Daily Papers

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

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

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

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

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

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

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.

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

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

Digital pathology enables automatic analysis of histopathological sections using artificial intelligence (AI). Automatic evaluation could improve diagnostic efficiency and help find associations between morphological features and clinical outcome. For development of such prediction models, identifying invasive epithelial cells, and separating these from benign epithelial cells and in situ lesions would be the first step. In this study, we aimed to develop an AI model for segmentation of epithelial cells in sections from breast cancer. We generated epithelial ground truth masks by restaining hematoxylin and eosin (HE) sections with cytokeratin (CK) AE1/AE3, and by pathologists' annotations. HE/CK image pairs were used to train a convolutional neural network, and data augmentation was used to make the model more robust. Tissue microarrays (TMAs) from 839 patients, and whole slide images from two patients were used for training and evaluation of the models. The sections were derived from four cohorts of breast cancer patients. TMAs from 21 patients from a fifth cohort was used as a second test set. In quantitative evaluation, a mean Dice score of 0.70, 0.79, and 0.75 for invasive epithelial cells, benign epithelial cells, and in situ lesions, respectively, were achieved. In qualitative scoring (0-5) by pathologists, results were best for all epithelium and invasive epithelium, with scores of 4.7 and 4.4. Scores for benign epithelium and in situ lesions were 3.7 and 2.0. The proposed model segmented epithelial cells in HE stained breast cancer slides well, but further work is needed for accurate division between the classes. Immunohistochemistry, together with pathologists' annotations, enabled the creation of accurate ground truths. The model is made freely available in FastPathology and the code is available at https://github.com/AICAN-Research/breast-epithelium-segmentation

Cell segmentation is a critical step for quantitative single-cell analysis in microscopy images. Existing cell segmentation methods are often tailored to specific modalities or require manual interventions to specify hyperparameters in different experimental settings. Here, we present a multi-modality cell segmentation benchmark, comprising over 1500 labeled images derived from more than 50 diverse biological experiments. The top participants developed a Transformer-based deep-learning algorithm that not only exceeds existing methods, but can also be applied to diverse microscopy images across imaging platforms and tissue types without manual parameter adjustments. This benchmark and the improved algorithm offer promising avenues for more accurate and versatile cell analysis in microscopy imaging.

Segmenting cells and tracking their motion over time is a common task in biomedical applications. However, predicting accurate instance-wise segmentation and cell motions from microscopy imagery remains a challenging task. Using microstructured environments for analyzing single cells in a constant flow of media adds additional complexity. While large-scale labeled microscopy datasets are available, we are not aware of any large-scale dataset, including both cells and microstructures. In this paper, we introduce the trapped yeast cell (TYC) dataset, a novel dataset for understanding instance-level semantics and motions of cells in microstructures. We release 105 dense annotated high-resolution brightfield microscopy images, including about 19k instance masks. We also release 261 curated video clips composed of 1293 high-resolution microscopy images to facilitate unsupervised understanding of cell motions and morphology. TYC offers ten times more instance annotations than the previously largest dataset, including cells and microstructures. Our effort also exceeds previous attempts in terms of microstructure variability, resolution, complexity, and capturing device (microscopy) variability. We facilitate a unified comparison on our novel dataset by introducing a standardized evaluation strategy. TYC and evaluation code are publicly available under CC BY 4.0 license.

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

Separating and labeling each instance of a nucleus (instance-aware segmentation) is the key challenge in segmenting single cell nuclei on fluorescence microscopy images. Deep Neural Networks can learn the implicit transformation of a nuclear image into a probability map indicating the class membership of each pixel (nucleus or background), but the use of post-processing steps to turn the probability map into a labeled object mask is error-prone. This especially accounts for nuclear images of tissue sections and nuclear images across varying tissue preparations. In this work, we aim to evaluate the performance of state-of-the-art deep learning architectures to segment nuclei in fluorescence images of various tissue origins and sample preparation types without post-processing. We compare architectures that operate on pixel to pixel translation and an architecture that operates on object detection and subsequent locally applied segmentation. In addition, we propose a novel strategy to create artificial images to extend the training set. We evaluate the influence of ground truth annotation quality, image scale and segmentation complexity on segmentation performance. Results show that three out of four deep learning architectures (U-Net, U-Net with ResNet34 backbone, Mask R-CNN) can segment fluorescent nuclear images on most of the sample preparation types and tissue origins with satisfactory segmentation performance. Mask R-CNN, an architecture designed to address instance aware segmentation tasks, outperforms other architectures. Equal nuclear mean size, consistent nuclear annotations and the use of artificially generated images result in overall acceptable precision and recall across different tissues and sample preparation types.

Cell instance segmentation in cytology images has significant importance for biology analysis and cancer screening, while remains challenging due to 1) the extensive overlapping translucent cell clusters that cause the ambiguous boundaries, and 2) the confusion of mimics and debris as nuclei. In this work, we proposed a De-overlapping Network (DoNet) in a decompose-and-recombined strategy. A Dual-path Region Segmentation Module (DRM) explicitly decomposes the cell clusters into intersection and complement regions, followed by a Semantic Consistency-guided Recombination Module (CRM) for integration. To further introduce the containment relationship of the nucleus in the cytoplasm, we design a Mask-guided Region Proposal Strategy (MRP) that integrates the cell attention maps for inner-cell instance prediction. We validate the proposed approach on ISBI2014 and CPS datasets. Experiments show that our proposed DoNet significantly outperforms other state-of-the-art (SOTA) cell instance segmentation methods. The code is available at https://github.com/DeepDoNet/DoNet.

Holistic 3D modeling of molecularly defined brain structures is crucial for understanding complex brain functions. Emerging tissue profiling technologies enable the construction of a comprehensive atlas of the mammalian brain with sub-cellular resolution and spatially resolved gene expression data. However, such tera-scale volumetric datasets present significant computational challenges in understanding complex brain functions within their native 3D spatial context. Here, we propose the novel generative approach Tera-MIND, which can simulate Tera-scale Mouse braINs in 3D using a patch-based and boundary-aware Diffusion model. Taking spatial transcriptomic data as the conditional input, we generate virtual mouse brains with comprehensive cellular morphological detail at teravoxel scale. Through the lens of 3D gene-gene self-attention, we identify spatial molecular interactions for key transcriptomic pathways in the murine brain, exemplified by glutamatergic and dopaminergic neuronal systems. Importantly, these in-silico biological findings are consistent and reproducible across three tera-scale virtual mouse brains. Therefore, Tera-MIND showcases a promising path toward efficient and generative simulations of whole organ systems for biomedical research. Project website: http://musikisomorphie.github.io/Tera-MIND.html{https}

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

The segmentation of cell nuclei in tissue images stained with the blood dye hematoxylin and eosin (H&E) is essential for various clinical applications and analyses. Due to the complex characteristics of cellular morphology, a large receptive field is considered crucial for generating high-quality segmentation. However, previous methods face challenges in achieving a balance between the receptive field and computational burden. To address this issue, we propose LKCell, a high-accuracy and efficient cell segmentation method. Its core insight lies in unleashing the potential of large convolution kernels to achieve computationally efficient large receptive fields. Specifically, (1) We transfer pre-trained large convolution kernel models to the medical domain for the first time, demonstrating their effectiveness in cell segmentation. (2) We analyze the redundancy of previous methods and design a new segmentation decoder based on large convolution kernels. It achieves higher performance while significantly reducing the number of parameters. We evaluate our method on the most challenging benchmark and achieve state-of-the-art results (0.5080 mPQ) in cell nuclei instance segmentation with only 21.6% FLOPs compared with the previous leading method. Our source code and models are available at https://github.com/hustvl/LKCell.

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.

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

In biological research, fluorescence staining is a key technique to reveal the locations and morphology of subcellular structures. However, it is slow, expensive, and harmful to cells. In this paper, we model it as a deep learning task termed subcellular structure prediction (SSP), aiming to predict the 3D fluorescent images of multiple subcellular structures from a 3D transmitted-light image. Unfortunately, due to the limitations of current biotechnology, each image is partially labeled in SSP. Besides, naturally, subcellular structures vary considerably in size, which causes the multi-scale issue of SSP. To overcome these challenges, we propose Re-parameterizing Mixture-of-Diverse-Experts (RepMode), a network that dynamically organizes its parameters with task-aware priors to handle specified single-label prediction tasks. In RepMode, the Mixture-of-Diverse-Experts (MoDE) block is designed to learn the generalized parameters for all tasks, and gating re-parameterization (GatRep) is performed to generate the specialized parameters for each task, by which RepMode can maintain a compact practical topology exactly like a plain network, and meanwhile achieves a powerful theoretical topology. Comprehensive experiments show that RepMode can achieve state-of-the-art overall performance in SSP.

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

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.

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.

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

Computational microscopy, in which hardware and algorithms of an imaging system are jointly designed, shows promise for making imaging systems that cost less, perform more robustly, and collect new types of information. Often, the performance of computational imaging systems, especially those that incorporate machine learning, is sample-dependent. Thus, standardized datasets are an essential tool for comparing the performance of different approaches. Here, we introduce the Berkeley Single Cell Computational Microscopy (BSCCM) dataset, which contains over ~12,000,000 images of 400,000 of individual white blood cells. The dataset contains images captured with multiple illumination patterns on an LED array microscope and fluorescent measurements of the abundance of surface proteins that mark different cell types. We hope this dataset will provide a valuable resource for the development and testing of new algorithms in computational microscopy and computer vision with practical biomedical applications.

Cell instance segmentation is a fundamental task in digital pathology with broad clinical applications. Recently, vision foundation models, which are predominantly based on Vision Transformers (ViTs), have achieved remarkable success in pathology image analysis. However, their improvements in cell instance segmentation remain limited. A key challenge arises from the tokenization process in ViTs, which substantially reduces the spatial resolution of input images, leading to suboptimal segmentation quality, especially for small and densely packed cells. To address this problem, we propose CellVTA (Cell Vision Transformer with Adapter), a novel method that improves the performance of vision foundation models for cell instance segmentation by incorporating a CNN-based adapter module. This adapter extracts high-resolution spatial information from input images and injects it into the ViT through a cross-attention mechanism. Our method preserves the core architecture of ViT, ensuring seamless integration with pretrained foundation models. Extensive experiments show that CellVTA achieves 0.538 mPQ on the CoNIC dataset and 0.506 mPQ on the PanNuke dataset, which significantly outperforms the state-of-the-art cell segmentation methods. Ablation studies confirm the superiority of our approach over other fine-tuning strategies, including decoder-only fine-tuning and full fine-tuning. Our code and models are publicly available at https://github.com/JieZheng-ShanghaiTech/CellVTA.

Nuclei detection and segmentation in hematoxylin and eosin-stained (H&E) tissue images are important clinical tasks and crucial for a wide range of applications. However, it is a challenging task due to nuclei variances in staining and size, overlapping boundaries, and nuclei clustering. While convolutional neural networks have been extensively used for this task, we explore the potential of Transformer-based networks in this domain. Therefore, we introduce a new method for automated instance segmentation of cell nuclei in digitized tissue samples using a deep learning architecture based on Vision Transformer called CellViT. CellViT is trained and evaluated on the PanNuke dataset, which is one of the most challenging nuclei instance segmentation datasets, consisting of nearly 200,000 annotated Nuclei into 5 clinically important classes in 19 tissue types. We demonstrate the superiority of large-scale in-domain and out-of-domain pre-trained Vision Transformers by leveraging the recently published Segment Anything Model and a ViT-encoder pre-trained on 104 million histological image patches - achieving state-of-the-art nuclei detection and instance segmentation performance on the PanNuke dataset with a mean panoptic quality of 0.50 and an F1-detection score of 0.83. The code is publicly available at https://github.com/TIO-IKIM/CellViT

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.

