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.

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.

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.