Daily Papers

Background: Cancer remains one of the leading causes of morbidity and mortality worldwide. Comprehensive datasets that combine histopathological images with genetic and survival data across various tumour sites are essential for advancing computational pathology and personalised medicine. Results: We present SurGen, a dataset comprising 1,020 H&E-stained whole slide images (WSIs) from 843 colorectal cancer cases. The dataset includes detailed annotations for key genetic mutations (KRAS, NRAS, BRAF) and mismatch repair status, as well as survival data for 426 cases. To demonstrate SurGen's practical utility, we conducted a proof-of-concept machine learning experiment predicting mismatch repair status from the WSIs, achieving a test AUROC of 0.8316. These preliminary results underscore the dataset's potential to facilitate research in biomarker discovery, prognostic modelling, and advanced machine learning applications in colorectal cancer. Conclusions: SurGen offers a valuable resource for the scientific community, enabling studies that require high-quality WSIs linked with comprehensive clinical and genetic information on colorectal cancer. Our initial findings affirm the dataset's capacity to advance diagnostic precision and foster the development of personalised treatment strategies in colorectal oncology. Data available online at https://doi.org/10.6019/S-BIAD1285.

The visual examination of tissue biopsy sections is fundamental for cancer diagnosis, with pathologists analyzing sections at multiple magnifications to discern tumor cells and their subtypes. However, existing attention-based multiple instance learning (MIL) models, used for analyzing Whole Slide Images (WSIs) in cancer diagnostics, often overlook the contextual information of tumor and neighboring tiles, leading to misclassifications. To address this, we propose the Context-Aware Multiple Instance Learning (CAMIL) architecture. CAMIL incorporates neighbor-constrained attention to consider dependencies among tiles within a WSI and integrates contextual constraints as prior knowledge into the MIL model. We evaluated CAMIL on subtyping non-small cell lung cancer (TCGA-NSCLC) and detecting lymph node (CAMELYON16) metastasis, achieving test AUCs of 0.959\% and 0.975\%, respectively, outperforming other state-of-the-art methods. Additionally, CAMIL enhances model interpretability by identifying regions of high diagnostic value.

Despite the progress made by multimodal large language models (MLLMs) in computational pathology, they remain limited by a predominant focus on patch-level analysis, missing essential contextual information at the whole-slide level. The lack of large-scale instruction datasets and the gigapixel scale of whole slide images (WSIs) pose significant developmental challenges. In this paper, we present SlideChat, the first vision-language assistant capable of understanding gigapixel whole-slide images, exhibiting excellent multimodal conversational capability and response complex instruction across diverse pathology scenarios. To support its development, we created SlideInstruction, the largest instruction-following dataset for WSIs consisting of 4.2K WSI captions and 176K VQA pairs with multiple categories. Furthermore, we propose SlideBench, a multimodal benchmark that incorporates captioning and VQA tasks to assess SlideChat's capabilities in varied clinical settings such as microscopy, diagnosis. Compared to both general and specialized MLLMs, SlideChat exhibits exceptional capabilities achieving state-of-the-art performance on 18 of 22 tasks. For example, it achieved an overall accuracy of 81.17% on SlideBench-VQA (TCGA), and 54.15% on SlideBench-VQA (BCNB). We will fully release SlideChat, SlideInstruction and SlideBench as open-source resources to facilitate research and development in computational pathology.

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.

Multiple Instance Learning (MIL) has demonstrated effectiveness in analyzing whole slide images (WSIs), yet it often encounters overfitting challenges in real-world applications, particularly in the form of attention over-concentration. While existing methods to alleviate this issue introduce complex modules or processing steps, such as multiple-stage training and teacher-student distillation, this paper proposes a simple yet effective regularization: Attention Entropy Maximization (AEM). Motivated by our investigation revealing a positive correlation between attention entropy and model performance, AEM incorporates a negative entropy loss for attention values into the standard MIL framework, penalizing overly concentrated attention and encouraging the model to consider a broader range of informative regions in WSIs, potentially improving its generalization capabilities. Compared to existing overfitting mitigation methods, our AEM approach offers advantages of simplicity, efficiency, and versatility. It requires no additional modules or processing steps, involves only one hyperparameter, and demonstrates compatibility with MIL frameworks and techniques. These advantages make AEM particularly attractive for practical applications. We evaluate AEM on three benchmark datasets, demonstrating consistent performance improvements over existing methods. Furthermore, AEM shows high versatility, integrating effectively with four feature extractors, two advanced MIL frameworks, three attention mechanisms, and Subsampling augmentation technique. The source code is available at https://github.com/dazhangyu123/AEM.

We present WeakSTIL, an interpretable two-stage weak label deep learning pipeline for scoring the percentage of stromal tumor infiltrating lymphocytes (sTIL%) in H&E-stained whole-slide images (WSIs) of breast cancer tissue. The sTIL% score is a prognostic and predictive biomarker for many solid tumor types. However, due to the high labeling efforts and high intra- and interobserver variability within and between expert annotators, this biomarker is currently not used in routine clinical decision making. WeakSTIL compresses tiles of a WSI using a feature extractor pre-trained with self-supervised learning on unlabeled histopathology data and learns to predict precise sTIL% scores for each tile in the tumor bed by using a multiple instance learning regressor that only requires a weak WSI-level label. By requiring only a weak label, we overcome the large annotation efforts required to train currently existing TIL detection methods. We show that WeakSTIL is at least as good as other TIL detection methods when predicting the WSI-level sTIL% score, reaching a coefficient of determination of 0.45pm0.15 when compared to scores generated by an expert pathologist, and an AUC of 0.89pm0.05 when treating it as the clinically interesting sTIL-high vs sTIL-low classification task. Additionally, we show that the intermediate tile-level predictions of WeakSTIL are highly interpretable, which suggests that WeakSTIL pays attention to latent features related to the number of TILs and the tissue type. In the future, WeakSTIL may be used to provide consistent and interpretable sTIL% predictions to stratify breast cancer patients into targeted therapy arms.

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.

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.

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.

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.

Stain normalization algorithms aim to transform the color and intensity characteristics of a source multi-gigapixel histology image to match those of a target image, mitigating inconsistencies in the appearance of stains used to highlight cellular components in the images. We propose a new approach, StainFuser, which treats this problem as a style transfer task using a novel Conditional Latent Diffusion architecture, eliminating the need for handcrafted color components. With this method, we curate SPI-2M the largest stain normalization dataset to date of over 2 million histology images with neural style transfer for high-quality transformations. Trained on this data, StainFuser outperforms current state-of-the-art GAN and handcrafted methods in terms of the quality of normalized images. Additionally, compared to existing approaches, it improves the performance of nuclei instance segmentation and classification models when used as a test time augmentation method on the challenging CoNIC dataset. Finally, we apply StainFuser on multi-gigapixel Whole Slide Images (WSIs) and demonstrate improved performance in terms of computational efficiency, image quality and consistency across tiles over current methods.

