Daily Papers

In breast cancer imaging, there has been a trend to directly predict pathological complete response (pCR) to neoadjuvant chemotherapy (NAC) from histological images based on deep learning (DL). However, it has been a commonly known problem that the constructed DL-based models numerically have better performances in internal validation than in external validation. The primary reason for this situation lies in that the distribution of the external data for validation is different from the distribution of the training data for the construction of the predictive model. In this paper, we aim to alleviate this situation with a more intrinsic approach. We propose an experts' cognition-driven ensemble deep learning (ECDEDL) approach for external validation of predicting pCR to NAC from histological images in breast cancer. The proposed ECDEDL, which takes the cognition of both pathology and artificial intelligence experts into consideration to improve the generalization of the predictive model to the external validation, more intrinsically approximates the working paradigm of a human being which will refer to his various working experiences to make decisions. The proposed ECDEDL approach was validated with 695 WSIs collected from the same center as the primary dataset to develop the predictive model and perform the internal validation, and 340 WSIs collected from other three centers as the external dataset to perform the external validation. In external validation, the proposed ECDEDL approach improves the AUCs of pCR prediction from 61.52(59.80-63.26) to 67.75(66.74-68.80) and the Accuracies of pCR prediction from 56.09(49.39-62.79) to 71.01(69.44-72.58). The proposed ECDEDL was quite effective for external validation, numerically more approximating the internal validation.

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

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.

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.

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

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.

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.

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.

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

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.

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.

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.

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

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.

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.

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.

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

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.

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

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

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

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

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

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

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.

To synthesize high-fidelity samples, diffusion models typically require auxiliary data to guide the generation process. However, it is impractical to procure the painstaking patch-level annotation effort required in specialized domains like histopathology and satellite imagery; it is often performed by domain experts and involves hundreds of millions of patches. Modern-day self-supervised learning (SSL) representations encode rich semantic and visual information. In this paper, we posit that such representations are expressive enough to act as proxies to fine-grained human labels. We introduce a novel approach that trains diffusion models conditioned on embeddings from SSL. Our diffusion models successfully project these features back to high-quality histopathology and remote sensing images. In addition, we construct larger images by assembling spatially consistent patches inferred from SSL embeddings, preserving long-range dependencies. Augmenting real data by generating variations of real images improves downstream classifier accuracy for patch-level and larger, image-scale classification tasks. Our models are effective even on datasets not encountered during training, demonstrating their robustness and generalizability. Generating images from learned embeddings is agnostic to the source of the embeddings. The SSL embeddings used to generate a large image can either be extracted from a reference image, or sampled from an auxiliary model conditioned on any related modality (e.g. class labels, text, genomic data). As proof of concept, we introduce the text-to-large image synthesis paradigm where we successfully synthesize large pathology and satellite images out of text descriptions.

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.

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

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

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.

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

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.

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.

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.

Nucleus instance segmentation in histology images is crucial for a broad spectrum of clinical applications. Current dominant algorithms rely on regression of nuclear proxy maps. Distinguishing nucleus instances from the estimated maps requires carefully curated post-processing, which is error-prone and parameter-sensitive. Recently, the Segment Anything Model (SAM) has earned huge attention in medical image segmentation, owing to its impressive generalization ability and promptable property. Nevertheless, its potential on nucleus instance segmentation remains largely underexplored. In this paper, we present a novel prompt-driven framework that consists of a nucleus prompter and SAM for automatic nucleus instance segmentation. Specifically, the prompter learns to generate a unique point prompt for each nucleus while the SAM is fine-tuned to output the corresponding mask for the prompted nucleus. Furthermore, we propose the inclusion of adjacent nuclei as negative prompts to enhance the model's capability to identify overlapping nuclei. Without complicated post-processing, our proposed method sets a new state-of-the-art performance on three challenging benchmarks. Code is available at github.com/windygoo/PromptNucSeg

Instance-level image classification tasks have traditionally relied on single-instance labels to train models, e.g., few-shot learning and transfer learning. However, set-level coarse-grained labels that capture relationships among instances can provide richer information in real-world scenarios. In this paper, we present a novel approach to enhance instance-level image classification by leveraging set-level labels. We provide a theoretical analysis of the proposed method, including recognition conditions for fast excess risk rate, shedding light on the theoretical foundations of our approach. We conducted experiments on two distinct categories of datasets: natural image datasets and histopathology image datasets. Our experimental results demonstrate the effectiveness of our approach, showcasing improved classification performance compared to traditional single-instance label-based methods. Notably, our algorithm achieves 13% improvement in classification accuracy compared to the strongest baseline on the histopathology image classification benchmarks. Importantly, our experimental findings align with the theoretical analysis, reinforcing the robustness and reliability of our proposed method. This work bridges the gap between instance-level and set-level image classification, offering a promising avenue for advancing the capabilities of image classification models with set-level coarse-grained labels.

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.

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)).

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.

The previous advancements in pathology image understanding primarily involved developing models tailored to specific tasks. Recent studies has demonstrated that the large vision-language model can enhance the performance of various downstream tasks in medical image understanding. In this study, we developed a domain-specific large language-vision assistant (PA-LLaVA) for pathology image understanding. Specifically, (1) we first construct a human pathology image-text dataset by cleaning the public medical image-text data for domain-specific alignment; (2) Using the proposed image-text data, we first train a pathology language-image pretraining (PLIP) model as the specialized visual encoder for pathology image, and then we developed scale-invariant connector to avoid the information loss caused by image scaling; (3) We adopt two-stage learning to train PA-LLaVA, first stage for domain alignment, and second stage for end to end visual question \& answering (VQA) task. In experiments, we evaluate our PA-LLaVA on both supervised and zero-shot VQA datasets, our model achieved the best overall performance among multimodal models of similar scale. The ablation experiments also confirmed the effectiveness of our design. We posit that our PA-LLaVA model and the datasets presented in this work can promote research in field of computational pathology. All codes are available at: https://github.com/ddw2AIGROUP2CQUPT/PA-LLaVA}{https://github.com/ddw2AIGROUP2CQUPT/PA-LLaVA

We propose a new model for digital pathology segmentation, based on the observation that histopathology images are inherently symmetric under rotation and reflection. Utilizing recent findings on rotation equivariant CNNs, the proposed model leverages these symmetries in a principled manner. We present a visual analysis showing improved stability on predictions, and demonstrate that exploiting rotation equivariance significantly improves tumor detection performance on a challenging lymph node metastases dataset. We further present a novel derived dataset to enable principled comparison of machine learning models, in combination with an initial benchmark. Through this dataset, the task of histopathology diagnosis becomes accessible as a challenging benchmark for fundamental machine learning research.

In this paper, a multi-scale visual transformer model, referred as GasHis-Transformer, is proposed for Gastric Histopathological Image Detection (GHID), which enables the automatic global detection of gastric cancer images. GasHis-Transformer model consists of two key modules designed to extract global and local information using a position-encoded transformer model and a convolutional neural network with local convolution, respectively. A publicly available hematoxylin and eosin (H&E) stained gastric histopathological image dataset is used in the experiment. Furthermore, a Dropconnect based lightweight network is proposed to reduce the model size and training time of GasHis-Transformer for clinical applications with improved confidence. Moreover, a series of contrast and extended experiments verify the robustness, extensibility and stability of GasHis-Transformer. In conclusion, GasHis-Transformer demonstrates high global detection performance and shows its significant potential in GHID task.

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

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.

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

Semantic segmentation of medical images aims to associate a pixel with a label in a medical image without human initialization. The success of semantic segmentation algorithms is contingent on the availability of high-quality imaging data with corresponding labels provided by experts. We sought to create a large collection of annotated medical image datasets of various clinically relevant anatomies available under open source license to facilitate the development of semantic segmentation algorithms. Such a resource would allow: 1) objective assessment of general-purpose segmentation methods through comprehensive benchmarking and 2) open and free access to medical image data for any researcher interested in the problem domain. Through a multi-institutional effort, we generated a large, curated dataset representative of several highly variable segmentation tasks that was used in a crowd-sourced challenge - the Medical Segmentation Decathlon held during the 2018 Medical Image Computing and Computer Aided Interventions Conference in Granada, Spain. Here, we describe these ten labeled image datasets so that these data may be effectively reused by the research community.

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.

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.

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.

