NOVA: A Benchmark for Anomaly Localization and Clinical Reasoning in Brain MRI

In many real-world applications, deployed models encounter inputs that differ from the data seen during training. Out-of-distribution detection identifies whether an input stems from an unseen distribution, while open-world recognition flags such inputs to ensure the system remains robust as ever-emerging, previously $unknown$ categories appear and must be addressed without retraining. Foundation and vision-language models are pre-trained on large and diverse datasets with the expectation of broad generalization across domains, including medical imaging. However, benchmarking these models on test sets with only a few common outlier types silently collapses the evaluation back to a closed-set problem, masking failures on rare or truly novel conditions encountered in clinical use. We therefore present $NOVA$, a challenging, real-life $evaluation-only$ benchmark of $\sim$900 brain MRI scans that span 281 rare pathologies and heterogeneous acquisition protocols. Each case includes rich clinical narratives and double-blinded expert bounding-box annotations. Together, these enable joint assessment of anomaly localisation, visual captioning, and diagnostic reasoning. Because NOVA is never used for training, it serves as an $extreme$ stress-test of out-of-distribution generalisation: models must bridge a distribution gap both in sample appearance and in semantic space. Baseline results with leading vision-language models (GPT-4o, Gemini 2.0 Flash, and Qwen2.5-VL-72B) reveal substantial performance drops across all tasks, establishing NOVA as a rigorous testbed for advancing models that can detect, localize, and reason about truly unknown anomalies.

Semantic Alignment of Unimodal Medical Text and Vision Representations

General-purpose AI models, particularly those designed for text and vision, demonstrate impressive versatility across a wide range of deep-learning tasks. However, they often underperform in specialised domains like medical imaging, where domain-specific solutions or alternative knowledge transfer approaches are typically required. Recent studies have noted that general-purpose models can exhibit similar latent spaces when processing semantically related data, although this alignment does not occur naturally. Building on this insight, it has been shown that applying a simple transformation - at most affine - estimated from a subset of semantically corresponding samples, known as anchors, enables model stitching across diverse training paradigms, architectures, and modalities. In this paper, we explore how semantic alignment - estimating transformations between anchors - can bridge general-purpose AI with specialised medical knowledge. Using multiple public chest X-ray datasets, we demonstrate that model stitching across model architectures allows general models to integrate domain-specific knowledge without additional training, leading to improved performance on medical tasks. Furthermore, we introduce a novel zero-shot classification approach for unimodal vision encoders that leverages semantic alignment across modalities. Our results show that our method not only outperforms general multimodal models but also approaches the performance levels of fully trained, medical-specific multimodal solutions

Enhancing Abnormality Grounding for Vision Language Models with Knowledge Descriptions

Visual Language Models (VLMs) have demonstrated impressive capabilities in visual grounding tasks. However, their effectiveness in the medical domain, particularly for abnormality detection and localization within medical images, remains underexplored. A major challenge is the complex and abstract nature of medical terminology, which makes it difficult to directly associate pathological anomaly terms with their corresponding visual features. In this work, we introduce a novel approach to enhance VLM performance in medical abnormality detection and localization by leveraging decomposed medical knowledge. Instead of directly prompting models to recognize specific abnormalities, we focus on breaking down medical concepts into fundamental attributes and common visual patterns. This strategy promotes a stronger alignment between textual descriptions and visual features, improving both the recognition and localization of abnormalities in medical images.We evaluate our method on the 0.23B Florence-2 base model and demonstrate that it achieves comparable performance in abnormality grounding to significantly larger 7B LLaVA-based medical VLMs, despite being trained on only 1.5% of the data used for such models. Experimental results also demonstrate the effectiveness of our approach in both known and previously unseen abnormalities, suggesting its strong generalization capabilities.

Motion-Robust T2* Quantification from Gradient Echo MRI with Physics-Informed Deep Learning

Purpose: T2* quantification from gradient echo magnetic resonance imaging is particularly affected by subject motion due to the high sensitivity to magnetic field inhomogeneities, which are influenced by motion and might cause signal loss. Thus, motion correction is crucial to obtain high-quality T2* maps. Methods: We extend our previously introduced learning-based physics-informed motion correction method, PHIMO, by utilizing acquisition knowledge to enhance the reconstruction performance for challenging motion patterns and increase PHIMO's robustness to varying strengths of magnetic field inhomogeneities across the brain. We perform comprehensive evaluations regarding motion detection accuracy and image quality for data with simulated and real motion. Results: Our extended version of PHIMO outperforms the learning-based baseline methods both qualitatively and quantitatively with respect to line detection and image quality. Moreover, PHIMO performs on-par with a conventional state-of-the-art motion correction method for T2* quantification from gradient echo MRI, which relies on redundant data acquisition. Conclusion: PHIMO's competitive motion correction performance, combined with a reduction in acquisition time by over 40% compared to the state-of-the-art method, make it a promising solution for motion-robust T2* quantification in research settings and clinical routine.

