Daily Papers

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.

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.

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.

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

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

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).

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)).

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.

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

Recent advancements in digital pathology 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.

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.

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.

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.

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

Magnetic resonance imaging (MRI) is a cornerstone of modern medical imaging. However, long image acquisition times, the need for qualitative expert analysis, and the lack of (and difficulty extracting) quantitative indicators that are sensitive to tissue health have curtailed widespread clinical and research studies. While recent machine learning methods for MRI reconstruction and analysis have shown promise for reducing this burden, these techniques are primarily validated with imperfect image quality metrics, which are discordant with clinically-relevant measures that ultimately hamper clinical deployment and clinician trust. To mitigate this challenge, we present the Stanford Knee MRI with Multi-Task Evaluation (SKM-TEA) dataset, a collection of quantitative knee MRI (qMRI) scans that enables end-to-end, clinically-relevant evaluation of MRI reconstruction and analysis tools. This 1.6TB dataset consists of raw-data measurements of ~25,000 slices (155 patients) of anonymized patient MRI scans, the corresponding scanner-generated DICOM images, manual segmentations of four tissues, and bounding box annotations for sixteen clinically relevant pathologies. We provide a framework for using qMRI parameter maps, along with image reconstructions and dense image labels, for measuring the quality of qMRI biomarker estimates extracted from MRI reconstruction, segmentation, and detection techniques. Finally, we use this framework to benchmark state-of-the-art baselines on this dataset. We hope our SKM-TEA dataset and code can enable a broad spectrum of research for modular image reconstruction and image analysis in a clinically informed manner. Dataset access, code, and benchmarks are available at https://github.com/StanfordMIMI/skm-tea.

Objective: We investigate whether deep learning techniques for natural language processing (NLP) can be used efficiently for patient phenotyping. Patient phenotyping is a classification task for determining whether a patient has a medical condition, and is a crucial part of secondary analysis of healthcare data. We assess the performance of deep learning algorithms and compare them with classical NLP approaches. Materials and Methods: We compare convolutional neural networks (CNNs), n-gram models, and approaches based on cTAKES that extract pre-defined medical concepts from clinical notes and use them to predict patient phenotypes. The performance is tested on 10 different phenotyping tasks using 1,610 discharge summaries extracted from the MIMIC-III database. Results: CNNs outperform other phenotyping algorithms in all 10 tasks. The average F1-score of our model is 76 (PPV of 83, and sensitivity of 71) with our model having an F1-score up to 37 points higher than alternative approaches. We additionally assess the interpretability of our model by presenting a method that extracts the most salient phrases for a particular prediction. Conclusion: We show that NLP methods based on deep learning improve the performance of patient phenotyping. Our CNN-based algorithm automatically learns the phrases associated with each patient phenotype. As such, it reduces the annotation complexity for clinical domain experts, who are normally required to develop task-specific annotation rules and identify relevant phrases. Our method performs well in terms of both performance and interpretability, which indicates that deep learning is an effective approach to patient phenotyping based on clinicians' notes.

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

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

A crucial step within secondary analysis of electronic health records (EHRs) is to identify the patient cohort under investigation. While EHRs contain medical billing codes that aim to represent the conditions and treatments patients may have, much of the information is only present in the patient notes. Therefore, it is critical to develop robust algorithms to infer patients' conditions and treatments from their written notes. In this paper, we introduce a dataset for patient phenotyping, a task that is defined as the identification of whether a patient has a given medical condition (also referred to as clinical indication or phenotype) based on their patient note. Nursing Progress Notes and Discharge Summaries from the Intensive Care Unit of a large tertiary care hospital were manually annotated for the presence of several high-context phenotypes relevant to treatment and risk of re-hospitalization. This dataset contains 1102 Discharge Summaries and 1000 Nursing Progress Notes. Each Discharge Summary and Progress Note has been annotated by at least two expert human annotators (one clinical researcher and one resident physician). Annotated phenotypes include treatment non-adherence, chronic pain, advanced/metastatic cancer, as well as 10 other phenotypes. This dataset can be utilized for academic and industrial research in medicine and computer science, particularly within the field of medical natural language processing.

Nailfold capillaroscopy is a well-established method for assessing health conditions, but the untapped potential of automated medical image analysis using machine learning remains despite recent advancements. In this groundbreaking study, we present a pioneering effort in constructing a comprehensive dataset-321 images, 219 videos, 68 clinic reports, with expert annotations-that serves as a crucial resource for training deep-learning models. Leveraging this dataset, we propose an end-to-end nailfold capillary analysis pipeline capable of automatically detecting and measuring diverse morphological and dynamic features. Experimental results demonstrate sub-pixel measurement accuracy and 90% accuracy in predicting abnormality portions, highlighting its potential for advancing quantitative medical research and enabling pervasive computing in healthcare. We've shared our open-source codes and data (available at https://github.com/THU-CS-PI-LAB/ANFC-Automated-Nailfold-Capillary) to contribute to transformative progress in computational medical image analysis.

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.

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.

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.

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.

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.

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.

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.

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

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

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

This paper presents a data-driven, task-specific paradigm for experimental design, to shorten acquisition time, reduce costs, and accelerate the deployment of imaging devices. Current approaches in experimental design focus on model-parameter estimation and require specification of a particular model, whereas in imaging, other tasks may drive the design. Furthermore, such approaches often lead to intractable optimization problems in real-world imaging applications. Here we present a new paradigm for experimental design that simultaneously optimizes the design (set of image channels) and trains a machine-learning model to execute a user-specified image-analysis task. The approach obtains data densely-sampled over the measurement space (many image channels) for a small number of acquisitions, then identifies a subset of channels of prespecified size that best supports the task. We propose a method: TADRED for TAsk-DRiven Experimental Design in imaging, to identify the most informative channel-subset whilst simultaneously training a network to execute the task given the subset. Experiments demonstrate the potential of TADRED in diverse imaging applications: several clinically-relevant tasks in magnetic resonance imaging; and remote sensing and physiological applications of hyperspectral imaging. Results show substantial improvement over classical experimental design, two recent application-specific methods within the new paradigm, and state-of-the-art approaches in supervised feature selection. We anticipate further applications of our approach. Code is available: https://github.com/sbb-gh/experimental-design-multichannel

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.

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.

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/

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

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.

Introduction: Blood vessels can be non-invasively visualized from a digital fundus image (DFI). Several studies have shown an association between cardiovascular risk and vascular features obtained from DFI. Recent advances in computer vision and image segmentation enable automatising DFI blood vessel segmentation. There is a need for a resource that can automatically compute digital vasculature biomarkers (VBM) from these segmented DFI. Methods: In this paper, we introduce a Python Vasculature BioMarker toolbox, denoted PVBM. A total of 11 VBMs were implemented. In particular, we introduce new algorithmic methods to estimate tortuosity and branching angles. Using PVBM, and as a proof of usability, we analyze geometric vascular differences between glaucomatous patients and healthy controls. Results: We built a fully automated vasculature biomarker toolbox based on DFI segmentations and provided a proof of usability to characterize the vascular changes in glaucoma. For arterioles and venules, all biomarkers were significant and lower in glaucoma patients compared to healthy controls except for tortuosity, venular singularity length and venular branching angles. Conclusion: We have automated the computation of 11 VBMs from retinal blood vessel segmentation. The PVBM toolbox is made open source under a GNU GPL 3 license and is available on physiozoo.com (following publication).

