Andrew Walker

Harshith Padigela, Shima Nofallah, Atchuth Naveen Chilaparasetti et al.

Foundation models trained on large-scale pathology image corpora have demonstrated strong transfer capabilities across diverse histopathology tasks. Building on this progress, we introduce PLUTO-4, our next generation of pathology foundation models that extend the Pathology-Universal Transformer (PLUTO) to frontier scale. We share two complementary Vision Transformer architectures in the PLUTO-4 family: a compact and efficient PLUTO-4S model optimized for multi-scale deployment using a FlexiViT setup with 2D-RoPE embeddings, and a frontier-scale PLUTO-4G model trained with a single patch size to maximize representation capacity and stability. Both models are pretrained using a self-supervised objective derived from DINOv2 on a large multi-institutional corpus containing 551,164 WSIs from 137,144 patients across over 50 institutions, spanning over 60 disease types and over 100 stains. Comprehensive evaluation across public and internal benchmarks demonstrates that PLUTO-4 achieves state-of-the-art performance on tasks requiring varying spatial and biological context, including tile classification, segmentation, and slide-level diagnosis. The compact PLUTO-4S provides high-throughput and robust performance for practical deployment, while PLUTO-4G establishes new performance frontiers across multiple pathology benchmarks, including an 11% improvement in dermatopathology diagnosis. These diverse improvements underscore PLUTO-4's potential to transform real-world applications as a backbone for translational research and diagnostic use cases.

Andrew Walker

In AI-based histopathology, domain shifts are common and well-studied. However, this research focuses on stain and scanner variations, which do not show the full picture -- shifts may be combinations of other shifts, or "invisible" shifts that are not obvious but still damage performance of machine learning models. Furthermore, it is important for models to generalize to these shifts without expensive or scarce annotations, especially in the histopathology space and if wanting to deploy models on a larger scale. Thus, there is a need for "reactive" domain generalization techniques: ones that adapt to domain shifts at test-time rather than requiring predictions of or examples of the shifts at training time. We conduct a literature review and introduce techniques that react to domain shifts rather than requiring a prediction of them in advance. We investigate test time training, a technique for domain generalization that adapts model parameters at test-time through optimization of a secondary self-supervised task.