arXiv subjects

Jeroen van der Laak

Publications and source records attributed to Jeroen van der Laak.

At least 19 recordsLinked to original sources

arXiv2026

Designing UNICORN: a Unified Benchmark for Imaging in Computational Pathology, Radiology, and Natural Language

Foundation models are changing the way we develop medical artificial intelligence. By learning broadly generalizable features across diverse data modalities, a single model can be rapidly adapted to address multiple modalities and tasks with minimal supervision. This potential comes with the urgent need to reliably benchmark, understand and compare the performance and clinical impact of foundation models across data modalities and clinical tasks. We introduce UNICORN, a fundamentally new benchmarking concept for medical foundation models. UNICORN brings four main contributions to medical artificial intelligence. First, a framework that enables a one-to-many benchmarking approach, where a single foundation model is tested across multiple tasks and data modalities. Here, we populate it with 20 tasks across radiology, pathology, and clinical text, covering classification, detection, segmentation, regression, and vision-language generation. Second, a publicly available evaluation platform that implements, for the first time, a two-step approach to run foundation models for data encoding followed by custom task-specific adaptation via few-shot learning and linear probing mechanisms. Third, we create a meta-model that combines state-of-the-art foundation models in pathology, radiology and language with novel task-specific adapters that address all UNICORN tasks, which we refer to as Unicorn Model-0 (UM-0). Finally, we design a novel UNICORN score to benchmark and compare model performance across all tasks. We present the results of UM-0 using sequestered test data from over 2,400 patients, 3,700 vision cases, and 2,400 clinical reports from 17 institutions across eight countries, spanning eight anatomical regions and four imaging modalities. Data, baselines, and evaluation platform are publicly accessible at unicorn.grand-challenge.org.

cs.CV↗

arXiv2026

A Distributional Robustness Margin For Pathology Foundation Models

Pathology foundation models encode non-biological variation introduced by tissue preparation, staining and scanning, enabling shortcut learning that undermines generalisation across institutions. The Robustness Index (RI) was proposed to assess whether local representation geometry is dominated by biological or non-biological variation. However, its construction suffers from structural limitations that make cross-model comparison unreliable, calling for a more principled metric. We introduce the Cross-confounder Robustness Margin (CRoMa), a signed, per-sample margin that measures whether samples sharing the same biology but different confounder lie closer than samples sharing the same confounder but different biology. It is defined for every sample, allowing models to be compared on the same cohort and robustness to be analysed as a distribution rather than reduced to a single pooled score. We evaluated CRoMa across 20 tile-level encoders on three benchmarks. Rankings by median CRoMa were highly consistent across benchmarks (Spearman rho ~ 0.90), yet every encoder retained confounder-dominated samples, whose prevalence and severity varied markedly. Similar patterns emerged for four slide-level encoders evaluated on a separate benchmark, extending the analysis beyond tile-level representations. Higher median CRoMa was associated with smaller shortcut-induced performance losses in downstream linear probes, supporting its use as a representation-level indicator of shortcut susceptibility.

cs.CV↗

arXiv2026

DALPHIN: Benchmarking Digital Pathology AI Copilots Against Pathologists on an Open Multicentric Dataset

Foundation models with visual question answering capabilities for digital pathology are emerging. Such unprecedented technology requires independent benchmarking to assess its potential in assisting pathologists in routine diagnostics. We created DALPHIN, the first multicentric open benchmark for pathology AI copilots, comprising 1236 images from 300 cases, spanning 130 rare to common diagnoses, 6 countries, and 14 subspecialties. The DALPHIN design and dataset are introduced alongside a human performance benchmark of 31 pathologists from 10 countries with varying expertise. We report results for two general-purpose (GPT-5, Gemini 2.5 Pro) and one pathology-specific copilot (PathChat+) for sequential and independent answer generation. We observed no statistically significant difference from expert-level performance in four of six tasks for PathChat, 2/6 tasks for Gemini, and 1/6 tasks for GPT. DALPHIN is publicly released with sequestered, indirectly accessible ground truth to foster robust and enduring benchmarking. Data, methods, and the evaluation platform are accessible through dalphin.grand-challenge.org.

cs.CV↗

arXiv2026

Democratising Pathology Co-Pilots: An Open Pipeline and Dataset for Whole-Slide Vision-Language Modelling

