Maria Vakalopoulou

Jingwei Zhang, Saarthak Kapse, Ke Ma et al.

Whole slide image (WSI) classification is a critical task in computational pathology, requiring the processing of gigapixel-sized images, which is challenging for current deep-learning methods. Current state of the art methods are based on multi-instance learning schemes (MIL), which usually rely on pretrained features to represent the instances. Due to the lack of task-specific annotated data, these features are either obtained from well-established backbones on natural images, or, more recently from self-supervised models pretrained on histopathology. However, both approaches yield task-agnostic features, resulting in performance loss compared to the appropriate task-related supervision, if available. In this paper, we show that when task-specific annotations are limited, we can inject such supervision into downstream task training, to reduce the gap between fully task-tuned and task agnostic features. We propose Prompt-MIL, an MIL framework that integrates prompts into WSI classification. Prompt-MIL adopts a prompt tuning mechanism, where only a small fraction of parameters calibrates the pretrained features to encode task-specific information, rather than the conventional full fine-tuning approaches. Extensive experiments on three WSI datasets, TCGA-BRCA, TCGA-CRC, and BRIGHT, demonstrate the superiority of Prompt-MIL over conventional MIL methods, achieving a relative improvement of 1.49%-4.03% in accuracy and 0.25%-8.97% in AUROC while using fewer than 0.3% additional parameters. Compared to conventional full fine-tuning approaches, we fine-tune less than 1.3% of the parameters, yet achieve a relative improvement of 1.29%-13.61% in accuracy and 3.22%-27.18% in AUROC and reduce GPU memory consumption by 38%-45% while training 21%-27% faster. Our code is available at https://github.com/cvlab-stonybrook/PromptMIL.

Joseph Boyd, Irène Villa, Marie-Christine Mathieu et al.

In whole slide imaging, commonly used staining techniques based on hematoxylin and eosin (H&E) and immunohistochemistry (IHC) stains accentuate different aspects of the tissue landscape. In the case of detecting metastases, IHC provides a distinct readout that is readily interpretable by pathologists. IHC, however, is a more expensive approach and not available at all medical centers. Virtually generating IHC images from H&E using deep neural networks thus becomes an attractive alternative. Deep generative models such as CycleGANs learn a semantically-consistent mapping between two image domains, while emulating the textural properties of each domain. They are therefore a suitable choice for stain transfer applications. However, they remain fully unsupervised, and possess no mechanism for enforcing biological consistency in stain transfer. In this paper, we propose an extension to CycleGANs in the form of a region of interest discriminator. This allows the CycleGAN to learn from unpaired datasets where, in addition, there is a partial annotation of objects for which one wishes to enforce consistency. We present a use case on whole slide images, where an IHC stain provides an experimentally generated signal for metastatic cells. We demonstrate the superiority of our approach over prior art in stain transfer on histopathology tiles over two datasets. Our code and model are available at https://github.com/jcboyd/miccai2022-roigan.

Jingwei Zhang, Xin Zhang, Ke Ma et al.

Histopathology whole slide images (WSIs) play a very important role in clinical studies and serve as the gold standard for many cancer diagnoses. However, generating automatic tools for processing WSIs is challenging due to their enormous sizes. Currently, to deal with this issue, conventional methods rely on a multiple instance learning (MIL) strategy to process a WSI at patch level. Although effective, such methods are computationally expensive, because tiling a WSI into patches takes time and does not explore the spatial relations between these tiles. To tackle these limitations, we propose a locally supervised learning framework which processes the entire slide by exploring the entire local and global information that it contains. This framework divides a pre-trained network into several modules and optimizes each module locally using an auxiliary model. We also introduce a random feature reconstruction unit (RFR) to preserve distinguishing features during training and improve the performance of our method by 1% to 3%. Extensive experiments on three publicly available WSI datasets: TCGA-NSCLC, TCGA-RCC and LKS, highlight the superiority of our method on different classification tasks. Our method outperforms the state-of-the-art MIL methods by 2% to 5% in accuracy, while being 7 to 10 times faster. Additionally, when dividing it into eight modules, our method requires as little as 20% of the total gpu memory required by end-to-end training. Our code is available at https://github.com/cvlab-stonybrook/local_learning_wsi.

Leo Fillioux, Joseph Boyd, Maria Vakalopoulou et al.

