A Foundation Model Framework for Multi-View MRI Classification of Extramural Vascular Invasion and Mesorectal Fascia Invasion in Rectal Cancer

Background: Accurate MRI-based identification of extramural vascular invasion (EVI) and mesorectal fascia invasion (MFI) is pivotal for risk-stratified management of rectal cancer, yet visual assessment is subjective and vulnerable to inter-institutional variability. Purpose: To develop and externally evaluate a multicenter, foundation-model-driven framework that automatically classifies EVI and MFI on axial and sagittal T2-weighted MRI. Methods: This retrospective study used 331 pre-treatment rectal cancer MRI examinations from three European hospitals. After TotalSegmentator-guided rectal patch extraction, a self-supervised frequency-domain harmonization pipeline was trained to minimize scanner-related contrast shifts. Four classifiers were compared: ResNet50, SeResNet, the universal biomedical pretrained transformer (UMedPT) with a lightweight MLP head, and a logistic-regression variant using frozen UMedPT features (UMedPT_LR). Results: UMedPT_LR achieved the best EVI detection when axial and sagittal features were fused (AUC = 0.82; sensitivity = 0.75; F1 score = 0.73), surpassing the Chaimeleon Grand-Challenge winner (AUC = 0.74). The highest MFI performance was attained by UMedPT on axial harmonized images (AUC = 0.77), surpassing the Chaimeleon Grand-Challenge winner (AUC = 0.75). Frequency-domain harmonization improved MFI classification but variably affected EVI performance. Conventional CNNs (ResNet50, SeResNet) underperformed, especially in F1 score and balanced accuracy. Conclusion: These findings demonstrate that combining foundation model features, harmonization, and multi-view fusion significantly enhances diagnostic performance in rectal MRI.

Explainable Anatomy-Guided AI for Prostate MRI: Foundation Models and In Silico Clinical Trials for Virtual Biopsy-based Risk Assessment

We present a fully automated, anatomically guided deep learning pipeline for prostate cancer (PCa) risk stratification using routine MRI. The pipeline integrates three key components: an nnU-Net module for segmenting the prostate gland and its zones on axial T2-weighted MRI; a classification module based on the UMedPT Swin Transformer foundation model, fine-tuned on 3D patches with optional anatomical priors and clinical data; and a VAE-GAN framework for generating counterfactual heatmaps that localize decision-driving image regions. The system was developed using 1,500 PI-CAI cases for segmentation and 617 biparametric MRIs with metadata from the CHAIMELEON challenge for classification (split into 70% training, 10% validation, and 20% testing). Segmentation achieved mean Dice scores of 0.95 (gland), 0.94 (peripheral zone), and 0.92 (transition zone). Incorporating gland priors improved AUC from 0.69 to 0.72, with a three-scale ensemble achieving top performance (AUC = 0.79, composite score = 0.76), outperforming the 2024 CHAIMELEON challenge winners. Counterfactual heatmaps reliably highlighted lesions within segmented regions, enhancing model interpretability. In a prospective multi-center in-silico trial with 20 clinicians, AI assistance increased diagnostic accuracy from 0.72 to 0.77 and Cohen's kappa from 0.43 to 0.53, while reducing review time per case by 40%. These results demonstrate that anatomy-aware foundation models with counterfactual explainability can enable accurate, interpretable, and efficient PCa risk assessment, supporting their potential use as virtual biopsies in clinical practice.

Pixels to Prognosis: Harmonized Multi-Region CT-Radiomics and Foundation-Model Signatures Across Multicentre NSCLC Data

Purpose: To evaluate the impact of harmonization and multi-region CT image feature integration on survival prediction in non-small cell lung cancer (NSCLC) patients, using handcrafted radiomics, pretrained foundation model (FM) features, and clinical data from a multicenter dataset. Methods: We analyzed CT scans and clinical data from 876 NSCLC patients (604 training, 272 test) across five centers. Features were extracted from the whole lung, tumor, mediastinal nodes, coronary arteries, and coronary artery calcium (CAC). Handcrafted radiomics and FM deep features were harmonized using ComBat, reconstruction kernel normalization (RKN), and RKN+ComBat. Regularized Cox models predicted overall survival; performance was assessed using the concordance index (C-index), 5-year time-dependent area under the curve (t-AUC), and hazard ratio (HR). SHapley Additive exPlanations (SHAP) values explained feature contributions. A consensus model used agreement across top region of interest (ROI) models to stratify patient risk. Results: TNM staging showed prognostic utility (C-index = 0.67; HR = 2.70; t-AUC = 0.85). The clinical + tumor radiomics model with ComBat achieved a C-index of 0.7552 and t-AUC of 0.8820. FM features (50-voxel cubes) combined with clinical data yielded the highest performance (C-index = 0.7616; t-AUC = 0.8866). An ensemble of all ROIs and FM features reached a C-index of 0.7142 and t-AUC of 0.7885. The consensus model, covering 78% of valid test cases, achieved a t-AUC of 0.92, sensitivity of 97.6%, and specificity of 66.7%. Conclusion: Harmonization and multi-region feature integration improve survival prediction in multicenter NSCLC data. Combining interpretable radiomics, FM features, and consensus modeling enables robust risk stratification across imaging centers.

