Julia A. Schnabel

Sophia J. Wagner, Daniel Reisenbüchler, Nicholas P. West et al.

Background: Deep learning (DL) can extract predictive and prognostic biomarkers from routine pathology slides in colorectal cancer. For example, a DL test for the diagnosis of microsatellite instability (MSI) in CRC has been approved in 2022. Current approaches rely on convolutional neural networks (CNNs). Transformer networks are outperforming CNNs and are replacing them in many applications, but have not been used for biomarker prediction in cancer at a large scale. In addition, most DL approaches have been trained on small patient cohorts, which limits their clinical utility. Methods: In this study, we developed a new fully transformer-based pipeline for end-to-end biomarker prediction from pathology slides. We combine a pre-trained transformer encoder and a transformer network for patch aggregation, capable of yielding single and multi-target prediction at patient level. We train our pipeline on over 9,000 patients from 10 colorectal cancer cohorts. Results: A fully transformer-based approach massively improves the performance, generalizability, data efficiency, and interpretability as compared with current state-of-the-art algorithms. After training on a large multicenter cohort, we achieve a sensitivity of 0.97 with a negative predictive value of 0.99 for MSI prediction on surgical resection specimens. We demonstrate for the first time that resection specimen-only training reaches clinical-grade performance on endoscopic biopsy tissue, solving a long-standing diagnostic problem. Interpretation: A fully transformer-based end-to-end pipeline trained on thousands of pathology slides yields clinical-grade performance for biomarker prediction on surgical resections and biopsies. Our new methods are freely available under an open source license.

Anna Reithmeir, Lina Felsner, Rickmer Braren et al.

Physics-inspired regularization is desired for intra-patient image registration since it can effectively capture the biomechanical characteristics of anatomical structures. However, a major challenge lies in the reliance on physical parameters: Parameter estimations vary widely across the literature, and the physical properties themselves are inherently subject-specific. In this work, we introduce a novel data-driven method that leverages hypernetworks to learn the tissue-dependent elasticity parameters of an elastic regularizer. Notably, our approach facilitates the estimation of patient-specific parameters without the need to retrain the network. We evaluate our method on three publicly available 2D and 3D lung CT and cardiac MR datasets. We find that with our proposed subject-specific tissue-dependent regularization, a higher registration quality is achieved across all datasets compared to using a global regularizer. The code is available at https://github.com/compai-lab/2024-miccai-reithmeir.

Fryderyk Kögl, Anna Reithmeir, Vasiliki Sideri-Lampretsa et al.

General vision encoders like DINOv2 and SAM have recently transformed computer vision. Even though they are trained on natural images, such encoder models have excelled in medical imaging, e.g., in classification, segmentation, and registration. However, no in-depth comparison of different state-of-the-art general vision encoders for medical registration is available. In this work, we investigate how well general vision encoder features can be used in the dissimilarity metrics for medical image registration. We explore two encoders that were trained on natural images as well as one that was fine-tuned on medical data. We apply the features within the well-established B-spline FFD registration framework. In extensive experiments on cardiac cine MRI data, we find that using features as additional guidance for conventional metrics improves the registration quality. The code is available at github.com/compai-lab/2024-miccai-koegl.

Veronika A. Zimmer, Alberto Gomez, Emily Skelton et al.

Automatic segmentation of the placenta in fetal ultrasound (US) is challenging due to the (i) high diversity of placenta appearance, (ii) the restricted quality in US resulting in highly variable reference annotations, and (iii) the limited field-of-view of US prohibiting whole placenta assessment at late gestation. In this work, we address these three challenges with a multi-task learning approach that combines the classification of placental location (e.g., anterior, posterior) and semantic placenta segmentation in a single convolutional neural network. Through the classification task the model can learn from larger and more diverse datasets while improving the accuracy of the segmentation task in particular in limited training set conditions. With this approach we investigate the variability in annotations from multiple raters and show that our automatic segmentations (Dice of 0.86 for anterior and 0.83 for posterior placentas) achieve human-level performance as compared to intra- and inter-observer variability. Lastly, our approach can deliver whole placenta segmentation using a multi-view US acquisition pipeline consisting of three stages: multi-probe image acquisition, image fusion and image segmentation. This results in high quality segmentation of larger structures such as the placenta in US with reduced image artifacts which are beyond the field-of-view of single probes.

Tim Nielen, Sameer Ambekar, Johannes Kiechle et al.

Entropy minimization (EM) is the dominant objective for test-time adaptation, yet its failure mode, model collapse, remains poorly understood. In this work, we show that distribution shifts can cause feature clusters corresponding to distinct classes in the model's representation space to merge, while the decision boundary remains fixed. This induces a systematic skew in the predicted class distribution, referred to as prediction bias. Prediction bias refers to a shift in the predicted class distribution, with some classes overrepresented and others suppressed. We show that entropy minimization amplifies this prediction bias by tightening the existing clusters, reinforcing the incorrect groupings until all predictions collapse to a trivial solution. Next, to demonstrate the significance of prediction bias and mitigate it, we further propose Distribution Shift Bias Reduction (DSBR), a bias-correcting objective that specifically targets this failure mode by equalizing the contribution of each predicted class to the unsupervised entropy minimization loss. To study this failure mode, we design suitable adaptation settings using four medical-imaging datasets and additionally evaluate on ImageNet-C. We find that DSBR consistently stabilizes test-time adaptation, prevents model collapse, and matches or outperforms state-of-the-art methods. Moreover, DSBR operates solely at test-time.

Stefan M. Fischer, Lina Felsner, Richard Osuala et al.