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.

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).

Survival prediction using whole slide images (WSIs) can be formulated as a multiple instance learning (MIL) problem. However, existing MIL methods often fail to explicitly capture pathological heterogeneity within WSIs, both globally -- through long-tailed morphological distributions, and locally through -- tile-level prediction uncertainty. Optimal transport (OT) provides a principled way of modeling such heterogeneity by incorporating marginal distribution constraints. Building on this insight, we propose OTSurv, a novel MIL framework from an optimal transport perspective. Specifically, OTSurv formulates survival predictions as a heterogeneity-aware OT problem with two constraints: (1) global long-tail constraint that models prior morphological distributions to avert both mode collapse and excessive uniformity by regulating transport mass allocation, and (2) local uncertainty-aware constraint that prioritizes high-confidence patches while suppressing noise by progressively raising the total transport mass. We then recast the initial OT problem, augmented by these constraints, into an unbalanced OT formulation that can be solved with an efficient, hardware-friendly matrix scaling algorithm. Empirically, OTSurv sets new state-of-the-art results across six popular benchmarks, achieving an absolute 3.6% improvement in average C-index. In addition, OTSurv achieves statistical significance in log-rank tests and offers high interpretability, making it a powerful tool for survival prediction in digital pathology. Our codes are available at https://github.com/Y-Research-SBU/OTSurv.

The gigapixel scale of whole slide images (WSIs) poses a challenge for histopathology multi-modal chatbots, requiring a global WSI analysis for diagnosis, compounding evidence from different WSI patches. Current visual instruction datasets, generated through large language models, focus on creating question/answer pairs for individual image patches, which may lack diagnostic capacity on their own in histopathology, further complicated by the absence of spatial grounding in histopathology image captions. To bridge this gap, we introduce Quilt-Instruct, a large-scale dataset of 107,131 histopathology-specific instruction question/answer pairs, that is collected by leveraging educational histopathology videos from YouTube, which provides spatial localization of captions by automatically extracting narrators' cursor movements. In addition, we provide contextual reasoning by extracting diagnosis and supporting facts from the entire video content to guide the extrapolative reasoning of GPT-4. Using Quilt-Instruct, we train Quilt-LLaVA, which can reason beyond the given single image patch, enabling diagnostic reasoning and the capability of spatial awareness. To evaluate Quilt-LLaVA, we propose a comprehensive evaluation dataset created from 985 images and 1283 human-generated question-answers. We also thoroughly evaluate Quilt-LLaVA using public histopathology datasets, where Quilt-LLaVA significantly outperforms SOTA by over 10% on relative GPT-4 score and 4% and 9% on open and closed set VQA. Our code, data, and model are publicly available at quilt-llava.github.io.

Digitizing pathological images into gigapixel Whole Slide Images (WSIs) has opened new avenues for Computational Pathology (CPath). As positive tissue comprises only a small fraction of gigapixel WSIs, existing Multiple Instance Learning (MIL) methods typically focus on identifying salient instances via attention mechanisms. However, this leads to a bias towards easy-to-classify instances while neglecting challenging ones. Recent studies have shown that hard examples are crucial for accurately modeling discriminative boundaries. Applying such an idea at the instance level, we elaborate a novel MIL framework with masked hard instance mining (MHIM-MIL), which utilizes a Siamese structure with a consistency constraint to explore the hard instances. Using a class-aware instance probability, MHIM-MIL employs a momentum teacher to mask salient instances and implicitly mine hard instances for training the student model. To obtain diverse, non-redundant hard instances, we adopt large-scale random masking while utilizing a global recycle network to mitigate the risk of losing key features. Furthermore, the student updates the teacher using an exponential moving average, which identifies new hard instances for subsequent training iterations and stabilizes optimization. Experimental results on cancer diagnosis, subtyping, survival analysis tasks, and 12 benchmarks demonstrate that MHIM-MIL outperforms the latest methods in both performance and efficiency. The code is available at: https://github.com/DearCaat/MHIM-MIL.

Computational pathology (CPath) digitizes pathology slides into whole slide images (WSIs), enabling analysis for critical healthcare tasks such as cancer diagnosis and prognosis. However, WSIs possess extremely long sequence lengths (up to 200K), significant length variations (from 200 to 200K), and limited supervision. These extreme variations in sequence length lead to high data heterogeneity and redundancy. Conventional methods often compromise on training efficiency and optimization to preserve such heterogeneity under limited supervision. To comprehensively address these challenges, we propose a pack-based MIL framework. It packs multiple sampled, variable-length feature sequences into fixed-length ones, enabling batched training while preserving data heterogeneity. Moreover, we introduce a residual branch that composes discarded features from multiple slides into a hyperslide which is trained with tailored labels. It offers multi-slide supervision while mitigating feature loss from sampling. Meanwhile, an attention-driven downsampler is introduced to compress features in both branches to reduce redundancy. By alleviating these challenges, our approach achieves an accuracy improvement of up to 8% while using only 12% of the training time in the PANDA(UNI). Extensive experiments demonstrate that focusing data challenges in CPath holds significant potential in the era of foundation models. The code is https://github.com/FangHeng/PackMIL

Application of deep learning on histopathological whole slide images (WSIs) holds promise of improving diagnostic efficiency and reproducibility but is largely dependent on the ability to write computer code or purchase commercial solutions. We present a code-free pipeline utilizing free-to-use, open-source software (QuPath, DeepMIB, and FastPathology) for creating and deploying deep learning-based segmentation models for computational pathology. We demonstrate the pipeline on a use case of separating epithelium from stroma in colonic mucosa. A dataset of 251 annotated WSIs, comprising 140 hematoxylin-eosin (HE)-stained and 111 CD3 immunostained colon biopsy WSIs, were developed through active learning using the pipeline. On a hold-out test set of 36 HE and 21 CD3-stained WSIs a mean intersection over union score of 96.6% and 95.3% was achieved on epithelium segmentation. We demonstrate pathologist-level segmentation accuracy and clinical acceptable runtime performance and show that pathologists without programming experience can create near state-of-the-art segmentation solutions for histopathological WSIs using only free-to-use software. The study further demonstrates the strength of open-source solutions in its ability to create generalizable, open pipelines, of which trained models and predictions can seamlessly be exported in open formats and thereby used in external solutions. All scripts, trained models, a video tutorial, and the full dataset of 251 WSIs with ~31k epithelium annotations are made openly available at https://github.com/andreped/NoCodeSeg to accelerate research in the field.