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.

This paper presents the challenge report for the 2021 Kidney and Kidney Tumor Segmentation Challenge (KiTS21) held in conjunction with the 2021 international conference on Medical Image Computing and Computer Assisted Interventions (MICCAI). KiTS21 is a sequel to its first edition in 2019, and it features a variety of innovations in how the challenge was designed, in addition to a larger dataset. A novel annotation method was used to collect three separate annotations for each region of interest, and these annotations were performed in a fully transparent setting using a web-based annotation tool. Further, the KiTS21 test set was collected from an outside institution, challenging participants to develop methods that generalize well to new populations. Nonetheless, the top-performing teams achieved a significant improvement over the state of the art set in 2019, and this performance is shown to inch ever closer to human-level performance. An in-depth meta-analysis is presented describing which methods were used and how they faired on the leaderboard, as well as the characteristics of which cases generally saw good performance, and which did not. Overall KiTS21 facilitated a significant advancement in the state of the art in kidney tumor segmentation, and provides useful insights that are applicable to the field of semantic segmentation as a whole.

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.

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.

Visible-light cameras can capture subtle physiological biomarkers without physical contact with the subject. We present the Multi-Site Physiological Monitoring (MSPM) dataset, which is the first dataset collected to support the study of simultaneous camera-based vital signs estimation from multiple locations on the body. MSPM enables research on remote photoplethysmography (rPPG), respiration rate, and pulse transit time (PTT); it contains ground-truth measurements of pulse oximetry (at multiple body locations) and blood pressure using contacting sensors. We provide thorough experiments demonstrating the suitability of MSPM to support research on rPPG, respiration rate, and PTT. Cross-dataset rPPG experiments reveal that MSPM is a challenging yet high quality dataset, with intra-dataset pulse rate mean absolute error (MAE) below 4 beats per minute (BPM), and cross-dataset pulse rate MAE below 2 BPM in certain cases. Respiration experiments find a MAE of 1.09 breaths per minute by extracting motion features from the chest. PTT experiments find that across the pairs of different body sites, there is high correlation between remote PTT and contact-measured PTT, which facilitates the possibility for future camera-based PTT research.

As advances in large language models (LLMs) and multimodal techniques continue to mature, the development of general-purpose multimodal large language models (MLLMs) has surged, offering significant applications in interpreting natural images. However, the field of pathology has largely remained untapped, particularly in gathering high-quality data and designing comprehensive model frameworks. To bridge the gap in pathology MLLMs, we present PathAsst, a multimodal generative foundation AI assistant to revolutionize diagnostic and predictive analytics in pathology. The development of PathAsst involves three pivotal steps: data acquisition, CLIP model adaptation, and the training of PathAsst's multimodal generative capabilities. Firstly, we collect over 207K high-quality pathology image-text pairs from authoritative sources. Leveraging the advanced power of ChatGPT, we generate over 180K instruction-following samples. Furthermore, we devise additional instruction-following data specifically tailored for invoking eight pathology-specific sub-models we prepared, allowing the PathAsst to effectively collaborate with these models, enhancing its diagnostic ability. Secondly, by leveraging the collected data, we construct PathCLIP, a pathology-dedicated CLIP, to enhance PathAsst's capabilities in interpreting pathology images. Finally, we integrate PathCLIP with the Vicuna-13b and utilize pathology-specific instruction-tuning data to enhance the multimodal generation capacity of PathAsst and bolster its synergistic interactions with sub-models. The experimental results of PathAsst show the potential of harnessing AI-powered generative foundation model to improve pathology diagnosis and treatment processes.

High-throughput screening techniques are commonly used to obtain large quantities of data in many fields of biology. It is well known that artifacts arising from variability in the technical execution of different experimental batches within such screens confound these observations and can lead to invalid biological conclusions. It is therefore necessary to account for these batch effects when analyzing outcomes. In this paper we describe RxRx1, a biological dataset designed specifically for the systematic study of batch effect correction methods. The dataset consists of 125,510 high-resolution fluorescence microscopy images of human cells under 1,138 genetic perturbations in 51 experimental batches across 4 cell types. Visual inspection of the images alone clearly demonstrates significant batch effects. We propose a classification task designed to evaluate the effectiveness of experimental batch correction methods on these images and examine the performance of a number of correction methods on this task. Our goal in releasing RxRx1 is to encourage the development of effective experimental batch correction methods that generalize well to unseen experimental batches. The dataset can be downloaded at https://rxrx.ai.

Pulmonary Hypertension (PH) is a severe disease characterized by an elevated pulmonary artery pressure. The gold standard for PH diagnosis is measurement of mean Pulmonary Artery Pressure (mPAP) during an invasive Right Heart Catheterization. In this paper, we investigate noninvasive approach to PH detection utilizing Magnetic Resonance Imaging, Computer Models and Machine Learning. We show using the ablation study, that physics-informed feature engineering based on models of blood circulation increases the performance of Gradient Boosting Decision Trees-based algorithms for classification of PH and regression of values of mPAP. We compare results of regression (with thresholding of estimated mPAP) and classification and demonstrate that metrics achieved in both experiments are comparable. The predicted mPAP values are more informative to the physicians than the probability of PH returned by classification models. They provide the intuitive explanation of the outcome of the machine learning model (clinicians are accustomed to the mPAP metric, contrary to the PH probability).

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

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.

Chromosome classification is critical for karyotyping in abnormality diagnosis. To expedite the diagnosis, we present a novel method named Varifocal-Net for simultaneous classification of chromosome's type and polarity using deep convolutional networks. The approach consists of one global-scale network (G-Net) and one local-scale network (L-Net). It follows three stages. The first stage is to learn both global and local features. We extract global features and detect finer local regions via the G-Net. By proposing a varifocal mechanism, we zoom into local parts and extract local features via the L-Net. Residual learning and multi-task learning strategies are utilized to promote high-level feature extraction. The detection of discriminative local parts is fulfilled by a localization subnet of the G-Net, whose training process involves both supervised and weakly-supervised learning. The second stage is to build two multi-layer perceptron classifiers that exploit features of both two scales to boost classification performance. The third stage is to introduce a dispatch strategy of assigning each chromosome to a type within each patient case, by utilizing the domain knowledge of karyotyping. Evaluation results from 1909 karyotyping cases showed that the proposed Varifocal-Net achieved the highest accuracy per patient case (%) 99.2 for both type and polarity tasks. It outperformed state-of-the-art methods, demonstrating the effectiveness of our varifocal mechanism, multi-scale feature ensemble, and dispatch strategy. The proposed method has been applied to assist practical karyotype diagnosis.

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

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.

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.