Colorectal cancer is one of the most common cancers worldwide, so early pathological examination is very important. However, it is time-consuming and labor-intensive to identify the number and type of cells on H&E images in clinical. Therefore, automatic segmentation and classification task and counting the cellular composition of H&E images from pathological sections is proposed by CoNIC Challenge 2022. We proposed a multi-scale Swin transformer with HTC for this challenge, and also applied the known normalization methods to generate more augmentation data. Finally, our strategy showed that the multi-scale played a crucial role to identify different scale features and the augmentation arose the recognition of model.

Over the last five years, deep generative models have gradually been adopted for various tasks in biological research. Notably, image-to-image translation methods showed to be effective in revealing subtle phenotypic cell variations otherwise invisible to the human eye. Current methods to achieve this goal mainly rely on Generative Adversarial Networks (GANs). However, these models are known to suffer from some shortcomings such as training instability and mode collapse. Furthermore, the lack of robustness to invert a real image into the latent of a trained GAN prevents flexible editing of real images. In this work, we propose PhenDiff, an image-to-image translation method based on conditional diffusion models to identify subtle phenotypes in microscopy images. We evaluate this approach on biological datasets against previous work such as CycleGAN. We show that PhenDiff outperforms this baseline in terms of quality and diversity of the generated images. We then apply this method to display invisible phenotypic changes triggered by a rare neurodevelopmental disorder on microscopy images of organoids. Altogether, we demonstrate that PhenDiff is able to perform high quality biological image-to-image translation allowing to spot subtle phenotype variations on a real image.

Development of artificial intelligence (AI) techniques in medical imaging requires access to large-scale and diverse datasets for training and evaluation. In dermatology, obtaining such datasets remains challenging due to significant variations in patient populations, illumination conditions, and acquisition system characteristics. In this work, we propose S-SYNTH, the first knowledge-based, adaptable open-source skin simulation framework to rapidly generate synthetic skin, 3D models and digitally rendered images, using an anatomically inspired multi-layer, multi-component skin and growing lesion model. The skin model allows for controlled variation in skin appearance, such as skin color, presence of hair, lesion shape, and blood fraction among other parameters. We use this framework to study the effect of possible variations on the development and evaluation of AI models for skin lesion segmentation, and show that results obtained using synthetic data follow similar comparative trends as real dermatologic images, while mitigating biases and limitations from existing datasets including small dataset size, lack of diversity, and underrepresentation.

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.

Identifying cell types and understanding their functional properties is crucial for unraveling the mechanisms underlying perception and cognition. In the retina, functional types can be identified by carefully selected stimuli, but this requires expert domain knowledge and biases the procedure towards previously known cell types. In the visual cortex, it is still unknown what functional types exist and how to identify them. Thus, for unbiased identification of the functional cell types in retina and visual cortex, new approaches are needed. Here we propose an optimization-based clustering approach using deep predictive models to obtain functional clusters of neurons using Most Discriminative Stimuli (MDS). Our approach alternates between stimulus optimization with cluster reassignment akin to an expectation-maximization algorithm. The algorithm recovers functional clusters in mouse retina, marmoset retina and macaque visual area V4. This demonstrates that our approach can successfully find discriminative stimuli across species, stages of the visual system and recording techniques. The resulting most discriminative stimuli can be used to assign functional cell types fast and on the fly, without the need to train complex predictive models or show a large natural scene dataset, paving the way for experiments that were previously limited by experimental time. Crucially, MDS are interpretable: they visualize the distinctive stimulus patterns that most unambiguously identify a specific type of neuron.

With the rapid development of computational pathology, many AI-assisted diagnostic tasks have emerged. Cellular nuclei segmentation can segment various types of cells for downstream analysis, but it relies on predefined categories and lacks flexibility. Moreover, pathology visual question answering can perform image-level understanding but lacks region-level detection capability. To address this, we propose a new benchmark called Pathology Visual Grounding (PathVG), which aims to detect regions based on expressions with different attributes. To evaluate PathVG, we create a new dataset named RefPath which contains 27,610 images with 33,500 language-grounded boxes. Compared to visual grounding in other domains, PathVG presents pathological images at multi-scale and contains expressions with pathological knowledge. In the experimental study, we found that the biggest challenge was the implicit information underlying the pathological expressions. Based on this, we proposed Pathology Knowledge-enhanced Network (PKNet) as the baseline model for PathVG. PKNet leverages the knowledge-enhancement capabilities of Large Language Models (LLMs) to convert pathological terms with implicit information into explicit visual features, and fuses knowledge features with expression features through the designed Knowledge Fusion Module (KFM). The proposed method achieves state-of-the-art performance on the PathVG benchmark.

Star-convex shapes arise across bio-microscopy and radiology in the form of nuclei, nodules, metastases, and other units. Existing instance segmentation networks for such structures train on densely labeled instances for each dataset, which requires substantial and often impractical manual annotation effort. Further, significant reengineering or finetuning is needed when presented with new datasets and imaging modalities due to changes in contrast, shape, orientation, resolution, and density. We present AnyStar, a domain-randomized generative model that simulates synthetic training data of blob-like objects with randomized appearance, environments, and imaging physics to train general-purpose star-convex instance segmentation networks. As a result, networks trained using our generative model do not require annotated images from unseen datasets. A single network trained on our synthesized data accurately 3D segments C. elegans and P. dumerilii nuclei in fluorescence microscopy, mouse cortical nuclei in micro-CT, zebrafish brain nuclei in EM, and placental cotyledons in human fetal MRI, all without any retraining, finetuning, transfer learning, or domain adaptation. Code is available at https://github.com/neel-dey/AnyStar.

Building a virtual cell capable of accurately simulating cellular behaviors in silico has long been a dream in computational biology. We introduce CellFlux, an image-generative model that simulates cellular morphology changes induced by chemical and genetic perturbations using flow matching. Unlike prior methods, CellFlux models distribution-wise transformations from unperturbed to perturbed cell states, effectively distinguishing actual perturbation effects from experimental artifacts such as batch effects -- a major challenge in biological data. Evaluated on chemical (BBBC021), genetic (RxRx1), and combined perturbation (JUMP) datasets, CellFlux generates biologically meaningful cell images that faithfully capture perturbation-specific morphological changes, achieving a 35% improvement in FID scores and a 12% increase in mode-of-action prediction accuracy over existing methods. Additionally, CellFlux enables continuous interpolation between cellular states, providing a potential tool for studying perturbation dynamics. These capabilities mark a significant step toward realizing virtual cell modeling for biomedical research. Project page: https://yuhui-zh15.github.io/CellFlux/.

In clinical radiology reports, doctors capture important information about the patient's health status. They convey their observations from raw medical imaging data about the inner structures of a patient. As such, formulating reports requires medical experts to possess wide-ranging knowledge about anatomical regions with their normal, healthy appearance as well as the ability to recognize abnormalities. This explicit grasp on both the patient's anatomy and their appearance is missing in current medical image-processing systems as annotations are especially difficult to gather. This renders the models to be narrow experts e.g. for identifying specific diseases. In this work, we recover this missing link by adding human anatomy into the mix and enable the association of content in medical reports to their occurrence in associated imagery (medical phrase grounding). To exploit anatomical structures in this scenario, we present a sophisticated automatic pipeline to gather and integrate human bodily structures from computed tomography datasets, which we incorporate in our PAXRay: A Projected dataset for the segmentation of Anatomical structures in X-Ray data. Our evaluation shows that methods that take advantage of anatomical information benefit heavily in visually grounding radiologists' findings, as our anatomical segmentations allow for up to absolute 50% better grounding results on the OpenI dataset as compared to commonly used region proposals. The PAXRay dataset is available at https://constantinseibold.github.io/paxray/.

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

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.

Extracting single-cell information from microscopy data requires accurate instance-wise segmentations. Obtaining pixel-wise segmentations from microscopy imagery remains a challenging task, especially with the added complexity of microstructured environments. This paper presents a novel dataset for segmenting yeast cells in microstructures. We offer pixel-wise instance segmentation labels for both cells and trap microstructures. In total, we release 493 densely annotated microscopy images. To facilitate a unified comparison between novel segmentation algorithms, we propose a standardized evaluation strategy for our dataset. The aim of the dataset and evaluation strategy is to facilitate the development of new cell segmentation approaches. The dataset is publicly available at https://christophreich1996.github.io/yeast_in_microstructures_dataset/ .

Deep learning-based image generation has seen significant advancements with diffusion models, notably improving the quality of generated images. Despite these developments, generating images with unseen characteristics beneficial for downstream tasks has received limited attention. To bridge this gap, we propose Style-Extracting Diffusion Models, featuring two conditioning mechanisms. Specifically, we utilize 1) a style conditioning mechanism which allows to inject style information of previously unseen images during image generation and 2) a content conditioning which can be targeted to a downstream task, e.g., layout for segmentation. We introduce a trainable style encoder to extract style information from images, and an aggregation block that merges style information from multiple style inputs. This architecture enables the generation of images with unseen styles in a zero-shot manner, by leveraging styles from unseen images, resulting in more diverse generations. In this work, we use the image layout as target condition and first show the capability of our method on a natural image dataset as a proof-of-concept. We further demonstrate its versatility in histopathology, where we combine prior knowledge about tissue composition and unannotated data to create diverse synthetic images with known layouts. This allows us to generate additional synthetic data to train a segmentation network in a semi-supervised fashion. We verify the added value of the generated images by showing improved segmentation results and lower performance variability between patients when synthetic images are included during segmentation training. Our code will be made publicly available at [LINK].

Instance segmentation is critical in biomedical imaging to accurately distinguish individual objects like cells, which often overlap and vary in size. Recent query-based methods, where object queries guide segmentation, have shown strong performance. While U-Net has been a go-to architecture in medical image segmentation, its potential in query-based approaches remains largely unexplored. In this work, we present IAUNet, a novel query-based U-Net architecture. The core design features a full U-Net architecture, enhanced by a novel lightweight convolutional Pixel decoder, making the model more efficient and reducing the number of parameters. Additionally, we propose a Transformer decoder that refines object-specific features across multiple scales. Finally, we introduce the 2025 Revvity Full Cell Segmentation Dataset, a unique resource with detailed annotations of overlapping cell cytoplasm in brightfield images, setting a new benchmark for biomedical instance segmentation. Experiments on multiple public datasets and our own show that IAUNet outperforms most state-of-the-art fully convolutional, transformer-based, and query-based models and cell segmentation-specific models, setting a strong baseline for cell instance segmentation tasks. Code is available at https://github.com/SlavkoPrytula/IAUNet

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.

