Label-free Concept Based Multiple Instance Learning for Gigapixel Histopathology

Multiple Instance Learning (MIL) methods allow for gigapixel Whole-Slide Image (WSI) analysis with only slide-level annotations. Interpretability is crucial for safely deploying such algorithms in high-stakes medical domains. Traditional MIL methods offer explanations by highlighting salient regions. However, such spatial heatmaps provide limited insights for end users. To address this, we propose a novel inherently interpretable WSI-classification approach that uses human-understandable pathology concepts to generate explanations. Our proposed Concept MIL model leverages recent advances in vision-language models to directly predict pathology concepts based on image features. The model's predictions are obtained through a linear combination of the concepts identified on the top-K patches of a WSI, enabling inherent explanations by tracing each concept's influence on the prediction. In contrast to traditional concept-based interpretable models, our approach eliminates the need for costly human annotations by leveraging the vision-language model. We validate our method on two widely used pathology datasets: Camelyon16 and PANDA. On both datasets, Concept MIL achieves AUC and accuracy scores over 0.9, putting it on par with state-of-the-art models. We further find that 87.1\% (Camelyon16) and 85.3\% (PANDA) of the top 20 patches fall within the tumor region. A user study shows that the concepts identified by our model align with the concepts used by pathologists, making it a promising strategy for human-interpretable WSI classification.

Navigating the landscape of multimodal AI in medicine: a scoping review on technical challenges and clinical applications

Recent technological advances in healthcare have led to unprecedented growth in patient data quantity and diversity. While artificial intelligence (AI) models have shown promising results in analyzing individual data modalities, there is increasing recognition that models integrating multiple complementary data sources, so-called multimodal AI, could enhance clinical decision-making. This scoping review examines the landscape of deep learning-based multimodal AI applications across the medical domain, analyzing 432 papers published between 2018 and 2024. We provide an extensive overview of multimodal AI development across different medical disciplines, examining various architectural approaches, fusion strategies, and common application areas. Our analysis reveals that multimodal AI models consistently outperform their unimodal counterparts, with an average improvement of 6.2 percentage points in AUC. However, several challenges persist, including cross-departmental coordination, heterogeneous data characteristics, and incomplete datasets. We critically assess the technical and practical challenges in developing multimodal AI systems and discuss potential strategies for their clinical implementation, including a brief overview of commercially available multimodal AI models for clinical decision-making. Additionally, we identify key factors driving multimodal AI development and propose recommendations to accelerate the field's maturation. This review provides researchers and clinicians with a thorough understanding of the current state, challenges, and future directions of multimodal AI in medicine.

Masked Attention as a Mechanism for Improving Interpretability of Vision Transformers

Vision Transformers are at the heart of the current surge of interest in foundation models for histopathology. They process images by breaking them into smaller patches following a regular grid, regardless of their content. Yet, not all parts of an image are equally relevant for its understanding. This is particularly true in computational pathology where background is completely non-informative and may introduce artefacts that could mislead predictions. To address this issue, we propose a novel method that explicitly masks background in Vision Transformers' attention mechanism. This ensures tokens corresponding to background patches do not contribute to the final image representation, thereby improving model robustness and interpretability. We validate our approach using prostate cancer grading from whole-slide images as a case study. Our results demonstrate that it achieves comparable performance with plain self-attention while providing more accurate and clinically meaningful attention heatmaps.

Hierarchical Vision Transformers for Context-Aware Prostate Cancer Grading in Whole Slide Images

Vision Transformers (ViTs) have ushered in a new era in computer vision, showcasing unparalleled performance in many challenging tasks. However, their practical deployment in computational pathology has largely been constrained by the sheer size of whole slide images (WSIs), which result in lengthy input sequences. Transformers faced a similar limitation when applied to long documents, and Hierarchical Transformers were introduced to circumvent it. Given the analogous challenge with WSIs and their inherent hierarchical structure, Hierarchical Vision Transformers (H-ViTs) emerge as a promising solution in computational pathology. This work delves into the capabilities of H-ViTs, evaluating their efficiency for prostate cancer grading in WSIs. Our results show that they achieve competitive performance against existing state-of-the-art solutions.

Understanding metric-related pitfalls in image analysis validation

Validation metrics are key for the reliable tracking of scientific progress and for bridging the current chasm between artificial intelligence (AI) research and its translation into practice. However, increasing evidence shows that particularly in image analysis, metrics are often chosen inadequately in relation to the underlying research problem. This could be attributed to a lack of accessibility of metric-related knowledge: While taking into account the individual strengths, weaknesses, and limitations of validation metrics is a critical prerequisite to making educated choices, the relevant knowledge is currently scattered and poorly accessible to individual researchers. Based on a multi-stage Delphi process conducted by a multidisciplinary expert consortium as well as extensive community feedback, the present work provides the first reliable and comprehensive common point of access to information on pitfalls related to validation metrics in image analysis. Focusing on biomedical image analysis but with the potential of transfer to other fields, the addressed pitfalls generalize across application domains and are categorized according to a newly created, domain-agnostic taxonomy. To facilitate comprehension, illustrations and specific examples accompany each pitfall. As a structured body of information accessible to researchers of all levels of expertise, this work enhances global comprehension of a key topic in image analysis validation.