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

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

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

Pretraining a deep learning model on large image datasets is a standard step before fine-tuning the model on small targeted datasets. The large dataset is usually general images (e.g. imagenet2012) while the small dataset can be specialized datasets that have different distributions from the large dataset. However, this 'large-to-small' strategy is not well-validated when the large dataset is specialized and has a similar distribution to small datasets. We newly compiled three hematoxylin and eosin-stained image datasets, one large (PTCGA200) and two magnification-adjusted small datasets (PCam200 and segPANDA200). Major deep learning models were trained with supervised and self-supervised learning methods and fine-tuned on the small datasets for tumor classification and tissue segmentation benchmarks. ResNet50 pretrained with MoCov2, SimCLR, and BYOL on PTCGA200 was better than imagenet2012 pretraining when fine-tuned on PTCGA200 (accuracy of 83.94%, 86.41%, 84.91%, and 82.72%, respectively). ResNet50 pre-trained on PTCGA200 with MoCov2 exceeded the COCOtrain2017-pretrained baseline and was the best in ResNet50 for the tissue segmentation benchmark (mIoU of 63.53% and 63.22%). We found re-training imagenet-pretrained models (ResNet50, BiT-M-R50x1, and ViT-S/16) on PTCGA200 improved downstream benchmarks.

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

In recent years, the advent of foundation models (FM) for digital pathology has relied heavily on scaling the pre-training datasets and the model size, yielding large and powerful models. While it resulted in improving the performance on diverse downstream tasks, it also introduced increased computational cost and inference time. In this work, we explore the distillation of a large foundation model into a smaller one, reducing the number of parameters by several orders of magnitude. Leveraging distillation techniques, our distilled model, H0-mini, achieves nearly comparable performance to large FMs at a significantly reduced inference cost. It is evaluated on several public benchmarks, achieving 3rd place on the HEST benchmark and 5th place on the EVA benchmark. Additionally, a robustness analysis conducted on the PLISM dataset demonstrates that our distilled model reaches excellent robustness to variations in staining and scanning conditions, significantly outperforming other state-of-the art models. This opens new perspectives to design lightweight and robust models for digital pathology, without compromising on performance.

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

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.

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.

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

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

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.

Medical images and radiology reports are crucial for diagnosing medical conditions, highlighting the importance of quantitative analysis for clinical decision-making. However, the diversity and cross-source heterogeneity of these data challenge the generalizability of current data-mining methods. Multimodal large language models (MLLMs) have recently transformed many domains, significantly affecting the medical field. Notably, Gemini-Vision-series (Gemini) and GPT-4-series (GPT-4) models have epitomized a paradigm shift in Artificial General Intelligence (AGI) for computer vision, showcasing their potential in the biomedical domain. In this study, we evaluated the performance of the Gemini, GPT-4, and 4 popular large models for an exhaustive evaluation across 14 medical imaging datasets, including 5 medical imaging categories (dermatology, radiology, dentistry, ophthalmology, and endoscopy), and 3 radiology report datasets. The investigated tasks encompass disease classification, lesion segmentation, anatomical localization, disease diagnosis, report generation, and lesion detection. Our experimental results demonstrated that Gemini-series models excelled in report generation and lesion detection but faces challenges in disease classification and anatomical localization. Conversely, GPT-series models exhibited proficiency in lesion segmentation and anatomical localization but encountered difficulties in disease diagnosis and lesion detection. Additionally, both the Gemini series and GPT series contain models that have demonstrated commendable generation efficiency. While both models hold promise in reducing physician workload, alleviating pressure on limited healthcare resources, and fostering collaboration between clinical practitioners and artificial intelligence technologies, substantial enhancements and comprehensive validations remain imperative before clinical deployment.

In the field of medical sciences, reliable detection and classification of brain tumors from images remains a formidable challenge due to the rarity of tumors within the population of patients. Therefore, the ability to detect tumors in anomaly scenarios is paramount for ensuring timely interventions and improved patient outcomes. This study addresses the issue by leveraging deep learning (DL) techniques to detect and classify brain tumors in challenging situations. The curated data set from the National Brain Mapping Lab (NBML) comprises 81 patients, including 30 Tumor cases and 51 Normal cases. The detection and classification pipelines are separated into two consecutive tasks. The detection phase involved comprehensive data analysis and pre-processing to modify the number of image samples and the number of patients of each class to anomaly distribution (9 Normal per 1 Tumor) to comply with real world scenarios. Next, in addition to common evaluation metrics for the testing, we employed a novel performance evaluation method called Patient to Patient (PTP), focusing on the realistic evaluation of the model. In the detection phase, we fine-tuned a YOLOv8n detection model to detect the tumor region. Subsequent testing and evaluation yielded competitive performance both in Common Evaluation Metrics and PTP metrics. Furthermore, using the Data Efficient Image Transformer (DeiT) module, we distilled a Vision Transformer (ViT) model from a fine-tuned ResNet152 as a teacher in the classification phase. This approach demonstrates promising strides in reliable tumor detection and classification, offering potential advancements in tumor diagnosis for real-world medical imaging scenarios.

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.

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.

Driven by the recent advances in deep learning methods and, in particular, by the development of modern self-supervised learning algorithms, increased interest and efforts have been devoted to build foundation models (FMs) for medical images. In this work, we present our scalable training pipeline for large pathology imaging data, and a comprehensive analysis of various hyperparameter choices and training techniques for building pathology FMs. We release and make publicly available the first batch of our pathology FMs (https://github.com/kaiko-ai/towards_large_pathology_fms) trained on open-access TCGA whole slide images, a commonly used collection of pathology images. The experimental evaluation shows that our models reach state-of-the-art performance on various patch-level downstream tasks, ranging from breast cancer subtyping to colorectal nuclear segmentation. Finally, to unify the evaluation approaches used in the field and to simplify future comparisons of different FMs, we present an open-source framework (https://github.com/kaiko-ai/eva) designed for the consistent evaluation of pathology FMs across various downstream tasks.

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

Multi-omics research has enhanced our understanding of cancer heterogeneity and progression. Investigating molecular data through multi-omics approaches is crucial for unraveling the complex biological mechanisms underlying cancer, thereby enabling effective diagnosis, treatment, and prevention strategies. However, predicting patient outcomes through integration of all available multi-omics data is an under-study research direction. Here, we present SeNMo (Self-normalizing Network for Multi-omics), a deep neural network trained on multi-omics data across 33 cancer types. SeNMo is efficient in handling multi-omics data characterized by high-width (many features) and low-length (fewer samples) attributes. We trained SeNMo for the task of overall survival using pan-cancer data involving 33 cancer sites from Genomics Data Commons (GDC). The training data includes gene expression, DNA methylation, miRNA expression, DNA mutations, protein expression modalities, and clinical data. We evaluated the model's performance in predicting overall survival using concordance index (C-Index). SeNMo performed consistently well in training regime, with the validation C-Index of 0.76 on GDC's public data. In the testing regime, SeNMo performed with a C-Index of 0.758 on a held-out test set. The model showed an average accuracy of 99.8% on the task of classifying the primary cancer type on the pan-cancer test cohort. SeNMo proved to be a mini-foundation model for multi-omics oncology data because it demonstrated robust performance, and adaptability not only across molecular data types but also on the classification task of predicting the primary cancer type of patients. SeNMo can be further scaled to any cancer site and molecular data type. We believe SeNMo and similar models are poised to transform the oncology landscape, offering hope for more effective, efficient, and patient-centric cancer care.