Deep learning has enabled the development of highly robust foundation models for various pathological tasks across diverse diseases and patient cohorts. Among these models, vision-language pre-training, which leverages large-scale paired data to align pathology image and text embedding spaces, and provides a novel zero-shot paradigm for downstream tasks. However, existing models have been primarily data-driven and lack the incorporation of domain-specific knowledge, which limits their performance in cancer diagnosis, especially for rare tumor subtypes. To address this limitation, we establish a Knowledge-enhanced Pathology (KEEP) foundation model that harnesses disease knowledge to facilitate vision-language pre-training. Specifically, we first construct a disease knowledge graph (KG) that covers 11,454 human diseases with 139,143 disease attributes, including synonyms, definitions, and hypernym relations. We then systematically reorganize the millions of publicly available noisy pathology image-text pairs, into 143K well-structured semantic groups linked through the hierarchical relations of the disease KG. To derive more nuanced image and text representations, we propose a novel knowledge-enhanced vision-language pre-training approach that integrates disease knowledge into the alignment within hierarchical semantic groups instead of unstructured image-text pairs. Validated on 18 diverse benchmarks with more than 14,000 whole slide images (WSIs), KEEP achieves state-of-the-art performance in zero-shot cancer diagnostic tasks. Notably, for cancer detection, KEEP demonstrates an average sensitivity of 89.8% at a specificity of 95.0% across 7 cancer types. For cancer subtyping, KEEP achieves a median balanced accuracy of 0.456 in subtyping 30 rare brain cancers, indicating strong generalizability for diagnosing rare tumors.

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.

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.

In recent years, the integration of advanced imaging techniques and deep learning methods has significantly advanced computer-aided diagnosis (CAD) systems for breast cancer detection and classification. Transformers, which have shown great promise in computer vision, are now being applied to medical image analysis. However, their application to histopathological images presents challenges due to the need for extensive manual annotations of whole-slide images (WSIs), as these models require large amounts of data to work effectively, which is costly and time-consuming. Furthermore, the quadratic computational cost of Vision Transformers (ViTs) is particularly prohibitive for large, high-resolution histopathological images, especially on edge devices with limited computational resources. In this study, we introduce a novel lightweight breast cancer classification approach using transformers that operates effectively without large datasets. By incorporating parallel processing pathways for Discrete Cosine Transform (DCT) Attention and MobileConv, we convert image data from the spatial domain to the frequency domain to utilize the benefits such as filtering out high frequencies in the image, which reduces computational cost. This demonstrates the potential of our approach to improve breast cancer classification in histopathological images, offering a more efficient solution with reduced reliance on extensive annotated datasets. Our proposed model achieves an accuracy of 96.00% pm 0.48% for binary classification and 87.85% pm 0.93% for multiclass classification, which is comparable to state-of-the-art models while significantly reducing computational costs. This demonstrates the potential of our approach to improve breast cancer classification in histopathological images, offering a more efficient solution with reduced reliance on extensive annotated datasets.

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

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.

Forensic pathology is critical in determining the cause and manner of death through post-mortem examinations, both macroscopic and microscopic. The field, however, grapples with issues such as outcome variability, laborious processes, and a scarcity of trained professionals. This paper presents SongCi, an innovative visual-language model (VLM) designed specifically for forensic pathology. SongCi utilizes advanced prototypical cross-modal self-supervised contrastive learning to enhance the accuracy, efficiency, and generalizability of forensic analyses. It was pre-trained and evaluated on a comprehensive multi-center dataset, which includes over 16 million high-resolution image patches, 2,228 vision-language pairs of post-mortem whole slide images (WSIs), and corresponding gross key findings, along with 471 distinct diagnostic outcomes. Our findings indicate that SongCi surpasses existing multi-modal AI models in many forensic pathology tasks, performs comparably to experienced forensic pathologists and significantly better than less experienced ones, and provides detailed multi-modal explainability, offering critical assistance in forensic investigations. To the best of our knowledge, SongCi is the first VLM specifically developed for forensic pathological analysis and the first large-vocabulary computational pathology (CPath) model that directly processes gigapixel WSIs in forensic science.

Multimodal learning significantly benefits cancer survival prediction, especially the integration of pathological images and genomic data. Despite advantages of multimodal learning for cancer survival prediction, massive redundancy in multimodal data prevents it from extracting discriminative and compact information: (1) An extensive amount of intra-modal task-unrelated information blurs discriminability, especially for gigapixel whole slide images (WSIs) with many patches in pathology and thousands of pathways in genomic data, leading to an ``intra-modal redundancy" issue. (2) Duplicated information among modalities dominates the representation of multimodal data, which makes modality-specific information prone to being ignored, resulting in an ``inter-modal redundancy" issue. To address these, we propose a new framework, Prototypical Information Bottlenecking and Disentangling (PIBD), consisting of Prototypical Information Bottleneck (PIB) module for intra-modal redundancy and Prototypical Information Disentanglement (PID) module for inter-modal redundancy. Specifically, a variant of information bottleneck, PIB, is proposed to model prototypes approximating a bunch of instances for different risk levels, which can be used for selection of discriminative instances within modality. PID module decouples entangled multimodal data into compact distinct components: modality-common and modality-specific knowledge, under the guidance of the joint prototypical distribution. Extensive experiments on five cancer benchmark datasets demonstrated our superiority over other methods.

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.

The emerging area of computational pathology (CPath) is ripe ground for the application of deep learning (DL) methods to healthcare due to the sheer volume of raw pixel data in whole-slide images (WSIs) of cancerous tissue slides. However, it is imperative for the DL algorithms relying on nuclei-level details to be able to cope with data from `the clinical wild', which tends to be quite challenging. We study, and extend recently released PanNuke dataset consisting of ~200,000 nuclei categorized into 5 clinically important classes for the challenging tasks of segmenting and classifying nuclei in WSIs. Previous pan-cancer datasets consisted of only up to 9 different tissues and up to 21,000 unlabeled nuclei and just over 24,000 labeled nuclei with segmentation masks. PanNuke consists of 19 different tissue types that have been semi-automatically annotated and quality controlled by clinical pathologists, leading to a dataset with statistics similar to the clinical wild and with minimal selection bias. We study the performance of segmentation and classification models when applied to the proposed dataset and demonstrate the application of models trained on PanNuke to whole-slide images. We provide comprehensive statistics about the dataset and outline recommendations and research directions to address the limitations of existing DL tools when applied to real-world CPath applications.

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/.