Methodological Explainability Evaluation of an Interpretable Deep Learning Model for Post-Hepatectomy Liver Failure Prediction Incorporating Counterfactual Explanations and Layerwise Relevance Propagation: A Prospective In Silico Trial

Artificial intelligence (AI)-based decision support systems have demonstrated value in predicting post-hepatectomy liver failure (PHLF) in hepatocellular carcinoma (HCC). However, they often lack transparency, and the impact of model explanations on clinicians' decisions has not been thoroughly evaluated. Building on prior research, we developed a variational autoencoder-multilayer perceptron (VAE-MLP) model for preoperative PHLF prediction. This model integrated counterfactuals and layerwise relevance propagation (LRP) to provide insights into its decision-making mechanism. Additionally, we proposed a methodological framework for evaluating the explainability of AI systems. This framework includes qualitative and quantitative assessments of explanations against recognized biomarkers, usability evaluations, and an in silico clinical trial. Our evaluations demonstrated that the model's explanation correlated with established biomarkers and exhibited high usability at both the case and system levels. Furthermore, results from the three-track in silico clinical trial showed that clinicians' prediction accuracy and confidence increased when AI explanations were provided.

Counterfactuals and Uncertainty-Based Explainable Paradigm for the Automated Detection and Segmentation of Renal Cysts in Computed Tomography Images: A Multi-Center Study

Routine computed tomography (CT) scans often detect a wide range of renal cysts, some of which may be malignant. Early and precise localization of these cysts can significantly aid quantitative image analysis. Current segmentation methods, however, do not offer sufficient interpretability at the feature and pixel levels, emphasizing the necessity for an explainable framework that can detect and rectify model inaccuracies. We developed an interpretable segmentation framework and validated it on a multi-centric dataset. A Variational Autoencoder Generative Adversarial Network (VAE-GAN) was employed to learn the latent representation of 3D input patches and reconstruct input images. Modifications in the latent representation using the gradient of the segmentation model generated counterfactual explanations for varying dice similarity coefficients (DSC). Radiomics features extracted from these counterfactual images, using a ground truth cyst mask, were analyzed to determine their correlation with segmentation performance. The DSCs for the original and VAE-GAN reconstructed images for counterfactual image generation showed no significant differences. Counterfactual explanations highlighted how variations in cyst image features influence segmentation outcomes and showed model discrepancies. Radiomics features correlating positively and negatively with dice scores were identified. The uncertainty of the predicted segmentation masks was estimated using posterior sampling of the weight space. The combination of counterfactual explanations and uncertainty maps provided a deeper understanding of the image features within the segmented renal cysts that lead to high uncertainty. The proposed segmentation framework not only achieved high segmentation accuracy but also increased interpretability regarding how image features impact segmentation performance.

Precision-medicine-toolbox: An open-source python package for facilitation of quantitative medical imaging and radiomics analysis

Medical image analysis plays a key role in precision medicine as it allows the clinicians to identify anatomical abnormalities and it is routinely used in clinical assessment. Data curation and pre-processing of medical images are critical steps in the quantitative medical image analysis that can have a significant impact on the resulting model performance. In this paper, we introduce a precision-medicine-toolbox that allows researchers to perform data curation, image pre-processing and handcrafted radiomics extraction (via Pyradiomics) and feature exploration tasks with Python. With this open-source solution, we aim to address the data preparation and exploration problem, bridge the gap between the currently existing packages, and improve the reproducibility of quantitative medical imaging research.

