arXiv subjects

Jakob Nikolas Kather

Publications and source records attributed to Jakob Nikolas Kather.

At least 19 recordsLinked to original sources

arXiv2026

VIPER: An Expert-Curated Benchmark for Vision-Language Models in Veterinary Pathology

Pathology vision-language models are advancing rapidly, yet existing benchmarks remain focused on human tissue, particularly oncology, leaving non-human pathology largely unaddressed. This gap is especially important in toxicologic pathology, where microscopic tissue examination of laboratory animals is a core component of preclinical drug safety assessment. To address it, we introduce VIPER, the first expert-curated benchmark for vision-language model evaluation in toxicologic pathology. VIPER contains 1,251 questions associated with 419 H&E-stained rat histology images across seven organ systems, covering multiple-choice, KPrim, and free-text formats. All questions were curated and validated by board-certified veterinary pathologists. In total, we benchmarked 16 models, including two newly introduced veterinary-pathology models, seven human pathology-specialized models, and seven general-purpose frontier models. The results identify a substantial domain gap between veterinary and human pathology, expose the risk of over-diagnosis of normal tissue in frontier models, and show that domain-specific training remains critical for visually grounded predictions. VIPER data and evaluation code are available at https://github.com/mahmoodlab/viper.

cs.CV↗

arXiv2026

Self-supervision drives representational convergence in medical foundation models more than clinical supervision

Medical image encoders from different groups are increasingly treated as interchangeable, on the assumption that scale and clinical supervision concentrate their representations onto a shared structure. Whether this convergence is real, what produces it, and whether it is clinically usable are untested, and the similarity measures behind such claims are fragile. We present a controlled dissection across 18 image and 7 text encoders, all open-weight and run locally, spanning 7M to 27B parameters and five imaging modalities, including 650,982 chest radiographs from six datasets. To isolate cause, we train encoders that vary only the objective under fixed data, architecture, and scale, and reproduce the effect in a synthetic model. Convergence is modest but above a random floor, driven by the self-supervised objective, not clinical supervision: matched self-supervised encoders aligned most (40.4% on chest radiography), with label-supervised (21.1%) and image-text (3.3%) far lower, and did not grow with size (Spearman 0.302, p=0.223) or capability. It is within-modality, does not reach clinical language, and does not reproduce how radiologists judge case similarity. Yet a linear classifier transfers across encoders and to five held-out hospitals, retaining about 85% of within-encoder performance. Convergence in medical imaging is therefore set by the pretraining objective, not inherited from scale or clinical supervision. Interoperability is accordingly something to design for through that objective, and to validate where the shared geometry is weakest, across patient subgroups and against clinical judgment.

cs.CV↗

arXiv2026

Bayesian uncertainty estimation improves clinical decision making in medical AI agents

Machine learning models for medical image analysis typically lack a reliable measure of confidence, limiting their use in ambiguous or atypical cases. Here we show that Monte Carlo dropout, applied to a multi-task chest-radiograph classifier (eight thoracic findings, 137,593 training images), provides an epistemic uncertainty signal that tracks generalisation across training-set scales and flags confident yet error-prone predictions. Adding this signal to the point prediction raised error-detection AUROC from 0.74 to 0.77 ($Δ$AUROC +0.023, 95% CI [+0.014, +0.033]). In a controlled 2x2 factorial experiment, a clinical-decision-support agent exploited this uncertainty only when it was delivered as a binary error-risk flag rather than as raw scores, cutting confident misdiagnoses on unreliable findings from 8.5% to 2.7%. Epistemic uncertainty estimation thus carries decision-relevant information beyond point predictions, but its value for downstream agents depends on how it is communicated.

cs.LG↗

arXiv2026

Foundation-model-guided radiogenomic discovery linking cancer genomes to cancer scans