In this work, we introduce Progressive Growing of Patch Size, a resource-efficient implicit curriculum learning approach for dense prediction tasks. Our curriculum approach is defined by growing the patch size during model training, which gradually increases the task's difficulty. We integrated our curriculum into the nnU-Net framework and evaluated the methodology on all 10 tasks of the Medical Segmentation Decathlon. With our approach, we are able to substantially reduce runtime, computational costs, and CO2 emissions of network training compared to classical constant patch size training. In our experiments, the curriculum approach resulted in improved convergence. We are able to outperform standard nnU-Net training, which is trained with constant patch size, in terms of Dice Score on 7 out of 10 MSD tasks while only spending roughly 50% of the original training runtime. To the best of our knowledge, our Progressive Growing of Patch Size is the first successful employment of a sample-length curriculum in the form of patch size in the field of computer vision. Our code is publicly available at https://github.com/compai-lab/2024-miccai-fischer.

Johannes Kiechle, Daniel M. Lang, Stefan M. Fischer et al.

Recent studies have underscored the capabilities of natural imaging foundation models to serve as powerful feature extractors, even in a zero-shot setting for medical imaging data. Most commonly, a shallow multi-layer perceptron (MLP) is appended to the feature extractor to facilitate end-to-end learning and downstream prediction tasks such as classification, thus representing the de facto standard. However, as graph neural networks (GNNs) have become a practicable choice for various tasks in medical research in the recent past, we direct attention to the question of how effective GNNs are compared to MLP prediction heads for the task of 3D medical image classification, proposing them as a potential alternative. In our experiments, we devise a subject-level graph for each volumetric dataset instance. Therein latent representations of all slices in the volume, encoded through a DINOv2 pretrained vision transformer (ViT), constitute the nodes and their respective node features. We use public datasets to compare the classification heads numerically and evaluate various graph construction and graph convolution methods in our experiments. Our findings show enhancements of the GNN in classification performance and substantial improvements in runtime compared to an MLP prediction head. Additional robustness evaluations further validate the promising performance of the GNN, promoting them as a suitable alternative to traditional MLP classification heads. Our code is publicly available at: https://github.com/compai-lab/2024-miccai-grail-kiechle

Mehmet Yigit Avci, Emily Chan, Veronika Zimmer et al.

With the increasing incidence of neurodegenerative diseases such as Alzheimer's Disease (AD), there is a need for further research that enhances detection and monitoring of the diseases. We present MORPHADE (Morphological Autoencoders for Alzheimer's Disease Detection), a novel unsupervised learning approach which uses deformations to allow the analysis of 3D T1-weighted brain images. To the best of our knowledge, this is the first use of deformations with deep unsupervised learning to not only detect, but also localize and assess the severity of structural changes in the brain due to AD. We obtain markedly higher anomaly scores in clinically important areas of the brain in subjects with AD compared to healthy controls, showcasing that our method is able to effectively locate AD-related atrophy. We additionally observe a visual correlation between the severity of atrophy highlighted in our anomaly maps and medial temporal lobe atrophy scores evaluated by a clinical expert. Finally, our method achieves an AUROC of 0.80 in detecting AD, out-performing several supervised and unsupervised baselines. We believe our framework shows promise as a tool towards improved understanding, monitoring and detection of AD. To support further research and application, we have made our code publicly available at github.com/ci-ber/MORPHADE.

Cosmin I. Bercea, Daniel Rueckert, Julia A. Schnabel

Even though auto-encoders (AEs) have the desirable property of learning compact representations without labels and have been widely applied to out-of-distribution (OoD) detection, they are generally still poorly understood and are used incorrectly in detecting outliers where the normal and abnormal distributions are strongly overlapping. In general, the learned manifold is assumed to contain key information that is only important for describing samples within the training distribution, and that the reconstruction of outliers leads to high residual errors. However, recent work suggests that AEs are likely to be even better at reconstructing some types of OoD samples. In this work, we challenge this assumption and investigate what auto-encoders actually learn when they are posed to solve two different tasks. First, we propose two metrics based on the Fréchet inception distance (FID) and confidence scores of a trained classifier to assess whether AEs can learn the training distribution and reliably recognize samples from other domains. Second, we investigate whether AEs are able to synthesize normal images from samples with abnormal regions, on a more challenging lung pathology detection task. We have found that state-of-the-art (SOTA) AEs are either unable to constrain the latent manifold and allow reconstruction of abnormal patterns, or they are failing to accurately restore the inputs from their latent distribution, resulting in blurred or misaligned reconstructions. We propose novel deformable auto-encoders (MorphAEus) to learn perceptually aware global image priors and locally adapt their morphometry based on estimated dense deformation fields. We demonstrate superior performance over unsupervised methods in detecting OoD and pathology.

Cosmin I. Bercea, Esther Puyol-Antón, Benedikt Wiestler et al.

Unsupervised anomaly detection methods offer a promising and flexible alternative to supervised approaches, holding the potential to revolutionize medical scan analysis and enhance diagnostic performance. In the current landscape, it is commonly assumed that differences between a test case and the training distribution are attributed solely to pathological conditions, implying that any disparity indicates an anomaly. However, the presence of other potential sources of distributional shift, including scanner, age, sex, or race, is frequently overlooked. These shifts can significantly impact the accuracy of the anomaly detection task. Prominent instances of such failures have sparked concerns regarding the bias, credibility, and fairness of anomaly detection. This work presents a novel analysis of biases in unsupervised anomaly detection. By examining potential non-pathological distributional shifts between the training and testing distributions, we shed light on the extent of these biases and their influence on anomaly detection results. Moreover, this study examines the algorithmic limitations that arise due to biases, providing valuable insights into the challenges encountered by anomaly detection algorithms in accurately learning and capturing the entire range of variability present in the normative distribution. Through this analysis, we aim to enhance the understanding of these biases and pave the way for future improvements in the field. Here, we specifically investigate Alzheimer's disease detection from brain MR imaging as a case study, revealing significant biases related to sex, race, and scanner variations that substantially impact the results. These findings align with the broader goal of improving the reliability, fairness, and effectiveness of anomaly detection in medical imaging.

Ha Young Kim, Jun Li, Ana Beatriz Solana et al.

