Daily Papers

Recent rapid progress in the field of computational pathology has been enabled by foundation models. These models are beginning to move beyond encoding image patches towards whole-slide understanding but their clinical utility remains limited. In this work, we present PRISM2, a multimodal slide-level foundation model trained on data from 700,000 diagnostic specimen-report pairs, the largest vision (2.3 million whole slide images) and language (14M question-answer pairs) histopathology dataset to date. By learning through clinical-dialogue supervision, PRISM2 aligns histomorphologic features with the language of diagnostic reasoning, producing slide-level representations that support both direct diagnostic question-answering and transferable embeddings for downstream tasks. Without additional training, PRISM2 matches or exceeds the cancer-detection performance of clinical-grade products. This is observed without loss of generality on other tasks, where PRISM2 achieves top performance. Finally, using survival prediction as the example, we show that task-specific finetuning with a large dataset can outperform task-specific models, further improving performance. These results demonstrate how language-supervised pretraining provides a scalable, clinically grounded signal for learning generalizable pathology representations, bridging human diagnostic reasoning and foundation-model performance.

We present HistoAtlas, a pan-cancer computational atlas that extracts 38 interpretable histomic features from 6,745 diagnostic H&E slides across 21 TCGA cancer types and systematically links every feature to survival, gene expression, somatic mutations, and immune subtypes. All associations are covariate-adjusted, multiple-testing corrected, and classified into evidence-strength tiers. The atlas recovers known biology, from immune infiltration and prognosis to proliferation and kinase signaling, while uncovering compartment-specific immune signals and morphological subtypes with divergent outcomes. Every result is spatially traceable to tissue compartments and individual cells, statistically calibrated, and openly queryable. HistoAtlas enables systematic, large-scale biomarker discovery from routine H&E without specialized staining or sequencing. Data and an interactive web atlas are freely available at https://histoatlas.com .

Morphological traits are physical characteristics of biological organisms that provide vital clues on how organisms interact with their environment. Yet extracting these traits remains a slow, expert-driven process, limiting their use in large-scale ecological studies. A major bottleneck is the absence of high-quality datasets linking biological images to trait-level annotations. In this work, we demonstrate that sparse autoencoders trained on foundation-model features yield monosemantic, spatially grounded neurons that consistently activate on meaningful morphological parts. Leveraging this property, we introduce a trait annotation pipeline that localizes salient regions and uses vision-language prompting to generate interpretable trait descriptions. Using this approach, we construct Bioscan-Traits, a dataset of 80K trait annotations spanning 19K insect images from BIOSCAN-5M. Human evaluation confirms the biological plausibility of the generated morphological descriptions. We assess design sensitivity through a comprehensive ablation study, systematically varying key design choices and measuring their impact on the quality of the resulting trait descriptions. By annotating traits with a modular pipeline rather than prohibitively expensive manual efforts, we offer a scalable way to inject biologically meaningful supervision into foundation models, enable large-scale morphological analyses, and bridge the gap between ecological relevance and machine-learning practicality.

Tissue phenotyping is a fundamental task in learning objective characterizations of histopathologic biomarkers within the tumor-immune microenvironment in cancer pathology. However, whole-slide imaging (WSI) is a complex computer vision in which: 1) WSIs have enormous image resolutions with precludes large-scale pixel-level efforts in data curation, and 2) diversity of morphological phenotypes results in inter- and intra-observer variability in tissue labeling. To address these limitations, current efforts have proposed using pretrained image encoders (transfer learning from ImageNet, self-supervised pretraining) in extracting morphological features from pathology, but have not been extensively validated. In this work, we conduct a search for good representations in pathology by training a variety of self-supervised models with validation on a variety of weakly-supervised and patch-level tasks. Our key finding is in discovering that Vision Transformers using DINO-based knowledge distillation are able to learn data-efficient and interpretable features in histology images wherein the different attention heads learn distinct morphological phenotypes. We make evaluation code and pretrained weights publicly-available at: https://github.com/Richarizardd/Self-Supervised-ViT-Path.

Histopathology and transcriptomics are fundamental modalities in oncology, encapsulating the morphological and molecular aspects of the disease. Multi-modal self-supervised learning has demonstrated remarkable potential in learning pathological representations by integrating diverse data sources. Conventional multi-modal integration methods primarily emphasize modality alignment, while paying insufficient attention to retaining the modality-specific structures. However, unlike conventional scenarios where multi-modal inputs share highly overlapping features, histopathology and transcriptomics exhibit pronounced heterogeneity, offering orthogonal yet complementary insights. Histopathology provides morphological and spatial context, elucidating tissue architecture and cellular topology, whereas transcriptomics delineates molecular signatures through gene expression patterns. This inherent disparity introduces a major challenge in aligning them while maintaining modality-specific fidelity. To address these challenges, we present MIRROR, a novel multi-modal representation learning method designed to foster both modality alignment and retention. MIRROR employs dedicated encoders to extract comprehensive features for each modality, which is further complemented by a modality alignment module to achieve seamless integration between phenotype patterns and molecular profiles. Furthermore, a modality retention module safeguards unique attributes from each modality, while a style clustering module mitigates redundancy and enhances disease-relevant information by modeling and aligning consistent pathological signatures within a clustering space. Extensive evaluations on TCGA cohorts for cancer subtyping and survival analysis highlight MIRROR's superior performance, demonstrating its effectiveness in constructing comprehensive oncological feature representations and benefiting the cancer diagnosis.

Representation learning of pathology whole-slide images (WSIs) has been has primarily relied on weak supervision with Multiple Instance Learning (MIL). However, the slide representations resulting from this approach are highly tailored to specific clinical tasks, which limits their expressivity and generalization, particularly in scenarios with limited data. Instead, we hypothesize that morphological redundancy in tissue can be leveraged to build a task-agnostic slide representation in an unsupervised fashion. To this end, we introduce PANTHER, a prototype-based approach rooted in the Gaussian mixture model that summarizes the set of WSI patches into a much smaller set of morphological prototypes. Specifically, each patch is assumed to have been generated from a mixture distribution, where each mixture component represents a morphological exemplar. Utilizing the estimated mixture parameters, we then construct a compact slide representation that can be readily used for a wide range of downstream tasks. By performing an extensive evaluation of PANTHER on subtyping and survival tasks using 13 datasets, we show that 1) PANTHER outperforms or is on par with supervised MIL baselines and 2) the analysis of morphological prototypes brings new qualitative and quantitative insights into model interpretability.

Recent advancements in Digital Pathology (DP), particularly through artificial intelligence and Foundation Models, have underscored the importance of large-scale, diverse, and richly annotated datasets. Despite their critical role, publicly available Whole Slide Image (WSI) datasets often lack sufficient scale, tissue diversity, and comprehensive clinical metadata, limiting the robustness and generalizability of AI models. In response, we introduce the HISTAI dataset, a large, multimodal, open-access WSI collection comprising over 60,000 slides from various tissue types. Each case in the HISTAI dataset is accompanied by extensive clinical metadata, including diagnosis, demographic information, detailed pathological annotations, and standardized diagnostic coding. The dataset aims to fill gaps identified in existing resources, promoting innovation, reproducibility, and the development of clinically relevant computational pathology solutions. The dataset can be accessed at https://github.com/HistAI/HISTAI.

Spatial transcriptomics (ST) enables interrogating the molecular composition of tissue with ever-increasing resolution, depth, and sensitivity. However, costs, rapidly evolving technology, and lack of standards have constrained computational methods in ST to narrow tasks and small cohorts. In addition, the underlying tissue morphology as reflected by H&E-stained whole slide images (WSIs) encodes rich information often overlooked in ST studies. Here, we introduce HEST-1k, a collection of 1,108 spatial transcriptomic profiles, each linked to a WSI and metadata. HEST-1k was assembled using HEST-Library from 131 public and internal cohorts encompassing 25 organs, two species (Homo Sapiens and Mus Musculus), and 320 cancer samples from 25 cancer types. HEST-1k processing enabled the identification of 1.5 million expression--morphology pairs and 60 million nuclei. HEST-1k is tested on three use cases: (1) benchmarking foundation models for histopathology (HEST-Benchmark), (2) biomarker identification, and (3) multimodal representation learning. HEST-1k, HEST-Library, and HEST-Benchmark can be freely accessed via https://github.com/mahmoodlab/hest.

In recent years, a standard computational pathology workflow has emerged where whole slide images are cropped into tiles, these tiles are processed using a foundation model, and task-specific models are built using the resulting representations. At least 15 different foundation models have been proposed, and the vast majority are trained exclusively with tiles using the 20times magnification. However, it is well known that certain histologic features can only be discerned with larger context windows and requires a pathologist to zoom in and out when analyzing a whole slide image. Furthermore, creating 224times224 pixel crops at 20times leads to a large number of tiles per slide, which can be gigapixel in size. To more accurately capture multi-resolution features and investigate the possibility of reducing the number of representations per slide, we propose a region-level mixing encoder. Our approach jointly fuses image tile representations of a mixed magnification foundation model using a masked embedding modeling pretraining step. We explore a design space for pretraining the proposed mixed-magnification region aggregators and evaluate our models on transfer to biomarker prediction tasks representing various cancer types. Results demonstrate cancer dependent improvements in predictive performance, highlighting the importance of spatial context and understanding.

While machine learning is currently transforming the field of histopathology, the domain lacks a comprehensive evaluation of state-of-the-art models based on essential but complementary quality requirements beyond a mere classification accuracy. In order to fill this gap, we developed a new methodology to extensively evaluate a wide range of classification models, including recent vision transformers, and convolutional neural networks such as: ConvNeXt, ResNet (BiT), Inception, ViT and Swin transformer, with and without supervised or self-supervised pretraining. We thoroughly tested the models on five widely used histopathology datasets containing whole slide images of breast, gastric, and colorectal cancer and developed a novel approach using an image-to-image translation model to assess the robustness of a cancer classification model against stain variations. Further, we extended existing interpretability methods to previously unstudied models and systematically reveal insights of the models' classifications strategies that can be transferred to future model architectures.

Histopathology plays a central role in clinical medicine and biomedical research. While artificial intelligence shows promising results on many pathological tasks, generalization and dealing with rare diseases, where training data is scarce, remains a challenge. Distilling knowledge from unlabeled data into a foundation model before learning from, potentially limited, labeled data provides a viable path to address these challenges. In this work, we extend the state of the art of foundation models for digital pathology whole slide images by semi-automated data curation and incorporating pathologist domain knowledge. Specifically, we combine computational and pathologist domain knowledge (1) to curate a diverse dataset of 103k slides corresponding to 750 million image patches covering data from different fixation, staining, and scanning protocols as well as data from different indications and labs across the EU and US, (2) for grouping semantically similar slides and tissue patches, and (3) to augment the input images during training. We evaluate the resulting model on a set of public and internal benchmarks and show that although our foundation model is trained with an order of magnitude less slides, it performs on par or better than competing models. We expect that scaling our approach to more data and larger models will further increase its performance and capacity to deal with increasingly complex real world tasks in diagnostics and biomedical research.

Foundation models have recently achieved impressive success in computational pathology, demonstrating strong generalization across diverse histopathology tasks. However, existing models overlook the heterogeneous and non-uniform organization of pathological regions of interest (ROIs) because they rely on natural image backbones not tailored for tissue morphology. Consequently, they often fail to capture the coherent tissue architecture beyond isolated patches, limiting interpretability and clinical relevance. To address these challenges, we present Cross-modal Adaptive Region Encoder (CARE), a foundation model for pathology that automatically partitions WSIs into several morphologically relevant regions. Specifically, CARE employs a two-stage pretraining strategy: (1) a self-supervised unimodal pretraining stage that learns morphological representations from 34,277 whole-slide images (WSIs) without segmentation annotations, and (2) a cross-modal alignment stage that leverages RNA and protein profiles to refine the construction and representation of adaptive regions. This molecular guidance enables CARE to identify biologically relevant patterns and generate irregular yet coherent tissue regions, selecting the most representative area as ROI. CARE supports a broad range of pathology-related tasks, using either the ROI feature or the slide-level feature obtained by aggregating adaptive regions. Based on only one-tenth of the pretraining data typically used by mainstream foundation models, CARE achieves superior average performance across 33 downstream benchmarks, including morphological classification, molecular prediction, and survival analysis, and outperforms other foundation model baselines overall.

Advancing AI in computational pathology requires large, high-quality, and diverse datasets, yet existing public datasets are often limited in organ diversity, class coverage, or annotation quality. To bridge this gap, we introduce SPIDER (Supervised Pathology Image-DEscription Repository), the largest publicly available patch-level dataset covering multiple organ types, including Skin, Colorectal, and Thorax, with comprehensive class coverage for each organ. SPIDER provides high-quality annotations verified by expert pathologists and includes surrounding context patches, which enhance classification performance by providing spatial context. Alongside the dataset, we present baseline models trained on SPIDER using the Hibou-L foundation model as a feature extractor combined with an attention-based classification head. The models achieve state-of-the-art performance across multiple tissue categories and serve as strong benchmarks for future digital pathology research. Beyond patch classification, the model enables rapid identification of significant areas, quantitative tissue metrics, and establishes a foundation for multimodal approaches. Both the dataset and trained models are publicly available to advance research, reproducibility, and AI-driven pathology development. Access them at: https://github.com/HistAI/SPIDER

Histopathological images contain rich phenotypic information that can be used to monitor underlying mechanisms contributing to diseases progression and patient survival outcomes. Recently, deep learning has become the mainstream methodological choice for analyzing and interpreting cancer histology images. In this paper, we present a comprehensive review of state-of-the-art deep learning approaches that have been used in the context of histopathological image analysis. From the survey of over 130 papers, we review the fields progress based on the methodological aspect of different machine learning strategies such as supervised, weakly supervised, unsupervised, transfer learning and various other sub-variants of these methods. We also provide an overview of deep learning based survival models that are applicable for disease-specific prognosis tasks. Finally, we summarize several existing open datasets and highlight critical challenges and limitations with current deep learning approaches, along with possible avenues for future research.

The tumor immune microenvironment (TIME) in non-small cell lung cancer (NSCLC) histopathology contains morphological and molecular characteristics predictive of immunotherapy response. Computational quantification of TIME characteristics, such as cell detection and tissue segmentation, can support biomarker development. However, currently available digital pathology datasets of NSCLC for the development of cell detection or tissue segmentation algorithms are limited in scope, lack annotations of clinically prevalent metastatic sites, and forgo molecular information such as PD-L1 immunohistochemistry (IHC). To fill this gap, we introduce the IGNITE data toolkit, a multi-stain, multi-centric, and multi-scanner dataset of annotated NSCLC whole-slide images. We publicly release 887 fully annotated regions of interest from 155 unique patients across three complementary tasks: (i) multi-class semantic segmentation of tissue compartments in H&E-stained slides, with 16 classes spanning primary and metastatic NSCLC, (ii) nuclei detection, and (iii) PD-L1 positive tumor cell detection in PD-L1 IHC slides. To the best of our knowledge, this is the first public NSCLC dataset with manual annotations of H&E in metastatic sites and PD-L1 IHC.

The evolution of biological morphology is critical for understanding the diversity of the natural world, yet traditional analyses often involve subjective biases in the selection and coding of morphological traits. This study employs deep learning techniques, utilising a ResNet34 model capable of recognising over 10,000 bird species, to explore avian morphological evolution. We extract weights from the model's final fully connected (fc) layer and investigate the semantic alignment between the high-dimensional embedding space learned by the model and biological phenotypes. The results demonstrate that the high-dimensional embedding space encodes phenotypic convergence. Subsequently, we assess the morphological disparity among various taxa and evaluate the association between morphological disparity and species richness, demonstrating that species richness is the primary driver of morphospace expansion. Moreover, the disparity-through-time analysis reveals a visual "early burst" after the K-Pg extinction. While mainly aimed at evolutionary analysis, this study also provides insights into the interpretability of Deep Neural Networks. We demonstrate that hierarchical semantic structures (biological taxonomy) emerged in the high-dimensional embedding space despite being trained on flat labels. Furthermore, through adversarial examples, we provide evidence that our model in this task can overcome texture bias and learn holistic shape representations (body plans), challenging the prevailing view that CNNs rely primarily on local textures.