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

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

Object segmentation is an important step in the workflow of computational pathology. Deep learning based models generally require large amount of labeled data for precise and reliable prediction. However, collecting labeled data is expensive because it often requires expert knowledge, particularly in medical imaging domain where labels are the result of a time-consuming analysis made by one or more human experts. As nuclei, cells and glands are fundamental objects for downstream analysis in computational pathology/cytology, in this paper we propose a simple CNN-based approach to speed up collecting annotations for these objects which requires minimum interaction from the annotator. We show that for nuclei and cells in histology and cytology images, one click inside each object is enough for NuClick to yield a precise annotation. For multicellular structures such as glands, we propose a novel approach to provide the NuClick with a squiggle as a guiding signal, enabling it to segment the glandular boundaries. These supervisory signals are fed to the network as auxiliary inputs along with RGB channels. With detailed experiments, we show that NuClick is adaptable to the object scale, robust against variations in the user input, adaptable to new domains, and delivers reliable annotations. An instance segmentation model trained on masks generated by NuClick achieved the first rank in LYON19 challenge. As exemplar outputs of our framework, we are releasing two datasets: 1) a dataset of lymphocyte annotations within IHC images, and 2) a dataset of segmented WBCs in blood smear images.

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

Sparse autoencoders (SAEs) emerged as a promising tool for mechanistic interpretability of transformer-based foundation models. Very recently, SAEs were also adopted for the visual domain, enabling the discovery of visual concepts and their patch-wise attribution to tokens in the transformer model. While a growing number of foundation models emerged for medical imaging, tools for explaining their inferences are still lacking. In this work, we show the applicability of SAEs for hematology. We propose CytoSAE, a sparse autoencoder which is trained on over 40,000 peripheral blood single-cell images. CytoSAE generalizes to diverse and out-of-domain datasets, including bone marrow cytology, where it identifies morphologically relevant concepts which we validated with medical experts. Furthermore, we demonstrate scenarios in which CytoSAE can generate patient-specific and disease-specific concepts, enabling the detection of pathognomonic cells and localized cellular abnormalities at the patch level. We quantified the effect of concepts on a patient-level AML subtype classification task and show that CytoSAE concepts reach performance comparable to the state-of-the-art, while offering explainability on the sub-cellular level. Source code and model weights are available at https://github.com/dynamical-inference/cytosae.

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

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.

Realistic human-centric rendering plays a key role in both computer vision and computer graphics. Rapid progress has been made in the algorithm aspect over the years, yet existing human-centric rendering datasets and benchmarks are rather impoverished in terms of diversity, which are crucial for rendering effect. Researchers are usually constrained to explore and evaluate a small set of rendering problems on current datasets, while real-world applications require methods to be robust across different scenarios. In this work, we present DNA-Rendering, a large-scale, high-fidelity repository of human performance data for neural actor rendering. DNA-Rendering presents several alluring attributes. First, our dataset contains over 1500 human subjects, 5000 motion sequences, and 67.5M frames' data volume. Second, we provide rich assets for each subject -- 2D/3D human body keypoints, foreground masks, SMPLX models, cloth/accessory materials, multi-view images, and videos. These assets boost the current method's accuracy on downstream rendering tasks. Third, we construct a professional multi-view system to capture data, which contains 60 synchronous cameras with max 4096 x 3000 resolution, 15 fps speed, and stern camera calibration steps, ensuring high-quality resources for task training and evaluation. Along with the dataset, we provide a large-scale and quantitative benchmark in full-scale, with multiple tasks to evaluate the existing progress of novel view synthesis, novel pose animation synthesis, and novel identity rendering methods. In this manuscript, we describe our DNA-Rendering effort as a revealing of new observations, challenges, and future directions to human-centric rendering. The dataset, code, and benchmarks will be publicly available at https://dna-rendering.github.io/

Pathological diagnosis remains the definitive standard for identifying tumors. The rise of multimodal large models has simplified the process of integrating image analysis with textual descriptions. Despite this advancement, the substantial costs associated with training and deploying these complex multimodal models, together with a scarcity of high-quality training datasets, create a significant divide between cutting-edge technology and its application in the clinical setting. We had meticulously compiled a dataset of approximately 45,000 cases, covering over 6 different tasks, including the classification of organ tissues, generating pathology report descriptions, and addressing pathology-related questions and answers. We have fine-tuned multimodal large models, specifically LLaVA, Qwen-VL, InternLM, with this dataset to enhance instruction-based performance. We conducted a qualitative assessment of the capabilities of the base model and the fine-tuned model in performing image captioning and classification tasks on the specific dataset. The evaluation results demonstrate that the fine-tuned model exhibits proficiency in addressing typical pathological questions. We hope that by making both our models and datasets publicly available, they can be valuable to the medical and research communities.

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

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.

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

Cell instance segmentation in fluorescence microscopy images is becoming essential for cancer dynamics and prognosis. Data extracted from cancer dynamics allows to understand and accurately model different metabolic processes such as proliferation. This enables customized and more precise cancer treatments. However, accurate cell instance segmentation, necessary for further cell tracking and behavior analysis, is still challenging in scenarios with high cell concentration and overlapping edges. Within this framework, we propose a novel cell instance segmentation approach based on the well-known U-Net architecture. To enforce the learning of morphological information per pixel, a deep distance transformer (DDT) acts as a back-bone model. The DDT output is subsequently used to train a top-model. The following top-models are considered: a three-class (e.g., foreground, background and cell border) U-net, and a watershed transform. The obtained results suggest a performance boost over traditional U-Net architectures. This opens an interesting research line around the idea of injecting morphological information into a fully convolutional model.

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

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

Virtual cell modeling represents an emerging frontier at the intersection of artificial intelligence and biology, aiming to predict quantities such as responses to diverse perturbations quantitatively. However, autonomously building computational models for virtual cells is challenging due to the complexity of biological systems, the heterogeneity of data modalities, and the need for domain-specific expertise across multiple disciplines. Here, we introduce CellForge, an agentic system that leverages a multi-agent framework that transforms presented biological datasets and research objectives directly into optimized computational models for virtual cells. More specifically, given only raw single-cell multi-omics data and task descriptions as input, CellForge outputs both an optimized model architecture and executable code for training virtual cell models and inference. The framework integrates three core modules: Task Analysis for presented dataset characterization and relevant literature retrieval, Method Design, where specialized agents collaboratively develop optimized modeling strategies, and Experiment Execution for automated generation of code. The agents in the Design module are separated into experts with differing perspectives and a central moderator, and have to collaboratively exchange solutions until they achieve a reasonable consensus. We demonstrate CellForge's capabilities in single-cell perturbation prediction, using six diverse datasets that encompass gene knockouts, drug treatments, and cytokine stimulations across multiple modalities. CellForge consistently outperforms task-specific state-of-the-art methods. Overall, CellForge demonstrates how iterative interaction between LLM agents with differing perspectives provides better solutions than directly addressing a modeling challenge. Our code is publicly available at https://github.com/gersteinlab/CellForge.

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

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.

High-throughput screening techniques, such as microscopy imaging of cellular responses to genetic and chemical perturbations, play a crucial role in drug discovery and biomedical research. However, robust perturbation screening for de novo cell lines remains challenging due to the significant morphological and biological heterogeneity across cell lines. To address this, we propose a novel framework that integrates external biological knowledge into existing pretraining strategies to enhance microscopy image profiling models. Our approach explicitly disentangles perturbation-specific and cell line-specific representations using external biological information. Specifically, we construct a knowledge graph leveraging protein interaction data from STRING and Hetionet databases to guide models toward perturbation-specific features during pretraining. Additionally, we incorporate transcriptomic features from single-cell foundation models to capture cell line-specific representations. By learning these disentangled features, our method improves the generalization of imaging models to de novo cell lines. We evaluate our framework on the RxRx database through one-shot fine-tuning on an RxRx1 cell line and few-shot fine-tuning on cell lines from the RxRx19a dataset. Experimental results demonstrate that our method enhances microscopy image profiling for de novo cell lines, highlighting its effectiveness in real-world phenotype-based drug discovery applications.

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.

Many methods have been proposed for removing batch effects and aligning single-cell RNA (scRNA) datasets. However, performance is typically evaluated based on multiple parameters and few datasets, creating challenges in assessing which method is best for aligning data at scale. Here, we introduce the K-Neighbors Intersection (KNI) score, a single score that both penalizes batch effects and measures accuracy at cross-dataset cell-type label prediction alongside carefully curated small (scMARK) and large (scREF) benchmarks comprising 11 and 46 human scRNA studies respectively, where we have standardized author labels. Using the KNI score, we evaluate and optimize approaches for cross-dataset single-cell RNA integration. We introduce Batch Adversarial single-cell Variational Inference (BA-scVI), as a new variant of scVI that uses adversarial training to penalize batch-effects in the encoder and decoder, and show this approach outperforms other methods. In the resulting aligned space, we find that the granularity of cell-type groupings is conserved, supporting the notion that whole-organism cell-type maps can be created by a single model without loss of information.

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

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

In hematology, computational models offer significant potential to improve diagnostic accuracy, streamline workflows, and reduce the tedious work of analyzing single cells in peripheral blood or bone marrow smears. However, clinical adoption of computational models has been hampered by the lack of generalization due to large batch effects, small dataset sizes, and poor performance in transfer learning from natural images. To address these challenges, we introduce DinoBloom, the first foundation model for single cell images in hematology, utilizing a tailored DINOv2 pipeline. Our model is built upon an extensive collection of 13 diverse, publicly available datasets of peripheral blood and bone marrow smears, the most substantial open-source cohort in hematology so far, comprising over 380,000 white blood cell images. To assess its generalization capability, we evaluate it on an external dataset with a challenging domain shift. We show that our model outperforms existing medical and non-medical vision models in (i) linear probing and k-nearest neighbor evaluations for cell-type classification on blood and bone marrow smears and (ii) weakly supervised multiple instance learning for acute myeloid leukemia subtyping by a large margin. A family of four DinoBloom models (small, base, large, and giant) can be adapted for a wide range of downstream applications, be a strong baseline for classification problems, and facilitate the assessment of batch effects in new datasets. All models are available at github.com/marrlab/DinoBloom.

Artificial intelligence is poised to augment dermatological care by enabling scalable image-based diagnostics. Yet, the development of robust and equitable models remains hindered by datasets that fail to capture the clinical and demographic complexity of real-world practice. This complexity stems from region-specific disease distributions, wide variation in skin tones, and the underrepresentation of outpatient scenarios from non-Western populations. We introduce DermaCon-IN, a prospectively curated dermatology dataset comprising over 5,450 clinical images from approximately 3,000 patients across outpatient clinics in South India. Each image is annotated by board-certified dermatologists with over 240 distinct diagnoses, structured under a hierarchical, etiology-based taxonomy adapted from Rook's classification. The dataset captures a wide spectrum of dermatologic conditions and tonal variation commonly seen in Indian outpatient care. We benchmark a range of architectures including convolutional models (ResNet, DenseNet, EfficientNet), transformer-based models (ViT, MaxViT, Swin), and Concept Bottleneck Models to establish baseline performance and explore how anatomical and concept-level cues may be integrated. These results are intended to guide future efforts toward interpretable and clinically realistic models. DermaCon-IN provides a scalable and representative foundation for advancing dermatology AI in real-world settings.