An increasing number of public datasets have shown a marked impact on automated organ segmentation and tumor detection. However, due to the small size and partially labeled problem of each dataset, as well as a limited investigation of diverse types of tumors, the resulting models are often limited to segmenting specific organs/tumors and ignore the semantics of anatomical structures, nor can they be extended to novel domains. To address these issues, we propose the CLIP-Driven Universal Model, which incorporates text embedding learned from Contrastive Language-Image Pre-training (CLIP) to segmentation models. This CLIP-based label encoding captures anatomical relationships, enabling the model to learn a structured feature embedding and segment 25 organs and 6 types of tumors. The proposed model is developed from an assembly of 14 datasets, using a total of 3,410 CT scans for training and then evaluated on 6,162 external CT scans from 3 additional datasets. We rank first on the Medical Segmentation Decathlon (MSD) public leaderboard and achieve state-of-the-art results on Beyond The Cranial Vault (BTCV). Additionally, the Universal Model is computationally more efficient (6x faster) compared with dataset-specific models, generalized better to CT scans from varying sites, and shows stronger transfer learning performance on novel tasks.

This paper introduces MedTrinity-25M, a comprehensive, large-scale multimodal dataset for medicine, covering over 25 million images across 10 modalities, with multigranular annotations for more than 65 diseases. These enriched annotations encompass both global textual information, such as disease/lesion type, modality, region-specific descriptions, and inter-regional relationships, as well as detailed local annotations for regions of interest (ROIs), including bounding boxes, segmentation masks. Unlike existing approach which is limited by the availability of image-text pairs, we have developed the first automated pipeline that scales up multimodal data by generating multigranular visual and texual annotations (in the form of image-ROI-description triplets) without the need for any paired text descriptions. Specifically, data from over 90 different sources have been collected, preprocessed, and grounded using domain-specific expert models to identify ROIs related to abnormal regions. We then build a comprehensive knowledge base and prompt multimodal large language models to perform retrieval-augmented generation with the identified ROIs as guidance, resulting in multigranular texual descriptions. Compared to existing datasets, MedTrinity-25M provides the most enriched annotations, supporting a comprehensive range of multimodal tasks such as captioning and report generation, as well as vision-centric tasks like classification and segmentation. Pretraining on MedTrinity-25M, our model achieves state-of-the-art performance on VQA-RAD and PathVQA, surpassing both multimodal large language models and other representative SoTA approaches. This dataset can also be utilized to support large-scale pre-training of multimodal medical AI models, contributing to the development of future foundation models in the medical domain.

Foundation models in computational pathology promise to unlock the development of new clinical decision support systems and models for precision medicine. However, there is a mismatch between most clinical analysis, which is defined at the level of one or more whole slide images, and foundation models to date, which process the thousands of image tiles contained in a whole slide image separately. The requirement to train a network to aggregate information across a large number of tiles in multiple whole slide images limits these models' impact. In this work, we present a slide-level foundation model for H&E-stained histopathology, PRISM, that builds on Virchow tile embeddings and leverages clinical report text for pre-training. Using the tile embeddings, PRISM produces slide-level embeddings with the ability to generate clinical reports, resulting in several modes of use. Using text prompts, PRISM achieves zero-shot cancer detection and sub-typing performance approaching and surpassing that of a supervised aggregator model. Using the slide embeddings with linear classifiers, PRISM surpasses supervised aggregator models. Furthermore, we demonstrate that fine-tuning of the PRISM slide encoder yields label-efficient training for biomarker prediction, a task that typically suffers from low availability of training data; an aggregator initialized with PRISM and trained on as little as 10% of the training data can outperform a supervised baseline that uses all of the data.

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.

Self-supervised learning (SSL) has recently achieved promising performance for 3D medical image analysis tasks. Most current methods follow existing SSL paradigm originally designed for photographic or natural images, which cannot explicitly and thoroughly exploit the intrinsic similar anatomical structures across varying medical images. This may in fact degrade the quality of learned deep representations by maximizing the similarity among features containing spatial misalignment information and different anatomical semantics. In this work, we propose a new self-supervised learning framework, namely Alice, that explicitly fulfills Anatomical invariance modeling and semantic alignment via elaborately combining discriminative and generative objectives. Alice introduces a new contrastive learning strategy which encourages the similarity between views that are diversely mined but with consistent high-level semantics, in order to learn invariant anatomical features. Moreover, we design a conditional anatomical feature alignment module to complement corrupted embeddings with globally matched semantics and inter-patch topology information, conditioned by the distribution of local image content, which permits to create better contrastive pairs. Our extensive quantitative experiments on three 3D medical image analysis tasks demonstrate and validate the performance superiority of Alice, surpassing the previous best SSL counterpart methods and showing promising ability for united representation learning. Codes are available at https://github.com/alibaba-damo-academy/alice.

Medical imaging analysis plays a critical role in the diagnosis and treatment of various medical conditions. This paper focuses on chest X-ray images and their corresponding radiological reports. It presents a new model that learns a joint X-ray image & report representation. The model is based on a novel alignment scheme between the visual data and the text, which takes into account both local and global information. Furthermore, the model integrates domain-specific information of two types -- lateral images and the consistent visual structure of chest images. Our representation is shown to benefit three types of retrieval tasks: text-image retrieval, class-based retrieval, and phrase-grounding.

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 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/.

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

Radiography imaging protocols focus on particular body regions, therefore producing images of great similarity and yielding recurrent anatomical structures across patients. To exploit this structured information, we propose the use of Space-aware Memory Queues for In-painting and Detecting anomalies from radiography images (abbreviated as SQUID). We show that SQUID can taxonomize the ingrained anatomical structures into recurrent patterns; and in the inference, it can identify anomalies (unseen/modified patterns) in the image. SQUID surpasses 13 state-of-the-art methods in unsupervised anomaly detection by at least 5 points on two chest X-ray benchmark datasets measured by the Area Under the Curve (AUC). Additionally, we have created a new dataset (DigitAnatomy), which synthesizes the spatial correlation and consistent shape in chest anatomy. We hope DigitAnatomy can prompt the development, evaluation, and interpretability of anomaly detection methods.

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].

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

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.

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

Self-supervised learning (SSL) approaches have recently shown substantial success in learning visual representations from unannotated images. Compared with photographic images, medical images acquired with the same imaging protocol exhibit high consistency in anatomy. To exploit this anatomical consistency, this paper introduces a novel SSL approach, called PEAC (patch embedding of anatomical consistency), for medical image analysis. Specifically, in this paper, we propose to learn global and local consistencies via stable grid-based matching, transfer pre-trained PEAC models to diverse downstream tasks, and extensively demonstrate that (1) PEAC achieves significantly better performance than the existing state-of-the-art fully/self-supervised methods, and (2) PEAC captures the anatomical structure consistency across views of the same patient and across patients of different genders, weights, and healthy statuses, which enhances the interpretability of our method for medical image analysis.

Multimodal models trained on large natural image-text pair datasets have exhibited astounding abilities in generating high-quality images. Medical imaging data is fundamentally different to natural images, and the language used to succinctly capture relevant details in medical data uses a different, narrow but semantically rich, domain-specific vocabulary. Not surprisingly, multi-modal models trained on natural image-text pairs do not tend to generalize well to the medical domain. Developing generative imaging models faithfully representing medical concepts while providing compositional diversity could mitigate the existing paucity of high-quality, annotated medical imaging datasets. In this work, we develop a strategy to overcome the large natural-medical distributional shift by adapting a pre-trained latent diffusion model on a corpus of publicly available chest x-rays (CXR) and their corresponding radiology (text) reports. We investigate the model's ability to generate high-fidelity, diverse synthetic CXR conditioned on text prompts. We assess the model outputs quantitatively using image quality metrics, and evaluate image quality and text-image alignment by human domain experts. We present evidence that the resulting model (RoentGen) is able to create visually convincing, diverse synthetic CXR images, and that the output can be controlled to a new extent by using free-form text prompts including radiology-specific language. Fine-tuning this model on a fixed training set and using it as a data augmentation method, we measure a 5% improvement of a classifier trained jointly on synthetic and real images, and a 3% improvement when trained on a larger but purely synthetic training set. Finally, we observe that this fine-tuning distills in-domain knowledge in the text-encoder and can improve its representation capabilities of certain diseases like pneumothorax by 25%.

Chest radiography is an extremely powerful imaging modality, allowing for a detailed inspection of a patient's thorax, but requiring specialized training for proper interpretation. With the advent of high performance general purpose computer vision algorithms, the accurate automated analysis of chest radiographs is becoming increasingly of interest to researchers. However, a key challenge in the development of these techniques is the lack of sufficient data. Here we describe MIMIC-CXR-JPG v2.0.0, a large dataset of 377,110 chest x-rays associated with 227,827 imaging studies sourced from the Beth Israel Deaconess Medical Center between 2011 - 2016. Images are provided with 14 labels derived from two natural language processing tools applied to the corresponding free-text radiology reports. MIMIC-CXR-JPG is derived entirely from the MIMIC-CXR database, and aims to provide a convenient processed version of MIMIC-CXR, as well as to provide a standard reference for data splits and image labels. All images have been de-identified to protect patient privacy. The dataset is made freely available to facilitate and encourage a wide range of research in medical computer vision.