The advent of large-scale vision foundation models, pre-trained on diverse natural images, has marked a paradigm shift in computer vision. However, how the frontier vision foundation models' efficacies transfer to specialized domains remains such as medical imaging remains an open question. This report investigates whether DINOv3, a state-of-the-art self-supervised vision transformer (ViT) that features strong capability in dense prediction tasks, can directly serve as a powerful, unified encoder for medical vision tasks without domain-specific pre-training. To answer this, we benchmark DINOv3 across common medical vision tasks, including 2D/3D classification and segmentation on a wide range of medical imaging modalities. We systematically analyze its scalability by varying model sizes and input image resolutions. Our findings reveal that DINOv3 shows impressive performance and establishes a formidable new baseline. Remarkably, it can even outperform medical-specific foundation models like BiomedCLIP and CT-Net on several tasks, despite being trained solely on natural images. However, we identify clear limitations: The model's features degrade in scenarios requiring deep domain specialization, such as in Whole-Slide Pathological Images (WSIs), Electron Microscopy (EM), and Positron Emission Tomography (PET). Furthermore, we observe that DINOv3 does not consistently obey scaling law in the medical domain; performance does not reliably increase with larger models or finer feature resolutions, showing diverse scaling behaviors across tasks. Ultimately, our work establishes DINOv3 as a strong baseline, whose powerful visual features can serve as a robust prior for multiple complex medical tasks. This opens promising future directions, such as leveraging its features to enforce multiview consistency in 3D reconstruction.

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.

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.

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.

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.

MIDOG 2025 Track 1 requires mitosis detection in whole-slideimages (WSIs) containing non-tumor, inflamed, and necrotic re-gions. Due to the complicated and heterogeneous context, aswell as possible artifacts, there are often false positives and falsenegatives, thus degrading the detection F1-score. To addressthis problem, we propose a two-stage framework. Firstly, an im-proved YOLO11x, integrated with EMA attention and LSConv,is employed to generate mitosis candidates. We use a low confi-dence threshold to generate as many proposals as possible, en-suring the detection recall. Then, a ConvNeXt-Tiny classifieris employed to filter out the false positives, ensuring the detec-tion precision. Consequently, the proposed two-stage frame-work can generate a high detection F1-score. Evaluated on afused dataset comprising MIDOG++, MITOS_WSI_CCMCT,and MITOS_WSI_CMC, our framework achieves an F1-scoreof 0.882, which is 0.035 higher than the single-stage YOLO11xbaseline. This performance gain is produced by a significantprecision improvement, from 0.762 to 0.839, and a comparablerecall. On the MIDOG 2025 Track 1 preliminary test set, thealgorithm scores an F1 score of 0.7587. The code is available athttps://github.com/xxiao0304/MIDOG-2025-Track-1-of-SZTU.

Whole slide image (WSI) analysis has become increasingly important in the medical imaging community, enabling automated and objective diagnosis, prognosis, and therapeutic-response prediction. However, in clinical practice, the ever-evolving environment hamper the utility of WSI analysis models. In this paper, we propose the FIRST continual learning framework for WSI analysis, named ConSlide, to tackle the challenges of enormous image size, utilization of hierarchical structure, and catastrophic forgetting by progressive model updating on multiple sequential datasets. Our framework contains three key components. The Hierarchical Interaction Transformer (HIT) is proposed to model and utilize the hierarchical structural knowledge of WSI. The Breakup-Reorganize (BuRo) rehearsal method is developed for WSI data replay with efficient region storing buffer and WSI reorganizing operation. The asynchronous updating mechanism is devised to encourage the network to learn generic and specific knowledge respectively during the replay stage, based on a nested cross-scale similarity learning (CSSL) module. We evaluated the proposed ConSlide on four public WSI datasets from TCGA projects. It performs best over other state-of-the-art methods with a fair WSI-based continual learning setting and achieves a better trade-off of the overall performance and forgetting on previous task

Whole Slide Image (WSI) analysis is a powerful method to facilitate the diagnosis of cancer in tissue samples. Automating this diagnosis poses various issues, most notably caused by the immense image resolution and limited annotations. WSIs commonly exhibit resolutions of 100Kx100K pixels. Annotating cancerous areas in WSIs on the pixel level is prohibitively labor-intensive and requires a high level of expert knowledge. Multiple instance learning (MIL) alleviates the need for expensive pixel-level annotations. In MIL, learning is performed on slide-level labels, in which a pathologist provides information about whether a slide includes cancerous tissue. Here, we propose Self-ViT-MIL, a novel approach for classifying and localizing cancerous areas based on slide-level annotations, eliminating the need for pixel-wise annotated training data. Self-ViT- MIL is pre-trained in a self-supervised setting to learn rich feature representation without relying on any labels. The recent Vision Transformer (ViT) architecture builds the feature extractor of Self-ViT-MIL. For localizing cancerous regions, a MIL aggregator with global attention is utilized. To the best of our knowledge, Self-ViT- MIL is the first approach to introduce self-supervised ViTs in MIL-based WSI analysis tasks. We showcase the effectiveness of our approach on the common Camelyon16 dataset. Self-ViT-MIL surpasses existing state-of-the-art MIL-based approaches in terms of accuracy and area under the curve (AUC).

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.

Whole-Slide Image (WSI) is an important tool for evaluating the prognosis of cancer patients. Present WSI-based prognosis studies generally follow a conventional paradigm -- cancer-specific model development -- where one cancer disease corresponds to one model and this model cannot make use of the prognostic knowledge from others. Despite its notable success in recent years, this paradigm has inherent limitations and has always been struggling with practical requirements: (i) scaling to the rare tumor diseases with very limited samples and (ii) benefiting from the generalizable prognostic knowledge in other cancers. To this end, this paper presents the first systematic study on Prognostic Knowledge Transfer in Pathology, called Path-PKT. It comprises three main parts. (1) We curate a large dataset (UNI2-h-DSS) with 13 cancers and use it to evaluate the transferability of prognostic knowledge between different cancers computationally. (2) We design experiments to understand what factors affect knowledge transfer and what causes positive transfers. (3) Motivated by empirical findings, we propose a new baseline approach (MoE-PKT) with a routing mechanism to utilize the generalizable prognostic knowledge in other cancers. Finally, we show the transferability of source models to rare tumor diseases. This study could lay solid foundations for the study of knowledge transfer in WSI-based cancer prognosis. Source code is available at https://github.com/liupei101/Path-PKT.

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.

Whole Slide Image (WSI) classification with multiple instance learning (MIL) in digital pathology faces significant computational challenges. Current methods mostly rely on extensive self-supervised learning (SSL) for satisfactory performance, requiring long training periods and considerable computational resources. At the same time, no pre-training affects performance due to domain shifts from natural images to WSIs. We introduce Snuffy architecture, a novel MIL-pooling method based on sparse transformers that mitigates performance loss with limited pre-training and enables continual few-shot pre-training as a competitive option. Our sparsity pattern is tailored for pathology and is theoretically proven to be a universal approximator with the tightest probabilistic sharp bound on the number of layers for sparse transformers, to date. We demonstrate Snuffy's effectiveness on CAMELYON16 and TCGA Lung cancer datasets, achieving superior WSI and patch-level accuracies. The code is available on https://github.com/jafarinia/snuffy.