Images of the natural world, collected by a variety of cameras, from drones to individual phones, are increasingly abundant sources of biological information. There is an explosion of computational methods and tools, particularly computer vision, for extracting biologically relevant information from images for science and conservation. Yet most of these are bespoke approaches designed for a specific task and are not easily adaptable or extendable to new questions, contexts, and datasets. A vision model for general organismal biology questions on images is of timely need. To approach this, we curate and release TreeOfLife-10M, the largest and most diverse ML-ready dataset of biology images. We then develop BioCLIP, a foundation model for the tree of life, leveraging the unique properties of biology captured by TreeOfLife-10M, namely the abundance and variety of images of plants, animals, and fungi, together with the availability of rich structured biological knowledge. We rigorously benchmark our approach on diverse fine-grained biology classification tasks, and find that BioCLIP consistently and substantially outperforms existing baselines (by 17% to 20% absolute). Intrinsic evaluation reveals that BioCLIP has learned a hierarchical representation conforming to the tree of life, shedding light on its strong generalizability. Our code, models and data will be made available at https://github.com/Imageomics/bioclip.

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.

Confocal fluorescence microscopy is one of the most accessible and widely used imaging techniques for the study of biological processes. Scanning confocal microscopy allows the capture of high-quality images from 3D samples, yet suffers from well-known limitations such as photobleaching and phototoxicity of specimens caused by intense light exposure, which limits its use in some applications, especially for living cells. Cellular damage can be alleviated by changing imaging parameters to reduce light exposure, often at the expense of image quality. Machine/deep learning methods for single-image super-resolution (SISR) can be applied to restore image quality by upscaling lower-resolution (LR) images to produce high-resolution images (HR). These SISR methods have been successfully applied to photo-realistic images due partly to the abundance of publicly available data. In contrast, the lack of publicly available data partly limits their application and success in scanning confocal microscopy. In this paper, we introduce a large scanning confocal microscopy dataset named SR-CACO-2 that is comprised of low- and high-resolution image pairs marked for three different fluorescent markers. It allows the evaluation of performance of SISR methods on three different upscaling levels (X2, X4, X8). SR-CACO-2 contains the human epithelial cell line Caco-2 (ATCC HTB-37), and it is composed of 22 tiles that have been translated in the form of 9,937 image patches for experiments with SISR methods. Given the new SR-CACO-2 dataset, we also provide benchmarking results for 15 state-of-the-art methods that are representative of the main SISR families. Results show that these methods have limited success in producing high-resolution textures, indicating that SR-CACO-2 represents a challenging problem. Our dataset, code and pretrained weights are available: https://github.com/sbelharbi/sr-caco-2.

Instance segmentation of neurons in volumetric light microscopy images of nervous systems enables groundbreaking research in neuroscience by facilitating joint functional and morphological analyses of neural circuits at cellular resolution. Yet said multi-neuron light microscopy data exhibits extremely challenging properties for the task of instance segmentation: Individual neurons have long-ranging, thin filamentous and widely branching morphologies, multiple neurons are tightly inter-weaved, and partial volume effects, uneven illumination and noise inherent to light microscopy severely impede local disentangling as well as long-range tracing of individual neurons. These properties reflect a current key challenge in machine learning research, namely to effectively capture long-range dependencies in the data. While respective methodological research is buzzing, to date methods are typically benchmarked on synthetic datasets. To address this gap, we release the FlyLight Instance Segmentation Benchmark (FISBe) dataset, the first publicly available multi-neuron light microscopy dataset with pixel-wise annotations. In addition, we define a set of instance segmentation metrics for benchmarking that we designed to be meaningful with regard to downstream analyses. Lastly, we provide three baselines to kick off a competition that we envision to both advance the field of machine learning regarding methodology for capturing long-range data dependencies, and facilitate scientific discovery in basic neuroscience.

Domain generalization is critical for real-world applications of machine learning to microscopy images, including histopathology and fluorescence imaging. Artifacts in these modalities arise through a complex combination of factors relating to tissue collection and laboratory processing, as well as factors intrinsic to patient samples. In fluorescence imaging, these artifacts stem from variations across experimental batches. The complexity and subtlety of these artifacts make the enumeration of data domains intractable. Therefore, augmentation-based methods of domain generalization that require domain identifiers and manual fine-tuning are inadequate in this setting. To overcome this challenge, we introduce ContriMix, a domain generalization technique that learns to generate synthetic images by disentangling and permuting the biological content ("content") and technical variations ("attributes") in microscopy images. ContriMix does not rely on domain identifiers or handcrafted augmentations and makes no assumptions about the input characteristics of images. We assess the performance of ContriMix on two pathology datasets dealing with patch classification and Whole Slide Image label prediction tasks respectively (Camelyon17-WILDS and RCC subtyping), and one fluorescence microscopy dataset (RxRx1-WILDS). Without any access to domain identifiers at train or test time, ContriMix performs similar or better than current state-of-the-art methods in all these datasets, motivating its usage for microscopy image analysis in real-world settings where domain information is hard to come by. The code for ContriMix can be found at https://gitlab.com/huutan86/contrimix

The rapid development of text-to-image (T2I) generation approaches has attracted extensive interest in evaluating the quality of generated images, leading to the development of various quality assessment methods for general-purpose T2I outputs. However, existing image quality assessment (IQA) methods are limited to providing global quality scores, failing to deliver fine-grained perceptual evaluations for structurally complex subjects like humans, which is a critical challenge considering the frequent anatomical and textural distortions in AI-generated human images (AGHIs). To address this gap, we introduce AGHI-QA, the first large-scale benchmark specifically designed for quality assessment of AGHIs. The dataset comprises 4,000 images generated from 400 carefully crafted text prompts using 10 state of-the-art T2I models. We conduct a systematic subjective study to collect multidimensional annotations, including perceptual quality scores, text-image correspondence scores, visible and distorted body part labels. Based on AGHI-QA, we evaluate the strengths and weaknesses of current T2I methods in generating human images from multiple dimensions. Furthermore, we propose AGHI-Assessor, a novel quality metric that integrates the large multimodal model (LMM) with domain-specific human features for precise quality prediction and identification of visible and distorted body parts in AGHIs. Extensive experimental results demonstrate that AGHI-Assessor showcases state-of-the-art performance, significantly outperforming existing IQA methods in multidimensional quality assessment and surpassing leading LMMs in detecting structural distortions in AGHIs.

Single-cell RNA sequencing (scRNA-seq) data are often confounded by technical or biological batch effects. Existing deep learning models mitigate these effects but often discard batch-specific information, potentially losing valuable biological insights. We propose a Mixed Effects Deep Learning (MEDL) autoencoder framework that separately models batch-invariant (fixed effects) and batch-specific (random effects) components. By decoupling batch-invariant biological states from batch variations, our framework integrates both into predictive models. Our approach also generates 2D visualizations of how the same cell appears across batches, enhancing interpretability. Retaining both fixed and random effect latent spaces improves classification accuracy. We applied our framework to three datasets spanning the cardiovascular system (Healthy Heart), Autism Spectrum Disorder (ASD), and Acute Myeloid Leukemia (AML). With 147 batches in the Healthy Heart dataset, far exceeding typical numbers, we tested our framework's ability to handle many batches. In the ASD dataset, our approach captured donor heterogeneity between autistic and healthy individuals. In the AML dataset, it distinguished donor heterogeneity despite missing cell types and diseased donors exhibiting both healthy and malignant cells. These results highlight our framework's ability to characterize fixed and random effects, enhance batch effect visualization, and improve prediction accuracy across diverse datasets.

Biomedical image analysis is fundamental for biomedical discovery in cell biology, pathology, radiology, and many other biomedical domains. Holistic image analysis comprises interdependent subtasks such as segmentation, detection, and recognition of relevant objects. Here, we propose BiomedParse, a biomedical foundation model for imaging parsing that can jointly conduct segmentation, detection, and recognition for 82 object types across 9 imaging modalities. Through joint learning, we can improve accuracy for individual tasks and enable novel applications such as segmenting all relevant objects in an image through a text prompt, rather than requiring users to laboriously specify the bounding box for each object. We leveraged readily available natural-language labels or descriptions accompanying those datasets and use GPT-4 to harmonize the noisy, unstructured text information with established biomedical object ontologies. We created a large dataset comprising over six million triples of image, segmentation mask, and textual description. On image segmentation, we showed that BiomedParse is broadly applicable, outperforming state-of-the-art methods on 102,855 test image-mask-label triples across 9 imaging modalities (everything). On object detection, which aims to locate a specific object of interest, BiomedParse again attained state-of-the-art performance, especially on objects with irregular shapes (everywhere). On object recognition, which aims to identify all objects in a given image along with their semantic types, we showed that BiomedParse can simultaneously segment and label all biomedical objects in an image (all at once). In summary, BiomedParse is an all-in-one tool for biomedical image analysis by jointly solving segmentation, detection, and recognition for all major biomedical image modalities, paving the path for efficient and accurate image-based biomedical discovery.

Skin tone as a demographic bias and inconsistent human labeling poses challenges in dermatology AI. We take another angle to investigate color contrast's impact, beyond skin tones, on malignancy detection in skin disease datasets: We hypothesize that in addition to skin tones, the color difference between the lesion area and skin also plays a role in malignancy detection performance of dermatology AI models. To study this, we first propose a robust labeling method to quantify color contrast scores of each image and validate our method by showing small labeling variations. More importantly, applying our method to the only diverse-skin tone and pathologically-confirmed skin disease dataset DDI, yields DDI-CoCo Dataset, and we observe a performance gap between the high and low color difference groups. This disparity remains consistent across various state-of-the-art (SoTA) image classification models, which supports our hypothesis. Furthermore, we study the interaction between skin tone and color difference effects and suggest that color difference can be an additional reason behind model performance bias between skin tones. Our work provides a complementary angle to dermatology AI for improving skin disease detection.

Tumor synthesis can generate examples that AI often misses or over-detects, improving AI performance by training on these challenging cases. However, existing synthesis methods, which are typically unconditional -- generating images from random variables -- or conditioned only by tumor shapes, lack controllability over specific tumor characteristics such as texture, heterogeneity, boundaries, and pathology type. As a result, the generated tumors may be overly similar or duplicates of existing training data, failing to effectively address AI's weaknesses. We propose a new text-driven tumor synthesis approach, termed TextoMorph, that provides textual control over tumor characteristics. This is particularly beneficial for examples that confuse the AI the most, such as early tumor detection (increasing Sensitivity by +8.5%), tumor segmentation for precise radiotherapy (increasing DSC by +6.3%), and classification between benign and malignant tumors (improving Sensitivity by +8.2%). By incorporating text mined from radiology reports into the synthesis process, we increase the variability and controllability of the synthetic tumors to target AI's failure cases more precisely. Moreover, TextoMorph uses contrastive learning across different texts and CT scans, significantly reducing dependence on scarce image-report pairs (only 141 pairs used in this study) by leveraging a large corpus of 34,035 radiology reports. Finally, we have developed rigorous tests to evaluate synthetic tumors, including Text-Driven Visual Turing Test and Radiomics Pattern Analysis, showing that our synthetic tumors is realistic and diverse in texture, heterogeneity, boundaries, and pathology.

