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.

Enhancing SAM with Efficient Prompting and Preference Optimization for Semi-supervised Medical Image Segmentation

Foundational models such as the Segment Anything Model (SAM) are gaining traction in medical imaging segmentation, supporting multiple downstream tasks. However, such models are supervised in nature, still relying on large annotated datasets or prompts supplied by experts. Conventional techniques such as active learning to alleviate such limitations are limited in scope and still necessitate continuous human involvement and complex domain knowledge for label refinement or establishing reward ground truth. To address these challenges, we propose an enhanced Segment Anything Model (SAM) framework that utilizes annotation-efficient prompts generated in a fully unsupervised fashion, while still capturing essential semantic, location, and shape information through contrastive language-image pretraining and visual question answering. We adopt the direct preference optimization technique to design an optimal policy that enables the model to generate high-fidelity segmentations with simple ratings or rankings provided by a virtual annotator simulating the human annotation process. State-of-the-art performance of our framework in tasks such as lung segmentation, breast tumor segmentation, and organ segmentation across various modalities, including X-ray, ultrasound, and abdominal CT, justifies its effectiveness in low-annotation data scenarios.

TopoCellGen: Generating Histopathology Cell Topology with a Diffusion Model

Accurately modeling multi-class cell topology is crucial in digital pathology, as it provides critical insights into tissue structure and pathology. The synthetic generation of cell topology enables realistic simulations of complex tissue environments, enhances downstream tasks by augmenting training data, aligns more closely with pathologists' domain knowledge, and offers new opportunities for controlling and generalizing the tumor microenvironment. In this paper, we propose a novel approach that integrates topological constraints into a diffusion model to improve the generation of realistic, contextually accurate cell topologies. Our method refines the simulation of cell distributions and interactions, increasing the precision and interpretability of results in downstream tasks such as cell detection and classification. To assess the topological fidelity of generated layouts, we introduce a new metric, Topological Frechet Distance (TopoFD), which overcomes the limitations of traditional metrics like FID in evaluating topological structure. Experimental results demonstrate the effectiveness of our approach in generating multi-class cell layouts that capture intricate topological relationships.

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.

ZoomLDM: Latent Diffusion Model for multi-scale image generation

Diffusion models have revolutionized image generation, yet several challenges restrict their application to large-image domains, such as digital pathology and satellite imagery. Given that it is infeasible to directly train a model on 'whole' images from domains with potential gigapixel sizes, diffusion-based generative methods have focused on synthesizing small, fixed-size patches extracted from these images. However, generating small patches has limited applicability since patch-based models fail to capture the global structures and wider context of large images, which can be crucial for synthesizing (semantically) accurate samples. In this paper, to overcome this limitation, we present ZoomLDM, a diffusion model tailored for generating images across multiple scales. Central to our approach is a novel magnification-aware conditioning mechanism that utilizes self-supervised learning (SSL) embeddings and allows the diffusion model to synthesize images at different 'zoom' levels, i.e., fixed-size patches extracted from large images at varying scales. ZoomLDM achieves state-of-the-art image generation quality across all scales, excelling particularly in the data-scarce setting of generating thumbnails of entire large images. The multi-scale nature of ZoomLDM unlocks additional capabilities in large image generation, enabling computationally tractable and globally coherent image synthesis up to $4096 \times 4096$ pixels and $4\times$ super-resolution. Additionally, multi-scale features extracted from ZoomLDM are highly effective in multiple instance learning experiments. We provide high-resolution examples of the generated images on our website https://histodiffusion.github.io/docs/publications/zoomldm/.

RankByGene: Gene-Guided Histopathology Representation Learning Through Cross-Modal Ranking Consistency

Spatial transcriptomics (ST) provides essential spatial context by mapping gene expression within tissue, enabling detailed study of cellular heterogeneity and tissue organization. However, aligning ST data with histology images poses challenges due to inherent spatial distortions and modality-specific variations. Existing methods largely rely on direct alignment, which often fails to capture complex cross-modal relationships. To address these limitations, we propose a novel framework that aligns gene and image features using a ranking-based alignment loss, preserving relative similarity across modalities and enabling robust multi-scale alignment. To further enhance the alignment's stability, we employ self-supervised knowledge distillation with a teacher-student network architecture, effectively mitigating disruptions from high dimensionality, sparsity, and noise in gene expression data. Extensive experiments on gene expression prediction and survival analysis demonstrate our framework's effectiveness, showing improved alignment and predictive performance over existing methods and establishing a robust tool for gene-guided image representation learning in digital pathology.