Rare diseases represent the long tail of medical imaging, where AI models often fail due to the scarcity of representative training data. In clinical workflows, radiologists frequently consult case reports and literature when confronted with unfamiliar findings. Following this line of reasoning, we introduce RADAR, Retrieval Augmented Diagnostic Reasoning Agents, an agentic system for rare disease detection in brain MRI. Our approach uses AI agents with access to external medical knowledge by embedding both case reports and literature using sentence transformers and indexing them with FAISS to enable efficient similarity search. The agent retrieves clinically relevant evidence to guide diagnostic decision making on unseen diseases, without the need of additional training. Designed as a model-agnostic reasoning module, RADAR can be seamlessly integrated with diverse large language models, consistently improving their rare pathology recognition and interpretability. On the NOVA dataset comprising 280 distinct rare diseases, RADAR achieves up to a 10.2% performance gain, with the strongest improvements observed for open source models such as DeepSeek. Beyond accuracy, the retrieved examples provide interpretable, literature grounded explanations, highlighting retrieval-augmented reasoning as a powerful paradigm for low-prevalence conditions in medical imaging.

Martin J. Menten, Johannes C. Paetzold, Veronika A. Zimmer et al.

The skeleton of a digital image is a compact representation of its topology, geometry, and scale. It has utility in many computer vision applications, such as image description, segmentation, and registration. However, skeletonization has only seen limited use in contemporary deep learning solutions. Most existing skeletonization algorithms are not differentiable, making it impossible to integrate them with gradient-based optimization. Compatible algorithms based on morphological operations and neural networks have been proposed, but their results often deviate from the geometry and topology of the true medial axis. This work introduces the first three-dimensional skeletonization algorithm that is both compatible with gradient-based optimization and preserves an object's topology. Our method is exclusively based on matrix additions and multiplications, convolutional operations, basic non-linear functions, and sampling from a uniform probability distribution, allowing it to be easily implemented in any major deep learning library. In benchmarking experiments, we prove the advantages of our skeletonization algorithm compared to non-differentiable, morphological, and neural-network-based baselines. Finally, we demonstrate the utility of our algorithm by integrating it with two medical image processing applications that use gradient-based optimization: deep-learning-based blood vessel segmentation, and multimodal registration of the mandible in computed tomography and magnetic resonance images.

Jun Li, Mingxuan Liu, Jiazhen Pan et al.

Clinical abnormality grounding for rare diseases is often hindered by data scarcity, making supervised fine-tuning impractical and single-pass inference highly unstable. We propose Dynamic Decision Learning (DDL), a framework that enables frozen large vision-language models (LVLMs) to refine their decisions across both language and visual spaces by optimizing instructions and consolidating predictions under visual perturbations. This process improves localization quality and produces a consensus-based reliability score that quantifies model confidence. Results on brain imaging benchmarks, including a rare-disease dataset with 281 pathology types across models ranging from 3B to 72B parameters, show that DDL improves mAP@75 by up to 105% on rare-disease cases and outperforms adaptation baselines and supervised fine-tuning. Furthermore, DDL demonstrates stronger calibration between reliability scores and localization accuracy under severe distribution shifts and increasing task difficulty. Code is available at: https://lijunrio.github.io/DDL/

Donnate Hooft, Stefan M. Fischer, Cosmin Bercea et al.

Patch-based methods are widely used in 3D medical image segmentation to address memory constraints in processing high-resolution volumetric data. However, these approaches often neglect the patch's location within the global volume, which can limit segmentation performance when anatomical context is important. In this paper, we investigate the role of location context in patch-based 3D segmentation and propose a novel attention mechanism, LocBAM, that explicitly processes spatial information. Experiments on BTCV, AMOS22, and KiTS23 demonstrate that incorporating location context stabilizes training and improves segmentation performance, particularly under low patch-to-volume coverage where global context is missing. Furthermore, LocBAM consistently outperforms classical coordinate encoding via CoordConv. Code is publicly available at https://github.com/compai-lab/2026-ISBI-hooft

Johannes Kiechle, Stefan M. Fischer, Daniel M. Lang et al.

The growing number of medical tomography examinations has necessitated the development of automated methods capable of extracting comprehensive imaging features to facilitate downstream tasks such as tumor characterization, while assisting physicians in managing their growing workload. However, 3D medical image classification remains a challenging task due to the complex spatial relationships and long-range dependencies inherent in volumetric data. Training models from scratch suffers from low data regimes, and the absence of 3D large-scale multimodal datasets has limited the development of 3D medical imaging foundation models. Recent studies, however, have highlighted the potential of 2D vision foundation models, originally trained on natural images, as powerful feature extractors for medical image analysis. Despite these advances, existing approaches that apply 2D models to 3D volumes via slice-based decomposition remain suboptimal. Conventional volume slicing strategies, which rely on canonical planes such as axial, sagittal, or coronal, may inadequately capture the spatial extent of target structures when these are misaligned with standardized viewing planes. Furthermore, existing slice-wise aggregation strategies rarely account for preserving the volumetric structure, resulting in a loss of spatial coherence across slices. To overcome these limitations, we propose TomoGraphView, a novel framework that integrates omnidirectional volume slicing with spherical graph-based feature aggregation. We publicly share our accessible code base at http://github.com/compai-lab/2025-MedIA-kiechle and provide a user-friendly library for omnidirectional volume slicing at https://pypi.org/project/OmniSlicer.

Richard Osuala, Daniel M. Lang, Anneliese Riess et al.

Deep learning holds immense promise for aiding radiologists in breast cancer detection. However, achieving optimal model performance is hampered by limitations in availability and sharing of data commonly associated to patient privacy concerns. Such concerns are further exacerbated, as traditional deep learning models can inadvertently leak sensitive training information. This work addresses these challenges exploring and quantifying the utility of privacy-preserving deep learning techniques, concretely, (i) differentially private stochastic gradient descent (DP-SGD) and (ii) fully synthetic training data generated by our proposed malignancy-conditioned generative adversarial network. We assess these methods via downstream malignancy classification of mammography masses using a transformer model. Our experimental results depict that synthetic data augmentation can improve privacy-utility tradeoffs in differentially private model training. Further, model pretraining on synthetic data achieves remarkable performance, which can be further increased with DP-SGD fine-tuning across all privacy guarantees. With this first in-depth exploration of privacy-preserving deep learning in breast imaging, we address current and emerging clinical privacy requirements and pave the way towards the adoption of private high-utility deep diagnostic models. Our reproducible codebase is publicly available at https://github.com/RichardObi/mammo_dp.