The emergence of large multimodal models has unlocked remarkable potential in AI, particularly in pathology. However, the lack of specialized, high-quality benchmark impeded their development and precise evaluation. To address this, we introduce PathMMU, the largest and highest-quality expert-validated pathology benchmark for LMMs. It comprises 33,573 multimodal multi-choice questions and 21,599 images from various sources, and an explanation for the correct answer accompanies each question. The construction of PathMMU capitalizes on the robust capabilities of GPT-4V, utilizing approximately 30,000 gathered image-caption pairs to generate Q\&As. Significantly, to maximize PathMMU's authority, we invite six pathologists to scrutinize each question under strict standards in PathMMU's validation and test sets, while simultaneously setting an expert-level performance benchmark for PathMMU. We conduct extensive evaluations, including zero-shot assessments of 14 open-sourced and three closed-sourced LMMs and their robustness to image corruption. We also fine-tune representative LMMs to assess their adaptability to PathMMU. The empirical findings indicate that advanced LMMs struggle with the challenging PathMMU benchmark, with the top-performing LMM, GPT-4V, achieving only a 51.7\% zero-shot performance, significantly lower than the 71.4\% demonstrated by human pathologists. After fine-tuning, even open-sourced LMMs can surpass GPT-4V with a performance of over 60\%, but still fall short of the expertise shown by pathologists. We hope that the PathMMU will offer valuable insights and foster the development of more specialized, next-generation LLMs for pathology.

The article presents a new multi-label comprehensive image dataset from flexible endoscopy, colonoscopy and capsule endoscopy, named ERS. The collection has been labeled according to the full medical specification of 'Minimum Standard Terminology 3.0' (MST 3.0), describing all possible findings in the gastrointestinal tract (104 possible labels), extended with an additional 19 labels useful in common machine learning applications. The dataset contains around 6000 precisely and 115,000 approximately labeled frames from endoscopy videos, 3600 precise and 22,600 approximate segmentation masks, and 1.23 million unlabeled frames from flexible and capsule endoscopy videos. The labeled data cover almost entirely the MST 3.0 standard. The data came from 1520 videos of 1135 patients. Additionally, this paper proposes and describes four exemplary experiments in gastrointestinal image classification task performed using the created dataset. The obtained results indicate the high usefulness and flexibility of the dataset in training and testing machine learning algorithms in the field of endoscopic data analysis.

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.

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

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.

Background. Fully automatic analysis of myocardial perfusion MRI datasets enables rapid and objective reporting of stress/rest studies in patients with suspected ischemic heart disease. Developing deep learning techniques that can analyze multi-center datasets despite limited training data and variations in software and hardware is an ongoing challenge. Methods. Datasets from 3 medical centers acquired at 3T (n = 150 subjects) were included: an internal dataset (inD; n = 95) and two external datasets (exDs; n = 55) used for evaluating the robustness of the trained deep neural network (DNN) models against differences in pulse sequence (exD-1) and scanner vendor (exD-2). A subset of inD (n = 85) was used for training/validation of a pool of DNNs for segmentation, all using the same spatiotemporal U-Net architecture and hyperparameters but with different parameter initializations. We employed a space-time sliding-patch analysis approach that automatically yields a pixel-wise "uncertainty map" as a byproduct of the segmentation process. In our approach, a given test case is segmented by all members of the DNN pool and the resulting uncertainty maps are leveraged to automatically select the "best" one among the pool of solutions. Results. The proposed DAUGS analysis approach performed similarly to the established approach on the internal dataset (p = n.s.) whereas it significantly outperformed on the external datasets (p < 0.005 for exD-1 and exD-2). Moreover, the number of image series with "failed" segmentation was significantly lower for the proposed vs. the established approach (4.3% vs. 17.1%, p < 0.0005). Conclusions. The proposed DAUGS analysis approach has the potential to improve the robustness of deep learning methods for segmentation of multi-center stress perfusion datasets with variations in the choice of pulse sequence, site location or scanner vendor.

Interrogating the evolution of biological changes at early stages of life requires longitudinal profiling of molecules, such as DNA methylation, which can be challenging with children. We introduce a probabilistic and longitudinal machine learning framework based on multi-mean Gaussian processes (GPs), accounting for individual and gene correlations across time. This method provides future predictions of DNA methylation status at different individual ages while accounting for uncertainty. Our model is trained on a birth cohort of children with methylation profiled at ages 0-4, and we demonstrated that the status of methylation sites for each child can be accurately predicted at ages 5-7. We show that methylation profiles predicted by multi-mean GPs can be used to estimate other phenotypes, such as epigenetic age, and enable comparison to other health measures of interest. This approach encourages epigenetic studies to move towards longitudinal design for investigating epigenetic changes during development, ageing and disease progression.

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.

Fluorescence Lifetime Imaging (FLI) is a critical molecular imaging modality that provides unique information about the tissue microenvironment, which is invaluable for biomedical applications. FLI operates by acquiring and analyzing photon time-of-arrival histograms to extract quantitative parameters associated with temporal fluorescence decay. These histograms are influenced by the intrinsic properties of the fluorophore, instrument parameters, time-of-flight distributions associated with pixel-wise variations in the topographic and optical characteristics of the sample. Recent advancements in Deep Learning (DL) have enabled improved fluorescence lifetime parameter estimation. However, existing models are primarily designed for planar surface samples, limiting their applicability in translational scenarios involving complex surface profiles, such as in-vivo whole-animal or imaged guided surgical applications. To address this limitation, we present MFliNet (Macroscopic FLI Network), a novel DL architecture that integrates the Instrument Response Function (IRF) as an additional input alongside experimental photon time-of-arrival histograms. Leveraging the capabilities of a Differential Transformer encoder-decoder architecture, MFliNet effectively focuses on critical input features, such as variations in photon time-of-arrival distributions. We evaluate MFliNet using rigorously designed tissue-mimicking phantoms and preclinical in-vivo cancer xenograft models. Our results demonstrate the model's robustness and suitability for complex macroscopic FLI applications, offering new opportunities for advanced biomedical imaging in diverse and challenging settings.

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.

Speech patterns have been identified as potential diagnostic markers for neuropsychiatric conditions. However, most studies only compare a single clinical group to healthy controls, whereas clinical practice often requires differentiating between multiple potential diagnoses (multiclass settings). To address this, we assembled a dataset of repeated recordings from 420 participants (67 with major depressive disorder, 106 with schizophrenia and 46 with autism, as well as matched controls), and tested the performance of a range of conventional machine learning models and advanced Transformer models on both binary and multiclass classification, based on voice and text features. While binary models performed comparably to previous research (F1 scores between 0.54-0.75 for autism spectrum disorder, ASD; 0.67-0.92 for major depressive disorder, MDD; and 0.71-0.83 for schizophrenia); when differentiating between multiple diagnostic groups performance decreased markedly (F1 scores between 0.35-0.44 for ASD, 0.57-0.75 for MDD, 0.15-0.66 for schizophrenia, and 0.38-0.52 macro F1). Combining voice and text-based models yielded increased performance, suggesting that they capture complementary diagnostic information. Our results indicate that models trained on binary classification may learn to rely on markers of generic differences between clinical and non-clinical populations, or markers of clinical features that overlap across conditions, rather than identifying markers specific to individual conditions. We provide recommendations for future research in the field, suggesting increased focus on developing larger transdiagnostic datasets that include more fine-grained clinical features, and that can support the development of models that better capture the complexity of neuropsychiatric conditions and naturalistic diagnostic assessment.