TopoTxR: A topology-guided deep convolutional network for breast parenchyma learning on DCE-MRIs

Characterization of breast parenchyma in dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is a challenging task owing to the complexity of underlying tissue structures. Existing quantitative approaches, like radiomics and deep learning models, lack explicit quantification of intricate and subtle parenchymal structures, including fibroglandular tissue. To address this, we propose a novel topological approach that explicitly extracts multi-scale topological structures to better approximate breast parenchymal structures, and then incorporates these structures into a deep-learning-based prediction model via an attention mechanism. Our topology-informed deep learning model, \emph{TopoTxR}, leverages topology to provide enhanced insights into tissues critical for disease pathophysiology and treatment response. We empirically validate \emph{TopoTxR} using the VICTRE phantom breast dataset, showing that the topological structures extracted by our model effectively approximate the breast parenchymal structures. We further demonstrate \emph{TopoTxR}'s efficacy in predicting response to neoadjuvant chemotherapy. Our qualitative and quantitative analyses suggest differential topological behavior of breast tissue in treatment-na\"ive imaging, in patients who respond favorably to therapy as achieving pathological complete response (pCR) versus those who do not. In a comparative analysis with several baselines on the publicly available I-SPY 1 dataset (N=161, including 47 patients with pCR and 114 without) and the Rutgers proprietary dataset (N=120, with 69 patients achieving pCR and 51 not), \emph{TopoTxR} demonstrates a notable improvement, achieving a 2.6\% increase in accuracy and a 4.6\% enhancement in AUC compared to the state-of-the-art method.

Hard Negative Sample Mining for Whole Slide Image Classification

Weakly supervised whole slide image (WSI) classification is challenging due to the lack of patch-level labels and high computational costs. State-of-the-art methods use self-supervised patch-wise feature representations for multiple instance learning (MIL). Recently, methods have been proposed to fine-tune the feature representation on the downstream task using pseudo labeling, but mostly focusing on selecting high-quality positive patches. In this paper, we propose to mine hard negative samples during fine-tuning. This allows us to obtain better feature representations and reduce the training cost. Furthermore, we propose a novel patch-wise ranking loss in MIL to better exploit these hard negative samples. Experiments on two public datasets demonstrate the efficacy of these proposed ideas. Our codes are available at https://github.com/winston52/HNM-WSI

Semi-Supervised Contrastive VAE for Disentanglement of Digital Pathology Images

Despite the strong prediction power of deep learning models, their interpretability remains an important concern. Disentanglement models increase interpretability by decomposing the latent space into interpretable subspaces. In this paper, we propose the first disentanglement method for pathology images. We focus on the task of detecting tumor-infiltrating lymphocytes (TIL). We propose different ideas including cascading disentanglement, novel architecture, and reconstruction branches. We achieve superior performance on complex pathology images, thus improving the interpretability and even generalization power of TIL detection deep learning models. Our codes are available at https://github.com/Shauqi/SS-cVAE.

Histo-Diffusion: A Diffusion Super-Resolution Method for Digital Pathology with Comprehensive Quality Assessment

Digital pathology has advanced significantly over the last decade, with Whole Slide Images (WSIs) encompassing vast amounts of data essential for accurate disease diagnosis. High-resolution WSIs are essential for precise diagnosis but technical limitations in scanning equipment and variablity in slide preparation can hinder obtaining these images. Super-resolution techniques can enhance low-resolution images; while Generative Adversarial Networks (GANs) have been effective in natural image super-resolution tasks, they often struggle with histopathology due to overfitting and mode collapse. Traditional evaluation metrics fall short in assessing the complex characteristics of histopathology images, necessitating robust histology-specific evaluation methods. We introduce Histo-Diffusion, a novel diffusion-based method specially designed for generating and evaluating super-resolution images in digital pathology. It includes a restoration module for histopathology prior and a controllable diffusion module for generating high-quality images. We have curated two histopathology datasets and proposed a comprehensive evaluation strategy which incorporates both full-reference and no-reference metrics to thoroughly assess the quality of digital pathology images. Comparative analyses on multiple datasets with state-of-the-art methods reveal that Histo-Diffusion outperforms GANs. Our method offers a versatile solution for histopathology image super-resolution, capable of handling multi-resolution generation from varied input sizes, providing valuable support in diagnostic processes.