Reuben Dorent, Roya Khajavi, Tagwa Idris et al.

Accurate assessment of lymph node size in 3D CT scans is crucial for cancer staging, therapeutic management, and monitoring treatment response. Existing state-of-the-art segmentation frameworks in medical imaging often rely on fully annotated datasets. However, for lymph node segmentation, these datasets are typically small due to the extensive time and expertise required to annotate the numerous lymph nodes in 3D CT scans. Weakly-supervised learning, which leverages incomplete or noisy annotations, has recently gained interest in the medical imaging community as a potential solution. Despite the variety of weakly-supervised techniques proposed, most have been validated only on private datasets or small publicly available datasets. To address this limitation, the Mediastinal Lymph Node Quantification (LNQ) challenge was organized in conjunction with the 26th International Conference on Medical Image Computing and Computer Assisted Intervention (MICCAI 2023). This challenge aimed to advance weakly-supervised segmentation methods by providing a new, partially annotated dataset and a robust evaluation framework. A total of 16 teams from 5 countries submitted predictions to the validation leaderboard, and 6 teams from 3 countries participated in the evaluation phase. The results highlighted both the potential and the current limitations of weakly-supervised approaches. On one hand, weakly-supervised approaches obtained relatively good performance with a median Dice score of $61.0\%$. On the other hand, top-ranked teams, with a median Dice score exceeding $70\%$, boosted their performance by leveraging smaller but fully annotated datasets to combine weak supervision and full supervision. This highlights both the promise of weakly-supervised methods and the ongoing need for high-quality, fully annotated data to achieve higher segmentation performance.

Tomáš Chobola, Yu Liu, Hanyi Zhang et al.

Current deep learning-based low-light image enhancement methods often struggle with high-resolution images, and fail to meet the practical demands of visual perception across diverse and unseen scenarios. In this paper, we introduce a novel approach termed CoLIE, which redefines the enhancement process through mapping the 2D coordinates of an underexposed image to its illumination component, conditioned on local context. We propose a reconstruction of enhanced-light images within the HSV space utilizing an implicit neural function combined with an embedded guided filter, thereby significantly reducing computational overhead. Moreover, we introduce a single image-based training loss function to enhance the model's adaptability to various scenes, further enhancing its practical applicability. Through rigorous evaluations, we analyze the properties of our proposed framework, demonstrating its superiority in both image quality and scene adaptability. Furthermore, our evaluation extends to applications in downstream tasks within low-light scenarios, underscoring the practical utility of CoLIE. The source code is available at https://github.com/ctom2/colie.

Veronika Spieker, Wenqi Huang, Hannah Eichhorn et al.

Motion-resolved reconstruction for abdominal magnetic resonance imaging (MRI) remains a challenge due to the trade-off between residual motion blurring caused by discretized motion states and undersampling artefacts. In this work, we propose to generate blurring-free motion-resolved abdominal reconstructions by learning a neural implicit representation directly in k-space (NIK). Using measured sampling points and a data-derived respiratory navigator signal, we train a network to generate continuous signal values. To aid the regularization of sparsely sampled regions, we introduce an additional informed correction layer (ICo), which leverages information from neighboring regions to correct NIK's prediction. Our proposed generative reconstruction methods, NIK and ICoNIK, outperform standard motion-resolved reconstruction techniques and provide a promising solution to address motion artefacts in abdominal MRI.

Emily Chan, Ciaran O'Hanlon, Carlota Asegurado Marquez et al.

Flow analysis carried out using phase contrast cardiac magnetic resonance imaging (PC-CMR) enables the quantification of important parameters that are used in the assessment of cardiovascular function. An essential part of this analysis is the identification of the correct CMR views and quality control (QC) to detect artefacts that could affect the flow quantification. We propose a novel deep learning based framework for the fully-automated analysis of flow from full CMR scans that first carries out these view selection and QC steps using two sequential convolutional neural networks, followed by automatic aorta and pulmonary artery segmentation to enable the quantification of key flow parameters. Accuracy values of 0.958 and 0.914 were obtained for view classification and QC, respectively. For segmentation, Dice scores were $>$0.969 and the Bland-Altman plots indicated excellent agreement between manual and automatic peak flow values. In addition, we tested our pipeline on an external validation data set, with results indicating good robustness of the pipeline. This work was carried out using multivendor clinical data consisting of 986 cases, indicating the potential for the use of this pipeline in a clinical setting.

Inês P. Machado, Esther Puyol-Antón, Kerstin Hammernik et al.

Cine cardiac magnetic resonance (CMR) imaging is considered the gold standard for cardiac function evaluation. However, cine CMR acquisition is inherently slow and in recent decades considerable effort has been put into accelerating scan times without compromising image quality or the accuracy of derived results. In this paper, we present a fully-automated, quality-controlled integrated framework for reconstruction, segmentation and downstream analysis of undersampled cine CMR data. The framework enables active acquisition of radial k-space data, in which acquisition can be stopped as soon as acquired data are sufficient to produce high quality reconstructions and segmentations. This results in reduced scan times and automated analysis, enabling robust and accurate estimation of functional biomarkers. To demonstrate the feasibility of the proposed approach, we perform realistic simulations of radial k-space acquisitions on a dataset of subjects from the UK Biobank and present results on in-vivo cine CMR k-space data collected from healthy subjects. The results demonstrate that our method can produce quality-controlled images in a mean scan time reduced from 12 to 4 seconds per slice, and that image quality is sufficient to allow clinically relevant parameters to be automatically estimated to within 5% mean absolute difference.

Malek Ben Alaya, Daniel M. Lang, Benedikt Wiestler et al.