Breast cancer survival prediction in computational pathology presents a remarkable challenge due to tumor heterogeneity. For instance, different regions of the same tumor in the pathology image can show distinct morphological and molecular characteristics. This makes it difficult to extract representative features from whole slide images (WSIs) that truly reflect the tumor's aggressive potential and likely survival outcomes. In this paper, we present PathoHR, a novel pipeline for accurate breast cancer survival prediction that enhances any size of pathological images to enable more effective feature learning. Our approach entails (1) the incorporation of a plug-and-play high-resolution Vision Transformer (ViT) to enhance patch-wise WSI representation, enabling more detailed and comprehensive feature extraction, (2) the systematic evaluation of multiple advanced similarity metrics for comparing WSI-extracted features, optimizing the representation learning process to better capture tumor characteristics, (3) the demonstration that smaller image patches enhanced follow the proposed pipeline can achieve equivalent or superior prediction accuracy compared to raw larger patches, while significantly reducing computational overhead. Experimental findings valid that PathoHR provides the potential way of integrating enhanced image resolution with optimized feature learning to advance computational pathology, offering a promising direction for more accurate and efficient breast cancer survival prediction. Code will be available at https://github.com/AIGeeksGroup/PathoHR.

The accelerated adoption of digital pathology and advances in deep learning have enabled the development of powerful models for various pathology tasks across a diverse array of diseases and patient cohorts. However, model training is often difficult due to label scarcity in the medical domain and the model's usage is limited by the specific task and disease for which it is trained. Additionally, most models in histopathology leverage only image data, a stark contrast to how humans teach each other and reason about histopathologic entities. We introduce CONtrastive learning from Captions for Histopathology (CONCH), a visual-language foundation model developed using diverse sources of histopathology images, biomedical text, and notably over 1.17 million image-caption pairs via task-agnostic pretraining. Evaluated on a suite of 13 diverse benchmarks, CONCH can be transferred to a wide range of downstream tasks involving either or both histopathology images and text, achieving state-of-the-art performance on histology image classification, segmentation, captioning, text-to-image and image-to-text retrieval. CONCH represents a substantial leap over concurrent visual-language pretrained systems for histopathology, with the potential to directly facilitate a wide array of machine learning-based workflows requiring minimal or no further supervised fine-tuning.

Colon Cancer is one of the most common types of cancer. The treatment is planned to depend on the grade or stage of cancer. One of the preconditions for grading of colon cancer is to segment the glandular structures of tissues. Manual segmentation method is very time-consuming, and it leads to life risk for the patients. The principal objective of this project is to assist the pathologist to accurate detection of colon cancer. In this paper, the authors have proposed an algorithm for an automatic segmentation of glands in colon histology using local intensity and texture features. Here the dataset images are cropped into patches with different window sizes and taken the intensity of those patches, and also calculated texture-based features. Random forest classifier has been used to classify this patch into different labels. A multilevel random forest technique in a hierarchical way is proposed. This solution is fast, accurate and it is very much applicable in a clinical setup.

Microscopic interpretation of histopathology images underlies many important diagnostic and treatment decisions. While advances in vision-language modeling raise new opportunities for analysis of such images, the gigapixel-scale size of whole slide images (WSIs) introduces unique challenges. Additionally, pathology reports simultaneously highlight key findings from small regions while also aggregating interpretation across multiple slides, often making it difficult to create robust image-text pairs. As such, pathology reports remain a largely untapped source of supervision in computational pathology, with most efforts relying on region-of-interest annotations or self-supervision at the patch-level. In this work, we develop a vision-language model based on the BLIP-2 framework using WSIs paired with curated text from pathology reports. This enables applications utilizing a shared image-text embedding space, such as text or image retrieval for finding cases of interest, as well as integration of the WSI encoder with a frozen large language model (LLM) for WSI-based generative text capabilities such as report generation or AI-in-the-loop interactions. We utilize a de-identified dataset of over 350,000 WSIs and diagnostic text pairs, spanning a wide range of diagnoses, procedure types, and tissue types. We present pathologist evaluation of text generation and text retrieval using WSI embeddings, as well as results for WSI classification and workflow prioritization (slide-level triaging). Model-generated text for WSIs was rated by pathologists as accurate, without clinically significant error or omission, for 78% of WSIs on average. This work demonstrates exciting potential capabilities for language-aligned WSI embeddings.

Histograms provide a powerful means of summarizing large data sets by representing their distribution in a compact, binned form. The HistogramTools R package enhances R built-in histogram functionality, offering advanced methods for manipulating and analyzing histograms, especially in large-scale data environments. Key features include the ability to serialize histograms using Protocol Buffers for distributed computing tasks, tools for merging and modifying histograms, and techniques for measuring and visualizing information loss in histogram representations. The package is particularly suited for environments utilizing MapReduce, where efficient storage and data sharing are critical. This paper presents various methods of histogram bin manipulation, distance measures, quantile approximation, and error estimation in cumulative distribution functions (CDFs) derived from histograms. Visualization techniques and efficient storage representations are also discussed alongside applications for large data processing and distributed computing tasks.

Computational pathology has made significant progress in recent years, fueling advances in both fundamental disease understanding and clinically ready tools. This evolution is driven by the availability of large amounts of digitized slides and specialized deep learning methods and models. Multiple self-supervised foundation feature extractors have been developed, enabling downstream predictive applications from cell segmentation to tumor sub-typing and survival analysis. In contrast, generative foundation models designed specifically for histopathology remain scarce. Such models could address tasks that are beyond the capabilities of feature extractors, such as virtual staining. In this paper, we introduce CytoSyn, a state-of-the-art foundation latent diffusion model that enables the guided generation of highly realistic and diverse histopathology H&E-stained images, as shown in an extensive benchmark. We explored methodological improvements, training set scaling, sampling strategies and slide-level overfitting, culminating in the improved CytoSyn-v2, and compared our work to PixCell, a state-of-the-art model, in an in-depth manner. This comparison highlighted the strong sensitivity of both diffusion models and performance metrics to preprocessing-specific details such as JPEG compression. Our model has been trained on a dataset obtained from more than 10,000 TCGA diagnostic whole-slide images of 32 different cancer types. Despite being trained only on oncology slides, it maintains state-of-the-art performance generating inflammatory bowel disease images. To support the research community, we publicly release CytoSyn's weights, its training and validation datasets, and a sample of synthetic images in this repository: https://huggingface.co/Owkin-Bioptimus/CytoSyn.

Cell detection, segmentation and classification are essential for analyzing tumor microenvironments (TME) on hematoxylin and eosin (H&E) slides. Existing methods suffer from poor performance on understudied cell types (rare or not present in public datasets) and limited cross-domain generalization. To address these shortcomings, we introduce HistoPLUS, a state-of-the-art model for cell analysis, trained on a novel curated pan-cancer dataset of 108,722 nuclei covering 13 cell types. In external validation across 4 independent cohorts, HistoPLUS outperforms current state-of-the-art models in detection quality by 5.2% and overall F1 classification score by 23.7%, while using 5x fewer parameters. Notably, HistoPLUS unlocks the study of 7 understudied cell types and brings significant improvements on 8 of 13 cell types. Moreover, we show that HistoPLUS robustly transfers to two oncology indications unseen during training. To support broader TME biomarker research, we release the model weights and inference code at https://github.com/owkin/histoplus/.

Recent accelerations in multi-modal applications have been made possible with the plethora of image and text data available online. However, the scarcity of analogous data in the medical field, specifically in histopathology, has halted comparable progress. To enable similar representation learning for histopathology, we turn to YouTube, an untapped resource of videos, offering 1,087 hours of valuable educational histopathology videos from expert clinicians. From YouTube, we curate Quilt: a large-scale vision-language dataset consisting of 768,826 image and text pairs. Quilt was automatically curated using a mixture of models, including large language models, handcrafted algorithms, human knowledge databases, and automatic speech recognition. In comparison, the most comprehensive datasets curated for histopathology amass only around 200K samples. We combine Quilt with datasets from other sources, including Twitter, research papers, and the internet in general, to create an even larger dataset: Quilt-1M, with 1M paired image-text samples, marking it as the largest vision-language histopathology dataset to date. We demonstrate the value of Quilt-1M by fine-tuning a pre-trained CLIP model. Our model outperforms state-of-the-art models on both zero-shot and linear probing tasks for classifying new histopathology images across 13 diverse patch-level datasets of 8 different sub-pathologies and cross-modal retrieval tasks.

Multi-class tissue-type classification of colorectal cancer (CRC) histopathologic images is a significant step in the development of downstream machine learning models for diagnosis and treatment planning. However, existing public CRC datasets often lack morphologic diversity, suffer from class imbalance, and contain low-quality image tiles, limiting model performance and generalizability. To address these issues, we introduce STARC-9 (STAnford coloRectal Cancer), a large-scale dataset for multi-class tissue classification. STARC-9 contains 630,000 hematoxylin and eosin-stained image tiles uniformly sampled across nine clinically relevant tissue classes (70,000 tiles per class) from 200 CRC patients at the Stanford University School of Medicine. The dataset was built using a novel framework, DeepCluster++, designed to ensure intra-class diversity and reduce manual curation. First, an encoder from a histopathology-specific autoencoder extracts feature vectors from tiles within each whole-slide image. Then, K-means clustering groups morphologically similar tiles, followed by equal-frequency binning to sample diverse morphologic patterns within each class. The selected tiles are subsequently verified by expert gastrointestinal pathologists to ensure accuracy. This semi-automated process significantly reduces manual effort while producing high-quality, diverse tiles. To evaluate STARC-9, we benchmarked convolutional neural networks, transformers, and pathology-specific foundation models on multi-class CRC tissue classification and segmentation tasks, showing superior generalizability compared to models trained on existing datasets. Although we demonstrate the utility of DeepCluster++ on CRC as a pilot use-case, it is a flexible framework that can be used for constructing high-quality datasets from large WSI repositories across a wide range of cancer and non-cancer applications.

Gene expression can be used to subtype breast cancer with improved prediction of risk of recurrence and treatment responsiveness over that obtained using routine immunohistochemistry (IHC). However, in the clinic, molecular profiling is primarily used for ER+ breast cancer, which is costly, tissue destructive, requires specialized platforms and takes several weeks to obtain a result. Deep learning algorithms can effectively extract morphological patterns in digital histopathology images to predict molecular phenotypes quickly and cost-effectively. We propose a new, computationally efficient approach called hist2RNA inspired by bulk RNA-sequencing techniques to predict the expression of 138 genes (incorporated from six commercially available molecular profiling tests), including luminal PAM50 subtype, from hematoxylin and eosin (H&E) stained whole slide images (WSIs). The training phase involves the aggregation of extracted features for each patient from a pretrained model to predict gene expression at the patient level using annotated H&E images from The Cancer Genome Atlas (TCGA, n=335). We demonstrate successful gene prediction on a held-out test set (n = 160, corr = 0.82 across patients, corr = 0.29 across genes) and perform exploratory analysis on an external tissue microarray (TMA) dataset (n = 498) with known IHC and survival information. Our model is able to predict gene expression and luminal PAM50 subtype (Luminal A versus Luminal B) on the TMA dataset with prognostic significance for overall survival in univariate analysis (c-index = 0.56, hazard ratio = 2.16 (95% CI 1.12-3.06), p < 5 x 10-3), and independent significance in multivariate analysis incorporating standard clinicopathological variables (c-index = 0.65, hazard ratio = 1.85 (95% CI 1.30-2.68), p < 5 x 10-3).

Task-specific deep learning models in histopathology offer promising opportunities for improving diagnosis, clinical research, and precision medicine. However, development of such models is often limited by availability of high-quality data. Foundation models in histopathology that learn general representations across a wide range of tissue types, diagnoses, and magnifications offer the potential to reduce the data, compute, and technical expertise necessary to develop task-specific deep learning models with the required level of model performance. In this work, we describe the development and evaluation of foundation models for histopathology via self-supervised learning (SSL). We first establish a diverse set of benchmark tasks involving 17 unique tissue types and 12 unique cancer types and spanning different optimal magnifications and task types. Next, we use this benchmark to explore and evaluate histopathology-specific SSL methods followed by further evaluation on held out patch-level and weakly supervised tasks. We found that standard SSL methods thoughtfully applied to histopathology images are performant across our benchmark tasks and that domain-specific methodological improvements can further increase performance. Our findings reinforce the value of using domain-specific SSL methods in pathology, and establish a set of high quality foundation models to enable further research across diverse applications.

Feature vectors provided by pre-trained deep artificial neural networks have become a dominant source for image representation in recent literature. Their contribution to the performance of image analysis can be improved through finetuning. As an ultimate solution, one might even train a deep network from scratch with the domain-relevant images, a highly desirable option which is generally impeded in pathology by lack of labeled images and the computational expense. In this study, we propose a new network, namely KimiaNet, that employs the topology of the DenseNet with four dense blocks, fine-tuned and trained with histopathology images in different configurations. We used more than 240,000 image patches with 1000x1000 pixels acquired at 20x magnification through our proposed "highcellularity mosaic" approach to enable the usage of weak labels of 7,126 whole slide images of formalin-fixed paraffin-embedded human pathology samples publicly available through the The Cancer Genome Atlas (TCGA) repository. We tested KimiaNet using three public datasets, namely TCGA, endometrial cancer images, and colorectal cancer images by evaluating the performance of search and classification when corresponding features of different networks are used for image representation. As well, we designed and trained multiple convolutional batch-normalized ReLU (CBR) networks. The results show that KimiaNet provides superior results compared to the original DenseNet and smaller CBR networks when used as feature extractor to represent histopathology images.

Predicting spatial gene expression from H&E histology offers a scalable and clinically accessible alternative to sequencing, but realizing clinical impact requires models that generalize across cancer types and capture biologically coherent signals. Prior work is often limited to per-cancer settings and variance-based evaluation, leaving functional relevance underexplored. We introduce HistoPrism, an efficient transformer-based architecture for pan-cancer prediction of gene expression from histology. To evaluate biological meaning, we introduce a pathway-level benchmark, shifting assessment from isolated gene-level variance to coherent functional pathways. HistoPrism not only surpasses prior state-of-the-art models on highly variable genes , but also more importantly, achieves substantial gains on pathway-level prediction, demonstrating its ability to recover biologically coherent transcriptomic patterns. With strong pan-cancer generalization and improved efficiency, HistoPrism establishes a new standard for clinically relevant transcriptomic modeling from routinely available histology.

Tissue phenotyping is a fundamental computational pathology (CPath) task in learning objective characterizations of histopathologic biomarkers in anatomic pathology. However, whole-slide imaging (WSI) poses a complex computer vision problem in which the large-scale image resolutions of WSIs and the enormous diversity of morphological phenotypes preclude large-scale data annotation. Current efforts have proposed using pretrained image encoders with either transfer learning from natural image datasets or self-supervised pretraining on publicly-available histopathology datasets, but have not been extensively developed and evaluated across diverse tissue types at scale. We introduce UNI, a general-purpose self-supervised model for pathology, pretrained using over 100 million tissue patches from over 100,000 diagnostic haematoxylin and eosin-stained WSIs across 20 major tissue types, and evaluated on 33 representative CPath clinical tasks in CPath of varying diagnostic difficulties. In addition to outperforming previous state-of-the-art models, we demonstrate new modeling capabilities in CPath such as resolution-agnostic tissue classification, slide classification using few-shot class prototypes, and disease subtyping generalization in classifying up to 108 cancer types in the OncoTree code classification system. UNI advances unsupervised representation learning at scale in CPath in terms of both pretraining data and downstream evaluation, enabling data-efficient AI models that can generalize and transfer to a gamut of diagnostically-challenging tasks and clinical workflows in anatomic pathology.