Vision-language models (VLMs) have the potential to become co-pilots for pathologists. However, most VLMs either focus on small regions of interest within whole-slide images, provide only static slide-level outputs, or rely on data that is not publicly available, limiting reproducibility. Furthermore, training data containing WSIs paired with detailed clinical reports is scarce, restricting progress toward transparent and generalisable VLMs. We address these limitations with three main contributions. First, we introduce Polysome, a standardised tool for synthetic instruction generation. Second, we apply Polysome to the public HISTAI dataset, generating HISTAI-Instruct, a large whole-slide instruction tuning dataset spanning 24,259 slides and over 1.1 million instruction-response pairs. Finally, we use HISTAI-Instruct to train ANTONI-α, a VLM capable of visual-question answering (VQA). We show that ANTONI-α outperforms MedGemma on WSI-level VQA tasks of tissue identification, neoplasm detection, and differential diagnosis. We also compare the performance of multiple incarnations of ANTONI-α trained with different amounts of data. All methods, data, and code are publicly available.

cs.CV↗

arXiv2026

Deep Learning From Routine Histology Improves Risk Stratification for Biochemical Recurrence in Prostate Cancer

Accurate prediction of biochemical recurrence (BCR) after radical prostatectomy is critical for guiding adjuvant treatment and surveillance decisions in prostate cancer. However, existing clinicopathological risk models reduce complex morphology to relatively coarse descriptors, leaving substantial prognostic information embedded in routine histopathology underexplored. We present a deep learning-based biomarker that predicts continuous, patient-specific risk of BCR directly from H&E-stained whole-slide prostatectomy specimens. Trained end-to-end on time-to-event outcomes and evaluated across four independent international cohorts, our model demonstrates robust generalization across institutions and patient populations. When integrated with the CAPRA-S clinical risk score, the deep learning risk score consistently improved discrimination for BCR, increasing concordance indices from 0.725-0.772 to 0.749-0.788 across cohorts. To support clinical interpretability, outcome-grounded analyses revealed subtle histomorphological patterns associated with recurrence risk that are not captured by conventional clinicopathological risk scores. This multicohort study demonstrates that deep learning applied to routine prostate histopathology can deliver reproducible and clinically generalizable biomarkers that augment postoperative risk stratification, with potential to support personalized management of prostate cancer in real-world clinical settings.

cs.CV↗

arXiv2025

A Multicentric Dataset for Training and Benchmarking Breast Cancer Segmentation in H&E Slides

Automated semantic segmentation of whole-slide images (WSIs) stained with hematoxylin and eosin (H&E) is essential for large-scale artificial intelligence-based biomarker analysis in breast cancer. However, existing public datasets for breast cancer segmentation lack the morphological diversity needed to support model generalizability and robust biomarker validation across heterogeneous patient cohorts. We introduce BrEast cancEr hisTopathoLogy sEgmentation (BEETLE), a dataset for multiclass semantic segmentation of H&E-stained breast cancer WSIs. It consists of 587 biopsies and resections from three collaborating clinical centers and two public datasets, digitized using seven scanners, and covers all molecular subtypes and histological grades. Using diverse annotation strategies, we collected annotations across four classes - invasive epithelium, non-invasive epithelium, necrosis, and other - with particular focus on morphologies underrepresented in existing datasets, such as ductal carcinoma in situ and dispersed lobular tumor cells. The dataset's diversity and relevance to the rapidly growing field of automated biomarker quantification in breast cancer ensure its high potential for reuse. Finally, we provide a well-curated, multicentric external evaluation set to enable standardized benchmarking of breast cancer segmentation models.

q-bio.QM↗

arXiv2025

"No negatives needed": weakly-supervised regression for interpretable tumor detection in whole-slide histopathology images