The function of many genes is still unknown, and conventional driver-discovery methods, which rely on how frequently a gene is mutated, cannot assess genes that are only rarely affected. Here we pair Evo~2-based genome analysis with routine clinical imaging to identify gene--phenotype associations at genome-wide scale. For every somatic mutation across three TCGA cohorts (cRCC=clear cell renal cell carcinoma, HCC=hepatocellular carcinoma, and BC=breast cancer; $n = 340$ total), Evo~2 predicts a severity score, with no task-specific training. Per-gene severity summaries are then correlated with radiomic features extracted from paired tumor segmentations, controlling for total mutation burden. In TCGA-cRCC ($n = 162$), this sweep recovers established renal-cancer drivers and identifies 46 additional genes reaching false discovery rate (FDR) significance absent from curated cancer-gene panels, several of which are Mendelian ciliopathy and cytoskeletal-disease genes. These results demonstrate that pairing a genomic language model with widely available clinical imaging can serve as a hypothesis-free discovery tool for gene--imaging associations invisible to conventional approaches.

q-bio.GN↗

arXiv2026

Multi-Teacher Contrastive Distillation for Edge-Efficient Pathology Foundation Models

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.

cs.CV↗

arXiv2026

From Clinical Intent to Clinical Model: Autonomous Coding-Agents for Clinician-driven AI Development

Developing AI models that are useful in clinical practice, requires efficient collaboration between clinicians and AI developers. This poses a practical challenge: clinicians must repeatedly communicate and refine their requirements with AI developers before those requirements can be translated into executable model development. This iterative process is time-consuming, and even after repeated discussion, misalignment may still exist because the two sides do not fully share each other's expertise. Coding agents may help close this gap. They can write and refine code on their own, and they carry working knowledge of both medicine and AI to understand commands formulated by both medical experts and developers. We present a prototype that lets clinicians drive AI development directly. A clinician describes the task in plain language, and the system turns the description into a working pipeline, refines it through repeated experiments together with the clinician, and returns a model that meets the stated clinical objective. Across five clinical tasks, the system reliably produces models that matched the clinician's request and reached competitive performance. Most notably, on chest radiographs the system sharply reduced the model's reliance on chest drains, a well-known shortcut for pneumothorax classification, from 60% to 31% on one dataset and from 50% to 18% on another. Our results suggest that coding agents can shift clinical AI development toward a more clinician-driven mode, allowing domain experts to shape models directly instead of relaying requirements through specialized AI teams.

cs.CV↗

arXiv2026

A European Multi-Center Breast Cancer MRI Dataset

Early detection of breast cancer is critical for improving patient outcomes. While mammography remains the primary screening modality, magnetic resonance imaging (MRI) is increasingly recommended as a supplemental tool for women with dense breast tissue and those at elevated risk. However, the acquisition and interpretation of multiparametric breast MRI are time-consuming and require specialized expertise, limiting scalability in clinical practice. Artificial intelligence (AI) methods have shown promise in supporting breast MRI interpretation, but their development is hindered by the limited availability of large, diverse, and publicly accessible datasets. To address this gap, we present a publicly available, multi-centre breast MRI dataset collected across six clinical institutions in five European countries. The dataset comprises 741 examinations from women undergoing screening or diagnostic breast MRI and includes malignant, benign, and non-lesion cases. Data were acquired using heterogeneous scanners, field strengths, and acquisition protocols, reflecting real-world clinical variability. In addition, we report baseline benchmark experiments using a transformer-based model to illustrate potential use cases of the dataset and to provide reference performance for future methodological comparisons.

eess.IV↗

arXiv2026

Quantifying the human visual exposome with vision language models

The visual environment is a fundamental yet unquantified determinant of mental health. While the concept of the environmental exposome is well established, current methods rely on coarse geospatial proxies or biased self reports, failing to capture the first person visual context of daily life. We addressed this gap by coupling ecological momentary assessment with vision language models (VLMs) to quantify the semantic richness of human visual experience. Across 2674 participant generated photographs, VLM derived estimates of greenness robustly predicted momentary affect and chronic stress, consistent with established benchmarks. We then developed a semi autonomous large language model (LLM) based pipeline that mined over seven million scientific publications to extract nearly 1000 environmental features empirically linked to mental health. When applied to real world imagery, up to 33 percent of VLM extracted context ratings significantly correlated with affect and stress. These findings establish a scalable objective paradigm for visual exposomics, enabling high throughput decoding of how the visible world is associated with mental health.

cs.AI↗

arXiv2026

Resolution scaling governs DINOv3 transfer performance in chest radiograph classification