Multiple instance learning is an ideal mode of analysis for histopathology data, where vast whole slide images are typically annotated with a single global label. In such cases, a whole slide image is modelled as a collection of tissue patches to be aggregated and classified. Common models for performing this classification include recurrent neural networks and transformers. Although powerful compression algorithms, such as deep pre-trained neural networks, are used to reduce the dimensionality of each patch, the sequences arising from whole slide images remain excessively long, routinely containing tens of thousands of patches. Structured state space models are an emerging alternative for sequence modelling, specifically designed for the efficient modelling of long sequences. These models invoke an optimal projection of an input sequence into memory units that compress the entire sequence. In this paper, we propose the use of state space models as a multiple instance learner to a variety of problems in digital pathology. Across experiments in metastasis detection, cancer subtyping, mutation classification, and multitask learning, we demonstrate the competitiveness of this new class of models with existing state of the art approaches. Our code is available at https://github.com/MICS-Lab/s4_digital_pathology.

Jingwei Zhang, Saarthak Kapse, Ke Ma et al.

Dense prediction tasks such as segmentation and detection of pathological entities hold crucial clinical value in computational pathology workflows. However, obtaining dense annotations on large cohorts is usually tedious and expensive. Contrastive learning (CL) is thus often employed to leverage large volumes of unlabeled data to pre-train the backbone network. To boost CL for dense prediction, some studies have proposed variations of dense matching objectives in pre-training. However, our analysis shows that employing existing dense matching strategies on histopathology images enforces invariance among incorrect pairs of dense features and, thus, is imprecise. To address this, we propose a precise location-based matching mechanism that utilizes the overlapping information between geometric transformations to precisely match regions in two augmentations. Extensive experiments on two pretraining datasets (TCGA-BRCA, NCT-CRC-HE) and three downstream datasets (GlaS, CRAG, BCSS) highlight the superiority of our method in semantic and instance segmentation tasks. Our method outperforms previous dense matching methods by up to 7.2% in average precision for detection and 5.6% in average precision for instance segmentation tasks. Additionally, by using our matching mechanism in the three popular contrastive learning frameworks, MoCo-v2, VICRegL, and ConCL, the average precision in detection is improved by 0.7% to 5.2%, and the average precision in segmentation is improved by 0.7% to 4.0%, demonstrating generalizability. Our code is available at https://github.com/cvlab-stonybrook/PLM_SSL.

Leo Milecki, Vicky Kalogeiton, Sylvain Bodard et al.

Renal transplantation emerges as the most effective solution for end-stage renal disease. Occurring from complex causes, a substantial risk of transplant chronic dysfunction persists and may lead to graft loss. Medical imaging plays a substantial role in renal transplant monitoring in clinical practice. However, graft supervision is multi-disciplinary, notably joining nephrology, urology, and radiology, while identifying robust biomarkers from such high-dimensional and complex data for prognosis is challenging. In this work, taking inspiration from the recent success of Large Language Models (LLMs), we propose MEDIMP -- Medical Images with clinical Prompts -- a model to learn meaningful multi-modal representations of renal transplant Dynamic Contrast-Enhanced Magnetic Resonance Imaging (DCE MRI) by incorporating structural clinicobiological data after translating them into text prompts. MEDIMP is based on contrastive learning from joint text-image paired embeddings to perform this challenging task. Moreover, we propose a framework that generates medical prompts using automatic textual data augmentations from LLMs. Our goal is to learn meaningful manifolds of renal transplant DCE MRI, interesting for the prognosis of the transplant or patient status (2, 3, and 4 years after the transplant), fully exploiting the limited available multi-modal data most efficiently. Extensive experiments and comparisons with other renal transplant representation learning methods with limited data prove the effectiveness of MEDIMP in a relevant clinical setting, giving new directions toward medical prompts. Our code is available at https://github.com/leomlck/MEDIMP.

Jingwei Zhang, Ke Ma, Saarthak Kapse et al.

Semantic segmentations of pathological entities have crucial clinical value in computational pathology workflows. Foundation models, such as the Segment Anything Model (SAM), have been recently proposed for universal use in segmentation tasks. SAM shows remarkable promise in instance segmentation on natural images. However, the applicability of SAM to computational pathology tasks is limited due to the following factors: (1) lack of comprehensive pathology datasets used in SAM training and (2) the design of SAM is not inherently optimized for semantic segmentation tasks. In this work, we adapt SAM for semantic segmentation by introducing trainable class prompts, followed by further enhancements through the incorporation of a pathology encoder, specifically a pathology foundation model. Our framework, SAM-Path enhances SAM's ability to conduct semantic segmentation in digital pathology without human input prompts. Through experiments on two public pathology datasets, the BCSS and the CRAG datasets, we demonstrate that the fine-tuning with trainable class prompts outperforms vanilla SAM with manual prompts and post-processing by 27.52% in Dice score and 71.63% in IOU. On these two datasets, the proposed additional pathology foundation model further achieves a relative improvement of 5.07% to 5.12% in Dice score and 4.50% to 8.48% in IOU.