Accurate tumor detection in digital pathology whole-slide images (WSIs) is crucial for cancer diagnosis and treatment planning. Multiple Instance Learning (MIL) has emerged as a widely used approach for weakly-supervised tumor detection with large-scale data without the need for manual annotations. However, traditional MIL methods often depend on classification tasks that require tumor-free cases as negative examples, which are challenging to obtain in real-world clinical workflows, especially for surgical resection specimens. We address this limitation by reformulating tumor detection as a regression task, estimating tumor percentages from WSIs, a clinically available target across multiple cancer types. In this paper, we provide an analysis of the proposed weakly-supervised regression framework by applying it to multiple organs, specimen types and clinical scenarios. We characterize the robustness of our framework to tumor percentage as a noisy regression target, and introduce a novel concept of amplification technique to improve tumor detection sensitivity when learning from small tumor regions. Finally, we provide interpretable insights into the model's predictions by analyzing visual attention and logit maps. Our code is available at https://github.com/DIAGNijmegen/tumor-percentage-mil-regression.

eess.IV↗

arXiv2024

Improving Quality Control of Whole Slide Images by Explicit Artifact Augmentation

The problem of artifacts in whole slide image acquisition, prevalent in both clinical workflows and research-oriented settings, necessitates human intervention and re-scanning. Overcoming this challenge requires developing quality control algorithms, that are hindered by the limited availability of relevant annotated data in histopathology. The manual annotation of ground-truth for artifact detection methods is expensive and time-consuming. This work addresses the issue by proposing a method dedicated to augmenting whole slide images with artifacts. The tool seamlessly generates and blends artifacts from an external library to a given histopathology dataset. The augmented datasets are then utilized to train artifact classification methods. The evaluation shows their usefulness in classification of the artifacts, where they show an improvement from 0.10 to 0.01 AUROC depending on the artifact type. The framework, model, weights, and ground-truth annotations are freely released to facilitate open science and reproducible research.

cs.CV↗

arXiv2024

Masked Attention as a Mechanism for Improving Interpretability of Vision Transformers

Vision Transformers are at the heart of the current surge of interest in foundation models for histopathology. They process images by breaking them into smaller patches following a regular grid, regardless of their content. Yet, not all parts of an image are equally relevant for its understanding. This is particularly true in computational pathology where background is completely non-informative and may introduce artefacts that could mislead predictions. To address this issue, we propose a novel method that explicitly masks background in Vision Transformers' attention mechanism. This ensures tokens corresponding to background patches do not contribute to the final image representation, thereby improving model robustness and interpretability. We validate our approach using prostate cancer grading from whole-slide images as a case study. Our results demonstrate that it achieves comparable performance with plain self-attention while providing more accurate and clinically meaningful attention heatmaps.

cs.CV↗

arXiv2024

Uncertainty-guided annotation enhances segmentation with the human-in-the-loop

Deep learning algorithms, often critiqued for their 'black box' nature, traditionally fall short in providing the necessary transparency for trusted clinical use. This challenge is particularly evident when such models are deployed in local hospitals, encountering out-of-domain distributions due to varying imaging techniques and patient-specific pathologies. Yet, this limitation offers a unique avenue for continual learning. The Uncertainty-Guided Annotation (UGA) framework introduces a human-in-the-loop approach, enabling AI to convey its uncertainties to clinicians, effectively acting as an automated quality control mechanism. UGA eases this interaction by quantifying uncertainty at the pixel level, thereby revealing the model's limitations and opening the door for clinician-guided corrections. We evaluated UGA on the Camelyon dataset for lymph node metastasis segmentation which revealed that UGA improved the Dice coefficient (DC), from 0.66 to 0.76 by adding 5 patches, and further to 0.84 with 10 patches. To foster broader application and community contribution, we have made our code accessible at

cs.CV↗

arXiv2023

Hierarchical Vision Transformers for Context-Aware Prostate Cancer Grading in Whole Slide Images

Vision Transformers (ViTs) have ushered in a new era in computer vision, showcasing unparalleled performance in many challenging tasks. However, their practical deployment in computational pathology has largely been constrained by the sheer size of whole slide images (WSIs), which result in lengthy input sequences. Transformers faced a similar limitation when applied to long documents, and Hierarchical Transformers were introduced to circumvent it. Given the analogous challenge with WSIs and their inherent hierarchical structure, Hierarchical Vision Transformers (H-ViTs) emerge as a promising solution in computational pathology. This work delves into the capabilities of H-ViTs, evaluating their efficiency for prostate cancer grading in WSIs. Our results show that they achieve competitive performance against existing state-of-the-art solutions.