Vision foundation models (FMs) are accelerating the development of digital pathology algorithms and transforming biomedical research. These models learn, in a self-supervised manner, to represent histological features in highly heterogeneous tiles extracted from whole-slide images (WSIs) of real-world patient samples. The performance of these FMs is significantly influenced by the size, diversity, and balance of the pre-training data. However, data selection has been primarily guided by expert knowledge at the WSI level, focusing on factors such as disease classification and tissue types, while largely overlooking the granular details available at the tile level. In this paper, we investigate the potential of unsupervised automatic data curation at the tile-level, taking into account 350 million tiles. Specifically, we apply hierarchical clustering trees to pre-extracted tile embeddings, allowing us to sample balanced datasets uniformly across the embedding space of the pretrained FM. We further identify these datasets are subject to a trade-off between size and balance, potentially compromising the quality of representations learned by FMs, and propose tailored batch sampling strategies to mitigate this effect. We demonstrate the effectiveness of our method through improved performance on a diverse range of clinically relevant downstream tasks.

Histopathological cancer diagnostics has become more complex, and the increasing number of biopsies is a challenge for most pathology laboratories. Thus, development of automatic methods for evaluation of histopathological cancer sections would be of value. In this study, we used 624 whole slide images (WSIs) of breast cancer from a Norwegian cohort. We propose a cascaded convolutional neural network design, called H2G-Net, for semantic segmentation of gigapixel histopathological images. The design involves a detection stage using a patch-wise method, and a refinement stage using a convolutional autoencoder. To validate the design, we conducted an ablation study to assess the impact of selected components in the pipeline on tumour segmentation. Guiding segmentation, using hierarchical sampling and deep heatmap refinement, proved to be beneficial when segmenting the histopathological images. We found a significant improvement when using a refinement network for postprocessing the generated tumour segmentation heatmaps. The overall best design achieved a Dice score of 0.933 on an independent test set of 90 WSIs. The design outperformed single-resolution approaches, such as cluster-guided, patch-wise high-resolution classification using MobileNetV2 (0.872) and a low-resolution U-Net (0.874). In addition, segmentation on a representative x400 WSI took ~58 seconds, using only the CPU. The findings demonstrate the potential of utilizing a refinement network to improve patch-wise predictions. The solution is efficient and does not require overlapping patch inference or ensembling. Furthermore, we showed that deep neural networks can be trained using a random sampling scheme that balances on multiple different labels simultaneously, without the need of storing patches on disk. Future work should involve more efficient patch generation and sampling, as well as improved clustering.

Spatial transcriptomics (ST) provides spatially resolved measurements of gene expression, enabling characterization of the molecular landscape of human tissue beyond histological assessment as well as localized readouts that can be aligned with morphology. Concurrently, the success of multimodal foundation models that integrate vision with complementary modalities suggests that morphomolecular coupling between local expression and morphology can be systematically used to improve histological representations themselves. We introduce Spatial Expression-Aligned Learning (SEAL), a vision-omics self-supervised learning framework that infuses localized molecular information into pathology vision encoders. Rather than training new encoders from scratch, SEAL is designed as a parameter-efficient vision-omics finetuning method that can be flexibly applied to widely used pathology foundation models. We instantiate SEAL by training on over 700,000 paired gene expression spot-tissue region examples spanning tumor and normal samples from 14 organs. Tested across 38 slide-level and 15 patch-level downstream tasks, SEAL provides a drop-in replacement for pathology foundation models that consistently improves performance over widely used vision-only and ST prediction baselines on slide-level molecular status, pathway activity, and treatment response prediction, as well as patch-level gene expression prediction tasks. Additionally, SEAL encoders exhibit robust domain generalization on out-of-distribution evaluations and enable new cross-modal capabilities such as gene-to-image retrieval. Our work proposes a general framework for ST-guided finetuning of pathology foundation models, showing that augmenting existing models with localized molecular supervision is an effective and practical step for improving visual representations and expanding their cross-modal utility.

Foundation models trained with self-supervised learning (SSL) on large-scale histological images have significantly accelerated the development of computational pathology. These models can serve as backbones for region-of-interest (ROI) image analysis or patch-level feature extractors in whole-slide images (WSIs) based on multiple instance learning (MIL). Existing pathology foundation models (PFMs) are typically pre-trained on Hematoxylin-Eosin (H&E) stained pathology images. However, images with special stains, such as immunohistochemistry, are also frequently used in clinical practice. PFMs pre-trained mainly on H\&E-stained images may be limited in clinical applications involving special stains. To address this issue, we propose StainNet, a specialized foundation model for special stains based on the vision transformer (ViT) architecture. StainNet adopts a self-distillation SSL approach and is trained on over 1.4 million patch images cropping from 20,231 publicly available special staining WSIs in the HISTAI database. To evaluate StainNet, we conduct experiments on an in-house slide-level liver malignancy classification task and two public ROI-level datasets to demonstrate its strong ability. We also perform few-ratio learning and retrieval evaluations, and compare StainNet with recently larger PFMs to further highlight its strengths. We have released the StainNet model weights at: https://huggingface.co/JWonderLand/StainNet.

Recent advancements in digital pathology have led to the development of numerous foundational models that utilize self-supervised learning on patches extracted from gigapixel whole slide images (WSIs). While this approach leverages vast amounts of unlabeled data, we have discovered a significant issue: features extracted from these self-supervised models tend to cluster by individual WSIs, a phenomenon we term WSI-specific feature collapse. This problem can potentially limit the model's generalization ability and performance on various downstream tasks. To address this issue, we introduce Stain Normalized Pathology Foundational Model, a novel foundational model trained on patches that have undergone stain normalization. Stain normalization helps reduce color variability arising from different laboratories and scanners, enabling the model to learn more consistent features. Stain Normalized Pathology Foundational Model is trained using 285,153,903 patches extracted from a total of 34,795 WSIs, combining data from The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) project. Our experiments demonstrate that Stain Normalized Pathology Foundational Model significantly mitigates the feature collapse problem, indicating that the model has learned more generalized features rather than overfitting to individual WSI characteristics. We compared Stain Normalized Pathology Foundational Model with state-of-the-art models across six downstream task datasets, and our results show that Stain Normalized Pathology Foundational Model achieves excellent performance relative to the number of WSIs used and the model's parameter count. This suggests that the application of stain normalization has substantially improved the model's efficiency and generalization capabilities.

Rapid progress in computational pathology is increasingly driven by vision foundation models pretrained on vast histopathology datasets. While recent efforts have prioritized training on an ever-larger amount of patches, we take an alternative approach focused on data diversity. Our foundation model, Athena, was initialized from a pretrained model and trained on just 115 million tissue patches, several times fewer than recent histopathology foundation models. Rather than relying on patch volume or complex sampling heuristics, we maximize data diversity by randomly selecting only a moderate number of patches per whole-slide image from our diverse internal repository, which spans multiple countries, institutions, and scanner types. Evaluated on a single patch-level benchmark and four slide-level downstream tasks (two molecular and two morphological), Athena approaches the state-of-the-art and even surpasses several models trained on substantially larger datasets. This indicates that diversity across whole-slide images, rather than patch quantity alone, drives learning in histopathology foundation models.

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.

Recent advances in multi-modal algorithms have driven and been driven by the increasing availability of large image-text datasets, leading to significant strides in various fields, including computational pathology. However, in most existing medical image-text datasets, the text typically provides high-level summaries that may not sufficiently describe sub-tile regions within a large pathology image. For example, an image might cover an extensive tissue area containing cancerous and healthy regions, but the accompanying text might only specify that this image is a cancer slide, lacking the nuanced details needed for in-depth analysis. In this study, we introduce STimage-1K4M, a novel dataset designed to bridge this gap by providing genomic features for sub-tile images. STimage-1K4M contains 1,149 images derived from spatial transcriptomics data, which captures gene expression information at the level of individual spatial spots within a pathology image. Specifically, each image in the dataset is broken down into smaller sub-image tiles, with each tile paired with 15,000-30,000 dimensional gene expressions. With 4,293,195 pairs of sub-tile images and gene expressions, STimage-1K4M offers unprecedented granularity, paving the way for a wide range of advanced research in multi-modal data analysis an innovative applications in computational pathology, and beyond.

Quantifying cell morphology using images and machine learning has proven to be a powerful tool to study the response of cells to treatments. However, models used to quantify cellular morphology are typically trained with a single microscopy imaging type. This results in specialized models that cannot be reused across biological studies because the technical specifications do not match (e.g., different number of channels), or because the target experimental conditions are out of distribution. Here, we present CHAMMI-75, an open access dataset of heterogeneous, multi-channel microscopy images from 75 diverse biological studies. We curated this resource from publicly available sources to investigate cellular morphology models that are channel-adaptive and can process any microscopy image type. Our experiments show that training with CHAMMI-75 can improve performance in multi-channel bioimaging tasks primarily because of its high diversity in microscopy modalities. This work paves the way to create the next generation of cellular morphology models for biological studies.

Histopathological analysis is a cornerstone of cancer diagnosis, with Hematoxylin and Eosin (H&E) staining routinely acquired for every patient to visualize cell morphology and tissue architecture. On the other hand, multiplex immunofluorescence (mIF) enables more precise cell type identification via proteomic markers, but has yet to achieve widespread clinical adoption due to cost and logistical constraints. To bridge this gap, we introduce MIPHEI (Multiplex Immunofluorescence Prediction from H&E), a U-Net-inspired architecture that integrates state-of-the-art ViT foundation models as encoders to predict mIF signals from H&E images. MIPHEI targets a comprehensive panel of markers spanning nuclear content, immune lineages (T cells, B cells, myeloid), epithelium, stroma, vasculature, and proliferation. We train our model using the publicly available ORION dataset of restained H&E and mIF images from colorectal cancer tissue, and validate it on two independent datasets. MIPHEI achieves accurate cell-type classification from H&E alone, with F1 scores of 0.88 for Pan-CK, 0.57 for CD3e, 0.56 for SMA, 0.36 for CD68, and 0.30 for CD20, substantially outperforming both a state-of-the-art baseline and a random classifier for most markers. Our results indicate that our model effectively captures the complex relationships between nuclear morphologies in their tissue context, as visible in H&E images and molecular markers defining specific cell types. MIPHEI offers a promising step toward enabling cell-type-aware analysis of large-scale H&E datasets, in view of uncovering relationships between spatial cellular organization and patient outcomes.

Mitotic figures are classified into typical and atypical variants, with atypical counts correlating strongly with tumor aggressiveness. Accurate differentiation is therefore essential for patient prognostication and resource allocation, yet remains challenging even for expert pathologists. Here, we leveraged Pathology Foundation Models (PFMs) pre-trained on large histopathology datasets and applied parameter-efficient fine-tuning via low-rank adaptation. In addition, we incorporated ConvNeXt V2, a state-of-the-art convolutional neural network architecture, to complement PFMs. During training, we employed a fisheye transform to emphasize mitoses and Fourier Domain Adaptation using ImageNet target images. Finally, we ensembled multiple PFMs to integrate complementary morphological insights, achieving competitive balanced accuracy on the Preliminary Evaluation Phase dataset.

The in-vivo identification of the kidney stone types during an ureteroscopy would be a major medical advance in urology, as it could reduce the time of the tedious renal calculi extraction process, while diminishing infection risks. Furthermore, such an automated procedure would make possible to prescribe anti-recurrence treatments immediately. Nowadays, only few experienced urologists are able to recognize the kidney stone types in the images of the videos displayed on a screen during the endoscopy. Thus, several deep learning (DL) models have recently been proposed to automatically recognize the kidney stone types using ureteroscopic images. However, these DL models are of black box nature whicl limits their applicability in clinical settings. This contribution proposes a case-based reasoning DL model which uses prototypical parts (PPs) and generates local and global descriptors. The PPs encode for each class (i.e., kidney stone type) visual feature information (hue, saturation, intensity and textures) similar to that used by biologists. The PPs are optimally generated due a new loss function used during the model training. Moreover, the local and global descriptors of PPs allow to explain the decisions ("what" information, "where in the images") in an understandable way for biologists and urologists. The proposed DL model has been tested on a database including images of the six most widespread kidney stone types. The overall average classification accuracy was 90.37. When comparing this results with that of the eight other DL models of the kidney stone state-of-the-art, it can be seen that the valuable gain in explanability was not reached at the expense of accuracy which was even slightly increased with respect to that (88.2) of the best method of the literature. These promising and interpretable results also encourage urologists to put their trust in AI-based solutions.

This paper addresses complex challenges in histopathological image analysis through three key contributions. Firstly, it introduces a fast patch selection method, FPS, for whole-slide image (WSI) analysis, significantly reducing computational cost while maintaining accuracy. Secondly, it presents PathDino, a lightweight histopathology feature extractor with a minimal configuration of five Transformer blocks and only 9 million parameters, markedly fewer than alternatives. Thirdly, it introduces a rotation-agnostic representation learning paradigm using self-supervised learning, effectively mitigating overfitting. We also show that our compact model outperforms existing state-of-the-art histopathology-specific vision transformers on 12 diverse datasets, including both internal datasets spanning four sites (breast, liver, skin, and colorectal) and seven public datasets (PANDA, CAMELYON16, BRACS, DigestPath, Kather, PanNuke, and WSSS4LUAD). Notably, even with a training dataset of 6 million histopathology patches from The Cancer Genome Atlas (TCGA), our approach demonstrates an average 8.5% improvement in patch-level majority vote performance. These contributions provide a robust framework for enhancing image analysis in digital pathology, rigorously validated through extensive evaluation. Project Page: https://rhazeslab.github.io/PathDino-Page/

The field of computational pathology has been transformed with recent advances in foundation models that encode histopathology region-of-interests (ROIs) into versatile and transferable feature representations via self-supervised learning (SSL). However, translating these advancements to address complex clinical challenges at the patient and slide level remains constrained by limited clinical data in disease-specific cohorts, especially for rare clinical conditions. We propose TITAN, a multimodal whole slide foundation model pretrained using 335,645 WSIs via visual self-supervised learning and vision-language alignment with corresponding pathology reports and 423,122 synthetic captions generated from a multimodal generative AI copilot for pathology. Without any finetuning or requiring clinical labels, TITAN can extract general-purpose slide representations and generate pathology reports that generalize to resource-limited clinical scenarios such as rare disease retrieval and cancer prognosis. We evaluate TITAN on diverse clinical tasks and find that TITAN outperforms both ROI and slide foundation models across machine learning settings such as linear probing, few-shot and zero-shot classification, rare cancer retrieval and cross-modal retrieval, and pathology report generation.

Large-scale cell microscopy screens are used in drug discovery and molecular biology research to study the effects of millions of chemical and genetic perturbations on cells. To use these images in downstream analysis, we need models that can map each image into a feature space that represents diverse biological phenotypes consistently, in the sense that perturbations with similar biological effects have similar representations. In this work, we present the largest foundation model for cell microscopy data to date, a new 1.9 billion-parameter ViT-G/8 MAE trained on over 8 billion microscopy image crops. Compared to a previous published ViT-L/8 MAE, our new model achieves a 60% improvement in linear separability of genetic perturbations and obtains the best overall performance on whole-genome biological relationship recall and replicate consistency benchmarks. Beyond scaling, we developed two key methods that improve performance: (1) training on a curated and diverse dataset; and, (2) using biologically motivated linear probing tasks to search across each transformer block for the best candidate representation of whole-genome screens. We find that many self-supervised vision transformers, pretrained on either natural or microscopy images, yield significantly more biologically meaningful representations of microscopy images in their intermediate blocks than in their typically used final blocks. More broadly, our approach and results provide insights toward a general strategy for successfully building foundation models for large-scale biological data.

