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.

Improving Contrastive Learning for Referring Expression Counting

Object counting has progressed from class-specific models, which count only known categories, to class-agnostic models that generalize to unseen categories. The next challenge is Referring Expression Counting (REC), where the goal is to count objects based on fine-grained attributes and contextual differences. Existing methods struggle with distinguishing visually similar objects that belong to the same category but correspond to different referring expressions. To address this, we propose C-REX, a novel contrastive learning framework, based on supervised contrastive learning, designed to enhance discriminative representation learning. Unlike prior works, C-REX operates entirely within the image space, avoiding the misalignment issues of image-text contrastive learning, thus providing a more stable contrastive signal. It also guarantees a significantly larger pool of negative samples, leading to improved robustness in the learned representations. Moreover, we showcase that our framework is versatile and generic enough to be applied to other similar tasks like class-agnostic counting. To support our approach, we analyze the key components of sota detection-based models and identify that detecting object centroids instead of bounding boxes is the key common factor behind their success in counting tasks. We use this insight to design a simple yet effective detection-based baseline to build upon. Our experiments show that C-REX achieves state-of-the-art results in REC, outperforming previous methods by more than 22\% in MAE and more than 10\% in RMSE, while also demonstrating strong performance in class-agnostic counting. Code is available at https://github.com/cvlab-stonybrook/c-rex.

GeoMaNO: Geometric Mamba Neural Operator for Partial Differential Equations

The neural operator (NO) framework has emerged as a powerful tool for solving partial differential equations (PDEs). Recent NOs are dominated by the Transformer architecture, which offers NOs the capability to capture long-range dependencies in PDE dynamics. However, existing Transformer-based NOs suffer from quadratic complexity, lack geometric rigor, and thus suffer from sub-optimal performance on regular grids. As a remedy, we propose the Geometric Mamba Neural Operator (GeoMaNO) framework, which empowers NOs with Mamba's modeling capability, linear complexity, plus geometric rigor. We evaluate GeoMaNO's performance on multiple standard and popularly employed PDE benchmarks, spanning from Darcy flow problems to Navier-Stokes problems. GeoMaNO improves existing baselines in solution operator approximation by as much as 58.9%.

PathSegDiff: Pathology Segmentation using Diffusion model representations

Image segmentation is crucial in many computational pathology pipelines, including accurate disease diagnosis, subtyping, outcome, and survivability prediction. The common approach for training a segmentation model relies on a pre-trained feature extractor and a dataset of paired image and mask annotations. These are used to train a lightweight prediction model that translates features into per-pixel classes. The choice of the feature extractor is central to the performance of the final segmentation model, and recent literature has focused on finding tasks to pre-train the feature extractor. In this paper, we propose PathSegDiff, a novel approach for histopathology image segmentation that leverages Latent Diffusion Models (LDMs) as pre-trained featured extractors. Our method utilizes a pathology-specific LDM, guided by a self-supervised encoder, to extract rich semantic information from H\&E stained histopathology images. We employ a simple, fully convolutional network to process the features extracted from the LDM and generate segmentation masks. Our experiments demonstrate significant improvements over traditional methods on the BCSS and GlaS datasets, highlighting the effectiveness of domain-specific diffusion pre-training in capturing intricate tissue structures and enhancing segmentation accuracy in histopathology images.

Few-shot Personalized Scanpath Prediction

A personalized model for scanpath prediction provides insights into the visual preferences and attention patterns of individual subjects. However, existing methods for training scanpath prediction models are data-intensive and cannot be effectively personalized to new individuals with only a few available examples. In this paper, we propose few-shot personalized scanpath prediction task (FS-PSP) and a novel method to address it, which aims to predict scanpaths for an unseen subject using minimal support data of that subject's scanpath behavior. The key to our method's adaptability is the Subject-Embedding Network (SE-Net), specifically designed to capture unique, individualized representations for each subject's scanpaths. SE-Net generates subject embeddings that effectively distinguish between subjects while minimizing variability among scanpaths from the same individual. The personalized scanpath prediction model is then conditioned on these subject embeddings to produce accurate, personalized results. Experiments on multiple eye-tracking datasets demonstrate that our method excels in FS-PSP settings and does not require any fine-tuning steps at test time. Code is available at: https://github.com/cvlab-stonybrook/few-shot-scanpath