Loïc Le Bescond, Maria Vakalopoulou, Stergios Christodoulidis et al.

The deployment of machine learning solutions in real-world scenarios often involves addressing the challenge of out-of-distribution (OOD) detection. While significant efforts have been devoted to OOD detection in classical supervised settings, the context of weakly supervised learning, particularly the Multiple Instance Learning (MIL) framework, remains under-explored. In this study, we tackle this challenge by adapting post-hoc OOD detection methods to the MIL setting while introducing a novel benchmark specifically designed to assess OOD detection performance in weakly supervised scenarios. Across extensive experiments based on diverse public datasets, KNN emerges as the best-performing method overall. However, it exhibits significant shortcomings on some datasets, emphasizing the complexity of this under-explored and challenging topic. Our findings shed light on the complex nature of OOD detection under the MIL framework, emphasizing the importance of developing novel, robust, and reliable methods that can generalize effectively in a weakly supervised context. The code for the paper is available here: https://github.com/loic-lb/OOD_MIL.

Aggelos Psiris, Yannis Panagakis, Maria Vakalopoulou et al.

Few-Shot Industrial Visual Anomaly Detection (FS-IVAD) comprises a critical task in modern manufacturing settings, where automated product inspection systems need to identify rare defects using only a handful of normal/defect-free training samples. In this context, the current study introduces a novel reconstruction-based approach termed GATE-AD. In particular, the proposed framework relies on the employment of a masked, representation-aligned Graph Attention Network (GAT) encoding scheme to learn robust appearance patterns of normal samples. By leveraging dense, patch-level, visual feature tokens as graph nodes, the model employs stacked self-attentional layers to adaptively encode complex, irregular, non-Euclidean, local relations. The graph is enhanced with a representation alignment component grounded on a learnable, latent space, where high reconstruction residual areas (i.e., defects) are assessed using a Scaled Cosine Error (SCE) objective function. Extensive comparative evaluation on the MVTec AD, VisA, and MPDD industrial defect detection benchmarks demonstrates that GATE-AD achieves state-of-the-art performance across the $1$- to $8$-shot settings, combining the highest detection accuracy (increase up to $1.8\%$ in image AUROC in the 8-shot case in MPDD) with the lowest per-image inference latency (at least $25.05\%$ faster), compared to the best-performing literature methods. In order to facilitate reproducibility and further research, the source code of GATE-AD is available at https://github.com/gthpapadopoulos/GATE-AD.

Leo Fillioux, Enzo Ferrante, Paul-Henry Cournède et al.

Large foundation models have emerged in the last years and are pushing performance boundaries for a variety of tasks. Training or even finetuning such models demands vast datasets and computational resources, which are often scarce and costly. Adaptation methods provide a computationally efficient solution to address these limitations by allowing such models to be finetuned on small amounts of data and computing power. This is achieved by appending new trainable modules to frozen backbones with only a fraction of the trainable parameters and fitting only these modules on novel tasks. Recently, the VeRA adapter was shown to excel in parameter-efficient adaptations by utilizing a pair of frozen random low-rank matrices shared across all layers. In this paper, we propose PVeRA, a probabilistic version of the VeRA adapter, which modifies the low-rank matrices of VeRA in a probabilistic manner. This modification naturally allows handling inherent ambiguities in the input and allows for different sampling configurations during training and testing. A comprehensive evaluation was performed on the VTAB-1k benchmark and seven adapters, with PVeRA outperforming VeRA and other adapters. Our code for training models with PVeRA and benchmarking all adapters is available https://github.com/leofillioux/pvera.

Andreas Lolos, Theofilos Christodoulou, Aris L. Moustakas et al.