Histopathology image analysis is fundamental to digital pathology, with hematoxylin and eosin (H&E) staining as the gold standard for diagnostic and prognostic assessments. While H&E imaging effectively highlights cellular and tissue structures, it lacks sensitivity to birefringence and tissue anisotropy, which are crucial for assessing collagen organization, fiber alignment, and microstructural alterations--key indicators of tumor progression, fibrosis, and other pathological conditions. To bridge this gap, we construct a polarization imaging system and curate a new dataset of over 13,000 paired Polar-H&E images. Visualizations of polarization properties reveal distinctive optical signatures in pathological tissues, underscoring its diagnostic value. Building on this dataset, we propose PolarHE, a dual-modality fusion framework that integrates H&E with polarization imaging, leveraging the latter ability to enhance tissue characterization. Our approach employs a feature decomposition strategy to disentangle common and modality specific features, ensuring effective multimodal representation learning. Through comprehensive validation, our approach significantly outperforms previous methods, achieving an accuracy of 86.70% on the Chaoyang dataset and 89.06% on the MHIST dataset. These results demonstrate that polarization imaging is a powerful and underutilized modality in computational pathology, enriching feature representation and improving diagnostic accuracy. PolarHE establishes a promising direction for multimodal learning, paving the way for more interpretable and generalizable pathology models.

Accurate anatomical labeling and analysis of the pulmonary structure and its surrounding anatomy from thoracic CT is getting increasingly important for understanding the etilogy of abnormalities or supporting targetted therapy and early interventions. Whilst lung and airway cell atlases have been attempted, there is a lack of fine-grained morphological atlases that are clinically deployable. In this work, we introduce AirMorph, a robust, end-to-end deep learning pipeline enabling fully automatic and comprehensive airway anatomical labeling at lobar, segmental, and subsegmental resolutions that can be used to create digital atlases of the lung. Evaluated across large-scale multi-center datasets comprising diverse pulmonary conditions, the AirMorph consistently outperformed existing segmentation and labeling methods in terms of accuracy, topological consistency, and completeness. To simplify clinical interpretation, we further introduce a compact anatomical signature quantifying critical morphological airway features, including stenosis, ectasia, tortuosity, divergence, length, and complexity. When applied to various pulmonary diseases such as pulmonary fibrosis, emphysema, atelectasis, consolidation, and reticular opacities, it demonstrates strong discriminative power, revealing disease-specific morphological patterns with high interpretability and explainability. Additionally, AirMorph supports efficient automated branching pattern analysis, potentially enhancing bronchoscopic navigation planning and procedural safety, offering a valuable clinical tool for improved diagnosis, targeted treatment, and personalized patient care.

Microscopic assessment of histopathology images is vital for accurate cancer diagnosis and treatment. Whole Slide Image (WSI) classification and captioning have become crucial tasks in computer-aided pathology. However, microscopic WSI face challenges such as redundant patches and unknown patch positions due to subjective pathologist captures. Moreover, generating automatic pathology captions remains a significant challenge. To address these issues, we introduce a novel GNN-ViTCap framework for classification and caption generation from histopathological microscopic images. First, a visual feature extractor generates patch embeddings. Redundant patches are then removed by dynamically clustering these embeddings using deep embedded clustering and selecting representative patches via a scalar dot attention mechanism. We build a graph by connecting each node to its nearest neighbors in the similarity matrix and apply a graph neural network to capture both local and global context. The aggregated image embeddings are projected into the language model's input space through a linear layer and combined with caption tokens to fine-tune a large language model. We validate our method on the BreakHis and PatchGastric datasets. GNN-ViTCap achieves an F1 score of 0.934 and an AUC of 0.963 for classification, along with a BLEU-4 score of 0.811 and a METEOR score of 0.569 for captioning. Experimental results demonstrate that GNN-ViTCap outperforms state of the art approaches, offering a reliable and efficient solution for microscopy based patient diagnosis.

The rapid identification and accurate diagnosis of breast cancer, known as the killer of women, have become greatly significant for those patients. Numerous breast cancer histopathological image classification methods have been proposed. But they still suffer from two problems. (1) These methods can only hand high-resolution (HR) images. However, the low-resolution (LR) images are often collected by the digital slide scanner with limited hardware conditions. Compared with HR images, LR images often lose some key features like texture, which deeply affects the accuracy of diagnosis. (2) The existing methods have fixed receptive fields, so they can not extract and fuse multi-scale features well for images with different magnification factors. To fill these gaps, we present a Single Histopathological Image Super-Resolution Classification network (SHISRCNet), which consists of two modules: Super-Resolution (SR) and Classification (CF) modules. SR module reconstructs LR images into SR ones. CF module extracts and fuses the multi-scale features of SR images for classification. In the training stage, we introduce HR images into the CF module to enhance SHISRCNet's performance. Finally, through the joint training of these two modules, super-resolution and classified of LR images are integrated into our model. The experimental results demonstrate that the effects of our method are close to the SOTA methods with taking HR images as inputs.

Whole Slide Images (WSIs) exhibit hierarchical structure, where diagnostic information emerges from cellular morphology, regional tissue organization, and global context. Existing Computational Pathology (CPath) Multimodal Large Language Models (MLLMs) typically compress an entire WSI into a single embedding, which hinders fine-grained grounding and ignores how pathologists synthesize evidence across different scales. We introduce MLLM-HWSI, a Hierarchical WSI-level MLLM that aligns visual features with pathology language at four distinct scales, cell as word, patch as phrase, region as sentence, and WSI as paragraph to support interpretable evidence-grounded reasoning. MLLM-HWSI decomposes each WSI into multi-scale embeddings with scale-specific projectors and jointly enforces (i) a hierarchical contrastive objective and (ii) a cross-scale consistency loss, preserving semantic coherence from cells to the WSI. We compute diagnostically relevant patches and aggregate segmented cell embeddings into a compact cellular token per-patch using a lightweight Cell-Cell Attention Fusion (CCAF) transformer. The projected multi-scale tokens are fused with text tokens and fed to an instruction-tuned LLM for open-ended reasoning, VQA, report, and caption generation tasks. Trained in three stages, MLLM-HWSI achieves new SOTA results on 13 WSI-level benchmarks across six CPath tasks. By aligning language with multi-scale visual evidence, MLLM-HWSI provides accurate, interpretable outputs that mirror diagnostic workflows and advance holistic WSI understanding. Code is available at: https://github.com/BasitAlawode/HWSI-MLLM{GitHub}.

We introduce ProtoPathway, an interpretable-by-design multimodal framework for cancer survival prediction that unifies whole slide imaging and transcriptomics through encoders producing biologically grounded representations on both sides of the fusion. On the histopathology side, K learnable morphological prototypes, trained end-to-end with the survival objective, serve as the slide representation itself: patches flow into prototype tokens via soft assignment, compressing variable-length patch sets into fixed task-adaptive tokens. On the genomic side, a bipartite graph neural network encodes gene expression within the Reactome pathway hierarchy, producing pathway embeddings that reflect both constituent genes and their broader biological context through bidirectional message passing over a shared gene--pathway graph. Cross-modal attention then operates over a compact prototype times pathway matrix in which prototypes query pathways, modeling the biological direction in which molecular programs give rise to tissue morphology. Because both axes carry stable task-learned identity, the attention matrix is itself an interpretability output, yielding native inference-time attribution across the full biological hierarchy, from genes through pathways and prototypes to spatial tissue maps. We evaluate on five TCGA cancer cohorts, demonstrating competitive or superior survival prediction with substantially improved biological interpretability and reduced computational cost, with interpretability claims validated through fold-stratified rank-based population-level analysis. Our source code, model weights, and Reactome pathways, together with a unified codebase reimplementing all multimodal survival baselines under identical preprocessing and evaluation, are available at: https://github.com/AmayaGS/ProtoPathway.

Developing self-supervised learning (SSL) models that can learn universal and transferable representations of H&E gigapixel whole-slide images (WSIs) is becoming increasingly valuable in computational pathology. These models hold the potential to advance critical tasks such as few-shot classification, slide retrieval, and patient stratification. Existing approaches for slide representation learning extend the principles of SSL from small images (e.g., 224 x 224 patches) to entire slides, usually by aligning two different augmentations (or views) of the slide. Yet the resulting representation remains constrained by the limited clinical and biological diversity of the views. Instead, we postulate that slides stained with multiple markers, such as immunohistochemistry, can be used as different views to form a rich task-agnostic training signal. To this end, we introduce Madeleine, a multimodal pretraining strategy for slide representation learning. Madeleine is trained with a dual global-local cross-stain alignment objective on large cohorts of breast cancer samples (N=4,211 WSIs across five stains) and kidney transplant samples (N=12,070 WSIs across four stains). We demonstrate the quality of slide representations learned by Madeleine on various downstream evaluations, ranging from morphological and molecular classification to prognostic prediction, comprising 21 tasks using 7,299 WSIs from multiple medical centers. Code is available at https://github.com/mahmoodlab/MADELEINE.

Computational pathology, which involves analyzing whole slide images for automated cancer diagnosis, relies on multiple instance learning, where performance depends heavily on the feature extractor and aggregator. Recent Pathology Foundation Models (PFMs), pretrained on large-scale histopathology data, have significantly enhanced both the extractor and aggregator, but they lack a systematic analysis framework. In this survey, we present a hierarchical taxonomy organizing PFMs through a top-down philosophy applicable to foundation model analysis in any domain: model scope, model pretraining, and model design. Additionally, we systematically categorize PFM evaluation tasks into slide-level, patch-level, multimodal, and biological tasks, providing comprehensive benchmarking criteria. Our analysis identifies critical challenges in both PFM development (pathology-specific methodology, end-to-end pretraining, data-model scalability) and utilization (effective adaptation, model maintenance), paving the way for future directions in this promising field. Resources referenced in this survey are available at https://github.com/BearCleverProud/AwesomeWSI.

Whole slide image (WSI) analysis in digital pathology presents unique challenges due to the gigapixel resolution of WSIs and the scarcity of dense supervision signals. While Multiple Instance Learning (MIL) is a natural fit for slide-level tasks, training robust models requires large and diverse datasets. Even though image augmentation techniques could be utilized to increase data variability and reduce overfitting, implementing them effectively is not a trivial task. Traditional patch-level augmentation is prohibitively expensive due to the large number of patches extracted from each WSI, and existing feature-level augmentation methods lack control over transformation semantics. We introduce HistAug, a fast and efficient generative model for controllable augmentations in the latent space for digital pathology. By conditioning on explicit patch-level transformations (e.g., hue, erosion), HistAug generates realistic augmented embeddings while preserving initial semantic information. Our method allows the processing of a large number of patches in a single forward pass efficiently, while at the same time consistently improving MIL model performance. Experiments across multiple slide-level tasks and diverse organs show that HistAug outperforms existing methods, particularly in low-data regimes. Ablation studies confirm the benefits of learned transformations over noise-based perturbations and highlight the importance of uniform WSI-wise augmentation. Code is available at https://github.com/MICS-Lab/HistAug.

Earlier diagnosis of Leukemia can save thousands of lives annually. The prognosis of leukemia is challenging without the morphological information of White Blood Cells (WBC) and relies on the accessibility of expensive microscopes and the availability of hematologists to analyze Peripheral Blood Samples (PBS). Deep Learning based methods can be employed to assist hematologists. However, these algorithms require a large amount of labeled data, which is not readily available. To overcome this limitation, we have acquired a realistic, generalized, and large dataset. To collect this comprehensive dataset for real-world applications, two microscopes from two different cost spectrums (high-cost HCM and low-cost LCM) are used for dataset capturing at three magnifications (100x, 40x, 10x) through different sensors (high-end camera for HCM, middle-level camera for LCM and mobile-phone camera for both). The high-sensor camera is 47 times more expensive than the middle-level camera and HCM is 17 times more expensive than LCM. In this collection, using HCM at high resolution (100x), experienced hematologists annotated 10.3k WBC types (14) and artifacts, having 55k morphological labels (Cell Size, Nuclear Chromatin, Nuclear Shape, etc.) from 2.4k images of several PBS leukemia patients. Later on, these annotations are transferred to other 2 magnifications of HCM, and 3 magnifications of LCM, and on each camera captured images. Along with the LeukemiaAttri dataset, we provide baselines over multiple object detectors and Unsupervised Domain Adaptation (UDA) strategies, along with morphological information-based attribute prediction. The dataset will be publicly available after publication to facilitate the research in this direction.

Deep convolutional neural networks (CNNs) are the current state-of-the-art for digital analysis of histopathological images. The large size of whole-slide microscopy images (WSIs) requires advanced memory handling to read, display and process these images. There are several open-source platforms for working with WSIs, but few support deployment of CNN models. These applications use third-party solutions for inference, making them less user-friendly and unsuitable for high-performance image analysis. To make deployment of CNNs user-friendly and feasible on low-end machines, we have developed a new platform, FastPathology, using the FAST framework and C++. It minimizes memory usage for reading and processing WSIs, deployment of CNN models, and real-time interactive visualization of results. Runtime experiments were conducted on four different use cases, using different architectures, inference engines, hardware configurations and operating systems. Memory usage for reading, visualizing, zooming and panning a WSI were measured, using FastPathology and three existing platforms. FastPathology performed similarly in terms of memory to the other C++ based application, while using considerably less than the two Java-based platforms. The choice of neural network model, inference engine, hardware and processors influenced runtime considerably. Thus, FastPathology includes all steps needed for efficient visualization and processing of WSIs in a single application, including inference of CNNs with real-time display of the results. Source code, binary releases and test data can be found online on GitHub at https://github.com/SINTEFMedtek/FAST-Pathology/.

Pathology is the study of microscopic inspection of tissue, and a pathology diagnosis is often the medical gold standard to diagnose disease. Pathology images provide a unique challenge for computer-vision-based analysis: a single pathology Whole Slide Image (WSI) is gigapixel-sized and often contains hundreds of thousands to millions of objects of interest across multiple resolutions. In this work, we propose PathoLogy Universal TransfOrmer (PLUTO): a light-weight pathology FM that is pre-trained on a diverse dataset of 195 million image tiles collected from multiple sites and extracts meaningful representations across multiple WSI scales that enable a large variety of downstream pathology tasks. In particular, we design task-specific adaptation heads that utilize PLUTO's output embeddings for tasks which span pathology scales ranging from subcellular to slide-scale, including instance segmentation, tile classification, and slide-level prediction. We compare PLUTO's performance to other state-of-the-art methods on a diverse set of external and internal benchmarks covering multiple biologically relevant tasks, tissue types, resolutions, stains, and scanners. We find that PLUTO matches or outperforms existing task-specific baselines and pathology-specific foundation models, some of which use orders-of-magnitude larger datasets and model sizes when compared to PLUTO. Our findings present a path towards a universal embedding to power pathology image analysis, and motivate further exploration around pathology foundation models in terms of data diversity, architectural improvements, sample efficiency, and practical deployability in real-world applications.

Computed tomography perfusion (CTP) at admission is routinely used to estimate the ischemic core and penumbra, while follow-up diffusion-weighted MRI (DWI) provides the definitive infarct outcome. However, single time-point segmentations fail to capture the biological heterogeneity and temporal evolution of stroke. We propose a bi-temporal analysis framework that characterizes ischemic tissue using statistical descriptors, radiomic texture features, and deep feature embeddings from two architectures (mJ-Net and nnU-Net). Bi-temporal refers to admission (T1) and post-treatment follow-up (T2). All features are extracted at T1 from CTP, with follow-up DWI aligned to ensure spatial correspondence. Manually delineated masks at T1 and T2 are intersected to construct six regions of interest (ROIs) encoding both initial tissue state and final outcome. Features were aggregated per region and analyzed in feature space. Evaluation on 18 patients with successful reperfusion demonstrated meaningful clustering of region-level representations. Regions classified as penumbra or healthy at T1 that ultimately recovered exhibited feature similarity to preserved brain tissue, whereas infarct-bound regions formed distinct groupings. Both baseline GLCM and deep embeddings showed a similar trend: penumbra regions exhibit features that are significantly different depending on final state, whereas this difference is not significant for core regions. Deep feature spaces, particularly mJ-Net, showed strong separation between salvageable and non-salvageable tissue, with a penumbra separation index that differed significantly from zero (Wilcoxon signed-rank test). These findings suggest that encoder-derived feature manifolds reflect underlying tissue phenotypes and state transitions, providing insight into imaging-based quantification of stroke evolution.