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

Although the preservation of shape continuity and physiological anatomy is a natural assumption in the segmentation of medical images, it is often neglected by deep learning methods that mostly aim for the statistical modeling of input data as pixels rather than interconnected structures. In biological structures, however, organs are not separate entities; for example, in reality, a severed vessel is an indication of an underlying problem, but traditional segmentation models are not designed to strictly enforce the continuity of anatomy, potentially leading to inaccurate medical diagnoses. To address this issue, we propose a graph-based approach that enforces the continuity and connectivity of anatomical topology in medical images. Our method encodes the continuity of shapes as a graph constraint, ensuring that the network's predictions maintain this continuity. We evaluate our method on two public benchmarks on retinal vessel segmentation, showing significant improvements in connectivity metrics compared to traditional methods while getting better or on-par performance on segmentation metrics.

Inferring biological relationships from cellular phenotypes in high-content microscopy screens provides significant opportunity and challenge in biological research. Prior results have shown that deep vision models can capture biological signal better than hand-crafted features. This work explores how self-supervised deep learning approaches scale when training larger models on larger microscopy datasets. Our results show that both CNN- and ViT-based masked autoencoders significantly outperform weakly supervised baselines. At the high-end of our scale, a ViT-L/8 trained on over 3.5-billion unique crops sampled from 93-million microscopy images achieves relative improvements as high as 28% over our best weakly supervised baseline at inferring known biological relationships curated from public databases. Relevant code and select models released with this work can be found at: https://github.com/recursionpharma/maes_microscopy.

The emergence of vision-language models has transformed medical AI, enabling unprecedented advances in diagnostic capability and clinical applications. However, progress in dermatology has lagged behind other medical domains due to the lack of standard image-text pairs. Existing dermatological datasets are limited in both scale and depth, offering only single-label annotations across a narrow range of diseases instead of rich textual descriptions, and lacking the crucial clinical context needed for real-world applications. To address these limitations, we present Derm1M, the first large-scale vision-language dataset for dermatology, comprising 1,029,761 image-text pairs. Built from diverse educational resources and structured around a standard ontology collaboratively developed by experts, Derm1M provides comprehensive coverage for over 390 skin conditions across four hierarchical levels and 130 clinical concepts with rich contextual information such as medical history, symptoms, and skin tone. To demonstrate Derm1M potential in advancing both AI research and clinical application, we pretrained a series of CLIP-like models, collectively called DermLIP, on this dataset. The DermLIP family significantly outperforms state-of-the-art foundation models on eight diverse datasets across multiple tasks, including zero-shot skin disease classification, clinical and artifacts concept identification, few-shot/full-shot learning, and cross-modal retrieval. Our dataset and code will be public.

Understanding the biological mechanism of disease is critical for medicine, and in particular drug discovery. AI-powered analysis of genome-scale biological data hold great potential in this regard. The increasing availability of single-cell RNA sequencing data has enabled the development of large foundation models for disease biology. However, existing foundation models either do not improve or only modestly improve over task-specific models in downstream applications. Here, we explored two avenues for improving the state-of-the-art. First, we scaled the pre-training dataset to 116 million cells, which is larger than those used by previous models. Second, we leveraged the availability of large-scale biological annotations as a form of supervision during pre-training. We trained the TEDDY family of models comprising six transformer-based state-of-the-art single-cell foundation models with 70 million, 160 million, and 400 million parameters. We vetted our models on two downstream evaluation tasks -- identifying the underlying disease state of held-out donors not seen during training and distinguishing healthy cells from diseased ones for disease conditions and donors not seen during training. Scaling experiments showed that performance improved predictably with both data volume and parameter count. Our models showed substantial improvement over existing work on the first task and more muted improvements on the second.

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

3D cellular image segmentation methods are commonly divided into non-2D-based and 2D-based approaches, the latter reconstructing 3D shapes from the segmentation results of 2D layers. However, errors in 2D results often propagate, leading to oversegmentations in the final 3D results. To tackle this issue, we introduce an interpretable geometric framework that addresses the oversegmentations by correcting the 2D segmentation results based on geometric information from adjacent layers. Leveraging both geometric (layer-to-layer, 2D) and topological (3D shape) features, we use binary classification to determine whether neighboring cells should be stitched. We develop a pre-trained classifier on public plant cell datasets and validate its performance on animal cell datasets, confirming its effectiveness in correcting oversegmentations under the transfer learning setting. Furthermore, we demonstrate that our framework can be extended to correcting oversegmentation on non-2D-based methods. A clear pipeline is provided for end-users to build the pre-trained model to any labeled dataset.

Advances in foundation modeling have reshaped computational pathology. However, the increasing number of available models and lack of standardized benchmarks make it increasingly complex to assess their strengths, limitations, and potential for further development. To address these challenges, we introduce a new suite of software tools for whole-slide image processing, foundation model benchmarking, and curated publicly available tasks. We anticipate that these resources will promote transparency, reproducibility, and continued progress in the field.

In 2015 we began a sub-challenge at the EndoVis workshop at MICCAI in Munich using endoscope images of ex-vivo tissue with automatically generated annotations from robot forward kinematics and instrument CAD models. However, the limited background variation and simple motion rendered the dataset uninformative in learning about which techniques would be suitable for segmentation in real surgery. In 2017, at the same workshop in Quebec we introduced the robotic instrument segmentation dataset with 10 teams participating in the challenge to perform binary, articulating parts and type segmentation of da Vinci instruments. This challenge included realistic instrument motion and more complex porcine tissue as background and was widely addressed with modifications on U-Nets and other popular CNN architectures. In 2018 we added to the complexity by introducing a set of anatomical objects and medical devices to the segmented classes. To avoid over-complicating the challenge, we continued with porcine data which is dramatically simpler than human tissue due to the lack of fatty tissue occluding many organs.

Our goal is to create a realistic 3D facial avatar with hair and accessories using only a text description. While this challenge has attracted significant recent interest, existing methods either lack realism, produce unrealistic shapes, or do not support editing, such as modifications to the hairstyle. We argue that existing methods are limited because they employ a monolithic modeling approach, using a single representation for the head, face, hair, and accessories. Our observation is that the hair and face, for example, have very different structural qualities that benefit from different representations. Building on this insight, we generate avatars with a compositional model, in which the head, face, and upper body are represented with traditional 3D meshes, and the hair, clothing, and accessories with neural radiance fields (NeRF). The model-based mesh representation provides a strong geometric prior for the face region, improving realism while enabling editing of the person's appearance. By using NeRFs to represent the remaining components, our method is able to model and synthesize parts with complex geometry and appearance, such as curly hair and fluffy scarves. Our novel system synthesizes these high-quality compositional avatars from text descriptions. The experimental results demonstrate that our method, Text-guided generation and Editing of Compositional Avatars (TECA), produces avatars that are more realistic than those of recent methods while being editable because of their compositional nature. For example, our TECA enables the seamless transfer of compositional features like hairstyles, scarves, and other accessories between avatars. This capability supports applications such as virtual try-on.

The VIP Cup offers a unique experience to undergraduates, allowing students to work together to solve challenging, real-world problems with video and image processing techniques. In this iteration of the VIP Cup, we challenged students to balance personalization and generalization when performing biomarker detection in 3D optical coherence tomography (OCT) images. Balancing personalization and generalization is an important challenge to tackle, as the variation within OCT scans of patients between visits can be minimal while the difference in manifestation of the same disease across different patients may be substantial. The domain difference between OCT scans can arise due to pathology manifestation across patients, clinical labels, and the visit along the treatment process when the scan is taken. Hence, we provided a multimodal OCT dataset to allow teams to effectively target this challenge. Overall, this competition gave undergraduates an opportunity to learn about how artificial intelligence can be a powerful tool for the medical field, as well as the unique challenges one faces when applying machine learning to biomedical data.

Detecting and segmenting object instances is a common task in biomedical applications. Examples range from detecting lesions on functional magnetic resonance images, to the detection of tumours in histopathological images and extracting quantitative single-cell information from microscopy imagery, where cell segmentation is a major bottleneck. Attention-based transformers are state-of-the-art in a range of deep learning fields. They have recently been proposed for segmentation tasks where they are beginning to outperforming other methods. We present a novel attention-based cell detection transformer (Cell-DETR) for direct end-to-end instance segmentation. While the segmentation performance is on par with a state-of-the-art instance segmentation method, Cell-DETR is simpler and faster. We showcase the method's contribution in a the typical use case of segmenting yeast in microstructured environments, commonly employed in systems or synthetic biology. For the specific use case, the proposed method surpasses the state-of-the-art tools for semantic segmentation and additionally predicts the individual object instances. The fast and accurate instance segmentation performance increases the experimental information yield for a posteriori data processing and makes online monitoring of experiments and closed-loop optimal experimental design feasible.

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.

Traditional fluorescence staining is phototoxic to live cells, slow, and expensive; thus, the subcellular structure prediction (SSP) from transmitted light (TL) images is emerging as a label-free, faster, low-cost alternative. However, existing approaches utilize 3D networks for one-to-one voxel level dense prediction, which necessitates a frequent and time-consuming Z-axis imaging process. Moreover, 3D convolutions inevitably lead to significant computation and GPU memory overhead. Therefore, we propose an efficient framework, SparseSSP, predicting fluorescent intensities within the target voxel grid in an efficient paradigm instead of relying entirely on 3D topologies. In particular, SparseSSP makes two pivotal improvements to prior works. First, SparseSSP introduces a one-to-many voxel mapping paradigm, which permits the sparse TL slices to reconstruct the subcellular structure. Secondly, we propose a hybrid dimensions topology, which folds the Z-axis information into channel features, enabling the 2D network layers to tackle SSP under low computational cost. We conduct extensive experiments to validate the effectiveness and advantages of SparseSSP on diverse sparse imaging ratios, and our approach achieves a leading performance compared to pure 3D topologies. SparseSSP reduces imaging frequencies compared to previous dense-view SSP (i.e., the number of imaging is reduced up to 87.5% at most), which is significant in visualizing rapid biological dynamics on low-cost devices and samples.

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.

Despite significant advances in large-scale text-to-image models, achieving hyper-realistic human image generation remains a desirable yet unsolved task. Existing models like Stable Diffusion and DALL-E 2 tend to generate human images with incoherent parts or unnatural poses. To tackle these challenges, our key insight is that human image is inherently structural over multiple granularities, from the coarse-level body skeleton to fine-grained spatial geometry. Therefore, capturing such correlations between the explicit appearance and latent structure in one model is essential to generate coherent and natural human images. To this end, we propose a unified framework, HyperHuman, that generates in-the-wild human images of high realism and diverse layouts. Specifically, 1) we first build a large-scale human-centric dataset, named HumanVerse, which consists of 340M images with comprehensive annotations like human pose, depth, and surface normal. 2) Next, we propose a Latent Structural Diffusion Model that simultaneously denoises the depth and surface normal along with the synthesized RGB image. Our model enforces the joint learning of image appearance, spatial relationship, and geometry in a unified network, where each branch in the model complements to each other with both structural awareness and textural richness. 3) Finally, to further boost the visual quality, we propose a Structure-Guided Refiner to compose the predicted conditions for more detailed generation of higher resolution. Extensive experiments demonstrate that our framework yields the state-of-the-art performance, generating hyper-realistic human images under diverse scenarios. Project Page: https://snap-research.github.io/HyperHuman/

Automated and semi-automated techniques in biomedical electron microscopy (EM) enable the acquisition of large datasets at a high rate. Segmentation methods are therefore essential to analyze and interpret these large volumes of data, which can no longer completely be labeled manually. In recent years, deep learning algorithms achieved impressive results in both pixel-level labeling (semantic segmentation) and the labeling of separate instances of the same class (instance segmentation). In this review, we examine how these algorithms were adapted to the task of segmenting cellular and sub-cellular structures in EM images. The special challenges posed by such images and the network architectures that overcame some of them are described. Moreover, a thorough overview is also provided on the notable datasets that contributed to the proliferation of deep learning in EM. Finally, an outlook of current trends and future prospects of EM segmentation is given, especially in the area of label-free learning.