In computational pathology, weak supervision has become the standard for deep learning due to the gigapixel scale of WSIs and the scarcity of pixel-level annotations, with Multiple Instance Learning (MIL) established as the principal framework for slide-level model training. In this paper, we introduce a novel setting for MIL methods, inspired by proceedings in Neural Partial Differential Equation (PDE) Solvers. Instead of relying on complex attention-based aggregation, we propose an efficient, aggregator-agnostic framework that removes the complexity of correlation learning from the MIL aggregator. CAPRMIL produces rich context-aware patch embeddings that promote effective correlation learning on downstream tasks. By projecting patch features -- extracted using a frozen patch encoder -- into a small set of global context/morphology-aware tokens and utilizing multi-head self-attention, CAPRMIL injects global context with linear computational complexity with respect to the bag size. Paired with a simple Mean MIL aggregator, CAPRMIL matches state-of-the-art slide-level performance across multiple public pathology benchmarks, while reducing the total number of trainable parameters by 48%-92.8% versus SOTA MILs, lowering FLOPs during inference by 52%-99%, and ranking among the best models on GPU memory efficiency and training time. Our results indicate that learning rich, context-aware instance representations before aggregation is an effective and scalable alternative to complex pooling for whole-slide analysis. Our code is available at https://github.com/mandlos/CAPRMIL

Othmane Laousy, Alexandre Araujo, Guillaume Chassagnon et al.

In medical imaging, segmentation models have known a significant improvement in the past decade and are now used daily in clinical practice. However, similar to classification models, segmentation models are affected by adversarial attacks. In a safety-critical field like healthcare, certifying model predictions is of the utmost importance. Randomized smoothing has been introduced lately and provides a framework to certify models and obtain theoretical guarantees. In this paper, we present for the first time a certified segmentation baseline for medical imaging based on randomized smoothing and diffusion models. Our results show that leveraging the power of denoising diffusion probabilistic models helps us overcome the limits of randomized smoothing. We conduct extensive experiments on five public datasets of chest X-rays, skin lesions, and colonoscopies, and empirically show that we are able to maintain high certified Dice scores even for highly perturbed images. Our work represents the first attempt to certify medical image segmentation models, and we aspire for it to set a foundation for future benchmarks in this crucial and largely uncharted area.

Marin Scalbert, Maria Vakalopoulou, Florent Couzinié-Devy

Histopathology whole slide images (WSIs) can reveal significant inter-hospital variability such as illumination, color or optical artifacts. These variations, caused by the use of different scanning protocols across medical centers (staining, scanner), can strongly harm algorithms generalization on unseen protocols. This motivates development of new methods to limit such drop of performances. In this paper, to enhance robustness on unseen target protocols, we propose a new test-time data augmentation based on multi domain image-to-image translation. It allows to project images from unseen protocol into each source domain before classifying them and ensembling the predictions. This test-time augmentation method results in a significant boost of performances for domain generalization. To demonstrate its effectiveness, our method has been evaluated on 2 different histopathology tasks where it outperforms conventional domain generalization, standard H&E specific color augmentation/normalization and standard test-time augmentation techniques. Our code is publicly available at https://gitlab.com/vitadx/articles/test-time-i2i-translation-ensembling.

Nicolás Gaggion, Maria Vakalopoulou, Diego H. Milone et al.

Learning anatomical segmentation from heterogeneous labels in multi-center datasets is a common situation encountered in clinical scenarios, where certain anatomical structures are only annotated in images coming from particular medical centers, but not in the full database. Here we first show how state-of-the-art pixel-level segmentation models fail in naively learning this task due to domain memorization issues and conflicting labels. We then propose to adopt HybridGNet, a landmark-based segmentation model which learns the available anatomical structures using graph-based representations. By analyzing the latent space learned by both models, we show that HybridGNet naturally learns more domain-invariant feature representations, and provide empirical evidence in the context of chest X-ray multiclass segmentation. We hope these insights will shed light on the training of deep learning models with heterogeneous labels from public and multi-center datasets.

Othmane Laousy, Alexandre Araujo, Guillaume Chassagnon et al.

The robustness of image segmentation has been an important research topic in the past few years as segmentation models have reached production-level accuracy. However, like classification models, segmentation models can be vulnerable to adversarial perturbations, which hinders their use in critical-decision systems like healthcare or autonomous driving. Recently, randomized smoothing has been proposed to certify segmentation predictions by adding Gaussian noise to the input to obtain theoretical guarantees. However, this method exhibits a trade-off between the amount of added noise and the level of certification achieved. In this paper, we address the problem of certifying segmentation prediction using a combination of randomized smoothing and diffusion models. Our experiments show that combining randomized smoothing and diffusion models significantly improves certified robustness, with results indicating a mean improvement of 21 points in accuracy compared to previous state-of-the-art methods on Pascal-Context and Cityscapes public datasets. Our method is independent of the selected segmentation model and does not need any additional specialized training procedure.

Leo Fillioux, Emilie Gontran, Jérôme Cartry et al.

