Explaining Digital Pathology Models via Clustering Activations

We present a clustering-based explainability technique for digital pathology models based on convolutional neural networks. Unlike commonly used methods based on saliency maps, such as occlusion, GradCAM, or relevance propagation, which highlight regions that contribute the most to the prediction for a single slide, our method shows the global behaviour of the model under consideration, while also providing more fine-grained information. The result clusters can be visualised not only to understand the model, but also to increase confidence in its operation, leading to faster adoption in clinical practice. We also evaluate the performance of our technique on an existing model for detecting prostate cancer, demonstrating its usefulness.

Anatomy-Aware Lymphoma Lesion Detection in Whole-Body PET/CT

Early cancer detection is crucial for improving patient outcomes, and 18F FDG PET/CT imaging plays a vital role by combining metabolic and anatomical information. Accurate lesion detection remains challenging due to the need to identify multiple lesions of varying sizes. In this study, we investigate the effect of adding anatomy prior information to deep learning-based lesion detection models. In particular, we add organ segmentation masks from the TotalSegmentator tool as auxiliary inputs to provide anatomical context to nnDetection, which is the state-of-the-art for lesion detection, and Swin Transformer. The latter is trained in two stages that combine self-supervised pre-training and supervised fine-tuning. The method is tested in the AutoPET and Karolinska lymphoma datasets. The results indicate that the inclusion of anatomical priors substantially improves the detection performance within the nnDetection framework, while it has almost no impact on the performance of the vision transformer. Moreover, we observe that Swin Transformer does not offer clear advantages over conventional convolutional neural network (CNN) encoders used in nnDetection. These findings highlight the critical role of the anatomical context in cancer lesion detection, especially in CNN-based models.

Real-time prediction of breast cancer sites using deformation-aware graph neural network

Early diagnosis of breast cancer is crucial, enabling the establishment of appropriate treatment plans and markedly enhancing patient prognosis. While direct magnetic resonance imaging-guided biopsy demonstrates promising performance in detecting cancer lesions, its practical application is limited by prolonged procedure times and high costs. To overcome these issues, an indirect MRI-guided biopsy that allows the procedure to be performed outside of the MRI room has been proposed, but it still faces challenges in creating an accurate real-time deformable breast model. In our study, we tackled this issue by developing a graph neural network (GNN)-based model capable of accurately predicting deformed breast cancer sites in real time during biopsy procedures. An individual-specific finite element (FE) model was developed by incorporating magnetic resonance (MR) image-derived structural information of the breast and tumor to simulate deformation behaviors. A GNN model was then employed, designed to process surface displacement and distance-based graph data, enabling accurate prediction of overall tissue displacement, including the deformation of the tumor region. The model was validated using phantom and real patient datasets, achieving an accuracy within 0.2 millimeters (mm) for cancer node displacement (RMSE) and a dice similarity coefficient (DSC) of 0.977 for spatial overlap with actual cancerous regions. Additionally, the model enabled real-time inference and achieved a speed-up of over 4,000 times in computational cost compared to conventional FE simulations. The proposed deformation-aware GNN model offers a promising solution for real-time tumor displacement prediction in breast biopsy, with high accuracy and real-time capability. Its integration with clinical procedures could significantly enhance the precision and efficiency of breast cancer diagnosis.

ProstNFound+: A Prospective Study using Medical Foundation Models for Prostate Cancer Detection

Purpose: Medical foundation models (FMs) offer a path to build high-performance diagnostic systems. However, their application to prostate cancer (PCa) detection from micro-ultrasound ({\mu}US) remains untested in clinical settings. We present ProstNFound+, an adaptation of FMs for PCa detection from {\mu}US, along with its first prospective validation. Methods: ProstNFound+ incorporates a medical FM, adapter tuning, and a custom prompt encoder that embeds PCa-specific clinical biomarkers. The model generates a cancer heatmap and a risk score for clinically significant PCa. Following training on multi-center retrospective data, the model is prospectively evaluated on data acquired five years later from a new clinical site. Model predictions are benchmarked against standard clinical scoring protocols (PRI-MUS and PI-RADS). Results: ProstNFound+ shows strong generalization to the prospective data, with no performance degradation compared to retrospective evaluation. It aligns closely with clinical scores and produces interpretable heatmaps consistent with biopsy-confirmed lesions. Conclusion: The results highlight its potential for clinical deployment, offering a scalable and interpretable alternative to expert-driven protocols.