Prior to the deep learning era, shape was commonly used to describe the objects. Nowadays, state-of-the-art (SOTA) algorithms in medical imaging are predominantly diverging from computer vision, where voxel grids, meshes, point clouds, and implicit surface models are used. This is seen from numerous shape-related publications in premier vision conferences as well as the growing popularity of ShapeNet (about 51,300 models) and Princeton ModelNet (127,915 models). For the medical domain, we present a large collection of anatomical shapes (e.g., bones, organs, vessels) and 3D models of surgical instrument, called MedShapeNet, created to facilitate the translation of data-driven vision algorithms to medical applications and to adapt SOTA vision algorithms to medical problems. As a unique feature, we directly model the majority of shapes on the imaging data of real patients. As of today, MedShapeNet includes 23 dataset with more than 100,000 shapes that are paired with annotations (ground truth). Our data is freely accessible via a web interface and a Python application programming interface (API) and can be used for discriminative, reconstructive, and variational benchmarks as well as various applications in virtual, augmented, or mixed reality, and 3D printing. Exemplary, we present use cases in the fields of classification of brain tumors, facial and skull reconstructions, multi-class anatomy completion, education, and 3D printing. In future, we will extend the data and improve the interfaces. The project pages are: https://medshapenet.ikim.nrw/ and https://github.com/Jianningli/medshapenet-feedback

Efficient Human Epithelial-2 (HEp-2) cell image classification can facilitate the diagnosis of many autoimmune diseases. This paper presents an automatic framework for this classification task, by utilizing the deep convolutional neural networks (CNNs) which have recently attracted intensive attention in visual recognition. This paper elaborates the important components of this framework, discusses multiple key factors that impact the efficiency of training a deep CNN, and systematically compares this framework with the well-established image classification models in the literature. Experiments on benchmark datasets show that i) the proposed framework can effectively outperform existing models by properly applying data augmentation; ii) our CNN-based framework demonstrates excellent adaptability across different datasets, which is highly desirable for classification under varying laboratory settings. Our system is ranked high in the cell image classification competition hosted by ICPR 2014.

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

Unlike color photography images, which are consistently encoded into RGB channels, biological images encompass various modalities, where the type of microscopy and the meaning of each channel varies with each experiment. Importantly, the number of channels can range from one to a dozen and their correlation is often comparatively much lower than RGB, as each of them brings specific information content. This aspect is largely overlooked by methods designed out of the bioimage field, and current solutions mostly focus on intra-channel spatial attention, often ignoring the relationship between channels, yet crucial in most biological applications. Importantly, the variable channel type and count prevent the projection of several experiments to a unified representation for large scale pre-training. In this study, we propose ChAda-ViT, a novel Channel Adaptive Vision Transformer architecture employing an Inter-Channel Attention mechanism on images with an arbitrary number, order and type of channels. We also introduce IDRCell100k, a bioimage dataset with a rich set of 79 experiments covering 7 microscope modalities, with a multitude of channel types, and channel counts varying from 1 to 10 per experiment. Our proposed architecture, trained in a self-supervised manner, outperforms existing approaches in several biologically relevant downstream tasks. Additionally, it can be used to bridge the gap for the first time between assays with different microscopes, channel numbers or types by embedding various image and experimental modalities into a unified biological image representation. The latter should facilitate interdisciplinary studies and pave the way for better adoption of deep learning in biological image-based analyses. Code and Data to be released soon.

Cell instance segmentation (CIS) is crucial for identifying individual cell morphologies in histopathological images, providing valuable insights for biological and medical research. While unsupervised CIS (UCIS) models aim to reduce the heavy reliance on labor-intensive image annotations, they fail to accurately capture cell boundaries, causing missed detections and poor performance. Recognizing the absence of error-free instances as a key limitation, we present COIN (COnfidence score-guided INstance distillation), a novel annotation-free framework with three key steps: (1) Increasing the sensitivity for the presence of error-free instances via unsupervised semantic segmentation with optimal transport, leveraging its ability to discriminate spatially minor instances, (2) Instance-level confidence scoring to measure the consistency between model prediction and refined mask and identify highly confident instances, offering an alternative to ground truth annotations, and (3) Progressive expansion of confidence with recursive self-distillation. Extensive experiments across six datasets show COIN outperforming existing UCIS methods, even surpassing semi- and weakly-supervised approaches across all metrics on the MoNuSeg and TNBC datasets. The code is available at https://github.com/shjo-april/COIN.

Background: Health datasets from clinical sources do not reflect the breadth and diversity of disease in the real world, impacting research, medical education, and artificial intelligence (AI) tool development. Dermatology is a suitable area to develop and test a new and scalable method to create representative health datasets. Methods: We used Google Search advertisements to invite contributions to an open access dataset of images of dermatology conditions, demographic and symptom information. With informed contributor consent, we describe and release this dataset containing 10,408 images from 5,033 contributions from internet users in the United States over 8 months starting March 2023. The dataset includes dermatologist condition labels as well as estimated Fitzpatrick Skin Type (eFST) and Monk Skin Tone (eMST) labels for the images. Results: We received a median of 22 submissions/day (IQR 14-30). Female (66.72%) and younger (52% < age 40) contributors had a higher representation in the dataset compared to the US population, and 32.6% of contributors reported a non-White racial or ethnic identity. Over 97.5% of contributions were genuine images of skin conditions. Dermatologist confidence in assigning a differential diagnosis increased with the number of available variables, and showed a weaker correlation with image sharpness (Spearman's P values <0.001 and 0.01 respectively). Most contributions were short-duration (54% with onset < 7 days ago ) and 89% were allergic, infectious, or inflammatory conditions. eFST and eMST distributions reflected the geographical origin of the dataset. The dataset is available at github.com/google-research-datasets/scin . Conclusion: Search ads are effective at crowdsourcing images of health conditions. The SCIN dataset bridges important gaps in the availability of representative images of common skin conditions.

The galaxy population is strongly bimodal in both colour and morphology, and the two measures correlate strongly, with most blue galaxies being late-types (spirals) and most early-types, typically ellipticals, being red. This observation has led to the use of colour as a convenient selection criteria to make samples which are then labelled by morphology. Such use of colour as a proxy for morphology results in necessarily impure and incomplete samples. In this paper, we make use of the morphological labels produced by Galaxy Zoo to measure how incomplete and impure such samples are, considering optical (ugriz), NUV and NIR (JHK) bands. The best single colour optical selection is found using a threshold of g-r = 0.742, but this still results in a sample where only 56% of red galaxies are smooth and 56% of smooth galaxies are red. Use of the NUV gives some improvement over purely optical bands, particularly for late-types, but still results in low purity/completeness for early-types. No significant improvement is found by adding NIR bands. With any two bands, including NUV, a sample of early-types with greater than two-thirds purity cannot be constructed. Advances in quantitative galaxy morphologies have made colour-morphology proxy selections largely unnecessary going forward; where such assumptions are still required, we recommend studies carefully consider the implications of sample incompleteness/impurity.

Cell type annotation is a key task in analyzing the heterogeneity of single-cell RNA sequencing data. Although recent foundation models automate this process, they typically annotate cells independently, without considering batch-level cellular context or providing explanatory reasoning. In contrast, human experts often annotate distinct cell types for different cell clusters based on their domain knowledge. To mimic this workflow, we introduce the CellPuzzles task, where the objective is to assign unique cell types to a batch of cells. This benchmark spans diverse tissues, diseases, and donor conditions, and requires reasoning across the batch-level cellular context to ensure label uniqueness. We find that off-the-shelf large language models (LLMs) struggle on CellPuzzles, with the best baseline (OpenAI's o1) achieving only 19.0% batch-level accuracy. To fill this gap, we propose Cell-o1, a 7B LLM trained via supervised fine-tuning on distilled reasoning traces, followed by reinforcement learning with batch-level rewards. Cell-o1 achieves state-of-the-art performance, outperforming o1 by over 73% and generalizing well across contexts. Further analysis of training dynamics and reasoning behaviors provides insights into batch-level annotation performance and emergent expert-like reasoning. Code and data are available at https://github.com/ncbi-nlp/cell-o1.

Diagnosing and treating skin diseases require advanced visual skills across domains and the ability to synthesize information from multiple imaging modalities. While current deep learning models excel at specific tasks like skin cancer diagnosis from dermoscopic images, they struggle to meet the complex, multimodal requirements of clinical practice. Here, we introduce PanDerm, a multimodal dermatology foundation model pretrained through self-supervised learning on over 2 million real-world skin disease images from 11 clinical institutions across 4 imaging modalities. We evaluated PanDerm on 28 diverse benchmarks, including skin cancer screening, risk stratification, differential diagnosis of common and rare skin conditions, lesion segmentation, longitudinal monitoring, and metastasis prediction and prognosis. PanDerm achieved state-of-the-art performance across all evaluated tasks, often outperforming existing models when using only 10% of labeled data. We conducted three reader studies to assess PanDerm's potential clinical utility. PanDerm outperformed clinicians by 10.2% in early-stage melanoma detection through longitudinal analysis, improved clinicians' skin cancer diagnostic accuracy by 11% on dermoscopy images, and enhanced non-dermatologist healthcare providers' differential diagnosis by 16.5% across 128 skin conditions on clinical photographs. These results demonstrate PanDerm's potential to improve patient care across diverse clinical scenarios and serve as a model for developing multimodal foundation models in other medical specialties, potentially accelerating the integration of AI support in healthcare. The code can be found at https://github.com/SiyuanYan1/PanDerm.

Cell segmentation is a major bottleneck in extracting quantitative single-cell information from microscopy data. The challenge is exasperated in the setting of microstructured environments. While deep learning approaches have proven useful for general cell segmentation tasks, existing segmentation tools for the yeast-microstructure setting rely on traditional machine learning approaches. Here we present convolutional neural networks trained for multiclass segmenting of individual yeast cells and discerning these from cell-similar microstructures. We give an overview of the datasets recorded for training, validating and testing the networks, as well as a typical use-case. We showcase the method's contribution to segmenting yeast in microstructured environments with a typical synthetic biology application in mind. The models achieve robust segmentation results, outperforming the previous state-of-the-art in both accuracy and speed. The combination of fast and accurate segmentation is not only beneficial for a posteriori data processing, it also makes online monitoring of thousands of trapped cells or closed-loop optimal experimental design feasible from an image processing perspective.