Over the last ten years, Patient-Derived Organoids (PDOs) emerged as the most reliable technology to generate ex-vivo tumor avatars. PDOs retain the main characteristics of their original tumor, making them a system of choice for pre-clinical and clinical studies. In particular, PDOs are attracting interest in the field of Functional Precision Medicine (FPM), which is based upon an ex-vivo drug test in which living tumor cells (such as PDOs) from a specific patient are exposed to a panel of anti-cancer drugs. Currently, the Adenosine Triphosphate (ATP) based cell viability assay is the gold standard test to assess the sensitivity of PDOs to drugs. The readout is measured at the end of the assay from a global PDO population and therefore does not capture single PDO responses and does not provide time resolution of drug effect. To this end, in this study, we explore for the first time the use of powerful large foundation models for the automatic processing of PDO data. In particular, we propose a novel imaging-based high-throughput screening method to assess real-time drug efficacy from a time-lapse microscopy video of PDOs. The recently proposed SAM algorithm for segmentation and DINOv2 model are adapted in a comprehensive pipeline for processing PDO microscopy frames. Moreover, an attention mechanism is proposed for fusing temporal and spatial features in a multiple instance learning setting to predict ATP. We report better results than other non-time-resolved methods, indicating that the temporality of data is an important factor for the prediction of ATP. Extensive ablations shed light on optimizing the experimental setting and automating the prediction both in real-time and for forecasting.

Panagiotis Koletsis, Vasilis Efthymiou, Maria Vakalopoulou et al.

In recent years, significant advances in computer vision have also propelled progress in remote sensing. Concurrently, the use of drones has expanded, with many organizations incorporating them into their operations. Most drones are equipped by default with RGB cameras, which are both robust and among the easiest sensors to use and interpret. The body of literature on optical remote sensing is vast, encompassing diverse tasks, capabilities, and methodologies. Each task or methodology could warrant a dedicated survey. This work provides a comprehensive overview of the capabilities of the field, while also presenting key information, such as datasets and insights. It aims to serve as a guide for researchers entering the field, offering high-level insights and helping them focus on areas most relevant to their interests. To the best of our knowledge, no existing survey addresses this holistic perspective.

Badr-Eddine Marani, Julio Silva-Rodriguez, Ismail Ben Ayed et al.

Deep neural networks have achieved remarkable success across a variety of tasks, yet they often suffer from unreliable probability estimates. As a result, they can be overconfident in their predictions. Conformal Prediction (CP) offers a principled framework for uncertainty quantification, yielding prediction sets with rigorous coverage guarantees. Existing conformal training methods optimize for overall set size, but shaping the prediction sets in a class-conditional manner is not straightforward and typically requires prior knowledge of the data distribution. In this work, we introduce Class Adaptive Conformal Training (CaCT), which formulates conformal training as an augmented Lagrangian optimization problem that adaptively learns to shape prediction sets class-conditionally without making any distributional assumptions. Experiments on multiple benchmark datasets, including standard and long-tailed image recognition as well as text classification, demonstrate that CaCT consistently outperforms prior conformal training methods, producing significantly smaller and more informative prediction sets while maintaining the desired coverage guarantees.

Leo Fillioux, Omprakash Chakraborty, Ismail Ben Ayed et al.

With the increasing adoption of vision-language models (VLMs) in critical decision-making systems such as healthcare or autonomous driving, the calibration of their uncertainty estimates becomes paramount. Yet, this dimension has been largely underexplored in the VLM test-time prompt-tuning (TPT) literature, which has predominantly focused on improving their discriminative performance. Recent state-of-the-art advocates for enforcing full orthogonality over pairs of text prompt embeddings to enhance separability, and therefore calibration. Nevertheless, as we theoretically show in this work, the inherent gradients from fully orthogonal constraints will strongly push semantically related classes away, ultimately making the model overconfident. Based on our findings, we propose Semantic Orthogonal Calibration (SoC), a Huber-based regularizer that enforces smooth prototype separation while preserving semantic proximity, thereby improving calibration compared to prior orthogonality-based approaches. Across a comprehensive empirical validation, we demonstrate that SoC consistently improves calibration performance, while also maintaining competitive discriminative capabilities.