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

Radiology reporting generative AI holds significant potential to alleviate clinical workloads and streamline medical care. However, achieving high clinical accuracy is challenging, as radiological images often feature subtle lesions and intricate structures. Existing systems often fall short, largely due to their reliance on fixed size, patch-level image features and insufficient incorporation of pathological information. This can result in the neglect of such subtle patterns and inconsistent descriptions of crucial pathologies. To address these challenges, we propose an innovative approach that leverages pathology-aware regional prompts to explicitly integrate anatomical and pathological information of various scales, significantly enhancing the precision and clinical relevance of generated reports. We develop an anatomical region detector that extracts features from distinct anatomical areas, coupled with a novel multi-label lesion detector that identifies global pathologies. Our approach emulates the diagnostic process of radiologists, producing clinically accurate reports with comprehensive diagnostic capabilities. Experimental results show that our model outperforms previous state-of-the-art methods on most natural language generation and clinical efficacy metrics, with formal expert evaluations affirming its potential to enhance radiology practice.

Purpose: To introduce a deep learning model capable of multi-organ segmentation in MRI scans, offering a solution to the current limitations in MRI analysis due to challenges in resolution, standardized intensity values, and variability in sequences. Materials and Methods: he model was trained on 1,200 manually annotated MRI scans from the UK Biobank, 221 in-house MRI scans and 1228 CT scans, leveraging cross-modality transfer learning from CT segmentation models. A human-in-the-loop annotation workflow was employed to efficiently create high-quality segmentations. The model's performance was evaluated on NAKO and the AMOS22 dataset containing 600 and 60 MRI examinations. Dice Similarity Coefficient (DSC) and Hausdorff Distance (HD) was used to assess segmentation accuracy. The model will be open sourced. Results: The model showcased high accuracy in segmenting well-defined organs, achieving Dice Similarity Coefficient (DSC) scores of 0.97 for the right and left lungs, and 0.95 for the heart. It also demonstrated robustness in organs like the liver (DSC: 0.96) and kidneys (DSC: 0.95 left, 0.95 right), which present more variability. However, segmentation of smaller and complex structures such as the portal and splenic veins (DSC: 0.54) and adrenal glands (DSC: 0.65 left, 0.61 right) revealed the need for further model optimization. Conclusion: The proposed model is a robust, tool for accurate segmentation of 40 anatomical structures in MRI and CT images. By leveraging cross-modality learning and interactive annotation, the model achieves strong performance and generalizability across diverse datasets, making it a valuable resource for researchers and clinicians. It is open source and can be downloaded from https://github.com/hhaentze/MRSegmentator.

A key requirement for the success of supervised deep learning is a large labeled dataset - a condition that is difficult to meet in medical image analysis. Self-supervised learning (SSL) can help in this regard by providing a strategy to pre-train a neural network with unlabeled data, followed by fine-tuning for a downstream task with limited annotations. Contrastive learning, a particular variant of SSL, is a powerful technique for learning image-level representations. In this work, we propose strategies for extending the contrastive learning framework for segmentation of volumetric medical images in the semi-supervised setting with limited annotations, by leveraging domain-specific and problem-specific cues. Specifically, we propose (1) novel contrasting strategies that leverage structural similarity across volumetric medical images (domain-specific cue) and (2) a local version of the contrastive loss to learn distinctive representations of local regions that are useful for per-pixel segmentation (problem-specific cue). We carry out an extensive evaluation on three Magnetic Resonance Imaging (MRI) datasets. In the limited annotation setting, the proposed method yields substantial improvements compared to other self-supervision and semi-supervised learning techniques. When combined with a simple data augmentation technique, the proposed method reaches within 8% of benchmark performance using only two labeled MRI volumes for training, corresponding to only 4% (for ACDC) of the training data used to train the benchmark. The code is made public at https://github.com/krishnabits001/domain_specific_cl.

Learning similarity is a key aspect in medical image analysis, particularly in recommendation systems or in uncovering the interpretation of anatomical data in images. Most existing methods learn such similarities in the embedding space over image sets using a single metric learner. Images, however, have a variety of object attributes such as color, shape, or artifacts. Encoding such attributes using a single metric learner is inadequate and may fail to generalize. Instead, multiple learners could focus on separate aspects of these attributes in subspaces of an overarching embedding. This, however, implies the number of learners to be found empirically for each new dataset. This work, Dynamic Subspace Learners, proposes to dynamically exploit multiple learners by removing the need of knowing apriori the number of learners and aggregating new subspace learners during training. Furthermore, the visual interpretability of such subspace learning is enforced by integrating an attention module into our method. This integrated attention mechanism provides a visual insight of discriminative image features that contribute to the clustering of image sets and a visual explanation of the embedding features. The benefits of our attention-based dynamic subspace learners are evaluated in the application of image clustering, image retrieval, and weakly supervised segmentation. Our method achieves competitive results with the performances of multiple learners baselines and significantly outperforms the classification network in terms of clustering and retrieval scores on three different public benchmark datasets. Moreover, our attention maps offer a proxy-labels, which improves the segmentation accuracy up to 15% in Dice scores when compared to state-of-the-art interpretation techniques.

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.

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

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.

Deep Learning (DL) has the potential to optimize machine learning in both the scientific and clinical communities. However, greater expertise is required to develop DL algorithms, and the variability of implementations hinders their reproducibility, translation, and deployment. Here we present the community-driven Generally Nuanced Deep Learning Framework (GaNDLF), with the goal of lowering these barriers. GaNDLF makes the mechanism of DL development, training, and inference more stable, reproducible, interpretable, and scalable, without requiring an extensive technical background. GaNDLF aims to provide an end-to-end solution for all DL-related tasks in computational precision medicine. We demonstrate the ability of GaNDLF to analyze both radiology and histology images, with built-in support for k-fold cross-validation, data augmentation, multiple modalities and output classes. Our quantitative performance evaluation on numerous use cases, anatomies, and computational tasks supports GaNDLF as a robust application framework for deployment in clinical workflows.

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.

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.

The burgeoning integration of 3D medical imaging into healthcare has led to a substantial increase in the workload of medical professionals. To assist clinicians in their diagnostic processes and alleviate their workload, the development of a robust system for retrieving similar case studies presents a viable solution. While the concept holds great promise, the field of 3D medical text-image retrieval is currently limited by the absence of robust evaluation benchmarks and curated datasets. To remedy this, our study presents a groundbreaking dataset, BIMCV-R (This dataset will be released upon acceptance.), which includes an extensive collection of 8,069 3D CT volumes, encompassing over 2 million slices, paired with their respective radiological reports. Expanding upon the foundational work of our dataset, we craft a retrieval strategy, MedFinder. This approach employs a dual-stream network architecture, harnessing the potential of large language models to advance the field of medical image retrieval beyond existing text-image retrieval solutions. It marks our preliminary step towards developing a system capable of facilitating text-to-image, image-to-text, and keyword-based retrieval tasks.

The aim of a Content-Based Image Retrieval (CBIR) system, also known as Query by Image Content (QBIC), is to help users to retrieve relevant images based on their contents. CBIR technologies provide a method to find images in large databases by using unique descriptors from a trained image. The image descriptors include texture, color, intensity and shape of the object inside an image. Several feature-extraction techniques viz., Average RGB, Color Moments, Co-occurrence, Local Color Histogram, Global Color Histogram and Geometric Moment have been critically compared in this paper. However, individually these techniques result in poor performance. So, combinations of these techniques have also been evaluated and results for the most efficient combination of techniques have been presented and optimized for each class of image query. We also propose an improvement in image retrieval performance by introducing the idea of Query modification through image cropping. It enables the user to identify a region of interest and modify the initial query to refine and personalize the image retrieval results.

Artificial intelligence has significantly advanced skin cancer diagnosis by enabling rapid and accurate detection of malignant lesions. In this domain, most publicly available image datasets consist of single, isolated skin lesions positioned at the center of the image. While these lesion-centric datasets have been fundamental for developing diagnostic algorithms, they lack the context of the surrounding skin, which is critical for improving lesion detection. The iToBoS dataset was created to address this challenge. It includes 16,954 images of skin regions from 100 participants, captured using 3D total body photography. Each image roughly corresponds to a 7 times 9 cm section of skin with all suspicious lesions annotated using bounding boxes. Additionally, the dataset provides metadata such as anatomical location, age group, and sun damage score for each image. This dataset aims to facilitate training and benchmarking of algorithms, with the goal of enabling early detection of skin cancer and deployment of this technology in non-clinical environments.