Self-supervised learning (SSL) has improved visual representation learning, but its value in chest radiography remains uncertain. DINOv3 extends earlier SSL models through Gram-anchored self-distillation and explicit high-resolution adaptation. Whether these changes improve transfer learning for chest radiograph classification has not been established. We benchmarked DINOv3 against DINOv2 and supervised ImageNet initialization across seven chest radiograph datasets comprising 816,183 radiographs from pediatric and adult cohorts. ViT-B/16 and ConvNeXt-B were evaluated under full fine-tuning at 224 and 512 pixels, with targeted 1024 experiments on three cohorts. Additional analyses examined parameter-efficient adaptation, synthetic label corruption, external validation, frozen 7B features, and computational efficiency. The primary outcome was mean AUROC across labels. In adult cohorts, DINOv3 did not consistently outperform DINOv2 at 224 x 224 pixels, but became the strongest initialization at 512 x 512, especially with ConvNeXt-B. Gains were greatest for small focal and boundary-dependent abnormalities, whereas large-structure findings changed little. The pediatric cohort showed no significant benefit from DINOv3, higher resolution, or backbone choice. Scaling to 1024 x 1024 rarely improved performance and markedly increased computational cost. ConvNeXt-B remained superior to ViT-B/16 under both full and parameter-efficient adaptation. External validation preserved the 512 x 512 DINOv3 advantage, whereas synthetic label corruption showed that this benefit should not be interpreted simply as superior noise robustness. For adult chest radiograph classification, DINOv3 provides its most reliable benefit at 512 x 512 pixels, particularly with ConvNeXt-B. Fully adapted mid-sized models at 512 x 512 pixels provided the best performance-cost trade-off in our benchmark.

cs.CV↗

arXiv2026

Class Visualizations and Activation Atlases for Enhancing Interpretability in Deep Learning-Based Computational Pathology

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.

cs.CV↗

arXiv2026

Hallucination Filtering in Radiology Vision-Language Models Using Discrete Semantic Entropy

To determine whether using discrete semantic entropy (DSE) to reject questions likely to generate hallucinations can improve the accuracy of black-box vision-language models (VLMs) in radiologic image based visual question answering (VQA). This retrospective study evaluated DSE using two publicly available, de-identified datasets: the VQA-Med 2019 benchmark (500 images with clinical questions and short-text answers) and a diagnostic radiology dataset (206 cases: 60 computed tomography scans, 60 magnetic resonance images, 60 radiographs, 26 angiograms) with corresponding ground-truth diagnoses. GPT-4o and GPT-4.1 (Generative Pretrained Transformer; OpenAI) answered each question 15 times using a temperature of 1.0. Baseline accuracy was determined using low-temperature answers (temperature 0.1). Meaning-equivalent responses were grouped using bidirectional entailment checks, and DSE was computed from the relative frequencies of the resulting semantic clusters. Accuracy was recalculated after excluding questions with DSE > 0.6 or > 0.3. p-values and 95% confidence intervals were obtained using bootstrap resampling and a Bonferroni-corrected threshold of p < .004 for statistical significance. Across 706 image-question pairs, baseline accuracy was 51.7% for GPT-4o and 54.8% for GPT-4.1. After filtering out high-entropy questions (DSE > 0.3), accuracy on the remaining questions was 76.3% (retained questions: 334/706) for GPT-4o and 63.8% (retained questions: 499/706) for GPT-4.1 (both p < .001). Accuracy gains were observed across both datasets and largely remained statistically significant after Bonferroni correction. DSE enables reliable hallucination detection in black-box VLMs by quantifying semantic inconsistency. This method significantly improves diagnostic answer accuracy and offers a filtering strategy for clinical VLM applications.

cs.CV↗

arXiv2026

MedicalPatchNet: A Patch-Based Self-Explainable AI Architecture for Chest X-ray Classification