Marin Scalbert, Maria Vakalopoulou, Florent Couzinié-Devy

In Self-Supervised Learning (SSL), models are typically pretrained, fine-tuned, and evaluated on the same domains. However, they tend to perform poorly when evaluated on unseen domains, a challenge that Unsupervised Domain Generalization (UDG) seeks to address. Current UDG methods rely on domain labels, which are often challenging to collect, and domain-specific architectures that lack scalability when confronted with numerous domains, making the current methodology impractical and rigid. Inspired by contrastive-based UDG methods that mitigate spurious correlations by restricting comparisons to examples from the same domain, we hypothesize that eliminating style variability within a batch could provide a more convenient and flexible way to reduce spurious correlations without requiring domain labels. To verify this hypothesis, we introduce Batch Styles Standardization (BSS), a relatively simple yet powerful Fourier-based method to standardize the style of images in a batch specifically designed for integration with SSL methods to tackle UDG. Combining BSS with existing SSL methods offers serious advantages over prior UDG methods: (1) It eliminates the need for domain labels or domain-specific network components to enhance domain-invariance in SSL representations, and (2) offers flexibility as BSS can be seamlessly integrated with diverse contrastive-based but also non-contrastive-based SSL methods. Experiments on several UDG datasets demonstrate that it significantly improves downstream task performances on unseen domains, often outperforming or rivaling with UDG methods. Finally, this work clarifies the underlying mechanisms contributing to BSS's effectiveness in improving domain-invariance in SSL representations and performances on unseen domain.

Badr-Eddine Marani, Mohamed Hanini, Nihitha Malayarukil et al.

The proliferation of machine learning models in critical decision making processes has underscored the need for bias discovery and mitigation strategies. Identifying the reasons behind a biased system is not straightforward, since in many occasions they are associated with hidden spurious correlations which are not easy to spot. Standard approaches rely on bias audits performed by analyzing model performance in pre-defined subgroups of data samples, usually characterized by common attributes like gender or ethnicity when it comes to people, or other specific attributes defining semantically coherent groups of images. However, it is not always possible to know a-priori the specific attributes defining the failure modes of visual recognition systems. Recent approaches propose to discover these groups by leveraging large vision language models, which enable the extraction of cross-modal embeddings and the generation of textual descriptions to characterize the subgroups where a certain model is underperforming. In this work, we argue that incorporating visual explanations (e.g. heatmaps generated via GradCAM or other approaches) can boost the performance of such bias discovery and mitigation frameworks. To this end, we introduce Visually Grounded Bias Discovery and Mitigation (ViG-Bias), a simple yet effective technique which can be integrated to a variety of existing frameworks to improve both, discovery and mitigation performance. Our comprehensive evaluation shows that incorporating visual explanations enhances existing techniques like DOMINO, FACTS and Bias-to-Text, across several challenging datasets, including CelebA, Waterbirds, and NICO++.

Cameron Dahan, Stergios Christodoulidis, Maria Vakalopoulou et al.

In the clinical setting of histopathology, whole-slide image (WSI) artifacts frequently arise, distorting regions of interest, and having a pernicious impact on WSI analysis. Image-to-image translation networks such as CycleGANs are in principle capable of learning an artifact removal function from unpaired data. However, we identify a surjection problem with artifact removal, and propose an weakly-supervised extension to CycleGAN to address this. We assemble a pan-cancer dataset comprising artifact and clean tiles from the TCGA database. Promising results highlight the soundness of our method.

Nicolás Gaggion, Maria J. Ledesma-Carbayo, Stergios Christodoulidis et al.

Graph-based medical image segmentation represents anatomical structures using boundary graphs, providing fixed-topology landmarks and inherent population-level correspondences. However, their clinical adoption has been hindered by a major requirement: training datasets with manually annotated landmarks that maintain point-to-point correspondences across patients rarely exist in practice. We introduce Mask-HybridGNet, a framework that trains graph-based models directly using standard pixel-wise masks, eliminating the need for manual landmark annotations. Our approach aligns variable-length ground truth boundaries with fixed-length landmark predictions by combining Chamfer distance supervision and edge-based regularization to ensure local smoothness and regular landmark distribution, further refined via differentiable rasterization. A significant emergent property of this framework is that predicted landmark positions become consistently associated with specific anatomical locations across patients without explicit correspondence supervision. This implicit atlas learning enables temporal tracking, cross-slice reconstruction, and morphological population analyses. Beyond direct segmentation, Mask-HybridGNet can extract correspondences from existing segmentation masks, allowing it to generate stable anatomical atlases from any high-quality pixel-based model. Experiments across chest radiography, cardiac ultrasound, cardiac MRI, and fetal imaging demonstrate that our model achieves competitive results against state-of-the-art pixel-based methods, while ensuring anatomical plausibility by enforcing boundary connectivity through a fixed graph adjacency matrix. This framework leverages the vast availability of standard segmentation masks to build structured models that maintain topological integrity and provide implicit correspondences.

Varun Belagali, Saarthak Kapse, Pierre Marza et al.