Domain adaptation strategies for cancer-independent detection of lymph node metastases

Recently, large, high-quality public datasets have led to the development of convolutional neural networks that can detect lymph node metastases of breast cancer at the level of expert pathologists. Many cancers, regardless of the site of origin, can metastasize to lymph nodes. However, collecting and annotating high-volume, high-quality datasets for every cancer type is challenging. In this paper we investigate how to leverage existing high-quality datasets most efficiently in multi-task settings for closely related tasks. Specifically, we will explore different training and domain adaptation strategies, including prevention of catastrophic forgetting, for colon and head-and-neck cancer metastasis detection in lymph nodes. Our results show state-of-the-art performance on both cancer metastasis detection tasks. Furthermore, we show the effectiveness of repeated adaptation of networks from one cancer type to another to obtain multi-task metastasis detection networks. Last, we show that leveraging existing high-quality datasets can significantly boost performance on new target tasks and that catastrophic forgetting can be effectively mitigated using regularization.

Metrics reloaded: Pitfalls and recommendations for image analysis validation

The field of automatic biomedical image analysis crucially depends on robust and meaningful performance metrics for algorithm validation. Current metric usage, however, is often ill-informed and does not reflect the underlying domain interest. Here, we present a comprehensive framework that guides researchers towards choosing performance metrics in a problem-aware manner. Specifically, we focus on biomedical image analysis problems that can be interpreted as a classification task at image, object or pixel level. The framework first compiles domain interest-, target structure-, data set- and algorithm output-related properties of a given problem into a problem fingerprint, while also mapping it to the appropriate problem category, namely image-level classification, semantic segmentation, instance segmentation, or object detection. It then guides users through the process of selecting and applying a set of appropriate validation metrics while making them aware of potential pitfalls related to individual choices. In this paper, we describe the current status of the Metrics Reloaded recommendation framework, with the goal of obtaining constructive feedback from the image analysis community. The current version has been developed within an international consortium of more than 60 image analysis experts and will be made openly available as a user-friendly toolkit after community-driven optimization.

Automatic tumour segmentation in H&E-stained whole-slide images of the pancreas

Pancreatic cancer will soon be the second leading cause of cancer-related death in Western society. Imaging techniques such as CT, MRI and ultrasound typically help providing the initial diagnosis, but histopathological assessment is still the gold standard for final confirmation of disease presence and prognosis. In recent years machine learning approaches and pathomics pipelines have shown potential in improving diagnostics and prognostics in other cancerous entities, such as breast and prostate cancer. A crucial first step in these pipelines is typically identification and segmentation of the tumour area. Ideally this step is done automatically to prevent time consuming manual annotation. We propose a multi-task convolutional neural network to balance disease detection and segmentation accuracy. We validated our approach on a dataset of 29 patients (for a total of 58 slides) at different resolutions. The best single task segmentation network achieved a median Dice of 0.885 (0.122) IQR at a resolution of 15.56 $\mu$m. Our multi-task network improved on that with a median Dice score of 0.934 (0.077) IQR.

The Medical Segmentation Decathlon

International challenges have become the de facto standard for comparative assessment of image analysis algorithms given a specific task. Segmentation is so far the most widely investigated medical image processing task, but the various segmentation challenges have typically been organized in isolation, such that algorithm development was driven by the need to tackle a single specific clinical problem. We hypothesized that a method capable of performing well on multiple tasks will generalize well to a previously unseen task and potentially outperform a custom-designed solution. To investigate the hypothesis, we organized the Medical Segmentation Decathlon (MSD) - a biomedical image analysis challenge, in which algorithms compete in a multitude of both tasks and modalities. The underlying data set was designed to explore the axis of difficulties typically encountered when dealing with medical images, such as small data sets, unbalanced labels, multi-site data and small objects. The MSD challenge confirmed that algorithms with a consistent good performance on a set of tasks preserved their good average performance on a different set of previously unseen tasks. Moreover, by monitoring the MSD winner for two years, we found that this algorithm continued generalizing well to a wide range of other clinical problems, further confirming our hypothesis. Three main conclusions can be drawn from this study: (1) state-of-the-art image segmentation algorithms are mature, accurate, and generalize well when retrained on unseen tasks; (2) consistent algorithmic performance across multiple tasks is a strong surrogate of algorithmic generalizability; (3) the training of accurate AI segmentation models is now commoditized to non AI experts.

Common Limitations of Image Processing Metrics: A Picture Story

While the importance of automatic image analysis is increasing at an enormous pace, recent meta-research revealed major flaws with respect to algorithm validation. Specifically, performance metrics are key for objective, transparent and comparative performance assessment, but relatively little attention has been given to the practical pitfalls when using specific metrics for a given image analysis task. A common mission of several international initiatives is therefore to provide researchers with guidelines and tools to choose the performance metrics in a problem-aware manner. This dynamically updated document has the purpose to illustrate important limitations of performance metrics commonly applied in the field of image analysis. The current version is based on a Delphi process on metrics conducted by an international consortium of image analysis experts.