PISCO: Self-Supervised k-Space Regularization for Improved Neural Implicit k-Space Representations of Dynamic MRI

Neural implicit k-space representations (NIK) have shown promising results for dynamic magnetic resonance imaging (MRI) at high temporal resolutions. Yet, reducing acquisition time, and thereby available training data, results in severe performance drops due to overfitting. To address this, we introduce a novel self-supervised k-space loss function $\mathcal{L}_\mathrm{PISCO}$, applicable for regularization of NIK-based reconstructions. The proposed loss function is based on the concept of parallel imaging-inspired self-consistency (PISCO), enforcing a consistent global k-space neighborhood relationship without requiring additional data. Quantitative and qualitative evaluations on static and dynamic MR reconstructions show that integrating PISCO significantly improves NIK representations. Particularly for high acceleration factors (R$\geq$54), NIK with PISCO achieves superior spatio-temporal reconstruction quality compared to state-of-the-art methods. Furthermore, an extensive analysis of the loss assumptions and stability shows PISCO's potential as versatile self-supervised k-space loss function for further applications and architectures. Code is available at: https://github.com/compai-lab/2025-pisco-spieker

From Model Based to Learned Regularization in Medical Image Registration: A Comprehensive Review

Image registration is fundamental in medical imaging applications, such as disease progression analysis or radiation therapy planning. The primary objective of image registration is to precisely capture the deformation between two or more images, typically achieved by minimizing an optimization problem. Due to its inherent ill-posedness, regularization is a key component in driving the solution toward anatomically meaningful deformations. A wide range of regularization methods has been proposed for both conventional and deep learning-based registration. However, the appropriate application of regularization techniques often depends on the specific registration problem, and no one-fits-all method exists. Despite its importance, regularization is often overlooked or addressed with default approaches, assuming existing methods are sufficient. A comprehensive and structured review remains missing. This review addresses this gap by introducing a novel taxonomy that systematically categorizes the diverse range of proposed regularization methods. It highlights the emerging field of learned regularization, which leverages data-driven techniques to automatically derive deformation properties from the data. Moreover, this review examines the transfer of regularization methods from conventional to learning-based registration, identifies open challenges, and outlines future research directions. By emphasizing the critical role of regularization in image registration, we hope to inspire the research community to reconsider regularization strategies in modern registration algorithms and to explore this rapidly evolving field further.

CellPilot

Histopathology, the microscopic study of diseased tissue, is increasingly digitized, enabling improved visualization and streamlined workflows. An important task in histopathology is the segmentation of cells and glands, essential for determining shape and frequencies that can serve as indicators of disease. Deep learning tools are widely used in histopathology. However, variability in tissue appearance and cell morphology presents challenges for achieving reliable segmentation, often requiring manual correction to improve accuracy. This work introduces CellPilot, a framework that bridges the gap between automatic and interactive segmentation by providing initial automatic segmentation as well as guided interactive refinement. Our model was trained on over 675,000 masks of nine diverse cell and gland segmentation datasets, spanning 16 organs. CellPilot demonstrates superior performance compared to other interactive tools on three held-out histopathological datasets while enabling automatic segmentation. We make the model and a graphical user interface designed to assist practitioners in creating large-scale annotated datasets available as open-source, fostering the development of more robust and generalized diagnostic models.

CellPilot: A unified approach to automatic and interactive segmentation in histopathology

Histopathology, the microscopic study of diseased tissue, is increasingly digitized, enabling improved visualization and streamlined workflows. An important task in histopathology is the segmentation of cells and glands, essential for determining shape and frequencies that can serve as indicators of disease. Deep learning tools are widely used in histopathology. However, variability in tissue appearance and cell morphology presents challenges for achieving reliable segmentation, often requiring manual correction to improve accuracy. This work introduces CellPilot, a framework that bridges the gap between automatic and interactive segmentation by providing initial automatic segmentation as well as guided interactive refinement. Our model was trained on over 675,000 masks of nine diverse cell and gland segmentation datasets, spanning 16 organs. CellPilot demonstrates superior performance compared to other interactive tools on three held-out histopathological datasets while enabling automatic segmentation. We make the model and a graphical user interface designed to assist practitioners in creating large-scale annotated datasets available as open-source, fostering the development of more robust and generalized diagnostic models.

Denoising Diffusion Models for Anomaly Localization in Medical Images

This chapter explores anomaly localization in medical images using denoising diffusion models. After providing a brief methodological background of these models, including their application to image reconstruction and their conditioning using guidance mechanisms, we provide an overview of available datasets and evaluation metrics suitable for their application to anomaly localization in medical images. In this context, we discuss supervision schemes ranging from fully supervised segmentation to semi-supervised, weakly supervised, self-supervised, and unsupervised methods, and provide insights into the effectiveness and limitations of these approaches. Furthermore, we highlight open challenges in anomaly localization, including detection bias, domain shift, computational cost, and model interpretability. Our goal is to provide an overview of the current state of the art in the field, outline research gaps, and highlight the potential of diffusion models for robust anomaly localization in medical images.

Selective Test-Time Adaptation for Unsupervised Anomaly Detection using Neural Implicit Representations

Deep learning models in medical imaging often encounter challenges when adapting to new clinical settings unseen during training. Test-time adaptation offers a promising approach to optimize models for these unseen domains, yet its application in anomaly detection (AD) remains largely unexplored. AD aims to efficiently identify deviations from normative distributions; however, full adaptation, including pathological shifts, may inadvertently learn the anomalies it intends to detect. We introduce a novel concept of \emph{selective} test-time adaptation that utilizes the inherent characteristics of deep pre-trained features to adapt \emph{selectively} in a zero-shot manner to any test image from an unseen domain. This approach employs a model-agnostic, lightweight multi-layer perceptron for neural implicit representations, enabling the adaptation of outputs from any reconstruction-based AD method without altering the source-trained model. Rigorous validation in brain AD demonstrated that our strategy substantially enhances detection accuracy for multiple conditions and different target distributions. Specifically, our method improves the detection rates by up to 78\% for enlarged ventricles and 24\% for edemas.