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 whole slide image (WSI) classification is often formulated as a multiple instance learning (MIL) problem. Since the positive tissue is only a small fraction of the gigapixel WSI, existing MIL methods intuitively focus on identifying salient instances via attention mechanisms. However, this leads to a bias towards easy-to-classify instances while neglecting hard-to-classify instances. Some literature has revealed that hard examples are beneficial for modeling a discriminative boundary accurately. By applying such an idea at the instance level, we elaborate a novel MIL framework with masked hard instance mining (MHIM-MIL), which uses a Siamese structure (Teacher-Student) with a consistency constraint to explore the potential hard instances. With several instance masking strategies based on attention scores, MHIM-MIL employs a momentum teacher to implicitly mine hard instances for training the student model, which can be any attention-based MIL model. This counter-intuitive strategy essentially enables the student to learn a better discriminating boundary. Moreover, the student is used to update the teacher with an exponential moving average (EMA), which in turn identifies new hard instances for subsequent training iterations and stabilizes the optimization. Experimental results on the CAMELYON-16 and TCGA Lung Cancer datasets demonstrate that MHIM-MIL outperforms other latest methods in terms of performance and training cost. The code is available at: https://github.com/DearCaat/MHIM-MIL.

Weakly supervised instance segmentation (WSIS) using only image-level labels is a challenging task due to the difficulty of aligning coarse annotations with the finer task. However, with the advancement of deep neural networks (DNNs), WSIS has garnered significant attention. Following a proposal-based paradigm, we encounter a redundant segmentation problem resulting from a single instance being represented by multiple proposals. For example, we feed a picture of a dog and proposals into the network and expect to output only one proposal containing a dog, but the network outputs multiple proposals. To address this problem, we propose a novel approach for WSIS that focuses on the online refinement of complete instances through the use of MaskIoU heads to predict the integrity scores of proposals and a Complete Instances Mining (CIM) strategy to explicitly model the redundant segmentation problem and generate refined pseudo labels. Our approach allows the network to become aware of multiple instances and complete instances, and we further improve its robustness through the incorporation of an Anti-noise strategy. Empirical evaluations on the PASCAL VOC 2012 and MS COCO datasets demonstrate that our method achieves state-of-the-art performance with a notable margin. Our implementation will be made available at https://github.com/ZechengLi19/CIM.

The field of computational pathology has recently seen rapid advances driven by the development of modern vision foundation models (FMs), typically trained on vast collections of pathology images. Recent studies demonstrate that increasing the training data set and model size and integrating domain-specific image processing techniques can significantly enhance the model's performance on downstream tasks. Building on these insights, our work incorporates several recent modifications to the standard DINOv2 framework from the literature to optimize the training of pathology FMs. We also apply a post-training procedure for fine-tuning models on higher-resolution images to further enrich the information encoded in the embeddings. We present three novel pathology FMs trained on up to two orders of magnitude fewer WSIs than those used to train other state-of-the-art FMs while demonstrating a comparable or superior performance on downstream tasks. Even the model trained on TCGA alone (12k WSIs) outperforms most existing FMs and, on average, matches Virchow2, the second-best FM published to date. This suggests that there still remains a significant potential for further improving the models and algorithms used to train pathology FMs to take full advantage of the vast data collections.

Diagnosing a whole-slide image is an interactive, multi-stage process involving changes in magnification and movement between fields. Although recent pathology foundation models are strong, practical agentic systems that decide what field to examine next, adjust magnification, and deliver explainable diagnoses are still lacking. The blocker is data: scalable, clinically aligned supervision of expert viewing behavior that is tacit and experience-based, not written in textbooks or online, and therefore absent from large language model training. We introduce the AI Session Recorder, which works with standard WSI viewers to unobtrusively record routine navigation and convert the viewer logs into standardized behavioral commands (inspect or peek at discrete magnifications) and bounding boxes. A lightweight human-in-the-loop review turns AI-drafted rationales into the Pathology-CoT dataset, a form of paired "where to look" and "why it matters" supervision produced at roughly six times lower labeling time. Using this behavioral data, we build Pathologist-o3, a two-stage agent that first proposes regions of interest and then performs behavior-guided reasoning. On gastrointestinal lymph-node metastasis detection, it achieved 84.5% precision, 100.0% recall, and 75.4% accuracy, exceeding the state-of-the-art OpenAI o3 model and generalizing across backbones. To our knowledge, this constitutes one of the first behavior-grounded agentic systems in pathology. Turning everyday viewer logs into scalable, expert-validated supervision, our framework makes agentic pathology practical and establishes a path to human-aligned, upgradeable clinical AI.

Vision Language Models (VLMs) like CLIP have attracted substantial attention in pathology, serving as backbones for applications such as zero-shot image classification and Whole Slide Image (WSI) analysis. Additionally, they can function as vision encoders when combined with large language models (LLMs) to support broader capabilities. Current efforts to train pathology VLMs rely on pathology image-text pairs from platforms like PubMed, YouTube, and Twitter, which provide limited, unscalable data with generally suboptimal image quality. In this work, we leverage large-scale WSI datasets like TCGA to extract numerous high-quality image patches. We then train a large multimodal model to generate captions for these images, creating PathGen-1.6M, a dataset containing 1.6 million high-quality image-caption pairs. Our approach involves multiple agent models collaborating to extract representative WSI patches, generating and refining captions to obtain high-quality image-text pairs. Extensive experiments show that integrating these generated pairs with existing datasets to train a pathology-specific CLIP model, PathGen-CLIP, significantly enhances its ability to analyze pathological images, with substantial improvements across nine pathology-related zero-shot image classification tasks and three whole-slide image tasks. Furthermore, we construct 200K instruction-tuning data based on PathGen-1.6M and integrate PathGen-CLIP with the Vicuna LLM to create more powerful multimodal models through instruction tuning. Overall, we provide a scalable pathway for high-quality data generation in pathology, paving the way for next-generation general pathology models.

In the past few years, convolutional neural networks (CNNs) have achieved impressive results in computer vision tasks, which however mainly focus on photos with natural scene content. Besides, non-sensor derived images such as illustrations, data visualizations, figures, etc. are typically used to convey complex information or to explore large datasets. However, this kind of images has received little attention in computer vision. CNNs and similar techniques use large volumes of training data. Currently, many document analysis systems are trained in part on scene images due to the lack of large datasets of educational image data. In this paper, we address this issue and present SlideImages, a dataset for the task of classifying educational illustrations. SlideImages contains training data collected from various sources, e.g., Wikimedia Commons and the AI2D dataset, and test data collected from educational slides. We have reserved all the actual educational images as a test dataset in order to ensure that the approaches using this dataset generalize well to new educational images, and potentially other domains. Furthermore, we present a baseline system using a standard deep neural architecture and discuss dealing with the challenge of limited training data.

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.