Denoising diffusion probabilistic models enable high-fidelity image synthesis and editing. In biomedicine, these models facilitate counterfactual image editing, producing pairs of images where one is edited to simulate hypothetical conditions. For example, they can model the progression of specific diseases, such as stroke lesions. However, current image editing techniques often fail to generate realistic biomedical counterfactuals, either by inadequately modeling indirect pathological effects like brain atrophy or by excessively altering the scan, which disrupts correspondence to the original images. Here, we propose MedEdit, a conditional diffusion model for medical image editing. MedEdit induces pathology in specific areas while balancing the modeling of disease effects and preserving the integrity of the original scan. We evaluated MedEdit on the Atlas v2.0 stroke dataset using Frechet Inception Distance and Dice scores, outperforming state-of-the-art diffusion-based methods such as Palette (by 45%) and SDEdit (by 61%). Additionally, clinical evaluations by a board-certified neuroradiologist confirmed that MedEdit generated realistic stroke scans indistinguishable from real ones. We believe this work will enable counterfactual image editing research to further advance the development of realistic and clinically useful imaging tools.

Maxime Di Folco, Cosmin Bercea, Julia A. Schnabel

Deep generative models have emerged as influential instruments for data generation and manipulation. Enhancing the controllability of these models by selectively modifying data attributes has been a recent focus. Variational Autoencoders (VAEs) have shown promise in capturing hidden attributes but often produce blurry reconstructions. Controlling these attributes through different imaging domains is difficult in medical imaging. Recently, Soft Introspective VAE leverage the benefits of both VAEs and Generative Adversarial Networks (GANs), which have demonstrated impressive image synthesis capabilities, by incorporating an adversarial loss into VAE training. In this work, we propose the Attributed Soft Introspective VAE (Attri-SIVAE) by incorporating an attribute regularized loss, into the Soft-Intro VAE framework. We evaluate experimentally the proposed method on cardiac MRI data from different domains, such as various scanner vendors and acquisition centers. The proposed method achieves similar performance in terms of reconstruction and regularization compared to the state-of-the-art Attributed regularized VAE but additionally also succeeds in keeping the same regularization level when tested on a different dataset, unlike the compared method.

Hassan Rasheed, Reuben Dorent, Maximilian Fehrentz et al.

We propose in this paper a texture-invariant 2D keypoints descriptor specifically designed for matching preoperative Magnetic Resonance (MR) images with intraoperative Ultrasound (US) images. We introduce a matching-by-synthesis strategy, where intraoperative US images are synthesized from MR images accounting for multiple MR modalities and intraoperative US variability. We build our training set by enforcing keypoints localization over all images then train a patient-specific descriptor network that learns texture-invariant discriminant features in a supervised contrastive manner, leading to robust keypoints descriptors. Our experiments on real cases with ground truth show the effectiveness of the proposed approach, outperforming the state-of-the-art methods and achieving 80.35% matching precision on average.

Anna Reithmeir, Julia A. Schnabel, Veronika A. Zimmer

Medical image registration aims at identifying the spatial deformation between images of the same anatomical region and is fundamental to image-based diagnostics and therapy. To date, the majority of the deep learning-based registration methods employ regularizers that enforce global spatial smoothness, e.g., the diffusion regularizer. However, such regularizers are not tailored to the data and might not be capable of reflecting the complex underlying deformation. In contrast, physics-inspired regularizers promote physically plausible deformations. One such regularizer is the linear elastic regularizer which models the deformation of elastic material. These regularizers are driven by parameters that define the material's physical properties. For biological tissue, a wide range of estimations of such parameters can be found in the literature and it remains an open challenge to identify suitable parameter values for successful registration. To overcome this problem and to incorporate physical properties into learning-based registration, we propose to use a hypernetwork that learns the effect of the physical parameters of a physics-inspired regularizer on the resulting spatial deformation field. In particular, we adapt the HyperMorph framework to learn the effect of the two elasticity parameters of the linear elastic regularizer. Our approach enables the efficient discovery of suitable, data-specific physical parameters at test time.

Richard Osuala, Smriti Joshi, Apostolia Tsirikoglou et al.

This paper presents a method for virtual contrast enhancement in breast MRI, offering a promising non-invasive alternative to traditional contrast agent-based DCE-MRI acquisition. Using a conditional generative adversarial network, we predict DCE-MRI images, including jointly-generated sequences of multiple corresponding DCE-MRI timepoints, from non-contrast-enhanced MRIs, enabling tumor localization and characterization without the associated health risks. Furthermore, we qualitatively and quantitatively evaluate the synthetic DCE-MRI images, proposing a multi-metric Scaled Aggregate Measure (SAMe), assessing their utility in a tumor segmentation downstream task, and conclude with an analysis of the temporal patterns in multi-sequence DCE-MRI generation. Our approach demonstrates promising results in generating realistic and useful DCE-MRI sequences, highlighting the potential of virtual contrast enhancement for improving breast cancer diagnosis and treatment, particularly for patients where contrast agent administration is contraindicated.

Deniz Daum, Richard Osuala, Anneliese Riess et al.

Generally, the small size of public medical imaging datasets coupled with stringent privacy concerns, hampers the advancement of data-hungry deep learning models in medical imaging. This study addresses these challenges for 3D cardiac MRI images in the short-axis view. We propose Latent Diffusion Models that generate synthetic images conditioned on medical attributes, while ensuring patient privacy through differentially private model training. To our knowledge, this is the first work to apply and quantify differential privacy in 3D medical image generation. We pre-train our models on public data and finetune them with differential privacy on the UK Biobank dataset. Our experiments reveal that pre-training significantly improves model performance, achieving a Fréchet Inception Distance (FID) of 26.77 at $ε=10$, compared to 92.52 for models without pre-training. Additionally, we explore the trade-off between privacy constraints and image quality, investigating how tighter privacy budgets affect output controllability and may lead to degraded performance. Our results demonstrate that proper consideration during training with differential privacy can substantially improve the quality of synthetic cardiac MRI images, but there are still notable challenges in achieving consistent medical realism.

