virchow: A Million-Slide Digital Pathology Foundation Model

Computational pathology uses artificial intelligence to enable precision medicine and decision support systems through the analysis of whole slide images. It has the potential to revolutionize the diagnosis and treatment of cancer. However, a major challenge to this objective is that for many specific computational pathology tasks the amount of data is inadequate for development. To address this challenge, we created Virchow, a 632 million parameter deep neural network foundation model for computational pathology. Using self-supervised learning, Virchow is trained on 1.5 million hematoxylin and eosin stained whole slide images from diverse tissue groups, which is orders of magnitude more data than previous works. When evaluated on downstream tasks including tile-level pan-cancer detection and subtyping and slide-level biomarker prediction, Virchow outperforms state-of-the-art systems both on internal datasets drawn from the same population as the pretraining data as well as external public datasets. Virchow achieves 93% balanced accuracy for pancancer tile classification, and AUCs of 0.983 for colon microsatellite instability status prediction and 0.967 for breast CDH1 status prediction. The gains in performance highlight the importance of pretraining on massive pathology image datasets, suggesting pretraining on even larger datasets could continue improving performance for many high-impact applications where limited amounts of training data are available, such as drug outcome prediction.