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.

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.

In this paper, a 3D-RegNet-based neural network is proposed for diagnosing the physical condition of patients with coronavirus (Covid-19) infection. In the application of clinical medicine, lung CT images are utilized by practitioners to determine whether a patient is infected with coronavirus. However, there are some laybacks can be considered regarding to this diagnostic method, such as time consuming and low accuracy. As a relatively large organ of human body, important spatial features would be lost if the lungs were diagnosed utilizing two dimensional slice image. Therefore, in this paper, a deep learning model with 3D image was designed. The 3D image as input data was comprised of two-dimensional pulmonary image sequence and from which relevant coronavirus infection 3D features were extracted and classified. The results show that the test set of the 3D model, the result: f1 score of 0.8379 and AUC value of 0.8807 have been achieved.

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.

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

Gathering histopathology slides from over 100 publicly available cohorts, we compile a diverse dataset of 460 million pathology tiles covering more than 30 cancer sites. Using this dataset, we train a large self-supervised vision transformer using DINOv2 and publicly release one iteration of this model for further experimentation, coined Phikon-v2. While trained on publicly available histology slides, Phikon-v2 surpasses our previously released model (Phikon) and performs on par with other histopathology foundation models (FM) trained on proprietary data. Our benchmarks include eight slide-level tasks with results reported on external validation cohorts avoiding any data contamination between pre-training and evaluation datasets. Our downstream training procedure follows a simple yet robust ensembling strategy yielding a +1.75 AUC increase across tasks and models compared to one-shot retraining (p<0.001). We compare Phikon (ViT-B) and Phikon-v2 (ViT-L) against 14 different histology feature extractors, making our evaluation the most comprehensive to date. Our result support evidences that DINOv2 handles joint model and data scaling better than iBOT. Also, we show that recent scaling efforts are overall beneficial to downstream performance in the context of biomarker prediction with GigaPath and H-Optimus-0 (two ViT-g with 1.1B parameters each) standing out. However, the statistical margins between the latest top-performing FMs remain mostly non-significant; some even underperform on specific indications or tasks such as MSI prediction - deposed by a 13x smaller model developed internally. While latest foundation models may exhibit limitations for clinical deployment, they nonetheless offer excellent grounds for the development of more specialized and cost-efficient histology encoders fueling AI-guided diagnostic tools.

We present a radiology-specific multimodal model for the task for generating radiological reports from chest X-rays (CXRs). Our work builds on the idea that large language model(s) can be equipped with multimodal capabilities through alignment with pre-trained vision encoders. On natural images, this has been shown to allow multimodal models to gain image understanding and description capabilities. Our proposed model (MAIRA-1) leverages a CXR-specific image encoder in conjunction with a fine-tuned large language model based on Vicuna-7B, and text-based data augmentation, to produce reports with state-of-the-art quality. In particular, MAIRA-1 significantly improves on the radiologist-aligned RadCliQ metric and across all lexical metrics considered. Manual review of model outputs demonstrates promising fluency and accuracy of generated reports while uncovering failure modes not captured by existing evaluation practices. More information and resources can be found on the project website: https://aka.ms/maira.

Computational pathology can lead to saving human lives, but models are annotation hungry and pathology images are notoriously expensive to annotate. Self-supervised learning has shown to be an effective method for utilizing unlabeled data, and its application to pathology could greatly benefit its downstream tasks. Yet, there are no principled studies that compare SSL methods and discuss how to adapt them for pathology. To address this need, we execute the largest-scale study of SSL pre-training on pathology image data, to date. Our study is conducted using 4 representative SSL methods on diverse downstream tasks. We establish that large-scale domain-aligned pre-training in pathology consistently out-performs ImageNet pre-training in standard SSL settings such as linear and fine-tuning evaluations, as well as in low-label regimes. Moreover, we propose a set of domain-specific techniques that we experimentally show leads to a performance boost. Lastly, for the first time, we apply SSL to the challenging task of nuclei instance segmentation and show large and consistent performance improvements under diverse settings.

We introduce a radiology-focused visual language model designed to generate radiology reports from chest X-rays. Building on previous findings that large language models (LLMs) can acquire multimodal capabilities when aligned with pretrained vision encoders, we demonstrate similar potential with chest X-ray images. This integration enhances the ability of model to understand and describe chest X-ray images. Our model combines an image encoder with a fine-tuned LLM based on the Vicuna-7B architecture, enabling it to generate different sections of a radiology report with notable accuracy. The training process involves a two-stage approach: (i) initial alignment of chest X-ray features with the LLM (ii) followed by fine-tuning for radiology report generation.

The chest X-ray is one of the most commonly accessible radiological examinations for screening and diagnosis of many lung diseases. A tremendous number of X-ray imaging studies accompanied by radiological reports are accumulated and stored in many modern hospitals' Picture Archiving and Communication Systems (PACS). On the other side, it is still an open question how this type of hospital-size knowledge database containing invaluable imaging informatics (i.e., loosely labeled) can be used to facilitate the data-hungry deep learning paradigms in building truly large-scale high precision computer-aided diagnosis (CAD) systems. In this paper, we present a new chest X-ray database, namely "ChestX-ray8", which comprises 108,948 frontal-view X-ray images of 32,717 unique patients with the text-mined eight disease image labels (where each image can have multi-labels), from the associated radiological reports using natural language processing. Importantly, we demonstrate that these commonly occurring thoracic diseases can be detected and even spatially-located via a unified weakly-supervised multi-label image classification and disease localization framework, which is validated using our proposed dataset. Although the initial quantitative results are promising as reported, deep convolutional neural network based "reading chest X-rays" (i.e., recognizing and locating the common disease patterns trained with only image-level labels) remains a strenuous task for fully-automated high precision CAD systems. Data download link: https://nihcc.app.box.com/v/ChestXray-NIHCC

Foundation models are rapidly being developed for computational pathology applications. However, it remains an open question which factors are most important for downstream performance with data scale and diversity, model size, and training algorithm all playing a role. In this work, we present the result of scaling both data and model size, surpassing previous studies in both dimensions, and introduce two new models: Virchow 2, a 632M parameter vision transformer, and Virchow 2G, a 1.85B parameter vision transformer, each trained with 3.1M histopathology whole slide images. To support this scale, we propose domain-inspired adaptations to the DINOv2 training algorithm, which is quickly becoming the default method in self-supervised learning for computational pathology. We achieve state of the art performance on twelve tile-level tasks, as compared to the top performing competing models. Our results suggest that data diversity and domain-specific training can outperform models that only scale in the number of parameters, but, on average, performance benefits from domain-tailoring, data scale, and model scale.

Self-supervised learning in vision-language processing exploits semantic alignment between imaging and text modalities. Prior work in biomedical VLP has mostly relied on the alignment of single image and report pairs even though clinical notes commonly refer to prior images. This does not only introduce poor alignment between the modalities but also a missed opportunity to exploit rich self-supervision through existing temporal content in the data. In this work, we explicitly account for prior images and reports when available during both training and fine-tuning. Our approach, named BioViL-T, uses a CNN-Transformer hybrid multi-image encoder trained jointly with a text model. It is designed to be versatile to arising challenges such as pose variations and missing input images across time. The resulting model excels on downstream tasks both in single- and multi-image setups, achieving state-of-the-art performance on (I) progression classification, (II) phrase grounding, and (III) report generation, whilst offering consistent improvements on disease classification and sentence-similarity tasks. We release a novel multi-modal temporal benchmark dataset, MS-CXR-T, to quantify the quality of vision-language representations in terms of temporal semantics. Our experimental results show the advantages of incorporating prior images and reports to make most use of the data.

We introduce MedMNIST v2, a large-scale MNIST-like dataset collection of standardized biomedical images, including 12 datasets for 2D and 6 datasets for 3D. All images are pre-processed into a small size of 28x28 (2D) or 28x28x28 (3D) with the corresponding classification labels so that no background knowledge is required for users. Covering primary data modalities in biomedical images, MedMNIST v2 is designed to perform classification on lightweight 2D and 3D images with various dataset scales (from 100 to 100,000) and diverse tasks (binary/multi-class, ordinal regression, and multi-label). The resulting dataset, consisting of 708,069 2D images and 10,214 3D images in total, could support numerous research / educational purposes in biomedical image analysis, computer vision, and machine learning. We benchmark several baseline methods on MedMNIST v2, including 2D / 3D neural networks and open-source / commercial AutoML tools. The data and code are publicly available at https://medmnist.com/.

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.

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.