Reza Nasirigerdeh, Nader Razmi, Julia A. Schnabel et al.

Machine unlearning is the process of removing the impact of a particular set of training samples from a pretrained model. It aims to fulfill the "right to be forgotten", which grants the individuals such as patients the right to reconsider their contribution in models including medical imaging models. In this study, we evaluate the effectiveness (performance) and computational efficiency of different unlearning algorithms in medical imaging domain. Our evaluations demonstrate that the considered unlearning algorithms perform well on the retain set (samples whose influence on the model is allowed to be retained) and forget set (samples whose contribution to the model should be eliminated), and show no bias against male or female samples. They, however, adversely impact the generalization of the model, especially for larger forget set sizes. Moreover, they might be biased against easy or hard samples, and need additional computational overhead for hyper-parameter tuning. In conclusion, machine unlearning seems promising for medical imaging, but the existing unlearning algorithms still needs further improvements to become more practical for medical applications.

Cosmin I. Bercea, Benedikt Wiestler, Daniel Rueckert et al.

Diffusion models have advanced unsupervised anomaly detection by improving the transformation of pathological images into pseudo-healthy equivalents. Nonetheless, standard approaches may compromise critical information during pathology removal, leading to restorations that do not align with unaffected regions in the original scans. Such discrepancies can inadvertently increase false positive rates and reduce specificity, complicating radiological evaluations. This paper introduces Temporal Harmonization for Optimal Restoration (THOR), which refines the de-noising process by integrating implicit guidance through temporal anomaly maps. THOR aims to preserve the integrity of healthy tissue in areas unaffected by pathology. Comparative evaluations show that THOR surpasses existing diffusion-based methods in detecting and segmenting anomalies in brain MRIs and wrist X-rays. Code: https://github.com/ci-ber/THOR_DDPM.

Richard Osuala, Daniel M. Lang, Preeti Verma et al.

Contrast agents in dynamic contrast enhanced magnetic resonance imaging allow to localize tumors and observe their contrast kinetics, which is essential for cancer characterization and respective treatment decision-making. However, contrast agent administration is not only associated with adverse health risks, but also restricted for patients during pregnancy, and for those with kidney malfunction, or other adverse reactions. With contrast uptake as key biomarker for lesion malignancy, cancer recurrence risk, and treatment response, it becomes pivotal to reduce the dependency on intravenous contrast agent administration. To this end, we propose a multi-conditional latent diffusion model capable of acquisition time-conditioned image synthesis of DCE-MRI temporal sequences. To evaluate medical image synthesis, we additionally propose and validate the Fréchet radiomics distance as an image quality measure based on biomarker variability between synthetic and real imaging data. Our results demonstrate our method's ability to generate realistic multi-sequence fat-saturated breast DCE-MRI and uncover the emerging potential of deep learning based contrast kinetics simulation. We publicly share our accessible codebase at https://github.com/RichardObi/ccnet and provide a user-friendly library for Fréchet radiomics distance calculation at https://pypi.org/project/frd-score.

Valentin Koch, Sabine Bauer, Valerio Luppberger et al.

Background: The integration of multi-stain histopathology images through deep learning poses a significant challenge in digital histopathology. Current multi-modal approaches struggle with data heterogeneity and missing data. This study aims to overcome these limitations by developing a novel transformer model for multi-stain integration that can handle missing data during training as well as inference. Methods: We propose UNICORN (UNiversal modality Integration Network for CORonary classificatioN) a multi-modal transformer capable of processing multi-stain histopathology for atherosclerosis severity class prediction. The architecture comprises a two-stage, end-to-end trainable model with specialized modules utilizing transformer self-attention blocks. The initial stage employs domain-specific expert modules to extract features from each modality. In the subsequent stage, an aggregation expert module integrates these features by learning the interactions between the different data modalities. Results: Evaluation was performed using a multi-class dataset of atherosclerotic lesions from the Munich Cardiovascular Studies Biobank (MISSION), using over 4,000 paired multi-stain whole slide images (WSIs) from 170 deceased individuals on 7 prespecified segments of the coronary tree, each stained according to four histopathological protocols. UNICORN achieved a classification accuracy of 0.67, outperforming other state-of-the-art models. The model effectively identifies relevant tissue phenotypes across stainings and implicitly models disease progression. Conclusion: Our proposed multi-modal transformer model addresses key challenges in medical data analysis, including data heterogeneity and missing modalities. Explainability and the model's effectiveness in predicting atherosclerosis progression underscores its potential for broader applications in medical research.

Jun Li, Su Hwan Kim, Philip Müller et al.

This research explores the integration of language models and unsupervised anomaly detection in medical imaging, addressing two key questions: (1) Can language models enhance the interpretability of anomaly detection maps? and (2) Can anomaly maps improve the generalizability of language models in open-set anomaly detection tasks? To investigate these questions, we introduce a new dataset for multi-image visual question-answering on brain magnetic resonance images encompassing multiple conditions. We propose KQ-Former (Knowledge Querying Transformer), which is designed to optimally align visual and textual information in limited-sample contexts. Our model achieves a 60.81% accuracy on closed questions, covering disease classification and severity across 15 different classes. For open questions, KQ-Former demonstrates a 70% improvement over the baseline with a BLEU-4 score of 0.41, and achieves the highest entailment ratios (up to 71.9%) and lowest contradiction ratios (down to 10.0%) among various natural language inference models. Furthermore, integrating anomaly maps results in an 18% accuracy increase in detecting open-set anomalies, thereby enhancing the language model's generalizability to previously unseen medical conditions. The code and dataset are available at https://github.com/compai-lab/miccai-2024-junli?tab=readme-ov-file

Sameer Ambekar, Reza Nasirigerdeh, Peter J. Schuffler et al.