Magnetic resonance imaging (MRI) is the standard modality to understand human brain structure and function in vivo (antemortem). Decades of research in human neuroimaging has led to the widespread development of methods and tools to provide automated volume-based segmentations and surface-based parcellations which help localize brain functions to specialized anatomical regions. Recently ex vivo (postmortem) imaging of the brain has opened-up avenues to study brain structure at sub-millimeter ultra high-resolution revealing details not possible to observe with in vivo MRI. Unfortunately, there has been limited methodological development in ex vivo MRI primarily due to lack of datasets and limited centers with such imaging resources. Therefore, in this work, we present one-of-its-kind dataset of 82 ex vivo T2w whole brain hemispheres MRI at 0.3 mm isotropic resolution spanning Alzheimer's disease and related dementias. We adapted and developed a fast and easy-to-use automated surface-based pipeline to parcellate, for the first time, ultra high-resolution ex vivo brain tissue at the native subject space resolution using the Desikan-Killiany-Tourville (DKT) brain atlas. This allows us to perform vertex-wise analysis in the template space and thereby link morphometry measures with pathology measurements derived from histology. We will open-source our dataset docker container, Jupyter notebooks for ready-to-use out-of-the-box set of tools and command line options to advance ex vivo MRI clinical brain imaging research on the project webpage.

The caliber and configuration of retinal blood vessels serve as important biomarkers for various diseases and medical conditions. A thorough analysis of the retinal vasculature requires the segmentation of the blood vessels and their classification into arteries and veins, typically performed on color fundus images obtained by retinography. However, manually performing these tasks is labor-intensive and prone to human error. While several automated methods have been proposed to address this task, the current state of art faces challenges due to manifest classification errors affecting the topological consistency of segmentation maps. In this work, we introduce RRWNet, a novel end-to-end deep learning framework that addresses this limitation. The framework consists of a fully convolutional neural network that recursively refines semantic segmentation maps, correcting manifest classification errors and thus improving topological consistency. In particular, RRWNet is composed of two specialized subnetworks: a Base subnetwork that generates base segmentation maps from the input images, and a Recursive Refinement subnetwork that iteratively and recursively improves these maps. Evaluation on three different public datasets demonstrates the state-of-the-art performance of the proposed method, yielding more topologically consistent segmentation maps with fewer manifest classification errors than existing approaches. In addition, the Recursive Refinement module within RRWNet proves effective in post-processing segmentation maps from other methods, further demonstrating its potential. The model code, weights, and predictions will be publicly available at https://github.com/j-morano/rrwnet.

Robust and accurate detection and segmentation of heterogenous tumors appearing in different anatomical organs with supervised methods require large-scale labeled datasets covering all possible types of diseases. Due to the unavailability of such rich datasets and the high cost of annotations, unsupervised anomaly detection (UAD) methods have been developed aiming to detect the pathologies as deviation from the normality by utilizing the unlabeled healthy image data. However, developed UAD models are often trained with an incomplete distribution of healthy anatomies and have difficulties in preserving anatomical constraints. This work intends to, first, propose a robust inpainting model to learn the details of healthy anatomies and reconstruct high-resolution images by preserving anatomical constraints. Second, we propose an autoinpainting pipeline to automatically detect tumors, replace their appearance with the learned healthy anatomies, and based on that segment the tumoral volumes in a purely unsupervised fashion. Three imaging datasets, including PET, CT, and PET-CT scans of lung tumors and head and neck tumors, are studied as benchmarks for evaluation. Experimental results demonstrate the significant superiority of the proposed method over a wide range of state-of-the-art UAD methods. Moreover, the unsupervised method we propose produces comparable results to a robust supervised segmentation method when applied to multimodal images.

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.

With applications ranging from metabolomics to histopathology, quantitative phase microscopy (QPM) is a powerful label-free imaging modality. Despite significant advances in fast multiplexed imaging sensors and deep-learning-based inverse solvers, the throughput of QPM is currently limited by the speed of electronic hardware. Complementarily, to improve throughput further, here we propose to acquire images in a compressed form such that more information can be transferred beyond the existing electronic hardware bottleneck. To this end, we present a learnable optical compression-decompression framework that learns content-specific features. The proposed differentiable quantitative phase microscopy (partial mu) first uses learnable optical feature extractors as image compressors. The intensity representation produced by these networks is then captured by the imaging sensor. Finally, a reconstruction network running on electronic hardware decompresses the QPM images. In numerical experiments, the proposed system achieves compression of times 64 while maintaining the SSIM of sim 0.90 and PSNR of sim 30 dB on cells. The results demonstrated by our experiments open up a new pathway for achieving end-to-end optimized (i.e., optics and electronic) compact QPM systems that may provide unprecedented throughput improvements.

Complex prediction models such as deep learning are the output from fitting machine learning, neural networks, or AI models to a set of training data. These are now standard tools in science. A key challenge with the current generation of models is that they are highly parameterized, which makes describing and interpreting the prediction strategies difficult. We use topological data analysis to transform these complex prediction models into pictures representing a topological view. The result is a map of the predictions that enables inspection. The methods scale up to large datasets across different domains and enable us to detect labeling errors in training data, understand generalization in image classification, and inspect predictions of likely pathogenic mutations in the BRCA1 gene.

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.

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.

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.

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

Polyps in the colon are widely known cancer precursors identified by colonoscopy. Whilst most polyps are benign, the polyp's number, size and surface structure are linked to the risk of colon cancer. Several methods have been developed to automate polyp detection and segmentation. However, the main issue is that they are not tested rigorously on a large multicentre purpose-built dataset, one reason being the lack of a comprehensive public dataset. As a result, the developed methods may not generalise to different population datasets. To this extent, we have curated a dataset from six unique centres incorporating more than 300 patients. The dataset includes both single frame and sequence data with 3762 annotated polyp labels with precise delineation of polyp boundaries verified by six senior gastroenterologists. To our knowledge, this is the most comprehensive detection and pixel-level segmentation dataset (referred to as PolypGen) curated by a team of computational scientists and expert gastroenterologists. The paper provides insight into data construction and annotation strategies, quality assurance, and technical validation. Our dataset can be downloaded from https://doi.org/10.7303/syn26376615.

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.

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

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.

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.

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.

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.

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.

Breast dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) plays an important role in the screening and prognosis assessment of high-risk breast cancer. The segmentation of cancerous regions is essential useful for the subsequent analysis of breast MRI. To alleviate the annotation effort to train the segmentation networks, we propose a weakly-supervised strategy using extreme points as annotations for breast cancer segmentation. Without using any bells and whistles, our strategy focuses on fully exploiting the learning capability of the routine training procedure, i.e., the train - fine-tune - retrain process. The network first utilizes the pseudo-masks generated using the extreme points to train itself, by minimizing a contrastive loss, which encourages the network to learn more representative features for cancerous voxels. Then the trained network fine-tunes itself by using a similarity-aware propagation learning (SimPLe) strategy, which leverages feature similarity between unlabeled and positive voxels to propagate labels. Finally the network retrains itself by employing the pseudo-masks generated using previous fine-tuned network. The proposed method is evaluated on our collected DCE-MRI dataset containing 206 patients with biopsy-proven breast cancers. Experimental results demonstrate our method effectively fine-tunes the network by using the SimPLe strategy, and achieves a mean Dice value of 81%.