The morphometry of a kidney tumor revealed by contrast-enhanced Computed Tomography (CT) imaging is an important factor in clinical decision making surrounding the lesion's diagnosis and treatment. Quantitative study of the relationship between kidney tumor morphology and clinical outcomes is difficult due to data scarcity and the laborious nature of manually quantifying imaging predictors. Automatic semantic segmentation of kidneys and kidney tumors is a promising tool towards automatically quantifying a wide array of morphometric features, but no sizeable annotated dataset is currently available to train models for this task. We present the KiTS19 challenge dataset: A collection of multi-phase CT imaging, segmentation masks, and comprehensive clinical outcomes for 300 patients who underwent nephrectomy for kidney tumors at our center between 2010 and 2018. 210 (70%) of these patients were selected at random as the training set for the 2019 MICCAI KiTS Kidney Tumor Segmentation Challenge and have been released publicly. With the presence of clinical context and surgical outcomes, this data can serve not only for benchmarking semantic segmentation models, but also for developing and studying biomarkers which make use of the imaging and semantic segmentation masks.

The ability to describe images with natural language sentences is the hallmark for image and language understanding. Such a system has wide ranging applications such as annotating images and using natural sentences to search for images.In this project we focus on the task of bidirectional image retrieval: such asystem is capable of retrieving an image based on a sentence (image search) andretrieve sentence based on an image query (image annotation). We present asystem based on a global ranking objective function which uses a combinationof convolutional neural networks (CNN) and multi layer perceptrons (MLP).It takes a pair of image and sentence and processes them in different channels,finally embedding it into a common multimodal vector space. These embeddingsencode abstract semantic information about the two inputs and can be comparedusing traditional information retrieval approaches. For each such pair, the modelreturns a score which is interpretted as a similarity metric. If this score is high,the image and sentence are likely to convey similar meaning, and if the score is low then they are likely not to. The visual input is modeled via deep convolutional neural network. On theother hand we explore three models for the textual module. The first one isbag of words with an MLP. The second one uses n-grams (bigram, trigrams,and a combination of trigram & skip-grams) with an MLP. The third is morespecialized deep network specific for modeling variable length sequences (SSE).We report comparable performance to recent work in the field, even though ouroverall model is simpler. We also show that the training time choice of how wecan generate our negative samples has a significant impact on performance, and can be used to specialize the bi-directional system in one particular task.

Automatic organ segmentation is an important yet challenging problem for medical image analysis. The pancreas is an abdominal organ with very high anatomical variability. This inhibits previous segmentation methods from achieving high accuracies, especially compared to other organs such as the liver, heart or kidneys. In this paper, we present a probabilistic bottom-up approach for pancreas segmentation in abdominal computed tomography (CT) scans, using multi-level deep convolutional networks (ConvNets). We propose and evaluate several variations of deep ConvNets in the context of hierarchical, coarse-to-fine classification on image patches and regions, i.e. superpixels. We first present a dense labeling of local image patches via P{-}ConvNet and nearest neighbor fusion. Then we describe a regional ConvNet (R_1{-}ConvNet) that samples a set of bounding boxes around each image superpixel at different scales of contexts in a "zoom-out" fashion. Our ConvNets learn to assign class probabilities for each superpixel region of being pancreas. Last, we study a stacked R_2{-}ConvNet leveraging the joint space of CT intensities and the P{-}ConvNet dense probability maps. Both 3D Gaussian smoothing and 2D conditional random fields are exploited as structured predictions for post-processing. We evaluate on CT images of 82 patients in 4-fold cross-validation. We achieve a Dice Similarity Coefficient of 83.6pm6.3% in training and 71.8pm10.7% in testing.

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

In this work, we present MedImageInsight, an open-source medical imaging embedding model. MedImageInsight is trained on medical images with associated text and labels across a diverse collection of domains, including X-Ray, CT, MRI, dermoscopy, OCT, fundus photography, ultrasound, histopathology, and mammography. Rigorous evaluations demonstrate MedImageInsight's ability to achieve state-of-the-art (SOTA) or human expert level performance across classification, image-image search, and fine-tuning tasks. Specifically, on public datasets, MedImageInsight achieves SOTA in CT 3D medical image retrieval, as well as SOTA in disease classification and search for chest X-ray, dermatology, and OCT imaging. Furthermore, MedImageInsight achieves human expert performance in bone age estimation (on both public and partner data), as well as AUC above 0.9 in most other domains. When paired with a text decoder, MedImageInsight achieves near SOTA level single image report findings generation with less than 10\% the parameters of other models. Compared to fine-tuning GPT-4o with only MIMIC-CXR data for the same task, MedImageInsight outperforms in clinical metrics, but underperforms on lexical metrics where GPT-4o sets a new SOTA. Importantly for regulatory purposes, MedImageInsight can generate ROC curves, adjust sensitivity and specificity based on clinical need, and provide evidence-based decision support through image-image search (which can also enable retrieval augmented generation). In an independent clinical evaluation of image-image search in chest X-ray, MedImageInsight outperformed every other publicly available foundation model evaluated by large margins (over 6 points AUC), and significantly outperformed other models in terms of AI fairness (across age and gender). We hope releasing MedImageInsight will help enhance collective progress in medical imaging AI research and development.

Contrastive pretraining on parallel image-text data has attained great success in vision-language processing (VLP), as exemplified by CLIP and related methods. However, prior explorations tend to focus on general domains in the web. Biomedical images and text are rather different, but publicly available datasets are small and skew toward chest X-ray, thus severely limiting progress. In this paper, we conducted by far the largest study on biomedical VLP, using 15 million figure-caption pairs extracted from biomedical research articles in PubMed Central. Our dataset (PMC-15M) is two orders of magnitude larger than existing biomedical image-text datasets such as MIMIC-CXR, and spans a diverse range of biomedical images. The standard CLIP method is suboptimal for the biomedical domain. We propose BiomedCLIP with domain-specific adaptations tailored to biomedical VLP. We conducted extensive experiments and ablation studies on standard biomedical imaging tasks from retrieval to classification to visual question-answering (VQA). BiomedCLIP established new state of the art in a wide range of standard datasets, substantially outperformed prior VLP approaches. Surprisingly, BiomedCLIP even outperformed radiology-specific state-of-the-art models such as BioViL on radiology-specific tasks such as RSNA pneumonia detection, thus highlighting the utility in large-scale pretraining across all biomedical image types. We will release our models at https://aka.ms/biomedclip to facilitate future research in biomedical VLP.

Multiple Instance learning (MIL) models have been extensively used in pathology to predict biomarkers and risk-stratify patients from gigapixel-sized images. Machine learning problems in medical imaging often deal with rare diseases, making it important for these models to work in a label-imbalanced setting. In pathology images, there is another level of imbalance, where given a positively labeled Whole Slide Image (WSI), only a fraction of pixels within it contribute to the positive label. This compounds the severity of imbalance and makes imbalanced classification in pathology challenging. Furthermore, these imbalances can occur in out-of-distribution (OOD) datasets when the models are deployed in the real-world. We leverage the idea that decoupling feature and classifier learning can lead to improved decision boundaries for label imbalanced datasets. To this end, we investigate the integration of supervised contrastive learning with multiple instance learning (SC-MIL). Specifically, we propose a joint-training MIL framework in the presence of label imbalance that progressively transitions from learning bag-level representations to optimal classifier learning. We perform experiments with different imbalance settings for two well-studied problems in cancer pathology: subtyping of non-small cell lung cancer and subtyping of renal cell carcinoma. SC-MIL provides large and consistent improvements over other techniques on both in-distribution (ID) and OOD held-out sets across multiple imbalanced settings.

Survival risk stratification is an important step in clinical decision making for breast cancer management. We propose a novel deep learning approach for this purpose by integrating histopathological imaging, genetic and clinical data. It employs vision transformers, specifically the MaxViT model, for image feature extraction, and self-attention to capture intricate image relationships at the patient level. A dual cross-attention mechanism fuses these features with genetic data, while clinical data is incorporated at the final layer to enhance predictive accuracy. Experiments on the public TCGA-BRCA dataset show that our model, trained using the negative log likelihood loss function, can achieve superior performance with a mean C-index of 0.64, surpassing existing methods. This advancement facilitates tailored treatment strategies, potentially leading to improved patient outcomes.

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.

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.

AI-generated medical images are gaining growing popularity due to their potential to address the data scarcity challenge in the real world. However, the issue of accurate identification of these synthetic images, particularly when they exhibit remarkable realism with their real copies, remains a concern. To mitigate this challenge, image generators such as DALLE and Imagen, have integrated digital watermarks aimed at facilitating the discernment of synthetic images' authenticity. These watermarks are embedded within the image pixels and are invisible to the human eye while remains their detectability. Nevertheless, a comprehensive investigation into the potential impact of these invisible watermarks on the utility of synthetic medical images has been lacking. In this study, we propose the incorporation of invisible watermarks into synthetic medical images and seek to evaluate their efficacy in the context of downstream classification tasks. Our goal is to pave the way for discussions on the viability of such watermarks in boosting the detectability of synthetic medical images, fortifying ethical standards, and safeguarding against data pollution and potential scams.