MeisenMeister: A Simple Two Stage Pipeline for Breast Cancer Classification on MRI

The ODELIA Breast MRI Challenge 2025 addresses a critical issue in breast cancer screening: improving early detection through more efficient and accurate interpretation of breast MRI scans. Even though methods for general-purpose whole-body lesion segmentation as well as multi-time-point analysis exist, breast cancer detection remains highly challenging, largely due to the limited availability of high-quality segmentation labels. Therefore, developing robust classification-based approaches is crucial for the future of early breast cancer detection, particularly in applications such as large-scale screening. In this write-up, we provide a comprehensive overview of our approach to the challenge. We begin by detailing the underlying concept and foundational assumptions that guided our work. We then describe the iterative development process, highlighting the key stages of experimentation, evaluation, and refinement that shaped the evolution of our solution. Finally, we present the reasoning and evidence that informed the design choices behind our final submission, with a focus on performance, robustness, and clinical relevance. We release our full implementation publicly at https://github.com/MIC-DKFZ/MeisenMeister

The Impact of Longitudinal Mammogram Alignment on Breast Cancer Risk Assessment

Regular mammography screening is crucial for early breast cancer detection. By leveraging deep learning-based risk models, screening intervals can be personalized, especially for high-risk individuals. While recent methods increasingly incorporate longitudinal information from prior mammograms, accurate spatial alignment across time points remains a key challenge. Misalignment can obscure meaningful tissue changes and degrade model performance. In this study, we provide insights into various alignment strategies, image-based registration, feature-level (representation space) alignment with and without regularization, and implicit alignment methods, for their effectiveness in longitudinal deep learning-based risk modeling. Using two large-scale mammography datasets, we assess each method across key metrics, including predictive accuracy, precision, recall, and deformation field quality. Our results show that image-based registration consistently outperforms the more recently favored feature-based and implicit approaches across all metrics, enabling more accurate, temporally consistent predictions and generating smooth, anatomically plausible deformation fields. Although regularizing the deformation field improves deformation quality, it reduces the risk prediction performance of feature-level alignment. Applying image-based deformation fields within the feature space yields the best risk prediction performance. These findings underscore the importance of image-based deformation fields for spatial alignment in longitudinal risk modeling, offering improved prediction accuracy and robustness. This approach has strong potential to enhance personalized screening and enable earlier interventions for high-risk individuals. The code is available at https://github.com/sot176/Mammogram_Alignment_Study_Risk_Prediction.git, allowing full reproducibility of the results.

A Second-Order Attention Mechanism For Prostate Cancer Segmentation and Detection in Bi-Parametric MRI

The detection of clinically significant prostate cancer lesions (csPCa) from biparametric magnetic resonance imaging (bp-MRI) has emerged as a noninvasive imaging technique for improving accurate diagnosis. Nevertheless, the analysis of such images remains highly dependent on the subjective expert interpretation. Deep learning approaches have been proposed for csPCa lesions detection and segmentation, but they remain limited due to their reliance on extensively annotated datasets. Moreover, the high lesion variability across prostate zones poses additional challenges, even for expert radiologists. This work introduces a second-order geometric attention (SOGA) mechanism that guides a dedicated segmentation network, through skip connections, to detect csPCa lesions. The proposed attention is modeled on the Riemannian manifold, learning from symmetric positive definitive (SPD) representations. The proposed mechanism was integrated into standard U-Net and nnU-Net backbones, and was validated on the publicly available PI-CAI dataset, achieving an Average Precision (AP) of 0.37 and an Area Under the ROC Curve (AUC-ROC) of 0.83, outperforming baseline networks and attention-based methods. Furthermore, the approach was evaluated on the Prostate158 dataset as an independent test cohort, achieving an AP of 0.37 and an AUC-ROC of 0.75, confirming robust generalization and suggesting discriminative learned representations.