The interpretation of small tiles in large whole slide images (WSI) often needs a larger image context. We introduce TICON, a transformer-based tile representation contextualizer that produces rich, contextualized embeddings for ''any'' application in computational pathology. Standard tile encoder-based pipelines, which extract embeddings of tiles stripped from their context, fail to model the rich slide-level information essential for both local and global tasks. Furthermore, different tile-encoders excel at different downstream tasks. Therefore, a unified model is needed to contextualize embeddings derived from ''any'' tile-level foundation model. TICON addresses this need with a single, shared encoder, pretrained using a masked modeling objective to simultaneously unify and contextualize representations from diverse tile-level pathology foundation models. Our experiments demonstrate that TICON-contextualized embeddings significantly improve performance across many different tasks, establishing new state-of-the-art results on tile-level benchmarks (i.e., HEST-Bench, THUNDER, CATCH) and slide-level benchmarks (i.e., Patho-Bench). Finally, we pretrain an aggregator on TICON to form a slide-level foundation model, using only 11K WSIs, outperforming SoTA slide-level foundation models pretrained with up to 350K WSIs.

David Restrepo, Ira Ktena, Maria Vakalopoulou et al.

Vision-language models (VLMs) are increasingly proposed for clinical decision support, yet their reliability in real-world scenarios that require integrating both visual and textual context from medical records remains poorly characterized. This paper identifies three failure modes: (1) modality over-reliance on text over images, (2) spurious reliance on irrelevant clinical history, and (3) prompt sensitivity across semantically equivalent inputs. We evaluate a diverse set of general-domain and medically-tuned open and closed VLMs on chest x-ray tasks using MIMIC-CXR. By systematically manipulating image-text alignment, clinical history, and prompt formulations, we found that VLM decisions are dominated by the text modality, even when visual evidence is available. Moreover, we observed that VLMs are heavily influenced by irrelevant reports, while minor prompt changes can reverse correct image-based predictions. Our findings underscore the need for explicit safeguards and stress-testing before considering the use of these models in clinical practice.

Julie Mordacq, Leo Milecki, Maria Vakalopoulou et al.

Multimodality has recently gained attention in the medical domain, where imaging or video modalities may be integrated with biomedical signals or health records. Yet, two challenges remain: balancing the contributions of modalities, especially in cases with a limited amount of data available, and tackling missing modalities. To address both issues, in this paper, we introduce the AnchoreD multimodAl Physiological Transformer (ADAPT), a multimodal, scalable framework with two key components: (i) aligning all modalities in the space of the strongest, richest modality (called anchor) to learn a joint embedding space, and (ii) a Masked Multimodal Transformer, leveraging both inter- and intra-modality correlations while handling missing modalities. We focus on detecting physiological changes in two real-life scenarios: stress in individuals induced by specific triggers and fighter pilots' loss of consciousness induced by $g$-forces. We validate the generalizability of ADAPT through extensive experiments on two datasets for these tasks, where we set the new state of the art while demonstrating its robustness across various modality scenarios and its high potential for real-life applications.

David Restrepo, Miguel L Martins, Chenwei Wu et al.

Vision-Language Models (VLMs) exhibit a characteristic "cone effect" in which nonlinear encoders map embeddings into highly concentrated regions of the representation space, contributing to cross-modal separation known as the modality gap. While this phenomenon has been widely observed, its practical impact on supervised multimodal learning -particularly in medical domains- remains unclear. In this work, we introduce a lightweight post-hoc mechanism that keeps pretrained VLM encoders frozen while continuously controlling cross-modal separation through a single hyperparameter {λ}. This enables systematic analysis of how the modality gap affects downstream multimodal performance without expensive retraining. We evaluate generalist (CLIP, SigLIP) and medically specialized (BioMedCLIP, MedSigLIP) models across diverse medical and natural datasets in a supervised multimodal settings. Results consistently show that reducing excessive modality gap improves downstream performance, with medical datasets exhibiting stronger sensitivity to gap modulation; however, fully collapsing the gap is not always optimal, and intermediate, task-dependent separation yields the best results. These findings position the modality gap as a tunable property of multimodal representations rather than a quantity that should be universally minimized.

Pablo Morales-Álvarez, Stergios Christodoulidis, Maria Vakalopoulou et al.