Model merging under unseen test-time distribution shifts often renders naive strategies, such as mean averaging unreliable. This challenge is especially acute in medical imaging, where models are fine-tuned locally at clinics on private data, producing domain-specific models that differ by scanner, protocol, and population. When deployed at an unseen clinical site, test cases arrive in unlabeled, non-i.i.d. batches, and the model must adapt immediately without labels. In this work, we introduce an entropy-adaptive, fully online model-merging method that yields a batch-specific merged model via only forward passes, effectively leveraging target information. We further demonstrate why mean merging is prone to failure and misaligned under heterogeneous domain shifts. Next, we mitigate encoder classifier mismatch by decoupling the encoder and classification head, merging with separate merging coefficients. We extensively evaluate our method with state-of-the-art baselines using two backbones across nine medical and natural-domain generalization image classification datasets, showing consistent gains across standard evaluation and challenging scenarios. These performance gains are achieved while retaining single-model inference at test-time, thereby demonstrating the effectiveness of our method.

Ben Schaper, Maxime Di Folco, Bernhard Kainz et al.

Vision-Language Models show strong zero-shot performance for chest X-ray classification, but standard flat metrics fail to distinguish between clinically minor and severe errors. This work investigates how to quantify and mitigate abstraction errors by leveraging medical taxonomies. We benchmark several state-of-the-art VLMs using hierarchical metrics and introduce Catastrophic Abstraction Errors to capture cross-branch mistakes. Our results reveal substantial misalignment of VLMs with clinical taxonomies despite high flat performance. To address this, we propose risk-constrained thresholding and taxonomy-aware fine-tuning with radial embeddings, which reduce severe abstraction errors to below 2 per cent while maintaining competitive performance. These findings highlight the importance of hierarchical evaluation and representation-level alignment for safer and more clinically meaningful deployment of VLMs.

Veronika Spieker, Hannah Eichhorn, Wenqi Huang et al.

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

Veronika Spieker, Hannah Eichhorn, Jonathan K. Stelter et al.

Neural implicit k-space representations have shown promising results for dynamic MRI at high temporal resolutions. Yet, their exclusive training in k-space limits the application of common image regularization methods to improve the final reconstruction. In this work, we introduce the concept of parallel imaging-inspired self-consistency (PISCO), which we incorporate as novel self-supervised k-space regularization enforcing a consistent neighborhood relationship. At no additional data cost, the proposed regularization significantly improves neural implicit k-space reconstructions on simulated data. Abdominal in-vivo reconstructions using PISCO result in enhanced spatio-temporal image quality compared to state-of-the-art methods. Code is available at https://github.com/vjspi/PISCO-NIK.

Xingyu Zhang, Anna Reithmeir, Fryderyk Kögl et al.

Accurate spatial correspondence between medical images is essential for longitudinal analysis, lesion tracking, and image-guided interventions. Medical image registration methods rely on local intensity-based similarity measures, which fail to capture global semantic structure and often yield mismatches in low-contrast or anatomically variable regions. Recent advances in diffusion models suggest that their intermediate representations encode rich geometric and semantic information. We present MedDIFT, a training-free 3D correspondence framework that leverages multi-scale features from a pretrained latent medical diffusion model as voxel descriptors. MedDIFT fuses diffusion activations into rich voxel-wise descriptors and matches them via cosine similarity, with an optional local-search prior. On a publicly available lung CT dataset, MedDIFT shows promising capability in identifying anatomical correspondence without requiring any task-specific model training. Ablation experiments confirm that multi-level feature fusion and modest diffusion noise improve performance. Code is available online.

Lina Felsner, Sevgi G. Kafali, Hannah Eichhorn et al.

We report the design, protocol, and outcomes of a student reproducibility hackathon focused on replicating the results of three influential MRI reconstruction papers: (a) MoDL, an unrolled model-based network with learned denoising; (b) HUMUS-Net, a hybrid unrolled multiscale CNN+Transformer architecture; and (c) an untrained, physics-regularized dynamic MRI method that uses a quantitative MR model for early stopping. We describe the setup of the hackathon and present reproduction outcomes alongside additional experiments, and we detail fundamental practices for building reproducible codebases.

Philipp Endres, Valentin Koch, Julia A. Schnabel et al.

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.

Cosmin I. Bercea, Benedikt Wiestler, Daniel Rueckert et al.

The increasing complexity of medical imaging data underscores the need for advanced anomaly detection methods to automatically identify diverse pathologies. Current methods face challenges in capturing the broad spectrum of anomalies, often limiting their use to specific lesion types in brain scans. To address this challenge, we introduce a novel unsupervised approach, termed \textit{Reversed Auto-Encoders (RA)}, designed to create realistic pseudo-healthy reconstructions that enable the detection of a wider range of pathologies. We evaluate the proposed method across various imaging modalities, including magnetic resonance imaging (MRI) of the brain, pediatric wrist X-ray, and chest X-ray, and demonstrate superior performance in detecting anomalies compared to existing state-of-the-art methods. Our unsupervised anomaly detection approach may enhance diagnostic accuracy in medical imaging by identifying a broader range of unknown pathologies. Our code is publicly available at: \url{https://github.com/ci-ber/RA}.

Daniel Grzech, Loïc le Folgoc, Mattias P. Heinrich et al.

We present an implementation of a new approach to diffeomorphic non-rigid registration of medical images. The method is based on optical flow and warps images via gradient flow with the standard $L^2$ inner product. To compute the transformation, we rely on accelerated optimisation on the manifold of diffeomorphisms. We achieve regularity properties of Sobolev gradient flows, which are expensive to compute, owing to a novel method of averaging the gradients in time rather than space. We successfully register brain MRI and challenging abdominal CT scans at speeds orders of magnitude faster than previous approaches. We make our code available in a public repository: https://github.com/dgrzech/fastreg

Josef Mayr, Anna Reithmeir, Maxime Di Folco et al.