Culling newly hatched male chicks in industrial hatcheries poses a serious ethical problem. Both laying and broiler breeders need males, but it is a problem because they are produced more than needed. Being able to determine the sex of chicks in the egg at the beginning or early stage of incubation can eliminate ethical problems as well as many additional costs. When we look at the literature, the methods used are very costly, low in applicability, invasive, inadequate in accuracy, or too late to eliminate ethical problems. Considering the embryo's development, the earliest observed candidate feature for sex determination is blood vessels. Detection from blood vessels can eliminate ethical issues, and these vessels can be seen when light is shined into the egg until the first seven days. In this study, sex determination was made by morphological analysis from embryonic vascular images obtained in the first week when the light was shined into the egg using a standard camera without any invasive procedure to the egg.

Accurate segmentation of regions of interest in biomedical images holds substantial value in image analysis. Although several foundation models for biomedical segmentation have currently achieved excellent performance on certain datasets, they typically demonstrate sub-optimal performance on unseen domain data. We owe the deficiency to lack of vision-language knowledge before segmentation. Multimodal Large Language Models (MLLMs) bring outstanding understanding and reasoning capabilities to multimodal tasks, which inspires us to leverage MLLMs to inject Vision-Language Knowledge (VLK), thereby enabling vision models to demonstrate superior generalization capabilities on cross-domain datasets. In this paper, we propose using MLLMs to guide SAM in learning microscopy crose-domain data, unifying Segment Anything in Microscopy, named uLLSAM. Specifically, we propose the Vision-Language Semantic Alignment (VLSA) module, which injects VLK into Segment Anything Model (SAM). We find that after SAM receives global VLK prompts, its performance improves significantly, but there are deficiencies in boundary contour perception. Therefore, we further propose Semantic Boundary Regularization (SBR) to prompt SAM. Our method achieves performance improvements of 7.71% in Dice and 12.10% in SA across 9 in-domain microscopy datasets, achieving state-of-the-art performance. Our method also demonstrates improvements of 6.79% in Dice and 10.08% in SA across 10 out-ofdomain datasets, exhibiting strong generalization capabilities. Code is available at https://github.com/ieellee/uLLSAM.

The development of vision-language models (VLMs) is driven by large-scale and diverse multimodal datasets. However, progress toward generalist biomedical VLMs is limited by the lack of annotated, publicly accessible datasets across biology and medicine. Existing efforts are restricted to narrow domains, missing the full diversity of biomedical knowledge encoded in scientific literature. To address this gap, we introduce BIOMEDICA, a scalable, open-source framework to extract, annotate, and serialize the entirety of the PubMed Central Open Access subset into an easy-to-use, publicly accessible dataset.Our framework produces a comprehensive archive with over 24 million unique image-text pairs from over 6 million articles. Metadata and expert-guided annotations are also provided. We demonstrate the utility and accessibility of our resource by releasing BMCA-CLIP, a suite of CLIP-style models continuously pre-trained on the BIOMEDICA dataset via streaming, eliminating the need to download 27 TB of data locally.On average, our models achieve state-of-the-art performance across 40 tasks - spanning pathology, radiology, ophthalmology, dermatology, surgery, molecular biology, parasitology, and cell biology - excelling in zero-shot classification with a 6.56% average improvement (as high as 29.8% and 17.5% in dermatology and ophthalmology, respectively), and stronger image-text retrieval, all while using 10x less compute. To foster reproducibility and collaboration, we release our codebase and dataset for the broader research community.

The use of artificial intelligence to enable precision medicine and decision support systems through the analysis of pathology images has the potential to revolutionize the diagnosis and treatment of cancer. Such applications will depend on models' abilities to capture the diverse patterns observed in pathology images. To address this challenge, we present Virchow, a foundation model for computational pathology. Using self-supervised learning empowered by the DINOv2 algorithm, Virchow is a vision transformer model with 632 million parameters trained on 1.5 million hematoxylin and eosin stained whole slide images from diverse tissue and specimen types, which is orders of magnitude more data than previous works. The Virchow model enables the development of a pan-cancer detection system with 0.949 overall specimen-level AUC across 17 different cancer types, while also achieving 0.937 AUC on 7 rare cancer types. The Virchow model sets the state-of-the-art on the internal and external image tile level benchmarks and slide level biomarker prediction tasks. The gains in performance highlight the importance of training on massive pathology image datasets, suggesting scaling up the data and network architecture can improve the accuracy for many high-impact computational pathology applications where limited amounts of training data are available.

Time-lapse fluorescent microscopy (TLFM) combined with predictive mathematical modelling is a powerful tool to study the inherently dynamic processes of life on the single-cell level. Such experiments are costly, complex and labour intensive. A complimentary approach and a step towards in silico experimentation, is to synthesise the imagery itself. Here, we propose Multi-StyleGAN as a descriptive approach to simulate time-lapse fluorescence microscopy imagery of living cells, based on a past experiment. This novel generative adversarial network synthesises a multi-domain sequence of consecutive timesteps. We showcase Multi-StyleGAN on imagery of multiple live yeast cells in microstructured environments and train on a dataset recorded in our laboratory. The simulation captures underlying biophysical factors and time dependencies, such as cell morphology, growth, physical interactions, as well as the intensity of a fluorescent reporter protein. An immediate application is to generate additional training and validation data for feature extraction algorithms or to aid and expedite development of advanced experimental techniques such as online monitoring or control of cells. Code and dataset is available at https://git.rwth-aachen.de/bcs/projects/tp/multi-stylegan.

Medical vision-language models (VLMs) have shown promise as clinical assistants across various medical fields. However, specialized dermatology VLM capable of delivering professional and detailed diagnostic analysis remains underdeveloped, primarily due to less specialized text descriptions in current dermatology multimodal datasets. To address this issue, we propose MM-Skin, the first large-scale multimodal dermatology dataset that encompasses 3 imaging modalities, including clinical, dermoscopic, and pathological and nearly 10k high-quality image-text pairs collected from professional textbooks. In addition, we generate over 27k diverse, instruction-following vision question answering (VQA) samples (9 times the size of current largest dermatology VQA dataset). Leveraging public datasets and MM-Skin, we developed SkinVL, a dermatology-specific VLM designed for precise and nuanced skin disease interpretation. Comprehensive benchmark evaluations of SkinVL on VQA, supervised fine-tuning (SFT) and zero-shot classification tasks across 8 datasets, reveal its exceptional performance for skin diseases in comparison to both general and medical VLM models. The introduction of MM-Skin and SkinVL offers a meaningful contribution to advancing the development of clinical dermatology VLM assistants. MM-Skin is available at https://github.com/ZwQ803/MM-Skin

We show, for the first time, that neural networks trained only on synthetic data achieve state-of-the-art accuracy on the problem of 3D human pose and shape (HPS) estimation from real images. Previous synthetic datasets have been small, unrealistic, or lacked realistic clothing. Achieving sufficient realism is non-trivial and we show how to do this for full bodies in motion. Specifically, our BEDLAM dataset contains monocular RGB videos with ground-truth 3D bodies in SMPL-X format. It includes a diversity of body shapes, motions, skin tones, hair, and clothing. The clothing is realistically simulated on the moving bodies using commercial clothing physics simulation. We render varying numbers of people in realistic scenes with varied lighting and camera motions. We then train various HPS regressors using BEDLAM and achieve state-of-the-art accuracy on real-image benchmarks despite training with synthetic data. We use BEDLAM to gain insights into what model design choices are important for accuracy. With good synthetic training data, we find that a basic method like HMR approaches the accuracy of the current SOTA method (CLIFF). BEDLAM is useful for a variety of tasks and all images, ground truth bodies, 3D clothing, support code, and more are available for research purposes. Additionally, we provide detailed information about our synthetic data generation pipeline, enabling others to generate their own datasets. See the project page: https://bedlam.is.tue.mpg.de/.

Deep learning models have shown promise in histopathology image analysis, but their opaque decision-making process poses challenges in high-risk medical scenarios. Here we introduce HIPPO, an explainable AI method that interrogates attention-based multiple instance learning (ABMIL) models in computational pathology by generating counterfactual examples through tissue patch modifications in whole slide images. Applying HIPPO to ABMIL models trained to detect breast cancer metastasis reveals that they may overlook small tumors and can be misled by non-tumor tissue, while attention mapsx2014widely used for interpretationx2014often highlight regions that do not directly influence predictions. By interpreting ABMIL models trained on a prognostic prediction task, HIPPO identified tissue areas with stronger prognostic effects than high-attention regions, which sometimes showed counterintuitive influences on risk scores. These findings demonstrate HIPPO's capacity for comprehensive model evaluation, bias detection, and quantitative hypothesis testing. HIPPO greatly expands the capabilities of explainable AI tools to assess the trustworthy and reliable development, deployment, and regulation of weakly-supervised models in computational pathology.

Complex cell signaling systems -- governed by varying protein abundances and interactions -- generate diverse cell types across organs. These systems evolve under influences such as age, sex, diet, environmental exposures, and diseases, making them challenging to decode given the involvement of tens of thousands of genes and proteins. Recently, hundreds of millions of single-cell omics data have provided a robust foundation for understanding these signaling networks within various cell subpopulations and conditions. Inspired by the success of large foundation models (for example, large language models and large vision models) pre-trained on massive datasets, we introduce OmniCellTOSG, the first dataset of cell text-omic signaling graphs (TOSGs). Each TOSG represents the signaling network of an individual or meta-cell and is labeled with information such as organ, disease, sex, age, and cell subtype. OmniCellTOSG offers two key contributions. First, it introduces a novel graph model that integrates human-readable annotations -- such as biological functions, cellular locations, signaling pathways, related diseases, and drugs -- with quantitative gene and protein abundance data, enabling graph reasoning to decode cell signaling. This approach calls for new joint models combining large language models and graph neural networks. Second, the dataset is built from single-cell RNA sequencing data of approximately 120 million cells from diverse tissues and conditions (healthy and diseased) and is fully compatible with PyTorch. This facilitates the development of innovative cell signaling models that could transform research in life sciences, healthcare, and precision medicine. The OmniCellTOSG dataset is continuously expanding and will be updated regularly. The dataset and code are available at https://github.com/FuhaiLiAiLab/OmniCellTOSG.

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.

Image-to-image translation (I2I) methods allow the generation of artificial images that share the content of the original image but have a different style. With the advances in Generative Adversarial Networks (GANs)-based methods, I2I methods enabled the generation of artificial images that are indistinguishable from natural images. Recently, I2I methods were also employed in histopathology for generating artificial images of in silico stained tissues from a different type of staining. We refer to this process as stain transfer. The number of I2I variants is constantly increasing, which makes a well justified choice of the most suitable I2I methods for stain transfer challenging. In our work, we compare twelve stain transfer approaches, three of which are based on traditional and nine on GAN-based image processing methods. The analysis relies on complementary quantitative measures for the quality of image translation, the assessment of the suitability for deep learning-based tissue grading, and the visual evaluation by pathologists. Our study highlights the strengths and weaknesses of the stain transfer approaches, thereby allowing a rational choice of the underlying I2I algorithms. Code, data, and trained models for stain transfer between H&E and Masson's Trichrome staining will be made available online.

Instance segmentation and classification of nuclei is an important task in computational pathology. We show that StarDist, a deep learning nuclei segmentation method originally developed for fluorescence microscopy, can be extended and successfully applied to histopathology images. This is substantiated by conducting experiments on the Lizard dataset, and through entering the Colon Nuclei Identification and Counting (CoNIC) challenge 2022, where our approach achieved the first spot on the leaderboard for the segmentation and classification task for both the preliminary and final test phase.