Transparency of Deep Neural Networks for Medical Image Analysis: A Review of Interpretability Methods

Artificial Intelligence has emerged as a useful aid in numerous clinical applications for diagnosis and treatment decisions. Deep neural networks have shown same or better performance than clinicians in many tasks owing to the rapid increase in the available data and computational power. In order to conform to the principles of trustworthy AI, it is essential that the AI system be transparent, robust, fair and ensure accountability. Current deep neural solutions are referred to as black-boxes due to a lack of understanding of the specifics concerning the decision making process. Therefore, there is a need to ensure interpretability of deep neural networks before they can be incorporated in the routine clinical workflow. In this narrative review, we utilized systematic keyword searches and domain expertise to identify nine different types of interpretability methods that have been used for understanding deep learning models for medical image analysis applications based on the type of generated explanations and technical similarities. Furthermore, we report the progress made towards evaluating the explanations produced by various interpretability methods. Finally we discuss limitations, provide guidelines for using interpretability methods and future directions concerning the interpretability of deep neural networks for medical imaging analysis.

FUTURE-AI: Guiding Principles and Consensus Recommendations for Trustworthy Artificial Intelligence in Medical Imaging

The recent advancements in artificial intelligence (AI) combined with the extensive amount of data generated by today's clinical systems, has led to the development of imaging AI solutions across the whole value chain of medical imaging, including image reconstruction, medical image segmentation, image-based diagnosis and treatment planning. Notwithstanding the successes and future potential of AI in medical imaging, many stakeholders are concerned of the potential risks and ethical implications of imaging AI solutions, which are perceived as complex, opaque, and difficult to comprehend, utilise, and trust in critical clinical applications. Despite these concerns and risks, there are currently no concrete guidelines and best practices for guiding future AI developments in medical imaging towards increased trust, safety and adoption. To bridge this gap, this paper introduces a careful selection of guiding principles drawn from the accumulated experiences, consensus, and best practices from five large European projects on AI in Health Imaging. These guiding principles are named FUTURE-AI and its building blocks consist of (i) Fairness, (ii) Universality, (iii) Traceability, (iv) Usability, (v) Robustness and (vi) Explainability. In a step-by-step approach, these guidelines are further translated into a framework of concrete recommendations for specifying, developing, evaluating, and deploying technically, clinically and ethically trustworthy AI solutions into clinical practice.

Leveraging SLIC Superpixel Segmentation and Cascaded Ensemble SVM for Fully Automated Mass Detection In Mammograms

Identification and segmentation of breast masses in mammograms face complex challenges, owing to the highly variable nature of malignant densities with regards to their shape, contours, texture and orientation. Additionally, classifiers typically suffer from high class imbalance in region candidates, where normal tissue regions vastly outnumber malignant masses. This paper proposes a rigorous segmentation method, supported by morphological enhancement using grayscale linear filters. A novel cascaded ensemble of support vector machines (SVM) is used to effectively tackle the class imbalance and provide significant predictions. For True Positive Rate (TPR) of 0.35, 0.69 and 0.82, the system generates only 0.1, 0.5 and 1.0 False Positives/Image (FPI), respectively.

Multi-Resolution 3D Convolutional Neural Networks for Automatic Coronary Centerline Extraction in Cardiac CT Angiography Scans

We propose a deep learning-based automatic coronary artery tree centerline tracker (AuCoTrack) extending the vessel tracker by Wolterink (arXiv:1810.03143). A dual pathway Convolutional Neural Network (CNN) operating on multi-scale 3D inputs predicts the direction of the coronary arteries as well as the presence of a bifurcation. A similar multi-scale dual pathway 3D CNN is trained to identify coronary artery endpoints for terminating the tracking process. Two or more continuation directions are derived based on the bifurcation detection. The iterative tracker detects the entire left and right coronary artery trees based on only two ostium landmarks derived from a model-based segmentation of the heart. The 3D CNNs were trained on a proprietary dataset consisting of 43 CCTA scans. An average sensitivity of 87.1% and clinically relevant overlap of 89.1% was obtained relative to a refined manual segmentation. In addition, the MICCAI 2008 Coronary Artery Tracking Challenge (CAT08) training and test datasets were used to benchmark the algorithm and to assess its generalization. An average overlap of 93.6% and a clinically relevant overlap of 96.4% were obtained. The proposed method achieved better overlap scores than the current state-of-the-art automatic centerline extraction techniques on the CAT08 dataset with a vessel detection rate of 95%.