The availability of large public datasets and the increased amount of computing power have shifted the interest of the medical community to high-performance algorithms. However, little attention is paid to the quality of the data and their annotations. High performance on benchmark datasets may be reported without considering possible shortcuts or artifacts in the data, besides, models are not tested on subpopulation groups. With this work, we aim to raise awareness about shortcuts problems. We validate previous findings, and present a case study on chest X-rays using two publicly available datasets. We share annotations for a subset of pneumothorax images with drains. We conclude with general recommendations for medical image classification.

This paper introduces an innovative methodology for producing high-quality 3D lung CT images guided by textual information. While diffusion-based generative models are increasingly used in medical imaging, current state-of-the-art approaches are limited to low-resolution outputs and underutilize radiology reports' abundant information. The radiology reports can enhance the generation process by providing additional guidance and offering fine-grained control over the synthesis of images. Nevertheless, expanding text-guided generation to high-resolution 3D images poses significant memory and anatomical detail-preserving challenges. Addressing the memory issue, we introduce a hierarchical scheme that uses a modified UNet architecture. We start by synthesizing low-resolution images conditioned on the text, serving as a foundation for subsequent generators for complete volumetric data. To ensure the anatomical plausibility of the generated samples, we provide further guidance by generating vascular, airway, and lobular segmentation masks in conjunction with the CT images. The model demonstrates the capability to use textual input and segmentation tasks to generate synthesized images. The results of comparative assessments indicate that our approach exhibits superior performance compared to the most advanced models based on GAN and diffusion techniques, especially in accurately retaining crucial anatomical features such as fissure lines, airways, and vascular structures. This innovation introduces novel possibilities. This study focuses on two main objectives: (1) the development of a method for creating images based on textual prompts and anatomical components, and (2) the capability to generate new images conditioning on anatomical elements. The advancements in image generation can be applied to enhance numerous downstream tasks.

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.

The scarcity of annotations poses a significant challenge in medical image analysis. Large-scale pre-training has emerged as a promising label-efficient solution, owing to the utilization of large-scale data, large models, and advanced pre-training techniques. However, its development in medical images remains underexplored. The primary challenge lies in harnessing large-scale unlabeled data and learning high-level semantics without annotations. We observe that 3D medical images exhibit consistent geometric context, i.e., consistent geometric relations between different organs, which leads to a promising way for learning consistent representations. Motivated by this, we introduce a simple-yet-effective Volume Contrast (VoCo) framework to leverage geometric context priors for self-supervision. Given an input volume, we extract base crops from different regions to construct positive and negative pairs for contrastive learning. Then we predict the contextual position of a random crop by contrasting its similarity to the base crops. In this way, VoCo encodes the inherent geometric context into model representations, facilitating high-level semantic learning without annotations. Specifically, we (1) introduce the largest medical pre-training dataset PreCT-160K; (2) investigate scaling laws and propose guidelines for tailoring different model sizes to various medical tasks; (3) build a benchmark encompassing 48 medical tasks. Extensive experiments highlight the superiority of VoCo. Codes at https://github.com/Luffy03/Large-Scale-Medical.

Conventional medical image segmentation methods have been found inadequate in facilitating physicians with the identification of specific lesions for diagnosis and treatment. Given the utility of text as an instructional format, we introduce a novel task termed Medical Image Referring Segmentation (MIRS), which requires segmenting specified lesions in images based on the given language expressions. Due to the varying object scales in medical images, MIRS demands robust vision-language modeling and comprehensive multi-scale interaction for precise localization and segmentation under linguistic guidance. However, existing medical image segmentation methods fall short in meeting these demands, resulting in insufficient segmentation accuracy. In response, we propose an approach named Language-guided Scale-aware MedSegmentor (LSMS), incorporating two appealing designs: (1)~a Scale-aware Vision-Language Attention module that leverages diverse convolutional kernels to acquire rich visual knowledge and interact closely with linguistic features, thereby enhancing lesion localization capability; (2)~a Full-Scale Decoder that globally models multi-modal features across various scales, capturing complementary information between scales to accurately outline lesion boundaries. Addressing the lack of suitable datasets for MIRS, we constructed a vision-language medical dataset called Reference Hepatic Lesion Segmentation (RefHL-Seg). This dataset comprises 2,283 abdominal CT slices from 231 cases, with corresponding textual annotations and segmentation masks for various liver lesions in images. We validated the performance of LSMS for MIRS and conventional medical image segmentation tasks across various datasets. Our LSMS consistently outperforms on all datasets with lower computational costs. The code and datasets will be released.

Breast cancer is a prevalent form of cancer among women, with over 1.5 million women being diagnosed each year. Unfortunately, the survival rates for breast cancer patients in certain third-world countries, like South Africa, are alarmingly low, with only 40% of diagnosed patients surviving beyond five years. The inadequate availability of resources, including qualified pathologists, delayed diagnoses, and ineffective therapy planning, contribute to this low survival rate. To address this pressing issue, medical specialists and researchers have turned to domain-specific AI approaches, specifically deep learning models, to develop end-to-end solutions that can be integrated into computer-aided diagnosis (CAD) systems. By improving the workflow of pathologists, these AI models have the potential to enhance the detection and diagnosis of breast cancer. This research focuses on evaluating the performance of various cutting-edge convolutional neural network (CNN) architectures in comparison to a relatively new model called the Vision Trans-former (ViT). The objective is to determine the superiority of these models in terms of their accuracy and effectiveness. The experimental results reveal that the ViT models outperform the other selected state-of-the-art CNN architectures, achieving an impressive accuracy rate of 95.15%. This study signifies a significant advancement in the field, as it explores the utilization of data augmentation and other relevant preprocessing techniques in conjunction with deep learning models for the detection and diagnosis of breast cancer using datasets of Breast Cancer Histopathological Image Classification.

We present a labeled large-scale, high resolution chest x-ray dataset for the automated exploration of medical images along with their associated reports. This dataset includes more than 160,000 images obtained from 67,000 patients that were interpreted and reported by radiologists at Hospital San Juan Hospital (Spain) from 2009 to 2017, covering six different position views and additional information on image acquisition and patient demography. The reports were labeled with 174 different radiographic findings, 19 differential diagnoses and 104 anatomic locations organized as a hierarchical taxonomy and mapped onto standard Unified Medical Language System (UMLS) terminology. Of these reports, 27% were manually annotated by trained physicians and the remaining set was labeled using a supervised method based on a recurrent neural network with attention mechanisms. The labels generated were then validated in an independent test set achieving a 0.93 Micro-F1 score. To the best of our knowledge, this is one of the largest public chest x-ray database suitable for training supervised models concerning radiographs, and the first to contain radiographic reports in Spanish. The PadChest dataset can be downloaded from http://bimcv.cipf.es/bimcv-projects/padchest/.

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.

Vision-language pre-training for chest X-rays has made significant strides, primarily by utilizing paired radiographs and radiology reports. However, existing approaches often face challenges in encoding medical knowledge effectively. While radiology reports provide insights into the current disease manifestation, medical definitions (as used by contemporary methods) tend to be overly abstract, creating a gap in knowledge. To address this, we propose DeViDe, a novel transformer-based method that leverages radiographic descriptions from the open web. These descriptions outline general visual characteristics of diseases in radiographs, and when combined with abstract definitions and radiology reports, provide a holistic snapshot of knowledge. DeViDe incorporates three key features for knowledge-augmented vision language alignment: First, a large-language model-based augmentation is employed to homogenise medical knowledge from diverse sources. Second, this knowledge is aligned with image information at various levels of granularity. Third, a novel projection layer is proposed to handle the complexity of aligning each image with multiple descriptions arising in a multi-label setting. In zero-shot settings, DeViDe performs comparably to fully supervised models on external datasets and achieves state-of-the-art results on three large-scale datasets. Additionally, fine-tuning DeViDe on four downstream tasks and six segmentation tasks showcases its superior performance across data from diverse distributions.