GECKO: Gigapixel Vision-Concept Contrastive Pretraining in Histopathology

Pretraining a Multiple Instance Learning (MIL) aggregator enables the derivation of Whole Slide Image (WSI)-level embeddings from patch-level representations without supervision. While recent multimodal MIL pretraining approaches leveraging auxiliary modalities have demonstrated performance gains over unimodal WSI pretraining, the acquisition of these additional modalities necessitates extensive clinical profiling. This requirement increases costs and limits scalability in existing WSI datasets lacking such paired modalities. To address this, we propose Gigapixel Vision-Concept Knowledge Contrastive pretraining (GECKO), which aligns WSIs with a Concept Prior derived from the available WSIs. First, we derive an inherently interpretable concept prior by computing the similarity between each WSI patch and textual descriptions of predefined pathology concepts. GECKO then employs a dual-branch MIL network: one branch aggregates patch embeddings into a WSI-level deep embedding, while the other aggregates the concept prior into a corresponding WSI-level concept embedding. Both aggregated embeddings are aligned using a contrastive objective, thereby pretraining the entire dual-branch MIL model. Moreover, when auxiliary modalities such as transcriptomics data are available, GECKO seamlessly integrates them. Across five diverse tasks, GECKO consistently outperforms prior unimodal and multimodal pretraining approaches while also delivering clinically meaningful interpretability that bridges the gap between computational models and pathology expertise. Code is made available at https://github.com/bmi-imaginelab/GECKO

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.

AV-Flow: Transforming Text to Audio-Visual Human-like Interactions

We introduce AV-Flow, an audio-visual generative model that animates photo-realistic 4D talking avatars given only text input. In contrast to prior work that assumes an existing speech signal, we synthesize speech and vision jointly. We demonstrate human-like speech synthesis, synchronized lip motion, lively facial expressions and head pose; all generated from just text characters. The core premise of our approach lies in the architecture of our two parallel diffusion transformers. Intermediate highway connections ensure communication between the audio and visual modalities, and thus, synchronized speech intonation and facial dynamics (e.g., eyebrow motion). Our model is trained with flow matching, leading to expressive results and fast inference. In case of dyadic conversations, AV-Flow produces an always-on avatar, that actively listens and reacts to the audio-visual input of a user. Through extensive experiments, we show that our method outperforms prior work, synthesizing natural-looking 4D talking avatars. Project page: https://aggelinacha.github.io/AV-Flow/

Hummingbird: High Fidelity Image Generation via Multimodal Context Alignment

While diffusion models are powerful in generating high-quality, diverse synthetic data for object-centric tasks, existing methods struggle with scene-aware tasks such as Visual Question Answering (VQA) and Human-Object Interaction (HOI) Reasoning, where it is critical to preserve scene attributes in generated images consistent with a multimodal context, i.e. a reference image with accompanying text guidance query. To address this, we introduce Hummingbird, the first diffusion-based image generator which, given a multimodal context, generates highly diverse images w.r.t. the reference image while ensuring high fidelity by accurately preserving scene attributes, such as object interactions and spatial relationships from the text guidance. Hummingbird employs a novel Multimodal Context Evaluator that simultaneously optimizes our formulated Global Semantic and Fine-grained Consistency Rewards to ensure generated images preserve the scene attributes of reference images in relation to the text guidance while maintaining diversity. As the first model to address the task of maintaining both diversity and fidelity given a multimodal context, we introduce a new benchmark formulation incorporating MME Perception and Bongard HOI datasets. Benchmark experiments show Hummingbird outperforms all existing methods by achieving superior fidelity while maintaining diversity, validating Hummingbird's potential as a robust multimodal context-aligned image generator in complex visual tasks.

Leveraging Registers in Vision Transformers for Robust Adaptation

Vision Transformers (ViTs) have shown success across a variety of tasks due to their ability to capture global image representations. Recent studies have identified the existence of high-norm tokens in ViTs, which can interfere with unsupervised object discovery. To address this, the use of "registers" which are additional tokens that isolate high norm patch tokens while capturing global image-level information has been proposed. While registers have been studied extensively for object discovery, their generalization properties particularly in out-of-distribution (OOD) scenarios, remains underexplored. In this paper, we examine the utility of register token embeddings in providing additional features for improving generalization and anomaly rejection. To that end, we propose a simple method that combines the special CLS token embedding commonly employed in ViTs with the average-pooled register embeddings to create feature representations which are subsequently used for training a downstream classifier. We find that this enhances OOD generalization and anomaly rejection, while maintaining in-distribution (ID) performance. Extensive experiments across multiple ViT backbones trained with and without registers reveal consistent improvements of 2-4\% in top-1 OOD accuracy and a 2-3\% reduction in false positive rates for anomaly detection. Importantly, these gains are achieved without additional computational overhead.