Deep neural networks excel in radiological image classification but frequently suffer from poor interpretability, limiting clinical acceptance. We present MedicalPatchNet, an inherently self-explainable architecture for chest X-ray classification that transparently attributes decisions to distinct image regions. MedicalPatchNet splits images into non-overlapping patches, independently classifies each patch, and aggregates predictions, enabling intuitive visualization of each patch's diagnostic contribution without post-hoc techniques. Trained on the CheXpert dataset (223,414 images), MedicalPatchNet matches the classification performance (AUROC 0.907 vs. 0.908) of EfficientNetV2-S, while improving interpretability: MedicalPatchNet demonstrates improved interpretability with higher pathology localization accuracy (mean hit-rate 0.485 vs. 0.376 with Grad-CAM) on the CheXlocalize dataset. By providing explicit, reliable explanations accessible even to non-AI experts, MedicalPatchNet mitigates risks associated with shortcut learning, thus improving clinical trust. Our model is publicly available with reproducible training and inference scripts and contributes to safer, explainable AI-assisted diagnostics across medical imaging domains. We make the code publicly available: https://github.com/TruhnLab/MedicalPatchNet

cs.CV↗

arXiv2026

A deep learning framework for efficient pathology image analysis

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 43 tasks from nine cancer types, spanning morphology, biomarker prediction, treatment response and prognosis. EAGLE outperformed state-of-the-art patch aggregation methods 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 rapid review of the exact tiles used for each prediction, and reduces dependence on high-performance computing, making AI-powered pathology more accessible. By reliably identifying meaningful regions and minimizing artifacts, EAGLE provides robust and auditable outputs, supported by systematic negative controls and attention concentration analyses. Its unified embedding enables rapid slide searches, integration into multi-omics pipelines and emerging clinical foundation models.

cs.CV↗

arXiv2026

HistoPrism: Unlocking Functional Pathway Analysis from Pan-Cancer Histology via Gene Expression Prediction

Predicting spatial gene expression from H&E histology offers a scalable and clinically accessible alternative to sequencing, but realizing clinical impact requires models that generalize across cancer types and capture biologically coherent signals. Prior work is often limited to per-cancer settings and variance-based evaluation, leaving functional relevance underexplored. We introduce HistoPrism, an efficient transformer-based architecture for pan-cancer prediction of gene expression from histology. To evaluate biological meaning, we introduce a pathway-level benchmark, shifting assessment from isolated gene-level variance to coherent functional pathways. HistoPrism not only surpasses prior state-of-the-art models on highly variable genes , but also more importantly, achieves substantial gains on pathway-level prediction, demonstrating its ability to recover biologically coherent transcriptomic patterns. With strong pan-cancer generalization and improved efficiency, HistoPrism establishes a new standard for clinically relevant transcriptomic modeling from routinely available histology.

cs.LG↗

arXiv2025

Gut decisions based on the liver: A radiomics approach to boost colorectal cancer screening

Non-invasive colorectal cancer (CRC) screening represents a key opportunity to improve colonoscopy participation rates and reduce CRC mortality. This study explores the potential of the gut-liver axis for predicting colorectal neoplasia through liver-derived radiomic features extracted from routine CT images as a novel opportunistic screening approach. In this retrospective study, we analyzed data from 1,997 patients who underwent colonoscopy and abdominal CT. Patients either had no colorectal neoplasia (n=1,189) or colorectal neoplasia (n_total=808; adenomas n=423, CRC n=385). Radiomics features were extracted from 3D liver segmentations using the Radiomics Processing ToolKit (RPTK), which performed feature extraction, filtering, and classification. The dataset was split into training (n=1,397) and test (n=600) cohorts. Five machine learning models were trained with 5-fold cross-validation on the 20 most informative features, and the best model ensemble was selected based on the validation AUROC. The best radiomics-based XGBoost model achieved a test AUROC of 0.810, clearly outperforming the best clinical-only model (test AUROC: 0.457). Subclassification between colorectal cancer and adenoma showed lower accuracy (test AUROC: 0.674). Our findings establish proof-of-concept that liver-derived radiomics from routine abdominal CT can predict colorectal neoplasia. Beyond offering a pragmatic, widely accessible adjunct to CRC screening, this approach highlights the gut-liver axis as a novel biomarker source for opportunistic screening and sparks new mechanistic hypotheses for future translational research.