In this work, we introduce Brain Latent Progression (BrLP), a novel spatiotemporal disease progression model based on latent diffusion. BrLP is designed to predict the evolution of diseases at the individual level on 3D brain MRIs. Existing deep generative models developed for this task are primarily data-driven and face challenges in learning disease progressions. BrLP addresses these challenges by incorporating prior knowledge from disease models to enhance the accuracy of predictions. To implement this, we propose to integrate an auxiliary model that infers volumetric changes in various brain regions. Additionally, we introduce Latent Average Stabilization (LAS), a novel technique to improve spatiotemporal consistency of the predicted progression. BrLP is trained and evaluated on a large dataset comprising 11,730 T1-weighted brain MRIs from 2,805 subjects, collected from three publicly available, longitudinal Alzheimer's Disease (AD) studies. In our experiments, we compare the MRI scans generated by BrLP with the actual follow-up MRIs available from the subjects, in both cross-sectional and longitudinal settings. BrLP demonstrates significant improvements over existing methods, with an increase of 22% in volumetric accuracy across AD-related brain regions and 43% in image similarity to the ground-truth scans. The ability of BrLP to generate conditioned 3D scans at the subject level, along with the novelty of integrating prior knowledge to enhance accuracy, represents a significant advancement in disease progression modeling, opening new avenues for precision medicine. The code of BrLP is available at the following link: https://github.com/LemuelPuglisi/BrLP.

When developing deep neural networks for segmenting intraoperative ultrasound images, several practical issues are encountered frequently, such as the presence of ultrasound frames that do not contain regions of interest and the high variance in ground-truth labels. In this study, we evaluate the utility of a pre-screening classification network prior to the segmentation network. Experimental results demonstrate that such a classifier, minimising frame classification errors, was able to directly impact the number of false positive and false negative frames. Importantly, the segmentation accuracy on the classifier-selected frames, that would be segmented, remains comparable to or better than those from standalone segmentation networks. Interestingly, the efficacy of the pre-screening classifier was affected by the sampling methods for training labels from multiple observers, a seemingly independent problem. We show experimentally that a previously proposed approach, combining random sampling and consensus labels, may need to be adapted to perform well in our application. Furthermore, this work aims to share practical experience in developing a machine learning application that assists highly variable interventional imaging for prostate cancer patients, to present robust and reproducible open-source implementations, and to report a set of comprehensive results and analysis comparing these practical, yet important, options in a real-world clinical application.

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

Echocardiography has been a prominent tool for the diagnosis of cardiac disease. However, these diagnoses can be heavily impeded by poor image quality. Acoustic clutter emerges due to multipath reflections imposed by layers of skin, subcutaneous fat, and intercostal muscle between the transducer and heart. As a result, haze and other noise artifacts pose a real challenge to cardiac ultrasound imaging. In many cases, especially with difficult-to-image patients such as patients with obesity, a diagnosis from B-Mode ultrasound imaging is effectively rendered unusable, forcing sonographers to resort to contrast-enhanced ultrasound examinations or refer patients to other imaging modalities. Tissue harmonic imaging has been a popular approach to combat haze, but in severe cases is still heavily impacted by haze. Alternatively, denoising algorithms are typically unable to remove highly structured and correlated noise, such as haze. It remains a challenge to accurately describe the statistical properties of structured haze, and develop an inference method to subsequently remove it. Diffusion models have emerged as powerful generative models and have shown their effectiveness in a variety of inverse problems. In this work, we present a joint posterior sampling framework that combines two separate diffusion models to model the distribution of both clean ultrasound and haze in an unsupervised manner. Furthermore, we demonstrate techniques for effectively training diffusion models on radio-frequency ultrasound data and highlight the advantages over image data. Experiments on both in-vitro and in-vivo cardiac datasets show that the proposed dehazing method effectively removes haze while preserving signals from weakly reflected tissue.

High-throughput drug screening -- using cell imaging or gene expression measurements as readouts of drug effect -- is a critical tool in biotechnology to assess and understand the relationship between the chemical structure and biological activity of a drug. Since large-scale screens have to be divided into multiple experiments, a key difficulty is dealing with batch effects, which can introduce systematic errors and non-biological associations in the data. We propose InfoCORE, an Information maximization approach for COnfounder REmoval, to effectively deal with batch effects and obtain refined molecular representations. InfoCORE establishes a variational lower bound on the conditional mutual information of the latent representations given a batch identifier. It adaptively reweighs samples to equalize their implied batch distribution. Extensive experiments on drug screening data reveal InfoCORE's superior performance in a multitude of tasks including molecular property prediction and molecule-phenotype retrieval. Additionally, we show results for how InfoCORE offers a versatile framework and resolves general distribution shifts and issues of data fairness by minimizing correlation with spurious features or removing sensitive attributes. The code is available at https://github.com/uhlerlab/InfoCORE.

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

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.

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

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

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.

Discovering evolutionary traits that are heritable across species on the tree of life (also referred to as a phylogenetic tree) is of great interest to biologists to understand how organisms diversify and evolve. However, the measurement of traits is often a subjective and labor-intensive process, making trait discovery a highly label-scarce problem. We present a novel approach for discovering evolutionary traits directly from images without relying on trait labels. Our proposed approach, Phylo-NN, encodes the image of an organism into a sequence of quantized feature vectors -- or codes -- where different segments of the sequence capture evolutionary signals at varying ancestry levels in the phylogeny. We demonstrate the effectiveness of our approach in producing biologically meaningful results in a number of downstream tasks including species image generation and species-to-species image translation, using fish species as a target example.

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.

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.

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.

Accurate analysis and modeling of renal functions require a precise segmentation of the renal blood vessels. Micro-CT scans provide image data at higher resolutions, making more small vessels near the renal cortex visible. Although deep-learning-based methods have shown state-of-the-art performance in automatic blood vessel segmentations, they require a large amount of labeled training data. However, voxel-wise labeling in micro-CT scans is extremely time-consuming given the huge volume sizes. To mitigate the problem, we simulate synthetic renal vascular trees physiologically while generating corresponding scans of the simulated trees by training a generative model on unlabeled scans. This enables the generative model to learn the mapping implicitly without the need for explicit functions to emulate the image acquisition process. We further propose an additional segmentation branch over the generative model trained on the generated scans. We demonstrate that the model can directly segment blood vessels on real scans and validate our method on both 3D micro-CT scans of rat kidneys and a proof-of-concept experiment on 2D retinal images. Code and 3D results are available at https://github.com/miccai2023anony/RenalVesselSeg

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.

In this work, we report the set-up and results of the Liver Tumor Segmentation Benchmark (LiTS), which was organized in conjunction with the IEEE International Symposium on Biomedical Imaging (ISBI) 2017 and the International Conferences on Medical Image Computing and Computer-Assisted Intervention (MICCAI) 2017 and 2018. The image dataset is diverse and contains primary and secondary tumors with varied sizes and appearances with various lesion-to-background levels (hyper-/hypo-dense), created in collaboration with seven hospitals and research institutions. Seventy-five submitted liver and liver tumor segmentation algorithms were trained on a set of 131 computed tomography (CT) volumes and were tested on 70 unseen test images acquired from different patients. We found that not a single algorithm performed best for both liver and liver tumors in the three events. The best liver segmentation algorithm achieved a Dice score of 0.963, whereas, for tumor segmentation, the best algorithms achieved Dices scores of 0.674 (ISBI 2017), 0.702 (MICCAI 2017), and 0.739 (MICCAI 2018). Retrospectively, we performed additional analysis on liver tumor detection and revealed that not all top-performing segmentation algorithms worked well for tumor detection. The best liver tumor detection method achieved a lesion-wise recall of 0.458 (ISBI 2017), 0.515 (MICCAI 2017), and 0.554 (MICCAI 2018), indicating the need for further research. LiTS remains an active benchmark and resource for research, e.g., contributing the liver-related segmentation tasks in http://medicaldecathlon.com/. In addition, both data and online evaluation are accessible via www.lits-challenge.com.