In this paper we present a hybrid method for the automatic detection of dermatological pathologies in medical reports. We use a large language model combined with medical ontologies to predict, given a first appointment or follow-up medical report, the pathology a person may suffer from. The results show that teaching the model to learn the type, severity and location on the body of a dermatological pathology, as well as in which order it has to learn these three features, significantly increases its accuracy. The article presents the demonstration of state-of-the-art results for classification of medical texts with a precision of 0.84, micro and macro F1-score of 0.82 and 0.75, and makes both the method and the data set used available to the community.

As lung cancer evolves, the presence of enlarged and potentially malignant lymph nodes must be assessed to properly estimate disease progression and select the best treatment strategy. Following the clinical guidelines, estimation of short-axis diameter and mediastinum station are paramount for correct diagnosis. A method for accurate and automatic segmentation is hence decisive for quantitatively describing lymph nodes. In this study, the use of 3D convolutional neural networks, either through slab-wise schemes or the leveraging of downsampled entire volumes, is investigated. Furthermore, the potential impact from simple ensemble strategies is considered. As lymph nodes have similar attenuation values to nearby anatomical structures, we suggest using the knowledge of other organs as prior information to guide the segmentation task. To assess the segmentation and instance detection performances, a 5-fold cross-validation strategy was followed over a dataset of 120 contrast-enhanced CT volumes. For the 1178 lymph nodes with a short-axis diameter geq10 mm, our best performing approach reached a patient-wise recall of 92%, a false positive per patient ratio of 5, and a segmentation overlap of 80.5%. The method performs similarly well across all stations. Fusing a slab-wise and a full volume approach within an ensemble scheme generated the best performances. The anatomical priors guiding strategy is promising, yet a larger set than four organs appears needed to generate an optimal benefit. A larger dataset is also mandatory, given the wide range of expressions a lymph node can exhibit (i.e., shape, location, and attenuation), and contrast uptake variations.

Image editing using diffusion models has witnessed extremely fast-paced growth recently. There are various ways in which previous works enable controlling and editing images. Some works use high-level conditioning such as text, while others use low-level conditioning. Nevertheless, most of them lack fine-grained control over the properties of the different objects present in the image, i.e. object-level image editing. In this work, we consider an image as a composition of multiple objects, each defined by various properties. Out of these properties, we identify structure and appearance as the most intuitive to understand and useful for editing purposes. We propose Structure-and-Appearance Paired Diffusion model (PAIR-Diffusion), which is trained using structure and appearance information explicitly extracted from the images. The proposed model enables users to inject a reference image's appearance into the input image at both the object and global levels. Additionally, PAIR-Diffusion allows editing the structure while maintaining the style of individual components of the image unchanged. We extensively evaluate our method on LSUN datasets and the CelebA-HQ face dataset, and we demonstrate fine-grained control over both structure and appearance at the object level. We also applied the method to Stable Diffusion to edit any real image at the object level.

Cancer has relational information residing at varying scales, modalities, and resolutions of the acquired data, such as radiology, pathology, genomics, proteomics, and clinical records. Integrating diverse data types can improve the accuracy and reliability of cancer diagnosis and treatment. There can be disease-related information that is too subtle for humans or existing technological tools to discern visually. Traditional methods typically focus on partial or unimodal information about biological systems at individual scales and fail to encapsulate the complete spectrum of the heterogeneous nature of data. Deep neural networks have facilitated the development of sophisticated multimodal data fusion approaches that can extract and integrate relevant information from multiple sources. Recent deep learning frameworks such as Graph Neural Networks (GNNs) and Transformers have shown remarkable success in multimodal learning. This review article provides an in-depth analysis of the state-of-the-art in GNNs and Transformers for multimodal data fusion in oncology settings, highlighting notable research studies and their findings. We also discuss the foundations of multimodal learning, inherent challenges, and opportunities for integrative learning in oncology. By examining the current state and potential future developments of multimodal data integration in oncology, we aim to demonstrate the promising role that multimodal neural networks can play in cancer prevention, early detection, and treatment through informed oncology practices in personalized settings.

To investigate whether the pleurae, airways and vessels surrounding a nodule on non-contrast computed tomography (CT) can discriminate benign and malignant pulmonary nodules. The LIDC-IDRI dataset, one of the largest publicly available CT database, was exploited for study. A total of 1556 nodules from 694 patients were involved in statistical analysis, where nodules with average scorings <3 and >3 were respectively denoted as benign and malignant. Besides, 339 nodules from 113 patients with diagnosis ground-truth were independently evaluated. Computer algorithms were developed to segment pulmonary structures and quantify the distances to pleural surface, airways and vessels, as well as the counting number and normalized volume of airways and vessels near a nodule. Odds ratio (OR) and Chi-square (\chi^2) testing were performed to demonstrate the correlation between features of surrounding structures and nodule malignancy. A non-parametric receiver operating characteristic (ROC) analysis was conducted in logistic regression to evaluate discrimination ability of each structure. For benign and malignant groups, the average distances from nodules to pleural surface, airways and vessels are respectively (6.56, 5.19), (37.08, 26.43) and (1.42, 1.07) mm. The correlation between nodules and the counting number of airways and vessels that contact or project towards nodules are respectively (OR=22.96, \chi^2=105.04) and (OR=7.06, \chi^2=290.11). The correlation between nodules and the volume of airways and vessels are (OR=9.19, \chi^2=159.02) and (OR=2.29, \chi^2=55.89). The areas-under-curves (AUCs) for pleurae, airways and vessels are respectively 0.5202, 0.6943 and 0.6529. Our results show that malignant nodules are often surrounded by more pulmonary structures compared with benign ones, suggesting that features of these structures could be viewed as lung cancer biomarkers.

Multimodal pathology-genomic analysis is critical for cancer survival prediction. However, existing approaches predominantly integrate formalin-fixed paraffin-embedded (FFPE) slides with genomic data, while neglecting the availability of other preservation slides, such as Fresh Froze (FF) slides. Moreover, as the high-resolution spatial nature of pathology data tends to dominate the cross-modality fusion process, it hinders effective multimodal fusion and leads to modality imbalance challenges between pathology and genomics. These methods also typically require complete data modalities, limiting their clinical applicability with incomplete modalities, such as missing either pathology or genomic data. In this paper, we propose a multimodal survival prediction framework that leverages hypergraph learning to effectively integrate multi-WSI information and cross-modality interactions between pathology slides and genomics data while addressing modality imbalance. In addition, we introduce a memory mechanism that stores previously learned paired pathology-genomic features and dynamically compensates for incomplete modalities. Experiments on five TCGA datasets demonstrate that our model outperforms advanced methods by over 2.3% in C-Index. Under incomplete modality scenarios, our approach surpasses pathology-only (3.3%) and gene-only models (7.9%). Code: https://github.com/MCPathology/M2Surv

Pathology plays a critical role in diagnosing a wide range of diseases, yet existing approaches often rely heavily on task-specific models trained on extensive, well-labeled datasets. These methods face sustainability challenges due to the diversity of pathologies and the labor-intensive nature of data collection. To address these limitations, we highlight the need for universal multimodal embeddings that can support multiple downstream tasks. Previous approaches often involve fine-tuning CLIP-based models, which handle images and text separately, limiting their ability to capture complex multimodal relationships. Additionally, these models are evaluated across diverse datasets without a unified benchmark for assessing multimodal embeddings in pathology. To address these challenges, we propose MLLM4PUE, a novel framework that leverages Multimodal Large Language Models (MLLMs) to generate Pathology Universal Embeddings. The MLLM4PUE framework not only facilitates robust integration of images and text but also enhances understanding and fusion capabilities across various tasks. We further introduce the Pathology Multimodal Embedding Benchmark (PMEB), a comprehensive benchmark designed to assess the quality of pathology multimodal embeddings. PMEB comprises 15 original tasks drawn from 14 datasets, organized into three meta-tasks: retrieval, classification, and composed retrieval. Experimental results demonstrate the superiority of MLLM4PUE, illustrating MLLM-based models can effectively support a wide range of downstream tasks and unify the research direction for foundation models in pathology.

In this paper, we propose a hybrid approach for multi-object microbial cell segmentation. The approach combines an ML-based detection with a geometry-aware variational-based segmentation using B-splines that are parametrized based on a geometric model of the cell shape. The detection is done first using YOLOv5. In a second step, each detected cell is segmented individually. Thus, the segmentation only needs to be done on a per-cell basis, which makes it amenable to a variational approach that incorporates prior knowledge on the geometry. Here, the contour of the segmentation is modelled as closed uniform cubic B-spline, whose control points are parametrized using the known cell geometry. Compared to purely ML-based segmentation approaches, which need accurate segmentation maps as training data that are very laborious to produce, our method just needs bounding boxes as training data. Still, the proposed method performs on par with ML-based segmentation approaches usually used in this context. We study the performance of the proposed method on time-lapse microscopy data of Corynebacterium glutamicum.

Brain tumor growth is unique to each glioma patient and extends beyond what is visible in imaging scans, infiltrating surrounding brain tissue. Understanding these hidden patient-specific progressions is essential for effective therapies. Current treatment plans for brain tumors, such as radiotherapy, typically involve delineating a uniform margin around the visible tumor on pre-treatment scans to target this invisible tumor growth. This "one size fits all" approach is derived from population studies and often fails to account for the nuances of individual patient conditions. We present the GliODIL framework, which infers the full spatial distribution of tumor cell concentration from available multi-modal imaging, leveraging a Fisher-Kolmogorov type physics model to describe tumor growth. This is achieved through the newly introduced method of Optimizing the Discrete Loss (ODIL), where both data and physics-based constraints are softly assimilated into the solution. Our test dataset comprises 152 glioblastoma patients with pre-treatment imaging and post-treatment follow-ups for tumor recurrence monitoring. By blending data-driven techniques with physics-based constraints, GliODIL enhances recurrence prediction in radiotherapy planning, challenging traditional uniform margins and strict adherence to the Fisher-Kolmogorov partial differential equation (PDE) model, which is adapted for complex cases.

This paper introduces a novel dataset to help researchers evaluate their computer vision and audio models for accuracy across a diverse set of age, genders, apparent skin tones and ambient lighting conditions. Our dataset is composed of 3,011 subjects and contains over 45,000 videos, with an average of 15 videos per person. The videos were recorded in multiple U.S. states with a diverse set of adults in various age, gender and apparent skin tone groups. A key feature is that each subject agreed to participate for their likenesses to be used. Additionally, our age and gender annotations are provided by the subjects themselves. A group of trained annotators labeled the subjects' apparent skin tone using the Fitzpatrick skin type scale. Moreover, annotations for videos recorded in low ambient lighting are also provided. As an application to measure robustness of predictions across certain attributes, we provide a comprehensive study on the top five winners of the DeepFake Detection Challenge (DFDC). Experimental evaluation shows that the winning models are less performant on some specific groups of people, such as subjects with darker skin tones and thus may not generalize to all people. In addition, we also evaluate the state-of-the-art apparent age and gender classification methods. Our experiments provides a thorough analysis on these models in terms of fair treatment of people from various backgrounds.