Obtaining large pre-trained models that can be fine-tuned to new tasks with limited annotated samples has remained an open challenge for medical imaging data. While pre-trained deep networks on ImageNet and vision-language foundation models trained on web-scale data are prevailing approaches, their effectiveness on medical tasks is limited due to the significant domain shift between natural and medical images. To bridge this gap, we introduce LVM-Med, the first family of deep networks trained on large-scale medical datasets. We have collected approximately 1.3 million medical images from 55 publicly available datasets, covering a large number of organs and modalities such as CT, MRI, X-ray, and Ultrasound. We benchmark several state-of-the-art self-supervised algorithms on this dataset and propose a novel self-supervised contrastive learning algorithm using a graph-matching formulation. The proposed approach makes three contributions: (i) it integrates prior pair-wise image similarity metrics based on local and global information; (ii) it captures the structural constraints of feature embeddings through a loss function constructed via a combinatorial graph-matching objective; and (iii) it can be trained efficiently end-to-end using modern gradient-estimation techniques for black-box solvers. We thoroughly evaluate the proposed LVM-Med on 15 downstream medical tasks ranging from segmentation and classification to object detection, and both for the in and out-of-distribution settings. LVM-Med empirically outperforms a number of state-of-the-art supervised, self-supervised, and foundation models. For challenging tasks such as Brain Tumor Classification or Diabetic Retinopathy Grading, LVM-Med improves previous vision-language models trained on 1 billion masks by 6-7% while using only a ResNet-50.

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.

Considering the increased workload in pathology laboratories today, automated tools such as artificial intelligence models can help pathologists with their tasks and ease the workload. In this paper, we are proposing a segmentation model (DRU-Net) that can provide a delineation of human non-small cell lung carcinomas and an augmentation method that can improve classification results. The proposed model is a fused combination of truncated pre-trained DenseNet201 and ResNet101V2 as a patch-wise classifier followed by a lightweight U-Net as a refinement model. We have used two datasets (Norwegian Lung Cancer Biobank and Haukeland University Hospital lung cancer cohort) to create our proposed model. The DRU-Net model achieves an average of 0.91 Dice similarity coefficient. The proposed spatial augmentation method (multi-lens distortion) improved the network performance by 3%. Our findings show that choosing image patches that specifically include regions of interest leads to better results for the patch-wise classifier compared to other sampling methods. The qualitative analysis showed that the DRU-Net model is generally successful in detecting the tumor. On the test set, some of the cases showed areas of false positive and false negative segmentation in the periphery, particularly in tumors with inflammatory and reactive changes.

Image description datasets play a crucial role in the advancement of various applications such as image understanding, text-to-image generation, and text-image retrieval. Currently, image description datasets primarily originate from two sources. One source is the scraping of image-text pairs from the web. Despite their abundance, these descriptions are often of low quality and noisy. Another is through human labeling. Datasets such as COCO are generally very short and lack details. Although detailed image descriptions can be annotated by humans, the high annotation cost limits the feasibility. These limitations underscore the need for more efficient and scalable methods to generate accurate and detailed image descriptions. In this paper, we propose an innovative framework termed Image Textualization (IT), which automatically produces high-quality image descriptions by leveraging existing multi-modal large language models (MLLMs) and multiple vision expert models in a collaborative manner, which maximally convert the visual information into text. To address the current lack of benchmarks for detailed descriptions, we propose several benchmarks for comprehensive evaluation, which verifies the quality of image descriptions created by our framework. Furthermore, we show that LLaVA-7B, benefiting from training on IT-curated descriptions, acquire improved capability to generate richer image descriptions, substantially increasing the length and detail of their output with less hallucination.

The skeleton of a digital image is a compact representation of its topology, geometry, and scale. It has utility in many computer vision applications, such as image description, segmentation, and registration. However, skeletonization has only seen limited use in contemporary deep learning solutions. Most existing skeletonization algorithms are not differentiable, making it impossible to integrate them with gradient-based optimization. Compatible algorithms based on morphological operations and neural networks have been proposed, but their results often deviate from the geometry and topology of the true medial axis. This work introduces the first three-dimensional skeletonization algorithm that is both compatible with gradient-based optimization and preserves an object's topology. Our method is exclusively based on matrix additions and multiplications, convolutional operations, basic non-linear functions, and sampling from a uniform probability distribution, allowing it to be easily implemented in any major deep learning library. In benchmarking experiments, we prove the advantages of our skeletonization algorithm compared to non-differentiable, morphological, and neural-network-based baselines. Finally, we demonstrate the utility of our algorithm by integrating it with two medical image processing applications that use gradient-based optimization: deep-learning-based blood vessel segmentation, and multimodal registration of the mandible in computed tomography and magnetic resonance images.

Medical image analysis is essential to clinical diagnosis and treatment, which is increasingly supported by multi-modal large language models (MLLMs). However, previous research has primarily focused on 2D medical images, leaving 3D images under-explored, despite their richer spatial information. This paper aims to advance 3D medical image analysis with MLLMs. To this end, we present a large-scale 3D multi-modal medical dataset, M3D-Data, comprising 120K image-text pairs and 662K instruction-response pairs specifically tailored for various 3D medical tasks, such as image-text retrieval, report generation, visual question answering, positioning, and segmentation. Additionally, we propose M3D-LaMed, a versatile multi-modal large language model for 3D medical image analysis. Furthermore, we introduce a new 3D multi-modal medical benchmark, M3D-Bench, which facilitates automatic evaluation across eight tasks. Through comprehensive evaluation, our method proves to be a robust model for 3D medical image analysis, outperforming existing solutions. All code, data, and models are publicly available at: https://github.com/BAAI-DCAI/M3D.

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

As deep learning models gain attraction in medical data, ensuring transparent and trustworthy decision-making is essential. In skin cancer diagnosis, while advancements in lesion detection and classification have improved accuracy, the black-box nature of these methods poses challenges in understanding their decision processes, leading to trust issues among physicians. This study leverages the CLIP (Contrastive Language-Image Pretraining) model, trained on different skin lesion datasets, to capture meaningful relationships between visual features and diagnostic criteria terms. To further enhance transparency, we propose a method called MedGrad E-CLIP, which builds on gradient-based E-CLIP by incorporating a weighted entropy mechanism designed for complex medical imaging like skin lesions. This approach highlights critical image regions linked to specific diagnostic descriptions. The developed integrated pipeline not only classifies skin lesions by matching corresponding descriptions but also adds an essential layer of explainability developed especially for medical data. By visually explaining how different features in an image relates to diagnostic criteria, this approach demonstrates the potential of advanced vision-language models in medical image analysis, ultimately improving transparency, robustness, and trust in AI-driven diagnostic systems.

Self-supervised pre-training of deep learning models with contrastive learning is a widely used technique in image analysis. Current findings indicate a strong potential for contrastive pre-training on medical images. However, further research is necessary to incorporate the particular characteristics of these images. We hypothesize that the similarity of medical images hinders the success of contrastive learning in the medical imaging domain. To this end, we investigate different strategies based on deep embedding, information theory, and hashing in order to identify and reduce redundancy in medical pre-training datasets. The effect of these different reduction strategies on contrastive learning is evaluated on two pre-training datasets and several downstream classification tasks. In all of our experiments, dataset reduction leads to a considerable performance gain in downstream tasks, e.g., an AUC score improvement from 0.78 to 0.83 for the COVID CT Classification Grand Challenge, 0.97 to 0.98 for the OrganSMNIST Classification Challenge and 0.73 to 0.83 for a brain hemorrhage classification task. Furthermore, pre-training is up to nine times faster due to the dataset reduction. In conclusion, the proposed approach highlights the importance of dataset quality and provides a transferable approach to improve contrastive pre-training for classification downstream tasks on medical images.

Instance level detection and segmentation of thoracic diseases or abnormalities are crucial for automatic diagnosis in chest X-ray images. Leveraging on constant structure and disease relations extracted from domain knowledge, we propose a structure-aware relation network (SAR-Net) extending Mask R-CNN. The SAR-Net consists of three relation modules: 1. the anatomical structure relation module encoding spatial relations between diseases and anatomical parts. 2. the contextual relation module aggregating clues based on query-key pair of disease RoI and lung fields. 3. the disease relation module propagating co-occurrence and causal relations into disease proposals. Towards making a practical system, we also provide ChestX-Det, a chest X-Ray dataset with instance-level annotations (boxes and masks). ChestX-Det is a subset of the public dataset NIH ChestX-ray14. It contains ~3500 images of 13 common disease categories labeled by three board-certified radiologists. We evaluate our SAR-Net on it and another dataset DR-Private. Experimental results show that it can enhance the strong baseline of Mask R-CNN with significant improvements. The ChestX-Det is released at https://github.com/Deepwise-AILab/ChestX-Det-Dataset.