To represent the biological variability of clinical neuroimaging populations, it is vital to be able to combine data across scanners and studies. However, different MRI scanners produce images with different characteristics, resulting in a domain shift known as the `harmonisation problem'. Additionally, neuroimaging data is inherently personal in nature, leading to data privacy concerns when sharing the data. To overcome these barriers, we propose an Unsupervised Source-Free Domain Adaptation (SFDA) method, SFHarmony. Through modelling the imaging features as a Gaussian Mixture Model and minimising an adapted Bhattacharyya distance between the source and target features, we can create a model that performs well for the target data whilst having a shared feature representation across the data domains, without needing access to the source data for adaptation or target labels. We demonstrate the performance of our method on simulated and real domain shifts, showing that the approach is applicable to classification, segmentation and regression tasks, requiring no changes to the algorithm. Our method outperforms existing SFDA approaches across a range of realistic data scenarios, demonstrating the potential utility of our approach for MRI harmonisation and general SFDA problems. Our code is available at https://github.com/nkdinsdale/SFHarmony.

Purpose: To evaluate the performance of an automated deep learning method in detecting ascites and subsequently quantifying its volume in patients with liver cirrhosis and ovarian cancer. Materials and Methods: This retrospective study included contrast-enhanced and non-contrast abdominal-pelvic CT scans of patients with cirrhotic ascites and patients with ovarian cancer from two institutions, National Institutes of Health (NIH) and University of Wisconsin (UofW). The model, trained on The Cancer Genome Atlas Ovarian Cancer dataset (mean age, 60 years +/- 11 [s.d.]; 143 female), was tested on two internal (NIH-LC and NIH-OV) and one external dataset (UofW-LC). Its performance was measured by the Dice coefficient, standard deviations, and 95% confidence intervals, focusing on ascites volume in the peritoneal cavity. Results: On NIH-LC (25 patients; mean age, 59 years +/- 14 [s.d.]; 14 male) and NIH-OV (166 patients; mean age, 65 years +/- 9 [s.d.]; all female), the model achieved Dice scores of 0.855 +/- 0.061 (CI: 0.831-0.878) and 0.826 +/- 0.153 (CI: 0.764-0.887), with median volume estimation errors of 19.6% (IQR: 13.2-29.0) and 5.3% (IQR: 2.4-9.7) respectively. On UofW-LC (124 patients; mean age, 46 years +/- 12 [s.d.]; 73 female), the model had a Dice score of 0.830 +/- 0.107 (CI: 0.798-0.863) and median volume estimation error of 9.7% (IQR: 4.5-15.1). The model showed strong agreement with expert assessments, with r^2 values of 0.79, 0.98, and 0.97 across the test sets. Conclusion: The proposed deep learning method performed well in segmenting and quantifying the volume of ascites in concordance with expert radiologist assessments.

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.

Disease progression simulation is a crucial area of research that has significant implications for clinical diagnosis, prognosis, and treatment. One major challenge in this field is the lack of continuous medical imaging monitoring of individual patients over time. To address this issue, we develop a novel framework termed Progressive Image Editing (PIE) that enables controlled manipulation of disease-related image features, facilitating precise and realistic disease progression simulation. Specifically, we leverage recent advancements in text-to-image generative models to simulate disease progression accurately and personalize it for each patient. We theoretically analyze the iterative refining process in our framework as a gradient descent with an exponentially decayed learning rate. To validate our framework, we conduct experiments in three medical imaging domains. Our results demonstrate the superiority of PIE over existing methods such as Stable Diffusion Walk and Style-Based Manifold Extrapolation based on CLIP score (Realism) and Disease Classification Confidence (Alignment). Our user study collected feedback from 35 veteran physicians to assess the generated progressions. Remarkably, 76.2% of the feedback agrees with the fidelity of the generated progressions. To our best knowledge, PIE is the first of its kind to generate disease progression images meeting real-world standards. It is a promising tool for medical research and clinical practice, potentially allowing healthcare providers to model disease trajectories over time, predict future treatment responses, and improve patient outcomes.

Accurate breast lesion risk estimation can significantly reduce unnecessary biopsies and help doctors decide optimal treatment plans. Most existing computer-aided systems rely solely on mammogram features to classify breast lesions. While this approach is convenient, it does not fully exploit useful information in clinical reports to achieve the optimal performance. Would clinical features significantly improve breast lesion classification compared to using mammograms alone? How to handle missing clinical information caused by variation in medical practice? What is the best way to combine mammograms and clinical features? There is a compelling need for a systematic study to address these fundamental questions. This paper investigates several multimodal deep networks based on feature concatenation, cross-attention, and co-attention to combine mammograms and categorical clinical variables. We show that the proposed architectures significantly increase the lesion classification performance (average area under ROC curves from 0.89 to 0.94). We also evaluate the model when clinical variables are missing.

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

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.

Objective: To allow efficient learning using the Recurrent Inference Machine (RIM) for image reconstruction whereas not being strictly dependent on the training data distribution so that unseen modalities and pathologies are still accurately recovered. Methods: Theoretically, the RIM learns to solve the inverse problem of accelerated-MRI reconstruction whereas being robust to variable imaging conditions. The efficiency and generalization capabilities with different training datasets were studied, as well as recurrent network units with decreasing complexity: the Gated Recurrent Unit (GRU), the Minimal Gated Unit (MGU), and the Independently Recurrent Neural Network (IndRNN), to reduce inference times. Validation was performed against Compressed Sensing (CS) and further assessed based on data unseen during training. A pathology study was conducted by reconstructing simulated white matter lesions and prospectively undersampled data of a Multiple Sclerosis patient. Results: Training on a single modality of 3T T_1-weighted brain data appeared sufficient to also reconstruct 7T T_{2}^*-weighted brain and 3T T_2-weighted knee data. The IndRNN is an efficient recurrent unit, reducing inference time by 68\% compared to CS, whereas maintaining performance. The RIM was able to reconstruct lesions unseen during training more accurately than CS when trained on T_2-weighted knee data. Training on T_1-weighted brain data and on combined data slightly enhanced the signal compared to CS. Conclusion: The RIM is efficient when decreasing its complexity, which reduces the inference time, whereas still being able to reconstruct data and pathology that was unseen during training.

With the rapid advances in high-throughput sequencing technologies, the focus of survival analysis has shifted from examining clinical indicators to incorporating genomic profiles with pathological images. However, existing methods either directly adopt a straightforward fusion of pathological features and genomic profiles for survival prediction, or take genomic profiles as guidance to integrate the features of pathological images. The former would overlook intrinsic cross-modal correlations. The latter would discard pathological information irrelevant to gene expression. To address these issues, we present a Cross-Modal Translation and Alignment (CMTA) framework to explore the intrinsic cross-modal correlations and transfer potential complementary information. Specifically, we construct two parallel encoder-decoder structures for multi-modal data to integrate intra-modal information and generate cross-modal representation. Taking the generated cross-modal representation to enhance and recalibrate intra-modal representation can significantly improve its discrimination for comprehensive survival analysis. To explore the intrinsic crossmodal correlations, we further design a cross-modal attention module as the information bridge between different modalities to perform cross-modal interactions and transfer complementary information. Our extensive experiments on five public TCGA datasets demonstrate that our proposed framework outperforms the state-of-the-art methods.