nnMIL: A generalizable multiple instance learning framework for computational pathology

Computational pathology holds substantial promise for improving diagnosis and guiding treatment decisions. Recent pathology foundation models enable the extraction of rich patch-level representations from large-scale whole-slide images (WSIs), but current approaches for aggregating these features into slide-level predictions remain constrained by design limitations that hinder generalizability and reliability. Here, we developed nnMIL, a simple yet broadly applicable multiple-instance learning framework that connects patch-level foundation models to robust slide-level clinical inference. nnMIL introduces random sampling at both the patch and feature levels, enabling large-batch optimization, task-aware sampling strategies, and efficient and scalable training across datasets and model architectures. A lightweight aggregator performs sliding-window inference to generate ensemble slide-level predictions and supports principled uncertainty estimation. Across 40,000 WSIs encompassing 35 clinical tasks and four pathology foundation models, nnMIL consistently outperformed existing MIL methods for disease diagnosis, histologic subtyping, molecular biomarker detection, and pan- cancer prognosis prediction. It further demonstrated strong cross-model generalization, reliable uncertainty quantification, and robust survival stratification in multiple external cohorts. In conclusion, nnMIL offers a practical and generalizable solution for translating pathology foundation models into clinically meaningful predictions, advancing the development and deployment of reliable AI systems in real-world settings.

General OOD Detection via Model-aware and Subspace-aware Variable Priority

Out-of-distribution (OOD) detection is essential for determining when a supervised model encounters inputs that differ meaningfully from its training distribution. While widely studied in classification, OOD detection for regression and survival analysis remains limited due to the absence of discrete labels and the challenge of quantifying predictive uncertainty. We introduce a framework for OOD detection that is simultaneously model aware and subspace aware, and that embeds variable prioritization directly into the detection step. The method uses the fitted predictor to construct localized neighborhoods around each test case that emphasize the features driving the model's learned relationship and downweight directions that are less relevant to prediction. It produces OOD scores without relying on global distance metrics or estimating the full feature density. The framework is applicable across outcome types, and in our implementation we use random forests, where the rule structure yields transparent neighborhoods and effective scoring. Experiments on synthetic and real data benchmarks designed to isolate functional shifts show consistent improvements over existing methods. We further demonstrate the approach in an esophageal cancer survival study, where distribution shifts related to lymphadenectomy identify patterns relevant to surgical guidelines.

PSO-XAI: A PSO-Enhanced Explainable AI Framework for Reliable Breast Cancer Detection

Breast cancer is considered the most critical and frequently diagnosed cancer in women worldwide, leading to an increase in cancer-related mortality. Early and accurate detection is crucial as it can help mitigate possible threats while improving survival rates. In terms of prediction, conventional diagnostic methods are often limited by variability, cost, and, most importantly, risk of misdiagnosis. To address these challenges, machine learning (ML) has emerged as a powerful tool for computer-aided diagnosis, with feature selection playing a vital role in improving model performance and interpretability. This research study proposes an integrated framework that incorporates customized Particle Swarm Optimization (PSO) for feature selection. This framework has been evaluated on a comprehensive set of 29 different models, spanning classical classifiers, ensemble techniques, neural networks, probabilistic algorithms, and instance-based algorithms. To ensure interpretability and clinical relevance, the study uses cross-validation in conjunction with explainable AI methods. Experimental evaluation showed that the proposed approach achieved a superior score of 99.1\% across all performance metrics, including accuracy and precision, while effectively reducing dimensionality and providing transparent, model-agnostic explanations. The results highlight the potential of combining swarm intelligence with explainable ML for robust, trustworthy, and clinically meaningful breast cancer diagnosis.