Nuclear segmentation, classification and quantification within Haematoxylin & Eosin stained histology images enables the extraction of interpretable cell-based features that can be used in downstream explainable models in computational pathology (CPath). However, automatic recognition of different nuclei is faced with a major challenge in that there are several different types of nuclei, some of them exhibiting large intraclass variability. In this work, we propose an approach that combine Separable-HoverNet and Instance-YOLOv5 to indentify colon nuclei small and unbalanced. Our approach can achieve mPQ+ 0.389 on the Segmentation and Classification-Preliminary Test Dataset and r2 0.599 on the Cellular Composition-Preliminary Test Dataset on ISBI 2022 CoNIC Challenge.

Computational pathology relies on effective representation learning to support cancer research and precision medicine. Although self-supervised learning has driven major progress at the patch and whole-slide image levels, representation learning at the single-cell level remains comparatively underexplored, despite its importance for characterizing cell types and cellular phenotypes. We introduce LEMON (Learning Embeddings from Morphology Of Nuclei), a self-supervised foundation model for scalable single-cell image representation learning. Trained on millions of cell images from diverse tissues and cancer types, LEMON learns robust and versatile morphological representations that support large-scale single-cell analyses in pathology. We evaluate LEMON on five benchmark datasets across a range of prediction tasks and show that it provides strong performance, highlighting its potential as a new paradigm for cell-level computational pathology. Model weights are available at https://huggingface.co/aliceblondel/LEMON.

While pathology foundation models have transformed cancer image analysis, they often lack integration with molecular data at single-cell resolution, limiting their utility for precision oncology. Here, we present PAST, a pan-cancer single-cell foundation model trained on 20 million paired histopathology images and single-cell transcriptomes spanning multiple tumor types and tissue contexts. By jointly encoding cellular morphology and gene expression, PAST learns unified cross-modal representations that capture both spatial and molecular heterogeneity at the cellular level. This approach enables accurate prediction of single-cell gene expression, virtual molecular staining, and multimodal survival analysis directly from routine pathology slides. Across diverse cancers and downstream tasks, PAST consistently exceeds the performance of existing approaches, demonstrating robust generalizability and scalability. Our work establishes a new paradigm for pathology foundation models, providing a versatile tool for high-resolution spatial omics, mechanistic discovery, and precision cancer research.

Remarkable strides in computational pathology have been made in the task-agnostic foundation model that advances the performance of a wide array of downstream clinical tasks. Despite the promising performance, there are still several challenges. First, prior works have resorted to either vision-only or image-caption data, disregarding pathology reports with more clinically authentic information from pathologists and gene expression profiles which respectively offer distinct knowledge for versatile clinical applications. Second, the current progress in pathology FMs predominantly concentrates on the patch level, where the restricted context of patch-level pretraining fails to capture whole-slide patterns. Even recent slide-level FMs still struggle to provide whole-slide context for patch representation. In this study, for the first time, we develop a pathology foundation model incorporating three levels of modalities: pathology slides, pathology reports, and gene expression data, which resulted in 26,169 slide-level modality pairs from 10,275 patients across 32 cancer types, amounting to over 116 million pathological patch images. To leverage these data for CPath, we propose a novel whole-slide pretraining paradigm that injects the multimodal whole-slide context into the patch representation, called Multimodal Self-TAught PRetraining (mSTAR). The proposed paradigm revolutionizes the pretraining workflow for CPath, enabling the pathology FM to acquire the whole-slide context. To the best of our knowledge, this is the first attempt to incorporate three modalities at the whole-slide context for enhancing pathology FMs. To systematically evaluate the capabilities of mSTAR, we built the largest spectrum of oncological benchmark, spanning 7 categories of oncological applications in 15 types of 97 practical oncological tasks.

Representation learning of pathology whole-slide images (WSIs) has primarily relied on weak supervision with Multiple Instance Learning (MIL). This approach leads to slide representations highly tailored to a specific clinical task. Self-supervised learning (SSL) has been successfully applied to train histopathology foundation models (FMs) for patch embedding generation. However, generating patient or slide level embeddings remains challenging. Existing approaches for slide representation learning extend the principles of SSL from patch level learning to entire slides by aligning different augmentations of the slide or by utilizing multimodal data. By integrating tile embeddings from multiple FMs, we propose a new single modality SSL method in feature space that generates useful slide representations. Our contrastive pretraining strategy, called COBRA, employs multiple FMs and an architecture based on Mamba-2. COBRA exceeds performance of state-of-the-art slide encoders on four different public CPTAC cohorts on average by at least +3.8% AUC, despite only being pretrained on 3048 WSIs from TCGA. Additionally, COBRA is readily compatible at inference time with previously unseen feature extractors.

Multiplex immunofluorescence and immunohistochemistry benefit patients by allowing cancer pathologists to identify several proteins expressed on the surface of cells, enabling cell classification, better understanding of the tumour micro-environment, more accurate diagnoses, prognoses, and tailored immunotherapy based on the immune status of individual patients. However, they are expensive and time consuming processes which require complex staining and imaging techniques by expert technicians. Hoechst staining is much cheaper and easier to perform, but is not typically used in this case as it binds to DNA rather than to the proteins targeted by immunofluorescent techniques, and it was not previously thought possible to differentiate cells expressing these proteins based only on DNA morphology. In this work we show otherwise, training a deep convolutional neural network to identify cells expressing three proteins (T lymphocyte markers CD3 and CD8, and the B lymphocyte marker CD20) with greater than 90% precision and recall, from Hoechst 33342 stained tissue only. Our model learns previously unknown morphological features associated with expression of these proteins which can be used to accurately differentiate lymphocyte subtypes for use in key prognostic metrics such as assessment of immune cell infiltration,and thereby predict and improve patient outcomes without the need for costly multiplex immunofluorescence.

We conducted more than 1.3 million comparisons of iris patterns encoded from images collected at two Nigerian universities, which constitute the newly available African Human Iris (AFHIRIS) database. The purpose was to discover whether ethnic differences in iris structure and appearance such as the textural feature size, as contrasted with an all-Chinese image database or an American database in which only 1.53% were of African-American heritage, made a material difference for iris discrimination. We measured a reduction in entropy for the AFHIRIS database due to the coarser iris features created by the thick anterior layer of melanocytes, and we found stochastic parameters that accurately model the relevant empirical distributions. Quantile-Quantile analysis revealed that a very small change in operational decision thresholds for the African database would compensate for the reduced entropy and generate the same performance in terms of resistance to False Matches. We conclude that despite demographic difference, individuality can be robustly discerned by comparison of iris patterns in this West African population.

Accurate prediction of biochemical recurrence (BCR) after radical prostatectomy is critical for guiding adjuvant treatment and surveillance decisions in prostate cancer. However, existing clinicopathological risk models reduce complex morphology to relatively coarse descriptors, leaving substantial prognostic information embedded in routine histopathology underexplored. We present a deep learning-based biomarker that predicts continuous, patient-specific risk of BCR directly from H&E-stained whole-slide prostatectomy specimens. Trained end-to-end on time-to-event outcomes and evaluated across four independent international cohorts, our model demonstrates robust generalization across institutions and patient populations. When integrated with the CAPRA-S clinical risk score, the deep learning risk score consistently improved discrimination for BCR, increasing concordance indices from 0.725-0.772 to 0.749-0.788 across cohorts. To support clinical interpretability, outcome-grounded analyses revealed subtle histomorphological patterns associated with recurrence risk that are not captured by conventional clinicopathological risk scores. This multicohort study demonstrates that deep learning applied to routine prostate histopathology can deliver reproducible and clinically generalizable biomarkers that augment postoperative risk stratification, with potential to support personalized management of prostate cancer in real-world clinical settings.

Immunohistochemistry (IHC) provides information on protein expression in tissue sections and is commonly used to support pathology diagnosis and disease triage. While AI models for H\&E-stained slides show promise, their applicability to IHC is limited due to domain-specific variations. Here we introduce HPA10M, a dataset that contains 10,495,672 IHC images from the Human Protein Atlas with comprehensive metadata included, and encompasses 45 normal tissue types and 20 major cancer types. Based on HPA10M, we trained iSight, a multi-task learning framework for automated IHC staining assessment. iSight combines visual features from whole-slide images with tissue metadata through a token-level attention mechanism, simultaneously predicting staining intensity, location, quantity, tissue type, and malignancy status. On held-out data, iSight achieved 85.5\% accuracy for location, 76.6\% for intensity, and 75.7\% for quantity, outperforming fine-tuned foundation models (PLIP, CONCH) by 2.5--10.2\%. In addition, iSight demonstrates well-calibrated predictions with expected calibration errors of 0.0150-0.0408. Furthermore, in a user study with eight pathologists evaluating 200 images from two datasets, iSight outperformed initial pathologist assessments on the held-out HPA dataset (79\% vs 68\% for location, 70\% vs 57\% for intensity, 68\% vs 52\% for quantity). Inter-pathologist agreement also improved after AI assistance in both held-out HPA (Cohen's κ increased from 0.63 to 0.70) and Stanford TMAD datasets (from 0.74 to 0.76), suggesting expert--AI co-assessment can improve IHC interpretation. This work establishes a foundation for AI systems that can improve IHC diagnostic accuracy and highlights the potential for integrating iSight into clinical workflows to enhance the consistency and reliability of IHC assessment.

Foundation models are reshaping computational pathology by enabling transfer learning, where models pre-trained on vast datasets can be adapted for downstream diagnostic, prognostic, and therapeutic response tasks. Despite these advances, foundation models are still limited in their ability to encode the entire gigapixel whole-slide images without additional training and often lack complementary multimodal data. Here, we introduce Threads, a slide-level foundation model capable of generating universal representations of whole-slide images of any size. Threads was pre-trained using a multimodal learning approach on a diverse cohort of 47,171 hematoxylin and eosin (H&E)-stained tissue sections, paired with corresponding genomic and transcriptomic profiles - the largest such paired dataset to be used for foundation model development to date. This unique training paradigm enables Threads to capture the tissue's underlying molecular composition, yielding powerful representations applicable to a wide array of downstream tasks. In extensive benchmarking across 54 oncology tasks, including clinical subtyping, grading, mutation prediction, immunohistochemistry status determination, treatment response prediction, and survival prediction, Threads outperformed all baselines while demonstrating remarkable generalizability and label efficiency. It is particularly well suited for predicting rare events, further emphasizing its clinical utility. We intend to make the model publicly available for the broader community.

This work contributes to breast cancer sub-type classification using histopathological images. We utilize masked autoencoders (MAEs) to learn a self-supervised embedding tailored for computer vision tasks in this domain. This embedding captures informative representations of histopathological data, facilitating feature learning without extensive labeled datasets. During pre-training, we investigate employing a random crop technique to generate a large dataset from WSIs automatically. Additionally, we assess the performance of linear probes for multi-class classification tasks of cancer sub-types using the representations learnt by the MAE. Our approach aims to achieve strong performance on downstream tasks by leveraging the complementary strengths of ViTs and autoencoders. We evaluate our model's performance on the BRACS dataset and compare it with existing benchmarks.

Mitotic figure (MF) detection in histopathology images is challenging due to large variations in slide scanners, staining protocols, tissue types, and the presence of artifacts. This paper presents a collection of training techniques - a bag of tricks - that enable robust, real-time MF detection across diverse domains. We build on the efficient RTMDet single stage object detector to achieve high inference speed suitable for clinical deployment. Our method addresses scanner variability and tumor heterogeneity via extensive multi-domain training data, balanced sampling, and careful augmentation. Additionally, we employ targeted, hard negative mining on necrotic and debris tissue to reduce false positives. In a grouped 5-fold cross-validation across multiple MF datasets, our model achieves an F1 score between 0.78 and 0.84. On the preliminary test set of the MItosis DOmain Generalization (MIDOG) 2025 challenge, our single-stage RTMDet-S based approach reaches an F1 of 0.81, outperforming larger models and demonstrating adaptability to new, unfamiliar domains. The proposed solution offers a practical trade-off between accuracy and speed, making it attractive for real-world clinical adoption.

Tissue segmentation is a routine preprocessing step to reduce the computational cost of whole slide image (WSI) analysis by excluding background regions. Traditional image processing techniques are commonly used for tissue segmentation, but often require manual adjustments to parameter values for atypical cases, fail to exclude all slide and scanning artifacts from the background, and are unable to segment adipose tissue. Pen marking artifacts in particular can be a potential source of bias for subsequent analyses if not removed. In addition, several applications require the separation of individual cross-sections, which can be challenging due to tissue fragmentation and adjacent positioning. To address these problems, we develop a convolutional neural network for tissue and pen marking segmentation using a dataset of 200 H&E stained WSIs. For separating tissue cross-sections, we propose a novel post-processing method based on clustering predicted centroid locations of the cross-sections in a 2D histogram. On an independent test set, the model achieved a mean Dice score of 0.981pm0.033 for tissue segmentation and a mean Dice score of 0.912pm0.090 for pen marking segmentation. The mean absolute difference between the number of annotated and separated cross-sections was 0.075pm0.350. Our results demonstrate that the proposed model can accurately segment H&E stained tissue cross-sections and pen markings in WSIs while being robust to many common slide and scanning artifacts. The model with trained model parameters and post-processing method are made publicly available as a Python package called SlideSegmenter.

Metadata are general characteristics of the data in a well-curated and condensed format, and have been proven to be useful for decision making, knowledge discovery, and also heterogeneous data organization of biobank. Among all data types in the biobank, pathology is the key component of the biobank and also serves as the gold standard of diagnosis. To maximize the utility of biobank and allow the rapid progress of biomedical science, it is essential to organize the data with well-populated pathology metadata. However, manual annotation of such information is tedious and time-consuming. In the study, we develop a multimodal multitask learning framework to predict four major slide-level metadata of pathology images. The framework learns generalizable representations across tissue slides, pathology reports, and case-level structured data. We demonstrate improved performance across all four tasks with the proposed method compared to a single modal single task baseline on two test sets, one external test set from a distinct data source (TCGA) and one internal held-out test set (TTH). In the test sets, the performance improvements on the averaged area under receiver operating characteristic curve across the four tasks are 16.48% and 9.05% on TCGA and TTH, respectively. Such pathology metadata prediction system may be adopted to mitigate the effort of expert annotation and ultimately accelerate the data-driven research by better utilization of the pathology biobank.

Masked image modelling (MIM) is a powerful self-supervised representation learning paradigm, whose potential has not been widely demonstrated in medical image analysis. In this work, we show the capacity of MIM to capture rich semantic representations of Haemotoxylin & Eosin (H&E)-stained images at the nuclear level. Inspired by Bidirectional Encoder representation from Image Transformers (BEiT), we split the images into smaller patches and generate corresponding discrete visual tokens. In addition to the regular grid-based patches, typically used in visual Transformers, we introduce patches of individual cell nuclei. We propose positional encoding of the irregular distribution of these structures within an image. We pre-train the model in a self-supervised manner on H&E-stained whole-slide images of diffuse large B-cell lymphoma, where cell nuclei have been segmented. The pre-training objective is to recover the original discrete visual tokens of the masked image on the one hand, and to reconstruct the visual tokens of the masked object instances on the other. Coupling these two pre-training tasks allows us to build powerful, context-aware representations of nuclei. Our model generalizes well and can be fine-tuned on downstream classification tasks, achieving improved cell classification accuracy on PanNuke dataset by more than 5% compared to current instance segmentation methods.