q-bio.QM↗

arXiv2025

Agentic Systems in Radiology: Design, Applications, Evaluation, and Challenges

Building agents, systems that perceive and act upon their environment with a degree of autonomy, has long been a focus of AI research. This pursuit has recently become vastly more practical with the emergence of large language models (LLMs) capable of using natural language to integrate information, follow instructions, and perform forms of "reasoning" and planning across a wide range of tasks. With its multimodal data streams and orchestrated workflows spanning multiple systems, radiology is uniquely suited to benefit from agents that can adapt to context and automate repetitive yet complex tasks. In radiology, LLMs and their multimodal variants have already demonstrated promising performance for individual tasks such as information extraction and report summarization. However, using LLMs in isolation underutilizes their potential to support complex, multi-step workflows where decisions depend on evolving context from multiple information sources. Equipping LLMs with external tools and feedback mechanisms enables them to drive systems that exhibit a spectrum of autonomy, ranging from semi-automated workflows to more adaptive agents capable of managing complex processes. This review examines the design of such LLM-driven agentic systems, highlights key applications, discusses evaluation methods for planning and tool use, and outlines challenges such as error cascades, tool-use efficiency, and health IT integration.

cs.AI↗

arXiv2025

Diagnostic Accuracy of Open-Source Vision-Language Models on Diverse Medical Imaging Tasks

This retrospective study evaluated five VLMs (Qwen2.5, Phi-4, Gemma3, Llama3.2, and Mistral3.1) using the MedFMC dataset. This dataset includes 22,349 images from 7,461 patients encompassing chest radiography (19 disease multi-label classifications), colon pathology (tumor detection), endoscopy (colorectal lesion identification), neonatal jaundice assessment (skin color-based treatment necessity), and retinal fundoscopy (5-point diabetic retinopathy grading). Diagnostic accuracy was compared in three experimental settings: visual input only, multimodal input, and chain-of-thought reasoning. Model accuracy was assessed against ground truth labels, with statistical comparisons using bootstrapped confidence intervals (p<.05). Qwen2.5 achieved the highest accuracy for chest radiographs (90.4%) and endoscopy images (84.2%), significantly outperforming the other models (p<.001). In colon pathology, Qwen2.5 (69.0%) and Phi-4 (69.6%) performed comparably (p=.41), both significantly exceeding other VLMs (p<.001). Similarly, for neonatal jaundice assessment, Qwen2.5 (58.3%) and Phi-4 (58.1%) showed comparable leading accuracies (p=.93) significantly exceeding their counterparts (p<.001). All models struggled with retinal fundoscopy; Qwen2.5 and Gemma3 achieved the highest, albeit modest, accuracies at 18.6% (comparable, p=.99), significantly better than other tested models (p<.001). Unexpectedly, multimodal input reduced accuracy for some models and modalities, and chain-of-thought reasoning prompts also failed to improve accuracy. The open-source VLMs demonstrated promising diagnostic capabilities, particularly in chest radiograph interpretation. However, performance in complex domains such as retinal fundoscopy was limited, underscoring the need for further development and domain-specific adaptation before widespread clinical application.

eess.IV↗

arXiv2025

Three-dimensional end-to-end deep learning for brain MRI analysis

Deep learning (DL) methods are increasingly outperforming classical approaches in brain imaging, yet their generalizability across diverse imaging cohorts remains inadequately assessed. As age and sex are key neurobiological markers in clinical neuroscience, influencing brain structure and disease risk, this study evaluates three of the existing three-dimensional architectures, namely Simple Fully Connected Network (SFCN), DenseNet, and Shifted Window (Swin) Transformers, for age and sex prediction using T1-weighted MRI from four independent cohorts: UK Biobank (UKB, n=47,390), Dallas Lifespan Brain Study (DLBS, n=132), Parkinson's Progression Markers Initiative (PPMI, n=108 healthy controls), and Information eXtraction from Images (IXI, n=319). We found that SFCN consistently outperformed more complex architectures with AUC of 1.00 [1.00-1.00] in UKB (internal test set) and 0.85-0.91 in external test sets for sex classification. For the age prediction task, SFCN demonstrated a mean absolute error (MAE) of 2.66 (r=0.89) in UKB and 4.98-5.81 (r=0.55-0.70) across external datasets. Pairwise DeLong and Wilcoxon signed-rank tests with Bonferroni corrections confirmed SFCN's superiority over Swin Transformer across most cohorts (p<0.017, for three comparisons). Explainability analysis further demonstrates the regional consistency of model attention across cohorts and specific to each task. Our findings reveal that simpler convolutional networks outperform the denser and more complex attention-based DL architectures in brain image analysis by demonstrating better generalizability across different datasets.

cs.CV↗