James Hall

Eugene Vorontsov, Alican Bozkurt, Adam Casson et al.

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.

Eric Zimmermann, Eugene Vorontsov, Julian Viret et al.

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 three new models: Virchow2, a 632 million parameter vision transformer, Virchow2G, a 1.9 billion parameter vision transformer, and Virchow2G Mini, a 22 million parameter distillation of Virchow2G, 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.

James Hall, Melvin Leok

In this paper, we present a new variational integrator for problems in Lagrangian mechanics. Using techniques from Galerkin variational integrators, we construct a scheme for numerical integration that converges geometrically, and is symplectic and momentum preserving. Furthermore, we prove that under appropriate assumptions, variational integrators constructed using Galerkin techniques will yield numerical methods that are in a certain sense optimal, converging at the same rate as the best possible approximation in a certain function space. We further prove that certain geometric invariants also converge at an optimal rate, and that the error associated with these geometric invariants is independent of the number of steps taken. We close with several numerical examples that demonstrate the predicted rates of convergence.

Ruiwen Ding, James Hall, Neil Tenenholtz et al.

In certain types of cancerous tissue, mitotic count has been shown to be associated with tumor proliferation, poor prognosis, and therapeutic resistance. Due to the high inter-rater variability of mitotic counting by pathologists, convolutional neural networks (CNNs) have been employed to reduce the subjectivity of mitosis detection in hematoxylin and eosin (H&E)-stained whole slide images. However, most existing models have performance that lags behind expert panel review and only incorporate visual information. In this work, we demonstrate that pre-trained large-scale vision-language models that leverage both visual features and natural language improve mitosis detection accuracy. We formulate the mitosis detection task as an image captioning task and a visual question answering (VQA) task by including metadata such as tumor and scanner types as context. The effectiveness of our pipeline is demonstrated via comparison with various baseline models using 9,501 mitotic figures and 11,051 hard negatives (non-mitotic figures that are difficult to characterize) from the publicly available Mitosis Domain Generalization Challenge (MIDOG22) dataset.

George Shaikovski, Adam Casson, Kristen Severson et al.

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.

Eric Zimmermann, Neil Tenenholtz, James Hall et al.

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.