This work investigates descriptive captions as an additional source of supervision for biological multimodal foundation models. Images and captions can be viewed as complementary samples from the latent morphospace of a species, each capturing certain biological traits. Incorporating captions during training encourages alignment with this shared latent structure, emphasizing potentially diagnostic characters while suppressing spurious correlations. The main challenge, however, lies in obtaining faithful, instance-specific captions at scale. This requirement has limited the utilization of natural language supervision in organismal biology compared with many other scientific domains. We complement this gap by generating synthetic captions with multimodal large language models (MLLMs), guided by Wikipedia-derived visual information and taxon-tailored format examples. These domain-specific contexts help reduce hallucination and yield accurate, instance-based descriptive captions. Using these captions, we train BIOCAP (i.e., BIOCLIP with Captions), a biological foundation model that captures rich semantics and achieves strong performance in species classification and text-image retrieval. These results demonstrate the value of descriptive captions beyond labels in bridging biological images with multimodal foundation models.

We present a method to build animatable dog avatars from monocular videos. This is challenging as animals display a range of (unpredictable) non-rigid movements and have a variety of appearance details (e.g., fur, spots, tails). We develop an approach that links the video frames via a 4D solution that jointly solves for animal's pose variation, and its appearance (in a canonical pose). To this end, we significantly improve the quality of template-based shape fitting by endowing the SMAL parametric model with Continuous Surface Embeddings, which brings image-to-mesh reprojection constaints that are denser, and thus stronger, than the previously used sparse semantic keypoint correspondences. To model appearance, we propose an implicit duplex-mesh texture that is defined in the canonical pose, but can be deformed using SMAL pose coefficients and later rendered to enforce a photometric compatibility with the input video frames. On the challenging CoP3D and APTv2 datasets, we demonstrate superior results (both in terms of pose estimates and predicted appearance) to existing template-free (RAC) and template-based approaches (BARC, BITE).

Recent advances in microscopy have enabled the rapid generation of terabytes of image data in cell biology and biomedical research. Vision-language models (VLMs) offer a promising solution for large-scale biological image analysis, enhancing researchers' efficiency, identifying new image biomarkers, and accelerating hypothesis generation and scientific discovery. However, there is a lack of standardized, diverse, and large-scale vision-language benchmarks to evaluate VLMs' perception and cognition capabilities in biological image understanding. To address this gap, we introduce {\mu}-Bench, an expert-curated benchmark encompassing 22 biomedical tasks across various scientific disciplines (biology, pathology), microscopy modalities (electron, fluorescence, light), scales (subcellular, cellular, tissue), and organisms in both normal and abnormal states. We evaluate state-of-the-art biomedical, pathology, and general VLMs on {\mu}-Bench and find that: i) current models struggle on all categories, even for basic tasks such as distinguishing microscopy modalities; ii) current specialist models fine-tuned on biomedical data often perform worse than generalist models; iii) fine-tuning in specific microscopy domains can cause catastrophic forgetting, eroding prior biomedical knowledge encoded in their base model. iv) weight interpolation between fine-tuned and pre-trained models offers one solution to forgetting and improves general performance across biomedical tasks. We release {\mu}-Bench under a permissive license to accelerate the research and development of microscopy foundation models.

The recent surge in performance for image analysis of digitised pathology slides can largely be attributed to the advances in deep learning. Deep models can be used to initially localise various structures in the tissue and hence facilitate the extraction of interpretable features for biomarker discovery. However, these models are typically trained for a single task and therefore scale poorly as we wish to adapt the model for an increasing number of different tasks. Also, supervised deep learning models are very data hungry and therefore rely on large amounts of training data to perform well. In this paper, we present a multi-task learning approach for segmentation and classification of nuclei, glands, lumina and different tissue regions that leverages data from multiple independent data sources. While ensuring that our tasks are aligned by the same tissue type and resolution, we enable meaningful simultaneous prediction with a single network. As a result of feature sharing, we also show that the learned representation can be used to improve the performance of additional tasks via transfer learning, including nuclear classification and signet ring cell detection. As part of this work, we train our developed Cerberus model on a huge amount of data, consisting of over 600K objects for segmentation and 440K patches for classification. We use our approach to process 599 colorectal whole-slide images from TCGA, where we localise 377 million, 900K and 2.1 million nuclei, glands and lumina, respectively and make the results available to the community for downstream analysis.

Cytology is essential for cancer diagnostics and screening due to its minimally invasive nature. However, the development of robust deep learning models for digital cytology is challenging due to the heterogeneity in staining and preparation methods of samples, differences across organs, and the limited availability of large, diverse, annotated datasets. Developing a task-specific model for every cytology application is impractical and non-cytology-specific foundation models struggle to generalize to tasks in this domain where the emphasis is on cell morphology. To address these challenges, we introduce CytoFM, the first cytology self-supervised foundation model. Using iBOT, a self-supervised Vision Transformer (ViT) training framework incorporating masked image modeling and self-distillation, we pretrain CytoFM on a diverse collection of cytology datasets to learn robust, transferable representations. We evaluate CytoFM on multiple downstream cytology tasks, including breast cancer classification and cell type identification, using an attention-based multiple instance learning framework. Our results demonstrate that CytoFM performs better on two out of three downstream tasks than existing foundation models pretrained on histopathology (UNI) or natural images (iBOT-Imagenet). Visualizations of learned representations demonstrate our model is able to attend to cytologically relevant features. Despite a small pre-training dataset, CytoFM's promising results highlight the ability of task-agnostic pre-training approaches to learn robust and generalizable features from cytology data.

The correlation between insect morphological traits and climate has been documented in physiological studies, but such studies remain limited by the time-consuming nature of the data analysis. In particular, the open source datasets often lack annotations of species' morphological traits, making dedicated annotations campaigns necessary; these efforts are typically local in scale and costly. In this paper, we propose a pipeline to identify and segment body parts of Odonates (dragonflies and damselflies) using deep neural networks, with the ultimate goal of extracting body parts' colouration. The pipeline is trained on a limited annotated dataset and refined with pseudo supervised data. We show that, by using open source images from citizen science platforms, our approach can segment each visible subject (Odonates) into head, thorax, abdomen, and wings and then extract a colour palette for each body part. This will enable large-scale statistical analysis of ecological correlations (e.g., between colouration and climate change, habitat loss, or geolocation) which are crucial for quantifying and assessing ecosystem biodiversity status.

Hepatocellular Carcinoma diagnosis relies heavily on the interpretation of gigapixel Whole Slide Images. However, current computational approaches are constrained by fixed-resolution processing mechanisms and inefficient feature aggregation, which inevitably lead to either severe information loss or high feature redundancy. To address these challenges, we propose Hepato-LLaVA, a specialized Multi-modal Large Language Model designed for fine-grained hepatocellular pathology analysis. We introduce a novel Sparse Topo-Pack Attention mechanism that explicitly models 2D tissue topology. This mechanism effectively aggregates local diagnostic evidence into semantic summary tokens while preserving global context. Furthermore, to overcome the lack of multi-scale data, we present HepatoPathoVQA, a clinically grounded dataset comprising 33K hierarchically structured question-answer pairs validated by expert pathologists. Our experiments demonstrate that Hepato-LLaVA achieves state-of-the-art performance on HCC diagnosis and captioning tasks, significantly outperforming existing methods. Our code and implementation details are available at https://pris-cv.github.io/Hepto-LLaVA/.

Pathology foundation models substantially advanced the possibilities in computational pathology -- yet tradeoffs in terms of performance, robustness, and computational requirements remained, which limited their clinical deployment. In this report, we present Atlas 2, Atlas 2-B, and Atlas 2-S, three pathology vision foundation models which bridge these shortcomings by showing state-of-the-art performance in prediction performance, robustness, and resource efficiency in a comprehensive evaluation across eighty public benchmarks. Our models were trained on the largest pathology foundation model dataset to date comprising 5.5 million histopathology whole slide images, collected from three medical institutions Charité - Universtätsmedizin Berlin, LMU Munich, and Mayo Clinic.

Detecting and classifying cells in histopathology H\&E stained whole-slide images is a core task in computational pathology, as it provides valuable insight into the tumor microenvironment. In this work we investigate the impact of ground truth formats on the models performance. Additionally, cell-tissue interactions are considered by providing tissue segmentation predictions as input to the cell detection model. We find that a "soft", probability-map instance segmentation ground truth leads to best model performance. Combined with cell-tissue interaction and test-time augmentation our Soft Cell-Tissue-Model (SoftCTM) achieves 0.7172 mean F1-Score on the Overlapped Cell On Tissue (OCELOT) test set, achieving the third best overall score in the OCELOT 2023 Challenge. The source code for our approach is made publicly available at https://github.com/lely475/ocelot23algo.

Pathology text mining is a challenging task given the reporting variability and constant new findings in cancer sub-type definitions. However, successful text mining of a large pathology database can play a critical role to advance 'big data' cancer research like similarity-based treatment selection, case identification, prognostication, surveillance, clinical trial screening, risk stratification, and many others. While there is a growing interest in developing language models for more specific clinical domains, no pathology-specific language space exist to support the rapid data-mining development in pathology space. In literature, a few approaches fine-tuned general transformer models on specialized corpora while maintaining the original tokenizer, but in fields requiring specialized terminology, these models often fail to perform adequately. We propose PathologyBERT - a pre-trained masked language model which was trained on 347,173 histopathology specimen reports and publicly released in the Huggingface repository. Our comprehensive experiments demonstrate that pre-training of transformer model on pathology corpora yields performance improvements on Natural Language Understanding (NLU) and Breast Cancer Diagnose Classification when compared to nonspecific language models.

Pathology Foundation Models (FMs) hold great promise for healthcare. Before they can be used in clinical practice, it is essential to ensure they are robust to variations between medical centers. We measure whether pathology FMs focus on biological features like tissue and cancer type, or on the well known confounding medical center signatures introduced by staining procedure and other differences. We introduce the Robustness Index. This novel robustness metric reflects to what degree biological features dominate confounding features. Ten current publicly available pathology FMs are evaluated. We find that all current pathology foundation models evaluated represent the medical center to a strong degree. Significant differences in the robustness index are observed. Only one model so far has a robustness index greater than one, meaning biological features dominate confounding features, but only slightly. A quantitative approach to measure the influence of medical center differences on FM-based prediction performance is described. We analyze the impact of unrobustness on classification performance of downstream models, and find that cancer-type classification errors are not random, but specifically attributable to same-center confounders: images of other classes from the same medical center. We visualize FM embedding spaces, and find these are more strongly organized by medical centers than by biological factors. As a consequence, the medical center of origin is predicted more accurately than the tissue source and cancer type. The robustness index introduced here is provided with the aim of advancing progress towards clinical adoption of robust and reliable pathology FMs.

The complexity and variability inherent in high-resolution pathological images present significant challenges in computational pathology. While pathology foundation models leveraging AI have catalyzed transformative advancements, their development demands large-scale datasets, considerable storage capacity, and substantial computational resources. Furthermore, ensuring their clinical applicability and generalizability requires rigorous validation across a broad spectrum of clinical tasks. Here, we present PathOrchestra, a versatile pathology foundation model trained via self-supervised learning on a dataset comprising 300K pathological slides from 20 tissue and organ types across multiple centers. The model was rigorously evaluated on 112 clinical tasks using a combination of 61 private and 51 public datasets. These tasks encompass digital slide preprocessing, pan-cancer classification, lesion identification, multi-cancer subtype classification, biomarker assessment, gene expression prediction, and the generation of structured reports. PathOrchestra demonstrated exceptional performance across 27,755 WSIs and 9,415,729 ROIs, achieving over 0.950 accuracy in 47 tasks, including pan-cancer classification across various organs, lymphoma subtype diagnosis, and bladder cancer screening. Notably, it is the first model to generate structured reports for high-incidence colorectal cancer and diagnostically complex lymphoma-areas that are infrequently addressed by foundational models but hold immense clinical potential. Overall, PathOrchestra exemplifies the feasibility and efficacy of a large-scale, self-supervised pathology foundation model, validated across a broad range of clinical-grade tasks. Its high accuracy and reduced reliance on extensive data annotation underline its potential for clinical integration, offering a pathway toward more efficient and high-quality medical services.

The field of Machine Learning, a subset of Artificial Intelligence, has led to remarkable advancements in many areas, including medicine. Machine Learning algorithms require large datasets to train computer models successfully. Although there are medical image datasets available, more image datasets are needed from a variety of medical entities, especially cancer pathology. Even more scarce are ML-ready image datasets. To address this need, we created an image dataset (LC25000) with 25,000 color images in 5 classes. Each class contains 5,000 images of the following histologic entities: colon adenocarcinoma, benign colonic tissue, lung adenocarcinoma, lung squamous cell carcinoma, and benign lung tissue. All images are de-identified, HIPAA compliant, validated, and freely available for download to AI researchers.

Medical domain automated text generation is an active area of research and development; however, evaluating the clinical quality of generated reports remains a challenge, especially in instances where domain-specific metrics are lacking, e.g. histopathology. We propose HARE (Histopathology Automated Report Evaluation), a novel entity and relation centric framework, composed of a benchmark dataset, a named entity recognition (NER) model, a relation extraction (RE) model, and a novel metric, which prioritizes clinically relevant content by aligning critical histopathology entities and relations between reference and generated reports. To develop the HARE benchmark, we annotated 813 de-identified clinical diagnostic histopathology reports and 652 histopathology reports from The Cancer Genome Atlas (TCGA) with domain-specific entities and relations. We fine-tuned GatorTronS, a domain-adapted language model to develop HARE-NER and HARE-RE which achieved the highest overall F1-score (0.915) among the tested models. The proposed HARE metric outperformed traditional metrics including ROUGE and Meteor, as well as radiology metrics such as RadGraph-XL, with the highest correlation and the best regression to expert evaluations (higher than the second best method, GREEN, a large language model based radiology report evaluator, by Pearson r = 0.168, Spearman ρ= 0.161, Kendall τ= 0.123, R^2 = 0.176, RMSE = 0.018). We release HARE, datasets, and the models at https://github.com/knowlab/HARE to foster advancements in histopathology report generation, providing a robust framework for improving the quality of reports.

Histopathology has played an essential role in cancer diagnosis. With the rapid advances in convolutional neural networks (CNN). Various CNN-based automated pathological image segmentation approaches have been developed in computer-assisted pathological image analysis. In the past few years, Transformer neural networks (Transformer) have shown the unique merit of capturing the global long-distance dependencies across the entire image as a new deep learning paradigm. Such merit is appealing for exploring spatially heterogeneous pathological images. However, there have been very few, if any, studies that have systematically evaluated the current Transformer-based approaches in pathological image segmentation. To assess the performance of Transformer segmentation models on whole slide images (WSI), we quantitatively evaluated six prevalent transformer-based models on tumor segmentation, using the widely used PAIP liver histopathological dataset. For a more comprehensive analysis, we also compare the transformer-based models with six major traditional CNN-based models. The results show that the Transformer-based models exhibit a general superior performance over the CNN-based models. In particular, Segmenter, Swin-Transformer and TransUNet-all transformer-based-came out as the best performers among the twelve evaluated models.

Survival prediction is a complicated ordinal regression task that aims to predict the ranking risk of death, which generally benefits from the integration of histology and genomic data. Despite the progress in joint learning from pathology and genomics, existing methods still suffer from challenging issues: 1) Due to the large size of pathological images, it is difficult to effectively represent the gigapixel whole slide images (WSIs). 2) Interactions within tumor microenvironment (TME) in histology are essential for survival analysis. Although current approaches attempt to model these interactions via co-attention between histology and genomic data, they focus on only dense local similarity across modalities, which fails to capture global consistency between potential structures, i.e. TME-related interactions of histology and co-expression of genomic data. To address these challenges, we propose a Multimodal Optimal Transport-based Co-Attention Transformer framework with global structure consistency, in which optimal transport (OT) is applied to match patches of a WSI and genes embeddings for selecting informative patches to represent the gigapixel WSI. More importantly, OT-based co-attention provides a global awareness to effectively capture structural interactions within TME for survival prediction. To overcome high computational complexity of OT, we propose a robust and efficient implementation over micro-batch of WSI patches by approximating the original OT with unbalanced mini-batch OT. Extensive experiments show the superiority of our method on five benchmark datasets compared to the state-of-the-art methods. The code is released.