Understanding how deep learning models predict oncology patient risk can provide critical insights into disease progression, support clinical decision-making, and pave the way for trustworthy and data-driven precision medicine. Building on recent advances in the spatial modeling of the tumor microenvironment using graph neural networks, we present an explainable cell graph (xCG) approach for survival prediction. We validate our model on a public cohort of imaging mass cytometry (IMC) data for 416 cases of lung adenocarcinoma. We explain survival predictions in terms of known phenotypes on the cell level by computing risk attributions over cell graphs, for which we propose an efficient grid-based layer-wise relevance propagation (LRP) method. Our ablation studies highlight the importance of incorporating the cancer stage and model ensembling to improve the quality of risk estimates. Our xCG method, together with the IMC data, is made publicly available to support further research.

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

Segmenting stroke lesions in Magnetic Resonance Imaging (MRI) is challenging due to diverse clinical imaging domains, with existing models struggling to generalise across different MRI acquisition parameters and sequences. In this work, we propose two novel physics-constrained approaches using synthetic quantitative MRI (qMRI) images to enhance the robustness and generalisability of segmentation models. We trained a qMRI estimation model to predict qMRI maps from MPRAGE images, which were used to simulate diverse MRI sequences for segmentation training. A second approach built upon prior work in synthetic data for stroke lesion segmentation, generating qMRI maps from a dataset of tissue labels. The proposed approaches improved over the baseline nnUNet on a variety of out-of-distribution datasets, with the second approach outperforming the prior synthetic data method.

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.

Knee Osteoarthritis (KOA) is a highly prevalent chronic musculoskeletal condition with no currently available treatment. The manifestation of KOA is heterogeneous and prediction of its progression is challenging. Current literature suggests that the use of multi-modal data and advanced modeling methods, such as the ones based on Deep Learning, has promise in tackling this challenge. To date, however, the evidence on the efficacy of this approach is limited. In this study, we leveraged recent advances in Deep Learning and, using a Transformer approach, developed a unified framework for the multi-modal fusion of knee imaging data. Subsequently, we analyzed its performance across a range of scenarios by investigating multiple progression horizons -- from short-term to long-term. We report our findings using a large cohort (n=2421-3967) derived from the Osteoarthritis Initiative dataset. We show that structural knee MRI allows identifying radiographic KOA progressors on par with multi-modal fusion approaches, achieving an area under the ROC curve (ROC AUC) of 0.70-0.76 and Average Precision (AP) of 0.15-0.54 in 2-8 year horizons. Progression within 1 year was better predicted with a multi-modal method using X-ray, structural, and compositional MR images -- ROC AUC of 0.76(0.04), AP of 0.13(0.04) -- or via clinical data. Our follow-up analysis generally shows that prediction from the imaging data is more accurate for post-traumatic subjects, and we further investigate which subject subgroups may benefit the most. The present study provides novel insights into multi-modal imaging of KOA and brings a unified data-driven framework for studying its progression in an end-to-end manner, providing new tools for the design of more efficient clinical trials. The source code of our framework and the pre-trained models are made publicly available.

Dynamic reconstruction of deformable tissues in endoscopic video is a key technology for robot-assisted surgery. Recent reconstruction methods based on neural radiance fields (NeRFs) have achieved remarkable results in the reconstruction of surgical scenes. However, based on implicit representation, NeRFs struggle to capture the intricate details of objects in the scene and cannot achieve real-time rendering. In addition, restricted single view perception and occluded instruments also propose special challenges in surgical scene reconstruction. To address these issues, we develop SurgicalGaussian, a deformable 3D Gaussian Splatting method to model dynamic surgical scenes. Our approach models the spatio-temporal features of soft tissues at each time stamp via a forward-mapping deformation MLP and regularization to constrain local 3D Gaussians to comply with consistent movement. With the depth initialization strategy and tool mask-guided training, our method can remove surgical instruments and reconstruct high-fidelity surgical scenes. Through experiments on various surgical videos, our network outperforms existing method on many aspects, including rendering quality, rendering speed and GPU usage. The project page can be found at https://surgicalgaussian.github.io.

This article describes the design, implementation, and results of the latest installment of the dermoscopic image analysis benchmark challenge. The goal is to support research and development of algorithms for automated diagnosis of melanoma, the most lethal skin cancer. The challenge was divided into 3 tasks: lesion segmentation, feature detection, and disease classification. Participation involved 593 registrations, 81 pre-submissions, 46 finalized submissions (including a 4-page manuscript), and approximately 50 attendees, making this the largest standardized and comparative study in this field to date. While the official challenge duration and ranking of participants has concluded, the dataset snapshots remain available for further research and development.

Identification of vessel structures of different sizes in biomedical images is crucial in the diagnosis of many neurodegenerative diseases. However, the sparsity of good-quality annotations of such images makes the task of vessel segmentation challenging. Deep learning offers an efficient way to segment vessels of different sizes by learning their high-level feature representations and the spatial continuity of such features across dimensions. Semi-supervised patch-based approaches have been effective in identifying small vessels of one to two voxels in diameter. This study focuses on improving the segmentation quality by considering the spatial correlation of the features using the Maximum Intensity Projection~(MIP) as an additional loss criterion. Two methods are proposed with the incorporation of MIPs of label segmentation on the single~(z-axis) and multiple perceivable axes of the 3D volume. The proposed MIP-based methods produce segmentations with improved vessel continuity, which is evident in visual examinations of ROIs. Patch-based training is improved by introducing an additional loss term, MIP loss, to penalise the predicted discontinuity of vessels. A training set of 14 volumes is selected from the StudyForrest dataset comprising of 18 7-Tesla 3D Time-of-Flight~(ToF) Magnetic Resonance Angiography (MRA) images. The generalisation performance of the method is evaluated using the other unseen volumes in the dataset. It is observed that the proposed method with multi-axes MIP loss produces better quality segmentations with a median Dice of 80.245 pm 0.129. Also, the method with single-axis MIP loss produces segmentations with a median Dice of 79.749 pm 0.109. Furthermore, a visual comparison of the ROIs in the predicted segmentation reveals a significant improvement in the continuity of the vessels when MIP loss is incorporated into training.

Accurate prediction of knee osteoarthritis (KOA) progression from structural MRI has a potential to enhance disease understanding and support clinical trials. Prior art focused on manually designed imaging biomarkers, which may not fully exploit all disease-related information present in MRI scan. In contrast, our method learns relevant representations from raw data end-to-end using Deep Learning, and uses them for progression prediction. The method employs a 2D CNN to process the data slice-wise and aggregate the extracted features using a Transformer. Evaluated on a large cohort (n=4,866), the proposed method outperforms conventional 2D and 3D CNN-based models and achieves average precision of 0.58pm0.03 and ROC AUC of 0.78pm0.01. This paper sets a baseline on end-to-end KOA progression prediction from structural MRI. Our code is publicly available at https://github.com/MIPT-Oulu/OAProgressionMR.