cs.CV↗

arXiv2023

LYSTO: The Lymphocyte Assessment Hackathon and Benchmark Dataset

We introduce LYSTO, the Lymphocyte Assessment Hackathon, which was held in conjunction with the MICCAI 2019 Conference in Shenzen (China). The competition required participants to automatically assess the number of lymphocytes, in particular T-cells, in histopathological images of colon, breast, and prostate cancer stained with CD3 and CD8 immunohistochemistry. Differently from other challenges setup in medical image analysis, LYSTO participants were solely given a few hours to address this problem. In this paper, we describe the goal and the multi-phase organization of the hackathon; we describe the proposed methods and the on-site results. Additionally, we present post-competition results where we show how the presented methods perform on an independent set of lung cancer slides, which was not part of the initial competition, as well as a comparison on lymphocyte assessment between presented methods and a panel of pathologists. We show that some of the participants were capable to achieve pathologist-level performance at lymphocyte assessment. After the hackathon, LYSTO was left as a lightweight plug-and-play benchmark dataset on grand-challenge website, together with an automatic evaluation platform. LYSTO has supported a number of research in lymphocyte assessment in oncology. LYSTO will be a long-lasting educational challenge for deep learning and digital pathology, it is available at https://lysto.grand-challenge.org/.

eess.IV↗

arXiv2022

Comparison of Consecutive and Re-stained Sections for Image Registration in Histopathology

Purpose: In digital histopathology, virtual multi-staining is important for diagnosis and biomarker research. Additionally, it provides accurate ground-truth for various deep-learning tasks. Virtual multi-staining can be obtained using different stains for consecutive sections or by re-staining the same section. Both approaches require image registration to compensate tissue deformations, but little attention has been devoted to comparing their accuracy. Approach: We compare variational image registration of consecutive and re-stained sections and analyze the effect of the image resolution which influences accuracy and required computational resources. We present a new hybrid dataset of re-stained and consecutive sections (HyReCo, 81 slide pairs, approx. 3000 landmarks) that we made publicly available and compare its image registration results to the automatic non-rigid histological image registration (ANHIR) challenge data (230 consecutive slide pairs). Results: We obtain a median landmark error after registration of 7.1 μm (HyReCo) and 16.0 μm (ANHIR) between consecutive sections. Between re-stained sections, the median registration error is 2.3 μm and 0.9 μm in the two subsets of the HyReCo dataset. We observe that deformable registration leads to lower landmark errors than affine registration in both cases, though the effect is smaller in re-stained sections. Conclusion: Deformable registration of consecutive and re-stained sections is a valuable tool for the joint analysis of different stains. Significance: While the registration of re-stained sections allows nucleus-level alignment which allows for a direct analysis of interacting biomarkers, consecutive sections only allow the transfer of region-level annotations. The latter can be achieved at low computational cost using coarser image resolutions.

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arXiv2022

Domain adaptation strategies for cancer-independent detection of lymph node metastases

Recently, large, high-quality public datasets have led to the development of convolutional neural networks that can detect lymph node metastases of breast cancer at the level of expert pathologists. Many cancers, regardless of the site of origin, can metastasize to lymph nodes. However, collecting and annotating high-volume, high-quality datasets for every cancer type is challenging. In this paper we investigate how to leverage existing high-quality datasets most efficiently in multi-task settings for closely related tasks. Specifically, we will explore different training and domain adaptation strategies, including prevention of catastrophic forgetting, for colon and head-and-neck cancer metastasis detection in lymph nodes. Our results show state-of-the-art performance on both cancer metastasis detection tasks. Furthermore, we show the effectiveness of repeated adaptation of networks from one cancer type to another to obtain multi-task metastasis detection networks. Last, we show that leveraging existing high-quality datasets can significantly boost performance on new target tasks and that catastrophic forgetting can be effectively mitigated using regularization.

eess.IV↗

arXiv2021

Automated risk classification of colon biopsies based on semantic segmentation of histopathology images

