Marco Gustav

Tim Lenz, Maurice Heide, Marco Gustav et al.

Computational pathology foundation models (PFMs) have advanced whole-slide image analysis. However, their size and inference cost hinder local deployment in pathology departments. We propose MuCoDi, a pretraining framework that distills frozen tile embeddings from multiple PFMs into compact edge-oriented encoders. Instead of regressing individual teacher features, MuCoDi trains lightweight MobileOne and RepViT students with a contrastive distillation objective adapted from MoCo v3, where cached Virchow2, UNI2, and H-Optimus-1 embeddings replace momentum-encoder keys. We pretrain students on 14.3M TCGA tiles from only 11.8K WSIs and evaluate frozen encoders on 23 clinically curated downstream classification tasks. RepViT-based MuCoEdge students retain near-teacher performance while reducing model size by orders of magnitude: MuCoEdge-R2.3 and MuCoEdge-R1.5 reach 71.0% external AUROC, within 0.8 percentage points of the best teacher (Virchow2, 71.8%), while MuCoEdge-R2.3 obtains the best external F1 and the second-best AUPRC (51.8% and 53.3%). MuCoEdge-R1.0 reaches 70.9% AUROC with only 6.4M parameters and 1.12 GFLOPs. On a Raspberry Pi 5, sub-million-parameter MobileOne students achieve up to 605-fold single-tile speedup over Virchow2 while retaining 66.5% to 66.9% external AUROC, demonstrating that PFM-quality pathology representations can be moved toward practical edge deployment. Code is available at https://anonymous.4open.science/r/mucodi-6243.

Peter Neidlinger, Tim Lenz, Sebastian Foersch et al.

Artificial intelligence (AI) has transformed digital pathology by enabling biomarker prediction from high-resolution whole slide images (WSIs). However, current methods are computationally inefficient, processing thousands of redundant tiles per WSI and requiring complex aggregator models. We introduce EAGLE (Efficient Approach for Guided Local Examination), a deep learning framework that emulates pathologists by selectively analyzing informative regions. EAGLE incorporates two foundation models: CHIEF for efficient tile selection and Virchow2 for extracting high-quality features. Benchmarking was conducted against leading slide- and tile-level foundation models across 31 tasks from four cancer types, spanning morphology, biomarker prediction and prognosis. EAGLE outperformed state-of-the-art foundation models by up to 23% and achieved the highest AUROC overall. It processed a slide in 2.27 seconds, reducing computational time by more than 99% compared to existing models. This efficiency enables real-time workflows, allows pathologists to validate all tiles which are used by the model during analysis, and eliminates dependence on high-performance computing, making AI-powered pathology more accessible. By reliably identifying meaningful regions and minimizing artifacts, EAGLE provides robust and interpretable outputs, supporting rapid slide searches, integration into multi-omics pipelines and emerging clinical foundation models.

Marco Gustav, Fabian Wolf, Christina Glasner et al.

The rapid adoption of transformer-based models in computational pathology has enabled prediction of molecular and clinical biomarkers from H&E whole-slide images, yet interpretability has not kept pace with model complexity. While attribution- and generative-based methods are common, feature visualization approaches such as class visualizations (CVs) and activation atlases (AAs) have not been systematically evaluated for these models. We developed a visualization framework and assessed CVs and AAs for a transformer-based foundation model across tissue and multi-organ cancer classification tasks with increasing label granularity. Four pathologists annotated real and generated images to quantify inter-observer agreement, complemented by attribution and similarity metrics. CVs preserved recognizability for morphologically distinct tissues but showed reduced separability for overlapping cancer subclasses. In tissue classification, agreement decreased from Fleiss k = 0.75 (scans) to k = 0.31 (CVs), with similar trends in cancer subclass tasks. AAs revealed layer-dependent organization: coarse tissue-level concepts formed coherent regions, whereas finer subclasses exhibited dispersion and overlap. Agreement was moderate for tissue classification (k = 0.58), high for coarse cancer groupings (k = 0.82), and low at subclass level (k = 0.11). Atlas separability closely tracked expert agreement on real images, indicating that representational ambiguity reflects intrinsic pathological complexity. Attribution-based metrics approximated expert variability in low-complexity settings, whereas perceptual and distributional metrics showed limited alignment. Overall, concept-level feature visualization reveals structured morphological manifolds in transformer-based pathology models and provides a framework for expert-centered interrogation of learned representations across label granularities.