Medical image classification in radiology faces significant challenges, particularly in generalizing to unseen pathologies. In contrast, CLIP offers a promising solution by leveraging multimodal learning to improve zero-shot classification performance. However, in the medical domain, lesions can be small and might not be well represented in the embedding space. Therefore, in this paper, we explore the potential of visual prompt engineering to enhance the capabilities of Vision Language Models (VLMs) in radiology. Leveraging BiomedCLIP, trained on extensive biomedical image-text pairs, we investigate the impact of embedding visual markers directly within radiological images to guide the model's attention to critical regions. Our evaluation on the JSRT dataset, focusing on lung nodule malignancy classification, demonstrates that incorporating visual prompts x2013 such as arrows, circles, and contours x2013 significantly improves classification metrics including AUROC, AUPRC, F1 score, and accuracy. Moreover, the study provides attention maps, showcasing enhanced model interpretability and focus on clinically relevant areas. These findings underscore the efficacy of visual prompt engineering as a straightforward yet powerful approach to advance VLM performance in medical image analysis.

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

Learning visual representations of medical images (e.g., X-rays) is core to medical image understanding but its progress has been held back by the scarcity of human annotations. Existing work commonly relies on fine-tuning weights transferred from ImageNet pretraining, which is suboptimal due to drastically different image characteristics, or rule-based label extraction from the textual report data paired with medical images, which is inaccurate and hard to generalize. Meanwhile, several recent studies show exciting results from unsupervised contrastive learning from natural images, but we find these methods help little on medical images because of their high inter-class similarity. We propose ConVIRT, an alternative unsupervised strategy to learn medical visual representations by exploiting naturally occurring paired descriptive text. Our new method of pretraining medical image encoders with the paired text data via a bidirectional contrastive objective between the two modalities is domain-agnostic, and requires no additional expert input. We test ConVIRT by transferring our pretrained weights to 4 medical image classification tasks and 2 zero-shot retrieval tasks, and show that it leads to image representations that considerably outperform strong baselines in most settings. Notably, in all 4 classification tasks, our method requires only 10\% as much labeled training data as an ImageNet initialized counterpart to achieve better or comparable performance, demonstrating superior data efficiency.

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 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.

Following the impressive development of LLMs, vision-language alignment in LLMs is actively being researched to enable multimodal reasoning and visual IO. This direction of research is particularly relevant to medical imaging because medical image analysis and generation consist of reasoning based on a combination of visual features and prior knowledge. Many recent works have focused on training adapter networks that serve as an information bridge between image processing networks and LLMs; but presumably, in order to achieve maximum reasoning potential of LLMs on visual information as well, visual and language features should be allowed to interact more freely. This is especially important in the medical domain because understanding and generating medical images such as chest X-rays (CXR) require not only accurate visual and language-based reasoning but also a more intimate mapping between the two modalities. Thus, taking inspiration from previous work on the transformer and VQ-GAN combination for bidirectional image and text generation, we build upon this approach and develop a method for instruction-tuning an LLM pre-trained only on text to gain vision-language capabilities for medical images. Specifically, we leverage a pretrained LLM's existing question-answering and instruction-following abilities to teach it to understand visual inputs by instructing it to answer questions about image inputs and, symmetrically, output both text and image responses appropriate to a given query by tuning the LLM with diverse tasks that encompass image-based text-generation and text-based image-generation. We show that our model, LLM-CXR, trained in this approach shows better image-text alignment in both CXR understanding and generation tasks while being smaller in size compared to previously developed models that perform a narrower range of tasks. The code is at https://github.com/hyn2028/llm-cxr.

Clinicians are often very sceptical about applying automatic image processing approaches, especially deep learning based methods, in practice. One main reason for this is the black-box nature of these approaches and the inherent problem of missing insights of the automatically derived decisions. In order to increase trust in these methods, this paper presents approaches that help to interpret and explain the results of deep learning algorithms by depicting the anatomical areas which influence the decision of the algorithm most. Moreover, this research presents a unified framework, TorchEsegeta, for applying various interpretability and explainability techniques for deep learning models and generate visual interpretations and explanations for clinicians to corroborate their clinical findings. In addition, this will aid in gaining confidence in such methods. The framework builds on existing interpretability and explainability techniques that are currently focusing on classification models, extending them to segmentation tasks. In addition, these methods have been adapted to 3D models for volumetric analysis. The proposed framework provides methods to quantitatively compare visual explanations using infidelity and sensitivity metrics. This framework can be used by data scientists to perform post-hoc interpretations and explanations of their models, develop more explainable tools and present the findings to clinicians to increase their faith in such models. The proposed framework was evaluated based on a use case scenario of vessel segmentation models trained on Time-of-fight (TOF) Magnetic Resonance Angiogram (MRA) images of the human brain. Quantitative and qualitative results of a comparative study of different models and interpretability methods are presented. Furthermore, this paper provides an extensive overview of several existing interpretability and explainability methods.

Multimodal large language models (LLMs) have demonstrated impressive capabilities in generating high-quality images from textual instructions. However, their performance in generating scientific images--a critical application for accelerating scientific progress--remains underexplored. In this work, we address this gap by introducing ScImage, a benchmark designed to evaluate the multimodal capabilities of LLMs in generating scientific images from textual descriptions. ScImage assesses three key dimensions of understanding: spatial, numeric, and attribute comprehension, as well as their combinations, focusing on the relationships between scientific objects (e.g., squares, circles). We evaluate five models, GPT-4o, Llama, AutomaTikZ, Dall-E, and StableDiffusion, using two modes of output generation: code-based outputs (Python, TikZ) and direct raster image generation. Additionally, we examine four different input languages: English, German, Farsi, and Chinese. Our evaluation, conducted with 11 scientists across three criteria (correctness, relevance, and scientific accuracy), reveals that while GPT-4o produces outputs of decent quality for simpler prompts involving individual dimensions such as spatial, numeric, or attribute understanding in isolation, all models face challenges in this task, especially for more complex prompts.

Automated medical image analysis systems often require large amounts of training data with high quality labels, which are difficult and time consuming to generate. This paper introduces Radiology Object in COntext version 2 (ROCOv2), a multimodal dataset consisting of radiological images and associated medical concepts and captions extracted from the PMC Open Access subset. It is an updated version of the ROCO dataset published in 2018, and adds 35,705 new images added to PMC since 2018. It further provides manually curated concepts for imaging modalities with additional anatomical and directional concepts for X-rays. The dataset consists of 79,789 images and has been used, with minor modifications, in the concept detection and caption prediction tasks of ImageCLEFmedical Caption 2023. The dataset is suitable for training image annotation models based on image-caption pairs, or for multi-label image classification using Unified Medical Language System (UMLS) concepts provided with each image. In addition, it can serve for pre-training of medical domain models, and evaluation of deep learning models for multi-task learning.

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.

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.

Recent work has investigated the distributions of learned convolution filters through a large-scale study containing hundreds of heterogeneous image models. Surprisingly, on average, the distributions only show minor drifts in comparisons of various studied dimensions including the learned task, image domain, or dataset. However, among the studied image domains, medical imaging models appeared to show significant outliers through "spikey" distributions, and, therefore, learn clusters of highly specific filters different from other domains. Following this observation, we study the collected medical imaging models in more detail. We show that instead of fundamental differences, the outliers are due to specific processing in some architectures. Quite the contrary, for standardized architectures, we find that models trained on medical data do not significantly differ in their filter distributions from similar architectures trained on data from other domains. Our conclusions reinforce previous hypotheses stating that pre-training of imaging models can be done with any kind of diverse image data.

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

Even though convolutional neural networks (CNNs) are driving progress in medical image segmentation, standard models still have some drawbacks. First, the use of multi-scale approaches, i.e., encoder-decoder architectures, leads to a redundant use of information, where similar low-level features are extracted multiple times at multiple scales. Second, long-range feature dependencies are not efficiently modeled, resulting in non-optimal discriminative feature representations associated with each semantic class. In this paper we attempt to overcome these limitations with the proposed architecture, by capturing richer contextual dependencies based on the use of guided self-attention mechanisms. This approach is able to integrate local features with their corresponding global dependencies, as well as highlight interdependent channel maps in an adaptive manner. Further, the additional loss between different modules guides the attention mechanisms to neglect irrelevant information and focus on more discriminant regions of the image by emphasizing relevant feature associations. We evaluate the proposed model in the context of semantic segmentation on three different datasets: abdominal organs, cardiovascular structures and brain tumors. A series of ablation experiments support the importance of these attention modules in the proposed architecture. In addition, compared to other state-of-the-art segmentation networks our model yields better segmentation performance, increasing the accuracy of the predictions while reducing the standard deviation. This demonstrates the efficiency of our approach to generate precise and reliable automatic segmentations of medical images. Our code is made publicly available at https://github.com/sinAshish/Multi-Scale-Attention