The task of synthesizing novel views from a single image has useful applications in virtual reality and mobile computing, and a number of approaches to the problem have been proposed in recent years. A Multiplane Image (MPI) estimates the scene as a stack of RGBA layers, and can model complex appearance effects, anti-alias depth errors and synthesize soft edges better than methods that use textured meshes or layered depth images. And unlike neural radiance fields, an MPI can be efficiently rendered on graphics hardware. However, MPIs are highly redundant and require a large number of depth layers to achieve plausible results. Based on the observation that the depth complexity in local image regions is lower than that over the entire image, we split an MPI into many small, tiled regions, each with only a few depth planes. We call this representation a Tiled Multiplane Image (TMPI). We propose a method for generating a TMPI with adaptive depth planes for single-view 3D photography in the wild. Our synthesized results are comparable to state-of-the-art single-view MPI methods while having lower computational overhead.

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.

In this paper, we introduce a novel learning scheme named weakly semi-supervised instance segmentation (WSSIS) with point labels for budget-efficient and high-performance instance segmentation. Namely, we consider a dataset setting consisting of a few fully-labeled images and a lot of point-labeled images. Motivated by the main challenge of semi-supervised approaches mainly derives from the trade-off between false-negative and false-positive instance proposals, we propose a method for WSSIS that can effectively leverage the budget-friendly point labels as a powerful weak supervision source to resolve the challenge. Furthermore, to deal with the hard case where the amount of fully-labeled data is extremely limited, we propose a MaskRefineNet that refines noise in rough masks. We conduct extensive experiments on COCO and BDD100K datasets, and the proposed method achieves promising results comparable to those of the fully-supervised model, even with 50% of the fully labeled COCO data (38.8% vs. 39.7%). Moreover, when using as little as 5% of fully labeled COCO data, our method shows significantly superior performance over the state-of-the-art semi-supervised learning method (33.7% vs. 24.9%). The code is available at https://github.com/clovaai/PointWSSIS.

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.

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/

Recent advancements in diffusion models have set new benchmarks in image and video generation, enabling realistic visual synthesis across single- and multi-frame contexts. However, these models still struggle with efficiently and explicitly generating 3D-consistent content. To address this, we propose World-consistent Video Diffusion (WVD), a novel framework that incorporates explicit 3D supervision using XYZ images, which encode global 3D coordinates for each image pixel. More specifically, we train a diffusion transformer to learn the joint distribution of RGB and XYZ frames. This approach supports multi-task adaptability via a flexible inpainting strategy. For example, WVD can estimate XYZ frames from ground-truth RGB or generate novel RGB frames using XYZ projections along a specified camera trajectory. In doing so, WVD unifies tasks like single-image-to-3D generation, multi-view stereo, and camera-controlled video generation. Our approach demonstrates competitive performance across multiple benchmarks, providing a scalable solution for 3D-consistent video and image generation with a single pretrained model.

Recent rapid advancements in text-to-video (T2V) generation, such as SoRA and Kling, have shown great potential for building world simulators. However, current T2V models struggle to grasp abstract physical principles and generate videos that adhere to physical laws. This challenge arises primarily from a lack of clear guidance on physical information due to a significant gap between abstract physical principles and generation models. To this end, we introduce the World Simulator Assistant (WISA), an effective framework for decomposing and incorporating physical principles into T2V models. Specifically, WISA decomposes physical principles into textual physical descriptions, qualitative physical categories, and quantitative physical properties. To effectively embed these physical attributes into the generation process, WISA incorporates several key designs, including Mixture-of-Physical-Experts Attention (MoPA) and a Physical Classifier, enhancing the model's physics awareness. Furthermore, most existing datasets feature videos where physical phenomena are either weakly represented or entangled with multiple co-occurring processes, limiting their suitability as dedicated resources for learning explicit physical principles. We propose a novel video dataset, WISA-32K, collected based on qualitative physical categories. It consists of 32,000 videos, representing 17 physical laws across three domains of physics: dynamics, thermodynamics, and optics. Experimental results demonstrate that WISA can effectively enhance the compatibility of T2V models with real-world physical laws, achieving a considerable improvement on the VideoPhy benchmark. The visual exhibitions of WISA and WISA-32K are available in the https://360cvgroup.github.io/WISA/.

Breast-conserving surgery (BCS) aims to completely remove malignant lesions while maximizing healthy tissue preservation. Intraoperative margin assessment is essential to achieve a balance between thorough cancer resection and tissue conservation. A deep ultraviolet fluorescence scanning microscope (DUV-FSM) enables rapid acquisition of whole surface images (WSIs) for excised tissue, providing contrast between malignant and normal tissues. However, breast cancer classification with DUV WSIs is challenged by high resolutions and complex histopathological features. This study introduces a DUV WSI classification framework using a patch-level vision transformer (ViT) model, capturing local and global features. Grad-CAM++ saliency weighting highlights relevant spatial regions, enhances result interpretability, and improves diagnostic accuracy for benign and malignant tissue classification. A comprehensive 5-fold cross-validation demonstrates the proposed approach significantly outperforms conventional deep learning methods, achieving a classification accuracy of 98.33%.

Synthetic Data Generation (SDG) based on Artificial Intelligence (AI) can transform the way clinical medicine is delivered by overcoming privacy barriers that currently render clinical data sharing difficult. This is the key to accelerating the development of digital tools contributing to enhanced patient safety. Such tools include robust data-driven clinical decision support systems, and example-based digital training tools that will enable healthcare professionals to improve their diagnostic performance for enhanced patient safety. This study focuses on the clinical evaluation of medical SDG, with a proof-of-concept investigation on diagnosing Inflammatory Bowel Disease (IBD) using Wireless Capsule Endoscopy (WCE) images. Its scientific contributions include a) a novel protocol for the systematic Clinical Evaluation of Medical Image Synthesis (CEMIS); b) a novel variational autoencoder-based model for the generation of high-resolution synthetic WCE images; and c) a comprehensive evaluation of the synthetic images using the CEMIS protocol by 10 international WCE specialists, in terms of image quality, diversity, and realism, as well as their utility for clinical decision-making. The results show that TIDE-II generates clinically plausible, very realistic WCE images, of improved quality compared to relevant state-of-the-art generative models. Concludingly, CEMIS can serve as a reference for future research on medical image-generation techniques, while the adaptation/extension of the architecture of TIDE-II to other imaging domains can be promising.

Generating flexible-view 3D scenes, including 360{\deg} rotation and zooming, from single images is challenging due to a lack of 3D data. To this end, we introduce FlexWorld, a novel framework consisting of two key components: (1) a strong video-to-video (V2V) diffusion model to generate high-quality novel view images from incomplete input rendered from a coarse scene, and (2) a progressive expansion process to construct a complete 3D scene. In particular, leveraging an advanced pre-trained video model and accurate depth-estimated training pairs, our V2V model can generate novel views under large camera pose variations. Building upon it, FlexWorld progressively generates new 3D content and integrates it into the global scene through geometry-aware scene fusion. Extensive experiments demonstrate the effectiveness of FlexWorld in generating high-quality novel view videos and flexible-view 3D scenes from single images, achieving superior visual quality under multiple popular metrics and datasets compared to existing state-of-the-art methods. Qualitatively, we highlight that FlexWorld can generate high-fidelity scenes with flexible views like 360{\deg} rotations and zooming. Project page: https://ml-gsai.github.io/FlexWorld.

