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.

States as Strings as Strategies: Steering Language Models with Game-Theoretic Solvers

Game theory is the study of mathematical models of strategic interactions among rational agents. Language is a key medium of interaction for humans, though it has historically proven difficult to model dialogue and its strategic motivations mathematically. A suitable model of the players, strategies, and payoffs associated with linguistic interactions (i.e., a binding to the conventional symbolic logic of game theory) would enable existing game-theoretic algorithms to provide strategic solutions in the space of language. In other words, a binding could provide a route to computing stable, rational conversational strategies in dialogue. Large language models (LLMs) have arguably reached a point where their generative capabilities can enable realistic, human-like simulations of natural dialogue. By prompting them in various ways, we can steer their responses towards different output utterances. Leveraging the expressivity of natural language, LLMs can also help us quickly generate new dialogue scenarios, which are grounded in real world applications. In this work, we present one possible binding from dialogue to game theory as well as generalizations of existing equilibrium finding algorithms to this setting. In addition, by exploiting LLMs generation capabilities along with our proposed binding, we can synthesize a large repository of formally-defined games in which one can study and test game-theoretic solution concepts. We also demonstrate how one can combine LLM-driven game generation, game-theoretic solvers, and imitation learning to construct a process for improving the strategic capabilities of LLMs.

Neural Population Learning beyond Symmetric Zero-sum Games

We study computationally efficient methods for finding equilibria in n-player general-sum games, specifically ones that afford complex visuomotor skills. We show how existing methods would struggle in this setting, either computationally or in theory. We then introduce NeuPL-JPSRO, a neural population learning algorithm that benefits from transfer learning of skills and converges to a Coarse Correlated Equilibrium (CCE) of the game. We show empirical convergence in a suite of OpenSpiel games, validated rigorously by exact game solvers. We then deploy NeuPL-JPSRO to complex domains, where our approach enables adaptive coordination in a MuJoCo control domain and skill transfer in capture-the-flag. Our work shows that equilibrium convergent population learning can be implemented at scale and in generality, paving the way towards solving real-world games between heterogeneous players with mixed motives.

Evaluating and Personalizing User-Perceived Quality of Text-to-Speech Voices for Delivering Mindfulness Meditation with Different Physical Embodiments

Mindfulness-based therapies have been shown to be effective in improving mental health, and technology-based methods have the potential to expand the accessibility of these therapies. To enable real-time personalized content generation for mindfulness practice in these methods, high-quality computer-synthesized text-to-speech (TTS) voices are needed to provide verbal guidance and respond to user performance and preferences. However, the user-perceived quality of state-of-the-art TTS voices has not yet been evaluated for administering mindfulness meditation, which requires emotional expressiveness. In addition, work has not yet been done to study the effect of physical embodiment and personalization on the user-perceived quality of TTS voices for mindfulness. To that end, we designed a two-phase human subject study. In Phase 1, an online Mechanical Turk between-subject study (N=471) evaluated 3 (feminine, masculine, child-like) state-of-the-art TTS voices with 2 (feminine, masculine) human therapists' voices in 3 different physical embodiment settings (no agent, conversational agent, socially assistive robot) with remote participants. Building on findings from Phase 1, in Phase 2, an in-person within-subject study (N=94), we used a novel framework we developed for personalizing TTS voices based on user preferences, and evaluated user-perceived quality compared to best-rated non-personalized voices from Phase 1. We found that the best-rated human voice was perceived better than all TTS voices; the emotional expressiveness and naturalness of TTS voices were poorly rated, while users were satisfied with the clarity of TTS voices. Surprisingly, by allowing users to fine-tune TTS voice features, the user-personalized TTS voices could perform almost as well as human voices, suggesting user personalization could be a simple and very effective tool to improve user-perceived quality of TTS voice.

Primitive-based 3D Human-Object Interaction Modelling and Programming

Embedding Human and Articulated Object Interaction (HAOI) in 3D is an important direction for a deeper human activity understanding. Different from previous works that use parametric and CAD models to represent humans and objects, in this work, we propose a novel 3D geometric primitive-based language to encode both humans and objects. Given our new paradigm, humans and objects are all compositions of primitives instead of heterogeneous entities. Thus, mutual information learning may be achieved between the limited 3D data of humans and different object categories. Moreover, considering the simplicity of the expression and the richness of the information it contains, we choose the superquadric as the primitive representation. To explore an effective embedding of HAOI for the machine, we build a new benchmark on 3D HAOI consisting of primitives together with their images and propose a task requiring machines to recover 3D HAOI using primitives from images. Moreover, we propose a baseline of single-view 3D reconstruction on HAOI. We believe this primitive-based 3D HAOI representation would pave the way for 3D HAOI studies. Our code and data are available at https://mvig-rhos.com/p3haoi.

Multi-stream Cell Segmentation with Low-level Cues for Multi-modality Images

Cell segmentation for multi-modal microscopy images remains a challenge due to the complex textures, patterns, and cell shapes in these images. To tackle the problem, we first develop an automatic cell classification pipeline to label the microscopy images based on their low-level image characteristics, and then train a classification model based on the category labels. Afterward, we train a separate segmentation model for each category using the images in the corresponding category. Besides, we further deploy two types of segmentation models to segment cells with roundish and irregular shapes respectively. Moreover, an efficient and powerful backbone model is utilized to enhance the efficiency of our segmentation model. Evaluated on the Tuning Set of NeurIPS 2022 Cell Segmentation Challenge, our method achieves an F1-score of 0.8795 and the running time for all cases is within the time tolerance.

Diffusion-based Data Augmentation for Nuclei Image Segmentation

Nuclei segmentation is a fundamental but challenging task in the quantitative analysis of histopathology images. Although fully-supervised deep learning-based methods have made significant progress, a large number of labeled images are required to achieve great segmentation performance. Considering that manually labeling all nuclei instances for a dataset is inefficient, obtaining a large-scale human-annotated dataset is time-consuming and labor-intensive. Therefore, augmenting a dataset with only a few labeled images to improve the segmentation performance is of significant research and application value. In this paper, we introduce the first diffusion-based augmentation method for nuclei segmentation. The idea is to synthesize a large number of labeled images to facilitate training the segmentation model. To achieve this, we propose a two-step strategy. In the first step, we train an unconditional diffusion model to synthesize the Nuclei Structure that is defined as the representation of pixel-level semantic and distance transform. Each synthetic nuclei structure will serve as a constraint on histopathology image synthesis and is further post-processed to be an instance map. In the second step, we train a conditioned diffusion model to synthesize histopathology images based on nuclei structures. The synthetic histopathology images paired with synthetic instance maps will be added to the real dataset for training the segmentation model. The experimental results show that by augmenting 10% labeled real dataset with synthetic samples, one can achieve comparable segmentation results with the fully-supervised baseline.

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.