Covariance descriptors capture second-order statistics of image features. They have shown strong performance in general computer vision tasks, but remain underexplored in medical imaging. We investigate their effectiveness for both conventional and learning-based medical image classification, with a particular focus on SPDNet, a classification network specifically designed for symmetric positive definite (SPD) matrices. We propose constructing covariance descriptors from features extracted by pre-trained general vision encoders (GVEs) and comparing them with handcrafted descriptors. Two GVEs - DINOv2 and MedSAM - are evaluated across eleven binary and multi-class datasets from the MedMNSIT benchmark. Our results show that covariance descriptors derived from GVE features consistently outperform those derived from handcrafted features. Moreover, SPDNet yields superior performance to state-of-the-art methods when combined with DINOv2 features. Our findings highlight the potential of combining covariance descriptors with powerful pretrained vision encoders for medical image analysis.

Benedikt Roth, Valentin Koch, Sophia J. Wagner et al.

To handle the large scale of whole slide images in computational pathology, most approaches first tessellate the images into smaller patches, extract features from these patches, and finally aggregate the feature vectors with weakly-supervised learning. The performance of this workflow strongly depends on the quality of the extracted features. Recently, foundation models in computer vision showed that leveraging huge amounts of data through supervised or self-supervised learning improves feature quality and generalizability for a variety of tasks. In this study, we benchmark the most popular vision foundation models as feature extractors for histopathology data. We evaluate the models in two settings: slide-level classification and patch-level classification. We show that foundation models are a strong baseline. Our experiments demonstrate that by finetuning a foundation model on a single GPU for only two hours or three days depending on the dataset, we can match or outperform state-of-the-art feature extractors for computational pathology. These findings imply that even with little resources one can finetune a feature extractor tailored towards a specific downstream task and dataset. This is a considerable shift from the current state, where only few institutions with large amounts of resources and datasets are able to train a feature extractor. We publish all code used for training and evaluation as well as the finetuned models.

Cosmin I. Bercea, Jun Li, Philipp Raffler et al.

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.

Jun Li, Che Liu, Wenjia Bai et al.

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.

Anna Reithmeir, Veronika Spieker, Vasiliki Sideri-Lampretsa et al.

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.

Josh Stein, Maxime Di Folco, Julia A. Schnabel

The Segment Anything Model (SAM) has recently emerged as a significant breakthrough in foundation models, demonstrating remarkable zero-shot performance in object segmentation tasks. While SAM is designed for generalization, it exhibits limitations in handling specific medical imaging tasks that require fine-structure segmentation or precise boundaries. In this paper, we focus on the task of cardiac magnetic resonance imaging (cMRI) short-axis view segmentation using the SAM foundation model. We conduct a comprehensive investigation of the impact of different prompting strategies (including bounding boxes, positive points, negative points, and their combinations) on segmentation performance. We evaluate on two public datasets using the baseline model and models fine-tuned with varying amounts of annotated data, ranging from a limited number of volumes to a fully annotated dataset. Our findings indicate that prompting strategies significantly influence segmentation performance. Combining positive points with either bounding boxes or negative points shows substantial benefits, but little to no benefit when combined simultaneously. We further observe that fine-tuning SAM with a few annotated volumes improves segmentation performance when properly prompted. Specifically, fine-tuning with bounding boxes has a positive impact, while fine-tuning without bounding boxes leads to worse results compared to baseline.

Nicholas Konz, Richard Osuala, Preeti Verma et al.

Determining whether two sets of images belong to the same or different distributions or domains is a crucial task in modern medical image analysis and deep learning; for example, to evaluate the output quality of image generative models. Currently, metrics used for this task either rely on the (potentially biased) choice of some downstream task, such as segmentation, or adopt task-independent perceptual metrics (e.g., Fréchet Inception Distance/FID) from natural imaging, which we show insufficiently capture anatomical features. To this end, we introduce a new perceptual metric tailored for medical images, FRD (Fréchet Radiomic Distance), which utilizes standardized, clinically meaningful, and interpretable image features. We show that FRD is superior to other image distribution metrics for a range of medical imaging applications, including out-of-domain (OOD) detection, the evaluation of image-to-image translation (by correlating more with downstream task performance as well as anatomical consistency and realism), and the evaluation of unconditional image generation. Moreover, FRD offers additional benefits such as stability and computational efficiency at low sample sizes, sensitivity to image corruptions and adversarial attacks, feature interpretability, and correlation with radiologist-perceived image quality. Additionally, we address key gaps in the literature by presenting an extensive framework for the multifaceted evaluation of image similarity metrics in medical imaging -- including the first large-scale comparative study of generative models for medical image translation -- and release an accessible codebase to facilitate future research. Our results are supported by thorough experiments spanning a variety of datasets, modalities, and downstream tasks, highlighting the broad potential of FRD for medical image analysis.

Cosmin I. Bercea, Philippe C. Cattin, Julia A. Schnabel et al.

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.

Anneliese Riess, Kristian Schwethelm, Johannes Kaiser et al.

The gold standard for privacy in machine learning, Differential Privacy (DP), is often interpreted through its guarantees against membership inference. However, translating DP budgets into quantitative protection against the more damaging threat of data reconstruction remains a challenging open problem. Existing theoretical analyses of reconstruction risk are typically based on an "identification" threat model, where an adversary with a candidate set seeks a perfect match. When applied to the realistic threat of "from-scratch" attacks, these bounds can lead to an inefficient privacy-utility trade-off. This paper bridges this critical gap by deriving the first formal privacy bounds tailored to the mechanics of demonstrated Analytic Gradient Inversion Attacks (AGIAs). We first formalize the optimal from-scratch attack strategy for an adversary with no prior knowledge, showing it reduces to a mean estimation problem. We then derive closed-form, probabilistic bounds on this adversary's success, measured by Mean Squared Error (MSE) and Peak Signal-to-Noise Ratio (PSNR). Our empirical evaluation confirms these bounds remain tight even when the attack is concealed within large, complex network architectures. Our work provides a crucial second anchor for risk assessment. By establishing a tight, worst-case bound for the from-scratch threat model, we enable practitioners to assess a "risk corridor" bounded by the identification-based worst case on one side and our from-scratch worst case on the other. This allows for a more holistic, context-aware judgment of privacy risk, empowering practitioners to move beyond abstract budgets toward a principled reasoning framework for calibrating the privacy of their models.