Humans can develop internal world models that encode common sense knowledge, telling them how the world works and predicting the consequences of their actions. This concept has emerged as a promising direction for establishing general-purpose machine-learning models in recent preliminary works, e.g., for visual representation learning. In this paper, we present CheXWorld, the first effort towards a self-supervised world model for radiographic images. Specifically, our work develops a unified framework that simultaneously models three aspects of medical knowledge essential for qualified radiologists, including 1) local anatomical structures describing the fine-grained characteristics of local tissues (e.g., architectures, shapes, and textures); 2) global anatomical layouts describing the global organization of the human body (e.g., layouts of organs and skeletons); and 3) domain variations that encourage CheXWorld to model the transitions across different appearance domains of radiographs (e.g., varying clarity, contrast, and exposure caused by collecting radiographs from different hospitals, devices, or patients). Empirically, we design tailored qualitative and quantitative analyses, revealing that CheXWorld successfully captures these three dimensions of medical knowledge. Furthermore, transfer learning experiments across eight medical image classification and segmentation benchmarks showcase that CheXWorld significantly outperforms existing SSL methods and large-scale medical foundation models. Code & pre-trained models are available at https://github.com/LeapLabTHU/CheXWorld.

We present LatentCSI, a novel method for generating images of the physical environment from WiFi CSI measurements that leverages a pretrained latent diffusion model (LDM). Unlike prior approaches that rely on complex and computationally intensive techniques such as GANs, our method employs a lightweight neural network to map CSI amplitudes directly into the latent space of an LDM. We then apply the LDM's denoising diffusion model to the latent representation with text-based guidance before decoding using the LDM's pretrained decoder to obtain a high-resolution image. This design bypasses the challenges of pixel-space image generation and avoids the explicit image encoding stage typically required in conventional image-to-image pipelines, enabling efficient and high-quality image synthesis. We validate our approach on two datasets: a wide-band CSI dataset we collected with off-the-shelf WiFi devices and cameras; and a subset of the publicly available MM-Fi dataset. The results demonstrate that LatentCSI outperforms baselines of comparable complexity trained directly on ground-truth images in both computational efficiency and perceptual quality, while additionally providing practical advantages through its unique capacity for text-guided controllability.

Designing structured visuals such as presentation slides is essential for communicative needs, necessitating both content creation and visual planning skills. In this work, we tackle the challenge of automated slide generation, where models produce slide presentations from natural language (NL) instructions. We first introduce the SlidesBench benchmark, the first benchmark for slide generation with 7k training and 585 testing examples derived from 310 slide decks across 10 domains. SlidesBench supports evaluations that are (i)reference-based to measure similarity to a target slide, and (ii)reference-free to measure the design quality of generated slides alone. We benchmark end-to-end image generation and program generation methods with a variety of models, and find that programmatic methods produce higher-quality slides in user-interactable formats. Built on the success of program generation, we create AutoPresent, an 8B Llama-based model trained on 7k pairs of instructions paired with code for slide generation, and achieve results comparable to the closed-source model GPT-4o. We further explore iterative design refinement where the model is tasked to self-refine its own output, and we found that this process improves the slide's quality. We hope that our work will provide a basis for future work on generating structured visuals.

In the application of Multiple Instance Learning (MIL) methods for Whole Slide Image (WSI) classification, attention mechanisms often focus on a subset of discriminative instances, which are closely linked to overfitting. To mitigate overfitting, we present Attention-Challenging MIL (ACMIL). ACMIL combines two techniques based on separate analyses for attention value concentration. Firstly, UMAP of instance features reveals various patterns among discriminative instances, with existing attention mechanisms capturing only some of them. To remedy this, we introduce Multiple Branch Attention (MBA) to capture more discriminative instances using multiple attention branches. Secondly, the examination of the cumulative value of Top-K attention scores indicates that a tiny number of instances dominate the majority of attention. In response, we present Stochastic Top-K Instance Masking (STKIM), which masks out a portion of instances with Top-K attention values and allocates their attention values to the remaining instances. The extensive experimental results on three WSI datasets with two pre-trained backbones reveal that our ACMIL outperforms state-of-the-art methods. Additionally, through heatmap visualization and UMAP visualization, this paper extensively illustrates ACMIL's effectiveness in suppressing attention value concentration and overcoming the overfitting challenge. The source code is available at https://github.com/dazhangyu123/ACMIL.

Lecture slide element detection and retrieval are key problems in slide understanding. Training effective models for these tasks often depends on extensive manual annotation. However, annotating large volumes of lecture slides for supervised training is labor intensive and requires domain expertise. To address this, we propose a large language model (LLM)-guided synthetic lecture slide generation pipeline, SynLecSlideGen, which produces high-quality, coherent and realistic slides. We also create an evaluation benchmark, namely RealSlide by manually annotating 1,050 real lecture slides. To assess the utility of our synthetic slides, we perform few-shot transfer learning on real data using models pre-trained on them. Experimental results show that few-shot transfer learning with pretraining on synthetic slides significantly improves performance compared to training only on real data. This demonstrates that synthetic data can effectively compensate for limited labeled lecture slides. The code and resources of our work are publicly available on our project website: https://synslidegen.github.io/.

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.

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.

Image-to-Image translation (I2I) is a subtype of Machine Learning (ML) that has tremendous potential in applications where two domains of images and the need for translation between the two exist, such as the removal of fog. For example, this could be useful for autonomous vehicles, which currently struggle with adverse weather conditions like fog. However, datasets for I2I tasks are not abundant and typically hard to acquire. Here, we introduce STEREOFOG, a dataset comprised of 10,067 paired fogged and clear images, captured using a custom-built device, with the purpose of exploring I2I's potential in this domain. It is the only real-world dataset of this kind to the best of our knowledge. Furthermore, we apply and optimize the pix2pix I2I ML framework to this dataset. With the final model achieving an average Complex Wavelet-Structural Similarity (CW-SSIM) score of 0.76, we prove the technique's suitability for the problem.

We present PRISM, a unified framework that enables multiple image generation and editing tasks in a single foundational model. Starting from a pre-trained text-to-image diffusion model, PRISM proposes an effective fine-tuning strategy to produce RGB images along with intrinsic maps (referred to as X layers) simultaneously. Unlike previous approaches, which infer intrinsic properties individually or require separate models for decomposition and conditional generation, PRISM maintains consistency across modalities by generating all intrinsic layers jointly. It supports diverse tasks, including text-to-RGBX generation, RGB-to-X decomposition, and X-to-RGBX conditional generation. Additionally, PRISM enables both global and local image editing through conditioning on selected intrinsic layers and text prompts. Extensive experiments demonstrate the competitive performance of PRISM both for intrinsic image decomposition and conditional image generation while preserving the base model's text-to-image generation capability.