Gastrointestinal (GI) diseases represent a clinically significant burden, necessitating precise diagnostic approaches to optimize patient outcomes. Conventional histopathological diagnosis suffers from limited reproducibility and diagnostic variability. To overcome these limitations, we develop Digepath, a specialized foundation model for GI pathology. Our framework introduces a dual-phase iterative optimization strategy combining pretraining with fine-screening, specifically designed to address the detection of sparsely distributed lesion areas in whole-slide images. Digepath is pretrained on over 353 million multi-scale images from 210,043 H&E-stained slides of GI diseases. It attains state-of-the-art performance on 33 out of 34 tasks related to GI pathology, including pathological diagnosis, protein expression status prediction, gene mutation prediction, and prognosis evaluation. We further translate the intelligent screening module for early GI cancer and achieve near-perfect 99.70% sensitivity across nine independent medical institutions. This work not only advances AI-driven precision pathology for GI diseases but also bridge critical gaps in histopathological practice.

Accurate detection and segmentation of cell nuclei in volumetric (3D) fluorescence microscopy datasets is an important step in many biomedical research projects. Although many automated methods for these tasks exist, they often struggle for images with low signal-to-noise ratios and/or dense packing of nuclei. It was recently shown for 2D microscopy images that these issues can be alleviated by training a neural network to directly predict a suitable shape representation (star-convex polygon) for cell nuclei. In this paper, we adopt and extend this approach to 3D volumes by using star-convex polyhedra to represent cell nuclei and similar shapes. To that end, we overcome the challenges of 1) finding parameter-efficient star-convex polyhedra representations that can faithfully describe cell nuclei shapes, 2) adapting to anisotropic voxel sizes often found in fluorescence microscopy datasets, and 3) efficiently computing intersections between pairs of star-convex polyhedra (required for non-maximum suppression). Although our approach is quite general, since star-convex polyhedra include common shapes like bounding boxes and spheres as special cases, our focus is on accurate detection and segmentation of cell nuclei. Finally, we demonstrate on two challenging datasets that our approach (StarDist-3D) leads to superior results when compared to classical and deep learning based methods.

Deep neural networks have introduced significant advancements in the field of machine learning-based analysis of digital pathology images including prostate tissue images. With the help of transfer learning, classification and segmentation performance of neural network models have been further increased. However, due to the absence of large, extensively annotated, publicly available prostate histopathology datasets, several previous studies employ datasets from well-studied computer vision tasks such as ImageNet dataset. In this work, we propose a transfer learning scheme from breast histopathology images to improve prostate cancer detection performance. We validate our approach on annotated prostate whole slide images by using a publicly available breast histopathology dataset as pre-training. We show that the proposed cross-cancer approach outperforms transfer learning from ImageNet dataset.

Sexual dimorphism is a critical factor in many biological and medical research fields. In biomechanics and bioengineering, understanding sex differences is crucial for studying musculoskeletal conditions such as temporomandibular disorder (TMD). This paper focuses on the association between the craniofacial skeletal morphology and temporomandibular joint (TMJ) related masticatory muscle attachments to discern sex differences. Data were collected from 10 male and 11 female cadaver heads to investigate sex-specific relationships between the skull and muscles. We propose a conditional cross-covariance reduction (CCR) model, designed to examine the dynamic association between two sets of random variables conditioned on a third binary variable (e.g., sex), highlighting the most distinctive sex-related relationships between skull and muscle attachments in the human cadaver data. Under the CCR model, we employ a sparse singular value decomposition algorithm and introduce a sequential permutation for selecting sparsity (SPSS) method to select important variables and to determine the optimal number of selected variables.

Single cell analysis of human skeletal muscle (SM) tissue cross-sections is a fundamental tool for understanding many neuromuscular disorders. For this analysis to be reliable and reproducible, identification of individual fibres within microscopy images (segmentation) of SM tissue should be automatic and precise. Biomedical scientists in this field currently rely on custom tools and general machine learning (ML) models, both followed by labour intensive and subjective manual interventions to fine-tune segmentation. We believe that fully automated, precise, reproducible segmentation is possible by training ML models. However, in this important biomedical domain, there are currently no good quality, publicly available annotated imaging datasets available for ML model training. In this paper we release NCL-SM: a high quality bioimaging dataset of 46 human SM tissue cross-sections from both healthy control subjects and from patients with genetically diagnosed muscle pathology. These images include > 50k manually segmented muscle fibres (myofibres). In addition we also curated high quality myofibre segmentations, annotating reasons for rejecting low quality myofibres and low quality regions in SM tissue images, making these annotations completely ready for downstream analysis. This, we believe, will pave the way for development of a fully automatic pipeline that identifies individual myofibres within images of tissue sections and, in particular, also classifies individual myofibres that are fit for further analysis.

Cell-level dense prediction is central to computational pathology, but remains challenging due to fine-grained histological structures, strong domain shifts, and costly dense annotations. Existing ViT-based pathology foundation models rely on patch tokenization, which can disrupt spatial continuity and weaken local morphological details needed for cell-level prediction. To address this, we propose Masked-Diffusion Convolutional Foundation Models, termed ConvNeXt Masked-Diffusion (CMD), a self-supervised convolutional generative pretraining framework for dense pathology representation learning. CMD uses a fully convolutional ConvNeXt-UNet backbone, performs masked-diffusion pretraining in pixel space, and incorporates frozen pathology foundation model features through adaptive normalization. Experimental results demonstrate that CMD consistently outperforms existing ViT-based pathology foundation models and even surpasses state-of-the-art end-to-end segmentation methods while fine-tuning only a small number of task-specific parameters across multiple pathology dense prediction tasks. The advantage is particularly pronounced under limited annotation settings, where CMD exhibits stronger robustness and generalization ability. Our findings suggest that purely convolutional architectures can also serve as competitive pathology foundation models for cell-level dense prediction, achieving leading performance within the current ViT-dominated paradigm and providing a scalable, high-performance solution that better preserves histological structural priors for fine-grained pathology understanding.

We present Galaxy Zoo DECaLS: detailed visual morphological classifications for Dark Energy Camera Legacy Survey images of galaxies within the SDSS DR8 footprint. Deeper DECaLS images (r=23.6 vs. r=22.2 from SDSS) reveal spiral arms, weak bars, and tidal features not previously visible in SDSS imaging. To best exploit the greater depth of DECaLS images, volunteers select from a new set of answers designed to improve our sensitivity to mergers and bars. Galaxy Zoo volunteers provide 7.5 million individual classifications over 314,000 galaxies. 140,000 galaxies receive at least 30 classifications, sufficient to accurately measure detailed morphology like bars, and the remainder receive approximately 5. All classifications are used to train an ensemble of Bayesian convolutional neural networks (a state-of-the-art deep learning method) to predict posteriors for the detailed morphology of all 314,000 galaxies. When measured against confident volunteer classifications, the networks are approximately 99% accurate on every question. Morphology is a fundamental feature of every galaxy; our human and machine classifications are an accurate and detailed resource for understanding how galaxies evolve.

Pathology, the microscopic examination of diseased tissue, is critical for diagnosing various medical conditions, particularly cancers. Traditional methods are labor-intensive and prone to human error. Digital pathology, which converts glass slides into high-resolution digital images for analysis by computer algorithms, revolutionizes the field by enhancing diagnostic accuracy, consistency, and efficiency through automated image analysis and large-scale data processing. Foundational transformer pretraining is crucial for developing robust, generalizable models as it enables learning from vast amounts of unannotated data. This paper introduces the Hibou family of foundational vision transformers for pathology, leveraging the DINOv2 framework to pretrain two model variants, Hibou-B and Hibou-L, on a proprietary dataset of over 1 million whole slide images (WSIs) representing diverse tissue types and staining techniques. Our pretrained models demonstrate superior performance on both patch-level and slide-level benchmarks, surpassing existing state-of-the-art methods. Notably, Hibou-L achieves the highest average accuracy across multiple benchmark datasets. To support further research and application in the field, we have open-sourced the Hibou-B model, which can be accessed at https://github.com/HistAI/hibou

Imaging features of knee articular cartilage have been shown to be potential imaging biomarkers for knee osteoarthritis. Despite recent methodological advancements in image analysis techniques like image segmentation, registration, and domain-specific image computing algorithms, only a few works focus on building fully automated pipelines for imaging feature extraction. In this study, we developed a deep-learning-based medical image analysis application for knee cartilage morphometrics, CartiMorph Toolbox (CMT). We proposed a 2-stage joint template learning and registration network, CMT-reg. We trained the model using the OAI-ZIB dataset and assessed its performance in template-to-image registration. The CMT-reg demonstrated competitive results compared to other state-of-the-art models. We integrated the proposed model into an automated pipeline for the quantification of cartilage shape and lesion (full-thickness cartilage loss, specifically). The toolbox provides a comprehensive, user-friendly solution for medical image analysis and data visualization. The software and models are available at https://github.com/YongchengYAO/CMT-AMAI24paper .

Recently, bladder cancer has been significantly increased in terms of incidence and mortality. Currently, two subtypes are known based on tumour growth: non-muscle invasive (NMIBC) and muscle-invasive bladder cancer (MIBC). In this work, we focus on the MIBC subtype because it is of the worst prognosis and can spread to adjacent organs. We present a self-learning framework to grade bladder cancer from histological images stained via immunohistochemical techniques. Specifically, we propose a novel Deep Convolutional Embedded Attention Clustering (DCEAC) which allows classifying histological patches into different severity levels of the disease, according to the patterns established in the literature. The proposed DCEAC model follows a two-step fully unsupervised learning methodology to discern between non-tumour, mild and infiltrative patterns from high-resolution samples of 512x512 pixels. Our system outperforms previous clustering-based methods by including a convolutional attention module, which allows refining the features of the latent space before the classification stage. The proposed network exceeds state-of-the-art approaches by 2-3% across different metrics, achieving a final average accuracy of 0.9034 in a multi-class scenario. Furthermore, the reported class activation maps evidence that our model is able to learn by itself the same patterns that clinicians consider relevant, without incurring prior annotation steps. This fact supposes a breakthrough in muscle-invasive bladder cancer grading which bridges the gap with respect to train the model on labelled data.

Precise and scalable instance segmentation of cell nuclei is essential for computational pathology, yet gigapixel Whole-Slide Images pose major computational challenges. Existing approaches rely on patch-based processing and costly post-processing for instance separation, sacrificing context and efficiency. We introduce LSP-DETR (Local Star Polygon DEtection TRansformer), a fully end-to-end framework that uses a lightweight transformer with linear complexity to process substantially larger images without additional computational cost. Nuclei are represented as star-convex polygons, and a novel radial distance loss function allows the segmentation of overlapping nuclei to emerge naturally, without requiring explicit overlap annotations or handcrafted post-processing. Evaluations on PanNuke and MoNuSeg show strong generalization across tissues and state-of-the-art efficiency, with LSP-DETR being over five times faster than the next-fastest leading method. Code and models are available at https://github.com/RationAI/lsp-detr.

Accurately predicting gene expression from histopathology images offers a scalable and non-invasive approach to molecular profiling, with significant implications for precision medicine and computational pathology. However, existing methods often underutilize the cross-modal representation alignment between histopathology images and gene expression profiles across multiple representational levels, thereby limiting their prediction performance. To address this, we propose Gene-DML, a unified framework that structures latent space through Dual-pathway Multi-Level discrimination to enhance correspondence between morphological and transcriptional modalities. The multi-scale instance-level discrimination pathway aligns hierarchical histopathology representations extracted at local, neighbor, and global levels with gene expression profiles, capturing scale-aware morphological-transcriptional relationships. In parallel, the cross-level instance-group discrimination pathway enforces structural consistency between individual (image/gene) instances and modality-crossed (gene/image, respectively) groups, strengthening the alignment across modalities. By jointly modelling fine-grained and structural-level discrimination, Gene-DML is able to learn robust cross-modal representations, enhancing both predictive accuracy and generalization across diverse biological contexts. Extensive experiments on public spatial transcriptomics datasets demonstrate that Gene-DML achieves state-of-the-art performance in gene expression prediction. The code and checkpoints will be released soon.

Image-based or morphological profiling is a rapidly expanding field wherein cells are "profiled" by extracting hundreds to thousands of unbiased, quantitative features from images of cells that have been perturbed by genetic or chemical perturbations. The Cell Painting assay is the most popular imaged-based profiling assay wherein six small-molecule dyes label eight cellular compartments and thousands of measurements are made, describing quantitative traits such as size, shape, intensity, and texture within the nucleus, cytoplasm, and whole cell (Cimini et al., 2023). We have created the Cell Painting Gallery, a publicly available collection of Cell Painting datasets, with granular dataset descriptions and access instructions. It is hosted by AWS on the Registry of Open Data (RODA). As of January 2024, the Cell Painting Gallery holds 656 terabytes (TB) of image and associated numerical data. It includes the largest publicly available Cell Painting dataset, in terms of perturbations tested (Joint Undertaking for Morphological Profiling or JUMP (Chandrasekaran et al., 2023)), along with many other canonical datasets using Cell Painting, close derivatives of Cell Painting (such as LipocyteProfiler (Laber et al., 2023) and Pooled Cell Painting (Ramezani et al., 2023)).

Part-based approaches for fine-grained recognition do not show the expected performance gain over global methods, although explicitly focusing on small details that are relevant for distinguishing highly similar classes. We assume that part-based methods suffer from a missing representation of local features, which is invariant to the order of parts and can handle a varying number of visible parts appropriately. The order of parts is artificial and often only given by ground-truth annotations, whereas viewpoint variations and occlusions result in not observable parts. Therefore, we propose integrating a Fisher vector encoding of part features into convolutional neural networks. The parameters for this encoding are estimated by an online EM algorithm jointly with those of the neural network and are more precise than the estimates of previous works. Our approach improves state-of-the-art accuracies for three bird species classification datasets.

The expanding ecosystem of pathology foundation models has produced powerful but fragmented tile-level representations, limiting their use in clinical tasks that require unified slide-level reasoning and interpretable linkage to clinically meaningful information. We present ASTRA, a pan-cancer framework that integrates heterogeneous foundation-model representations into a shared slide-level representation space and semantically grounds that space using structured pathology annotation fields, including classification category, cancer type, and anatomic site. ASTRA combines sparse mixture-of-experts contextualization, masked multi-model reconstruction, and contrastive alignment to structured pathology prompts to learn slide representations that support 4-category classification, 3-class solid tumor typing, 16-class cancer typing, and text-guided tumor localization without pixel-level supervision. Developed on a CHTN cohort of 10,359 whole-slide images (WSIs) spanning 16 tumor types, ASTRA consistently improves pan-cancer classification across four pathology foundation-model backbones, achieving up to 97.8% macro-AUC for 4-category classification, 99.7% for 3-class solid tumor typing, and 99.2% for 16-class cancer typing. For tumor localization, ASTRA achieves a mean Dice of 0.897 on an annotated in-domain CHTN subset (n = 380) spanning 16 cancer types and 0.738 on an external TCGA cohort (n = 1,686) spanning four cancer types. These results demonstrate that minimal structured pathology annotation fields derived from slide-level metadata can provide effective semantic supervision for unified slide representation learning, enabling both pan-cancer prediction and weakly supervised tumor localization within a single framework.

Learning 3D models of all animals on the Earth requires massively scaling up existing solutions. With this ultimate goal in mind, we develop 3D-Fauna, an approach that learns a pan-category deformable 3D animal model for more than 100 animal species jointly. One crucial bottleneck of modeling animals is the limited availability of training data, which we overcome by simply learning from 2D Internet images. We show that prior category-specific attempts fail to generalize to rare species with limited training images. We address this challenge by introducing the Semantic Bank of Skinned Models (SBSM), which automatically discovers a small set of base animal shapes by combining geometric inductive priors with semantic knowledge implicitly captured by an off-the-shelf self-supervised feature extractor. To train such a model, we also contribute a new large-scale dataset of diverse animal species. At inference time, given a single image of any quadruped animal, our model reconstructs an articulated 3D mesh in a feed-forward fashion within seconds.

