PixCell: A generative foundation model for digital histopathology images

The digitization of histology slides has revolutionized pathology, providing massive datasets for cancer diagnosis and research. Contrastive self-supervised and vision-language models have been shown to effectively mine large pathology datasets to learn discriminative representations. On the other hand, generative models, capable of synthesizing realistic and diverse images, present a compelling solution to address unique problems in pathology that involve synthesizing images; overcoming annotated data scarcity, enabling privacy-preserving data sharing, and performing inherently generative tasks, such as virtual staining. We introduce PixCell, the first diffusion-based generative foundation model for histopathology. We train PixCell on PanCan-30M, a vast, diverse dataset derived from 69,184 H\&E-stained whole slide images covering various cancer types. We employ a progressive training strategy and a self-supervision-based conditioning that allows us to scale up training without any annotated data. PixCell generates diverse and high-quality images across multiple cancer types, which we find can be used in place of real data to train a self-supervised discriminative model. Synthetic images shared between institutions are subject to fewer regulatory barriers than would be the case with real clinical images. Furthermore, we showcase the ability to precisely control image generation using a small set of annotated images, which can be used for both data augmentation and educational purposes. Testing on a cell segmentation task, a mask-guided PixCell enables targeted data augmentation, improving downstream performance. Finally, we demonstrate PixCell's ability to use H\&E structural staining to infer results from molecular marker studies; we use this capability to infer IHC staining from H\&E images. Our trained models are publicly released to accelerate research in computational pathology.

Pathology Image Compression with Pre-trained Autoencoders

The growing volume of high-resolution Whole Slide Images in digital histopathology poses significant storage, transmission, and computational efficiency challenges. Standard compression methods, such as JPEG, reduce file sizes but often fail to preserve fine-grained phenotypic details critical for downstream tasks. In this work, we repurpose autoencoders (AEs) designed for Latent Diffusion Models as an efficient learned compression framework for pathology images. We systematically benchmark three AE models with varying compression levels and evaluate their reconstruction ability using pathology foundation models. We introduce a fine-tuning strategy to further enhance reconstruction fidelity that optimizes a pathology-specific learned perceptual metric. We validate our approach on downstream tasks, including segmentation, patch classification, and multiple instance learning, showing that replacing images with AE-compressed reconstructions leads to minimal performance degradation. Additionally, we propose a K-means clustering-based quantization method for AE latents, improving storage efficiency while maintaining reconstruction quality. We provide the weights of the fine-tuned autoencoders at https://huggingface.co/collections/StonyBrook-CVLab/pathology-fine-tuned-aes-67d45f223a659ff2e3402dd0.

Gen-SIS: Generative Self-augmentation Improves Self-supervised Learning

Self-supervised learning (SSL) methods have emerged as strong visual representation learners by training an image encoder to maximize similarity between features of different views of the same image. To perform this view-invariance task, current SSL algorithms rely on hand-crafted augmentations such as random cropping and color jittering to create multiple views of an image. Recently, generative diffusion models have been shown to improve SSL by providing a wider range of data augmentations. However, these diffusion models require pre-training on large-scale image-text datasets, which might not be available for many specialized domains like histopathology. In this work, we introduce Gen-SIS, a diffusion-based augmentation technique trained exclusively on unlabeled image data, eliminating any reliance on external sources of supervision such as text captions. We first train an initial SSL encoder on a dataset using only hand-crafted augmentations. We then train a diffusion model conditioned on embeddings from that SSL encoder. Following training, given an embedding of the source image, this diffusion model can synthesize its diverse views. We show that these `self-augmentations', i.e. generative augmentations based on the vanilla SSL encoder embeddings, facilitate the training of a stronger SSL encoder. Furthermore, based on the ability to interpolate between images in the encoder latent space, we introduce the novel pretext task of disentangling the two source images of an interpolated synthetic image. We validate Gen-SIS's effectiveness by demonstrating performance improvements across various downstream tasks in both natural images, which are generally object-centric, as well as digital histopathology images, which are typically context-based.