Artificial Intelligence (AI) can potentially support histopathologists in the diagnosis of a broad spectrum of cancer types. In colorectal cancer (CRC), AI can alleviate the laborious task of characterization and reporting on resected biopsies, including polyps, the numbers of which are increasing as a result of CRC population screening programs, ongoing in many countries all around the globe. Here, we present an approach to address two major challenges in automated assessment of CRC histopathology whole-slide images. First, we present an AI-based method to segment multiple tissue compartments in the H\&E-stained whole-slide image, which provides a different, more perceptible picture of tissue morphology and composition. We test and compare a panel of state-of-the-art loss functions available for segmentation models, and provide indications about their use in histopathology image segmentation, based on the analysis of a) a multi-centric cohort of CRC cases from five medical centers in the Netherlands and Germany, and b) two publicly available datasets on segmentation in CRC. Second, we use the best performing AI model as the basis for a computer-aided diagnosis system (CAD) that classifies colon biopsies into four main categories that are relevant pathologically. We report the performance of this system on an independent cohort of more than 1,000 patients. The results show the potential of such an AI-based system to assist pathologists in diagnosis of CRC in the context of population screening. We have made the segmentation model available for research use on https://grand-challenge.org/algorithms/colon-tissue-segmentation/.

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arXiv2020

Automated Scoring of Nuclear Pleomorphism Spectrum with Pathologist-level Performance in Breast Cancer

Nuclear pleomorphism, defined herein as the extent of abnormalities in the overall appearance of tumor nuclei, is one of the components of the three-tiered breast cancer grading. Given that nuclear pleomorphism reflects a continuous spectrum of variation, we trained a deep neural network on a large variety of tumor regions from the collective knowledge of several pathologists, without constraining the network to the traditional three-category classification. We also motivate an additional approach in which we discuss the additional benefit of normal epithelium as baseline, following the routine clinical practice where pathologists are trained to score nuclear pleomorphism in tumor, having the normal breast epithelium for comparison. In multiple experiments, our fully-automated approach could achieve top pathologist-level performance in select regions of interest as well as at whole slide images, compared to ten and four pathologists, respectively.

eess.IV↗

arXiv2020

HookNet: multi-resolution convolutional neural networks for semantic segmentation in histopathology whole-slide images

We propose HookNet, a semantic segmentation model for histopathology whole-slide images, which combines context and details via multiple branches of encoder-decoder convolutional neural networks. Concentricpatches at multiple resolutions with different fields of view are used to feed different branches of HookNet, and intermediate representations are combined via a hooking mechanism. We describe a framework to design and train HookNet for achieving high-resolution semantic segmentation and introduce constraints to guarantee pixel-wise alignment in feature maps during hooking. We show the advantages of using HookNet in two histopathology image segmentation tasks where tissue type prediction accuracy strongly depends on contextual information, namely (1) multi-class tissue segmentation in breast cancer and, (2) segmentation of tertiary lymphoid structures and germinal centers in lung cancer. Weshow the superiority of HookNet when compared with single-resolution U-Net models working at different resolutions as well as with a recently published multi-resolution model for histopathology image segmentation

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arXiv2020

Detection of prostate cancer in whole-slide images through end-to-end training with image-level labels

Prostate cancer is the most prevalent cancer among men in Western countries, with 1.1 million new diagnoses every year. The gold standard for the diagnosis of prostate cancer is a pathologists' evaluation of prostate tissue. To potentially assist pathologists deep-learning-based cancer detection systems have been developed. Many of the state-of-the-art models are patch-based convolutional neural networks, as the use of entire scanned slides is hampered by memory limitations on accelerator cards. Patch-based systems typically require detailed, pixel-level annotations for effective training. However, such annotations are seldom readily available, in contrast to the clinical reports of pathologists, which contain slide-level labels. As such, developing algorithms which do not require manual pixel-wise annotations, but can learn using only the clinical report would be a significant advancement for the field. In this paper, we propose to use a streaming implementation of convolutional layers, to train a modern CNN (ResNet-34) with 21 million parameters end-to-end on 4712 prostate biopsies. The method enables the use of entire biopsy images at high-resolution directly by reducing the GPU memory requirements by 2.4 TB. We show that modern CNNs, trained using our streaming approach, can extract meaningful features from high-resolution images without additional heuristics, reaching similar performance as state-of-the-art patch-based and multiple-instance learning methods. By circumventing the need for manual annotations, this approach can function as a blueprint for other tasks in histopathological diagnosis. The source code to reproduce the streaming models is available at https://github.com/DIAGNijmegen/pathology-streaming-pipeline .

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