Immunohistochemical (IHC) staining highlights the molecular information critical to diagnostics in tissue samples. However, compared to H&E staining, IHC staining can be much more expensive in terms of both labor and the laboratory equipment required. This motivates recent research that demonstrates that the correlations between the morphological information present in the H&E-stained slides and the molecular information in the IHC-stained slides can be used for H&E-to-IHC stain translation. However, due to a lack of pixel-perfect H&E-IHC groundtruth pairs, most existing methods have resorted to relying on expert annotations. To remedy this situation, we present a new loss function, Adaptive Supervised PatchNCE (ASP), to directly deal with the input to target inconsistencies in a proposed H&E-to-IHC image-to-image translation framework. The ASP loss is built upon a patch-based contrastive learning criterion, named Supervised PatchNCE (SP), and augments it further with weight scheduling to mitigate the negative impact of noisy supervision. Lastly, we introduce the Multi-IHC Stain Translation (MIST) dataset, which contains aligned H&E-IHC patches for 4 different IHC stains critical to breast cancer diagnosis. In our experiment, we demonstrate that our proposed method outperforms existing image-to-image translation methods for stain translation to multiple IHC stains. All of our code and datasets are available at https://github.com/lifangda01/AdaptiveSupervisedPatchNCE.

Liver Cirrhosis plays a critical role in the prognosis of chronic liver disease. Early detection and timely intervention are critical in significantly reducing mortality rates. However, the intricate anatomical architecture and diverse pathological changes of liver tissue complicate the accurate detection and characterization of lesions in clinical settings. Existing methods underutilize the spatial anatomical details in volumetric MRI data, thereby hindering their clinical effectiveness and explainability. To address this challenge, we introduce a novel Mamba-based network, SRMA-Mamba, designed to model the spatial relationships within the complex anatomical structures of MRI volumes. By integrating the Spatial Anatomy-Based Mamba module (SABMamba), SRMA-Mamba performs selective Mamba scans within liver cirrhotic tissues and combines anatomical information from the sagittal, coronal, and axial planes to construct a global spatial context representation, enabling efficient volumetric segmentation of pathological liver structures. Furthermore, we introduce the Spatial Reverse Attention module (SRMA), designed to progressively refine cirrhotic details in the segmentation map, utilizing both the coarse segmentation map and hierarchical encoding features. Extensive experiments demonstrate that SRMA-Mamba surpasses state-of-the-art methods, delivering exceptional performance in 3D pathological liver segmentation. Our code is available for public: https://github.com/JunZengz/SRMA-Mamba.

Unified Medical Image Segmentation (UMIS) is critical for comprehensive anatomical assessment but faces challenges due to multi-scale structural heterogeneity. Conventional pixel-based approaches, lacking object-level anatomical insight and inter-organ relational modeling, struggle with morphological complexity and feature conflicts, limiting their efficacy in UMIS. We propose Mamba Snake, a novel deep snake framework enhanced by state space modeling for UMIS. Mamba Snake frames multi-contour evolution as a hierarchical state space atlas, effectively modeling macroscopic inter-organ topological relationships and microscopic contour refinements. We introduce a snake-specific vision state space module, the Mamba Evolution Block (MEB), which leverages effective spatiotemporal information aggregation for adaptive refinement of complex morphologies. Energy map shape priors further ensure robust long-range contour evolution in heterogeneous data. Additionally, a dual-classification synergy mechanism is incorporated to concurrently optimize detection and segmentation, mitigating under-segmentation of microstructures in UMIS. Extensive evaluations across five clinical datasets reveal Mamba Snake's superior performance, with an average Dice improvement of 3\% over state-of-the-art methods.

High-content screening (HCS) assays based on high-throughput microscopy techniques such as Cell Painting have enabled the interrogation of cells' morphological responses to perturbations at an unprecedented scale. The collection of such data promises to facilitate a better understanding of the relationships between different perturbations and their effects on cellular state. Towards achieving this goal, recent advances in cross-modal contrastive learning could, in theory, be leveraged to learn a unified latent space that aligns perturbations with their corresponding morphological effects. However, the application of such methods to HCS data is not straightforward due to substantial differences in the semantics of Cell Painting images compared to natural images, and the difficulty of representing different classes of perturbations (e.g., small molecule vs CRISPR gene knockout) in a single latent space. In response to these challenges, here we introduce CellCLIP, a cross-modal contrastive learning framework for HCS data. CellCLIP leverages pre-trained image encoders coupled with a novel channel encoding scheme to better capture relationships between different microscopy channels in image embeddings, along with natural language encoders for representing perturbations. Our framework outperforms current open-source models, demonstrating the best performance in both cross-modal retrieval and biologically meaningful downstream tasks while also achieving significant reductions in computation time.

In standard hospital blood tests, the traditional process requires doctors to manually isolate leukocytes from microscopic images of patients' blood using microscopes. These isolated leukocytes are then categorized via automatic leukocyte classifiers to determine the proportion and volume of different types of leukocytes present in the blood samples, aiding disease diagnosis. This methodology is not only time-consuming and labor-intensive, but it also has a high propensity for errors due to factors such as image quality and environmental conditions, which could potentially lead to incorrect subsequent classifications and misdiagnosis. To address these issues, this paper proposes an innovative method of leukocyte detection: the Multi-level Feature Fusion and Deformable Self-attention DETR (MFDS-DETR). To tackle the issue of leukocyte scale disparity, we designed the High-level Screening-feature Fusion Pyramid (HS-FPN), enabling multi-level fusion. This model uses high-level features as weights to filter low-level feature information via a channel attention module and then merges the screened information with the high-level features, thus enhancing the model's feature expression capability. Further, we address the issue of leukocyte feature scarcity by incorporating a multi-scale deformable self-attention module in the encoder and using the self-attention and cross-deformable attention mechanisms in the decoder, which aids in the extraction of the global features of the leukocyte feature maps. The effectiveness, superiority, and generalizability of the proposed MFDS-DETR method are confirmed through comparisons with other cutting-edge leukocyte detection models using the private WBCDD, public LISC and BCCD datasets. Our source code and private WBCCD dataset are available at https://github.com/JustlfC03/MFDS-DETR.

This paper presents a Patherea, a framework for point-based cell detection and classification that provides a complete solution for developing and evaluating state-of-the-art approaches. We introduce a large-scale dataset collected to directly replicate a clinical workflow for Ki-67 proliferation index estimation and use it to develop an efficient point-based approach that directly predicts point-based predictions, without the need for intermediate representations. The proposed approach effectively utilizes point proposal candidates with the hybrid Hungarian matching strategy and a flexible architecture that enables the usage of various backbones and (pre)training strategies. We report state-of-the-art results on existing public datasets - Lizard, BRCA-M2C, BCData, and the newly proposed Patherea dataset. We show that the performance on existing public datasets is saturated and that the newly proposed Patherea dataset represents a significantly harder challenge for the recently proposed approaches. We also demonstrate the effectiveness of recently proposed pathology foundational models that our proposed approach can natively utilize and benefit from. We also revisit the evaluation protocol that is used in the broader field of cell detection and classification and identify the erroneous calculation of performance metrics. Patherea provides a benchmarking utility that addresses the identified issues and enables a fair comparison of different approaches. The dataset and the code will be publicly released upon acceptance.

Purpose: This study investigated how nodule segmentation and surrounding peritumoral regions influence radionics-based lung cancer classification. Methods: Using 3D CT scans with bounding box annotated nodules, we generated 3D segmentations using four techniques: Otsu, Fuzzy C-Means (FCM), Gaussian Mixture Model (GMM), and K-Nearest Neighbors (KNN). Radiomics features were extracted using the PyRadiomics library, and multiple machine-learning-based classifiers, including Random Forest, Logistic Regression, and KNN, were employed to classify nodules as cancerous or non-cancerous. The best-performing segmentation and model were further analyzed by expanding the initial nodule segmentation into the peritumoral region (2, 4, 6, 8, 10, and 12 mm) to understand the influence of the surrounding area on classification. Additionally, we compared our results to deep learning-based feature extractors Foundation Model for Cancer Biomarkers (FMCB) and other state-of-the-art baseline models. Results: Incorporating peritumoral regions significantly enhanced performance, with the best result obtained at 8 mm expansion (AUC = 0.78). Compared to image-based deep learning models, such as FMCB (AUC = 0.71) and ResNet50-SWS++ (AUC = 0.71), our radiomics-based approach demonstrated superior classification accuracy. Conclusion: The study highlights the importance of peritumoral expansion in improving lung cancer classification using radiomics. These findings can inform the development of more robust AI-driven diagnostic tools.

Accurate delineation of pathological lungs from computed tomography (CT) images remains mostly unsolved because available methods fail to provide a reliable generic solution due to high variability of abnormality appearance. Local descriptor-based classification methods have shown to work well in annotating pathologies; however, these methods are usually computationally intensive which restricts their widespread use in real-time or near-real-time clinical applications. In this paper, we present a novel approach for fast, accurate, reliable segmentation of pathological lungs from CT scans by combining region-based segmentation method with local descriptor classification that is performed on an optimized sampling grid. Our method works in two stages; during stage one, we adapted the fuzzy connectedness (FC) image segmentation algorithm to perform initial lung parenchyma extraction. In the second stage, texture-based local descriptors are utilized to segment abnormal imaging patterns using a near optimal keypoint analysis by employing centroid of supervoxel as grid points. The quantitative results show that our pathological lung segmentation method is fast, robust, and improves on current standards and has potential to enhance the performance of routine clinical tasks.

Vision-language models in pathology enable multimodal case retrieval and automated report generation. Many of the models developed so far, however, have been trained on pathology reports that include information which cannot be inferred from paired whole slide images (e.g., patient history), potentially leading to hallucinated sentences in generated reports. To this end, we investigate how the selection of information from pathology reports for vision-language modeling affects the quality of the multimodal representations and generated reports. More concretely, we compare a model trained on full reports against a model trained on preprocessed reports that only include sentences describing the cell and tissue appearances based on the H&E-stained slides. For the experiments, we built upon the BLIP-2 framework and used a cutaneous melanocytic lesion dataset of 42,433 H&E-stained whole slide images and 19,636 corresponding pathology reports. Model performance was assessed using image-to-text and text-to-image retrieval, as well as qualitative evaluation of the generated reports by an expert pathologist. Our results demonstrate that text preprocessing prevents hallucination in report generation. Despite the improvement in the quality of the generated reports, training the vision-language model on full reports showed better cross-modal retrieval performance.

Spatial Transcriptomics (ST) technologies provide biologists with rich insights into single-cell biology by preserving spatial context of cells. Building foundational models for ST can significantly enhance the analysis of vast and complex data sources, unlocking new perspectives on the intricacies of biological tissues. However, modeling ST data is inherently challenging due to the need to extract multi-scale information from tissue slices containing vast numbers of cells. This process requires integrating macro-scale tissue morphology, micro-scale cellular microenvironment, and gene-scale gene expression profile. To address this challenge, we propose SToFM, a multi-scale Spatial Transcriptomics Foundation Model. SToFM first performs multi-scale information extraction on each ST slice, to construct a set of ST sub-slices that aggregate macro-, micro- and gene-scale information. Then an SE(2) Transformer is used to obtain high-quality cell representations from the sub-slices. Additionally, we construct SToCorpus-88M, the largest high-resolution spatial transcriptomics corpus for pretraining. SToFM achieves outstanding performance on a variety of downstream tasks, such as tissue region semantic segmentation and cell type annotation, demonstrating its comprehensive understanding of ST data through capturing and integrating multi-scale information.

Millions of melanocytic skin lesions are examined by pathologists each year, the majority of which concern common nevi (i.e., ordinary moles). While most of these lesions can be diagnosed in seconds, writing the corresponding pathology report is much more time-consuming. Automating part of the report writing could, therefore, alleviate the increasing workload of pathologists. In this work, we develop a vision-language model specifically for the pathology domain of cutaneous melanocytic lesions. The model follows the Contrastive Captioner framework and was trained and evaluated using a melanocytic lesion dataset of 42,512 H&E-stained whole slide images and 19,645 corresponding pathology reports. Our results show that the quality scores of model-generated reports were on par with pathologist-written reports for common nevi, assessed by an expert pathologist in a reader study. While report generation revealed to be more difficult for rare melanocytic lesion subtypes, the cross-modal retrieval performance for these cases was considerably better.

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.

Accurate individual identification is essential for monitoring rare amphibians, yet invasive marking is often unsuitable for critically endangered species. We evaluate state-of-the-art computer-vision methods for photographic re-identification of the Hula painted frog (Latonia nigriventer) using 1,233 ventral images from 191 individuals collected during 2013-2020 capture-recapture surveys. We compare deep local-feature matching in a zero-shot setting with deep global-feature embedding models. The local-feature pipeline achieves 98% top-1 closed-set identification accuracy, outperforming all global-feature models; fine-tuning improves the best global-feature model to 60% top-1 (91% top-10) but remains below local matching. To combine scalability with accuracy, we implement a two-stage workflow in which a fine-tuned global-feature model retrieves a short candidate list that is re-ranked by local-feature matching, reducing end-to-end runtime from 6.5-7.8 hours to ~38 minutes while maintaining ~96% top-1 closed-set accuracy on the labeled dataset. Separation of match scores between same- and different-individual pairs supports thresholding for open-set identification, enabling practical handling of novel individuals. We deploy this pipeline as a web application for routine field use, providing rapid, standardized, non-invasive identification to support conservation monitoring and capture-recapture analyses. Overall, in this species, zero-shot deep local-feature matching outperformed global-feature embedding and provides a strong default for photo-identification.

With the advent of novel cancer treatment options such as immunotherapy, studying the tumour immune micro-environment (TIME) is crucial to inform on prognosis and understand potential response to therapeutic agents. A key approach to characterising the TIME may be through combining (1) digitised microscopic high-resolution optical images of hematoxylin and eosin (H&E) stained tissue sections obtained in routine histopathology examinations with (2) automated immune cell detection and classification methods. In this work, we introduce a workflow to automatically generate robust single cell contours and labels from dually stained tissue sections with H&E and multiplexed immunofluorescence (IF) markers. The approach harnesses the Segment Anything Model and requires minimal human intervention compared to existing single cell databases. With this methodology, we create Immunocto, a massive, multi-million automatically generated database of 6,848,454 human cells and objects, including 2,282,818 immune cells distributed across 4 subtypes: CD4^+ T cell lymphocytes, CD8^+ T cell lymphocytes, CD20^+ B cell lymphocytes, and CD68^+/CD163^+ macrophages. For each cell, we provide a 64times64 pixels^2 H&E image at 40times magnification, along with a binary mask of the nucleus and a label. The database, which is made publicly available, can be used to train models to study the TIME on routine H&E slides. We show that deep learning models trained on Immunocto result in state-of-the-art performance for lymphocyte detection. The approach demonstrates the benefits of using matched H&E and IF data to generate robust databases for computational pathology applications.

Multiple Instance Learning (MIL) has emerged as a dominant paradigm to extract discriminative feature representations within Whole Slide Images (WSIs) in computational pathology. Despite driving notable progress, existing MIL approaches suffer from limitations in facilitating comprehensive and efficient interactions among instances, as well as challenges related to time-consuming computations and overfitting. In this paper, we incorporate the Selective Scan Space State Sequential Model (Mamba) in Multiple Instance Learning (MIL) for long sequence modeling with linear complexity, termed as MambaMIL. By inheriting the capability of vanilla Mamba, MambaMIL demonstrates the ability to comprehensively understand and perceive long sequences of instances. Furthermore, we propose the Sequence Reordering Mamba (SR-Mamba) aware of the order and distribution of instances, which exploits the inherent valuable information embedded within the long sequences. With the SR-Mamba as the core component, MambaMIL can effectively capture more discriminative features and mitigate the challenges associated with overfitting and high computational overhead. Extensive experiments on two public challenging tasks across nine diverse datasets demonstrate that our proposed framework performs favorably against state-of-the-art MIL methods. The code is released at https://github.com/isyangshu/MambaMIL.