Omnidirectional images (ODIs) are commonly used in real-world visual tasks, and high-resolution ODIs help improve the performance of related visual tasks. Most existing super-resolution methods for ODIs use end-to-end learning strategies, resulting in inferior realness of generated images and a lack of effective out-of-domain generalization capabilities in training methods. Image generation methods represented by diffusion model provide strong priors for visual tasks and have been proven to be effectively applied to image restoration tasks. Leveraging the image priors of the Stable Diffusion (SD) model, we achieve omnidirectional image super-resolution with both fidelity and realness, dubbed as OmniSSR. Firstly, we transform the equirectangular projection (ERP) images into tangent projection (TP) images, whose distribution approximates the planar image domain. Then, we use SD to iteratively sample initial high-resolution results. At each denoising iteration, we further correct and update the initial results using the proposed Octadecaplex Tangent Information Interaction (OTII) and Gradient Decomposition (GD) technique to ensure better consistency. Finally, the TP images are transformed back to obtain the final high-resolution results. Our method is zero-shot, requiring no training or fine-tuning. Experiments of our method on two benchmark datasets demonstrate the effectiveness of our proposed method.

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.

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.

To improve Multimodal Large Language Models' (MLLMs) ability to process images and complex instructions, researchers predominantly curate large-scale visual instruction tuning datasets, which are either sourced from existing vision tasks or synthetically generated using LLMs and image descriptions. However, they often suffer from critical flaws, including misaligned instruction-image pairs and low-quality images. Such issues hinder training efficiency and limit performance improvements, as models waste resources on noisy or irrelevant data with minimal benefit to overall capability. To address this issue, we propose a Visual-Centric Selection approach via Agents Collaboration (ViSA), which centers on image quality assessment and image-instruction relevance evaluation. Specifically, our approach consists of 1) an image information quantification method via visual agents collaboration to select images with rich visual information, and 2) a visual-centric instruction quality assessment method to select high-quality instruction data related to high-quality images. Finally, we reorganize 80K instruction data from large open-source datasets. Extensive experiments demonstrate that ViSA outperforms or is comparable to current state-of-the-art models on seven benchmarks, using only 2.5\% of the original data, highlighting the efficiency of our data selection approach. Moreover, we conduct ablation studies to validate the effectiveness of each component of our method. The code is available at https://github.com/HITsz-TMG/ViSA.

This paper presents a versatile image-to-image visual assistant, PixWizard, designed for image generation, manipulation, and translation based on free-from language instructions. To this end, we tackle a variety of vision tasks into a unified image-text-to-image generation framework and curate an Omni Pixel-to-Pixel Instruction-Tuning Dataset. By constructing detailed instruction templates in natural language, we comprehensively include a large set of diverse vision tasks such as text-to-image generation, image restoration, image grounding, dense image prediction, image editing, controllable generation, inpainting/outpainting, and more. Furthermore, we adopt Diffusion Transformers (DiT) as our foundation model and extend its capabilities with a flexible any resolution mechanism, enabling the model to dynamically process images based on the aspect ratio of the input, closely aligning with human perceptual processes. The model also incorporates structure-aware and semantic-aware guidance to facilitate effective fusion of information from the input image. Our experiments demonstrate that PixWizard not only shows impressive generative and understanding abilities for images with diverse resolutions but also exhibits promising generalization capabilities with unseen tasks and human instructions. The code and related resources are available at https://github.com/AFeng-x/PixWizard

Diffusion-weighted magnetic resonance imaging (DW-MRI) can be used to characterise the microstructure of the nervous tissue, e.g. to delineate brain white matter connections in a non-invasive manner via fibre tracking. Magnetic Resonance Imaging (MRI) in high spatial resolution would play an important role in visualising such fibre tracts in a superior manner. However, obtaining an image of such resolution comes at the expense of longer scan time. Longer scan time can be associated with the increase of motion artefacts, due to the patient's psychological and physical conditions. Single Image Super-Resolution (SISR), a technique aimed to obtain high-resolution (HR) details from one single low-resolution (LR) input image, achieved with Deep Learning, is the focus of this study. Compared to interpolation techniques or sparse-coding algorithms, deep learning extracts prior knowledge from big datasets and produces superior MRI images from the low-resolution counterparts. In this research, a deep learning based super-resolution technique is proposed and has been applied for DW-MRI. Images from the IXI dataset have been used as the ground-truth and were artificially downsampled to simulate the low-resolution images. The proposed method has shown statistically significant improvement over the baselines and achieved an SSIM of 0.913pm0.045.

While text-to-image (T2I) models can synthesize high-quality images, their performance degrades significantly when prompted with novel or out-of-distribution (OOD) entities due to inherent knowledge cutoffs. We introduce World-To-Image, a novel framework that bridges this gap by empowering T2I generation with agent-driven world knowledge. We design an agent that dynamically searches the web to retrieve images for concepts unknown to the base model. This information is then used to perform multimodal prompt optimization, steering powerful generative backbones toward an accurate synthesis. Critically, our evaluation goes beyond traditional metrics, utilizing modern assessments like LLMGrader and ImageReward to measure true semantic fidelity. Our experiments show that World-To-Image substantially outperforms state-of-the-art methods in both semantic alignment and visual aesthetics, achieving +8.1% improvement in accuracy-to-prompt on our curated NICE benchmark. Our framework achieves these results with high efficiency in less than three iterations, paving the way for T2I systems that can better reflect the ever-changing real world. Our demo code is available herehttps://github.com/mhson-kyle/World-To-Image.

Zero-shot and prompt-based technologies capitalized on using frequently occurring images to transform visual reasoning tasks, which explains why such technologies struggle with valuable yet scarce scientific image sets. In this work, we propose Zenesis, a comprehensive no-code interactive platform designed to minimize barriers posed by data readiness for scientific images. We develop lightweight multi-modal adaptation techniques that enable zero-shot operation on raw scientific data, along with human-in-the-loop refinement and heuristic-based temporal enhancement options. We demonstrate the performance of our approach through comprehensive comparison and validation on challenging Focused Ion Beam Scanning Electron Microscopy (FIB-SEM) data of catalyst-loaded membranes. Zenesis significantly outperforms baseline methods, achieving an average accuracy of 0.947, an Intersection over Union (IOU) of 0.858, and a Dice score of 0.923 for amorphous catalyst samples and accuracy of 0.987, an IOU of 0.857, and a Dice score of 0.923 for crystalline samples. These results mark a substantial improvement over traditional methods like Otsu thresholding and even advanced models like Segment Anything Model (SAM) when used in isolation. Our results demonstrate that Zenesis is a powerful tool for scientific applications, particularly in fields where high-quality annotated datasets are unavailable, accelerating accurate analysis of experimental imaging.