The emergence of large pre-trained vision-language models (VLMs) represents a paradigm shift in machine learning, with unprecedented results in a broad span of visual recognition tasks. CLIP, one of the most popular VLMs, has exhibited remarkable zero-shot and transfer learning capabilities in classification. To transfer CLIP to downstream tasks, adapters constitute a parameter-efficient approach that avoids backpropagation through the large model (unlike related prompt learning methods). However, CLIP adapters have been developed to target discriminative performance, and the quality of their uncertainty estimates has been overlooked. In this work we show that the discriminative performance of state-of-the-art CLIP adapters does not always correlate with their uncertainty estimation capabilities, which are essential for a safe deployment in real-world scenarios. We also demonstrate that one of such adapters is obtained through MAP inference from a more general probabilistic framework. Based on this observation we introduce BayesAdapter, which leverages Bayesian inference to estimate a full probability distribution instead of a single point, better capturing the variability inherent in the parameter space. In a comprehensive empirical evaluation we show that our approach obtains high quality uncertainty estimates in the predictions, standing out in calibration and selective classification. Our code will be publicly available upon acceptance of the paper.

Pierre Marza, Leo Fillioux, Sofiène Boutaj et al.

Progress in a research field can be hard to assess, in particular when many concurrent methods are proposed in a short period of time. This is the case in digital pathology, where many foundation models have been released recently to serve as feature extractors for tile-level images, being used in a variety of downstream tasks, both for tile- and slide-level problems. Benchmarking available methods then becomes paramount to get a clearer view of the research landscape. In particular, in critical domains such as healthcare, a benchmark should not only focus on evaluating downstream performance, but also provide insights about the main differences between methods, and importantly, further consider uncertainty and robustness to ensure a reliable usage of proposed models. For these reasons, we introduce THUNDER, a tile-level benchmark for digital pathology foundation models, allowing for efficient comparison of many models on diverse datasets with a series of downstream tasks, studying their feature spaces and assessing the robustness and uncertainty of predictions informed by their embeddings. THUNDER is a fast, easy-to-use, dynamic benchmark that can already support a large variety of state-of-the-art foundation, as well as local user-defined models for direct tile-based comparison. In this paper, we provide a comprehensive comparison of 23 foundation models on 16 different datasets covering diverse tasks, feature analysis, and robustness. The code for THUNDER is publicly available at https://github.com/MICS-Lab/thunder.

Konstantinos Barmpounakis, Theodoros P. Vagenas, Maria Vakalopoulou et al.

Radiotherapy workflows for oncological patients increasingly rely on multi-modal medical imaging, commonly involving both Magnetic Resonance Imaging (MRI) and Computed Tomography (CT). MRI-only treatment planning has emerged as an attractive alternative, as it reduces patient exposure to ionizing radiation and avoids errors introduced by inter-modality registration. While nnU-Net-based frameworks are predominantly used for MRI-to-CT synthesis, we explore Mamba-based architectures for this task, aiming to showcase the advantages of state-space modeling for cross-modality translation compared to standard convolutional neural networks. Specifically, we adapt both the U-Mamba and the SegMamba architecture, originally proposed for segmentation, to perform cross-modality image generation. Our 3D Mamba architecture effectively captures complex volumetric features and long-range dependencies, thus allowing accurate CT synthesis while maintaining fast inference times. Experiments were conducted on a subset of SynthRAD2025 dataset, comprising registered single-channel MRI-CT volume pairs across three anatomical regions. Quantitative evaluation is performed via a combination of image similarity metrics computed in Hounsefield Units (HU) and segmentation-based metrics obtained from TotalSegmentator to ensure geometric consistency is preserved. The findings pave the way for the integration of state-space models into radiotherapy workflows.

Daphne Tsolissou, Theofanis Ganitidis, Konstantinos Mitsis et al.

Reliable risk assessment for carotid atheromatous disease remains a major clinical challenge, as it requires integrating diverse clinical and imaging information in a manner that is transparent and interpretable to clinicians. This study investigates the potential of state-of-the-art and recent large vision-language models (LVLMs) for multimodal carotid plaque assessment by integrating ultrasound imaging (USI) with structured clinical, demographic, laboratory, and protein biomarker data. A framework that simulates realistic diagnostic scenarios through interview-style question sequences is proposed, comparing a range of open-source LVLMs, including both general-purpose and medically tuned models. Zero-shot experiments reveal that even if they are very powerful, not all LVLMs can accurately identify imaging modality and anatomy, while all of them perform poorly in accurate risk classification. To address this limitation, LLaVa-NeXT-Vicuna is adapted to the ultrasound domain using low-rank adaptation (LoRA), resulting in substantial improvements in stroke risk stratification. The integration of multimodal tabular data in the form of text further enhances specificity and balanced accuracy, yielding competitive performance compared to prior convolutional neural network (CNN) baselines trained on the same dataset. Our findings highlight both the promise and limitations of LVLMs in ultrasound-based cardiovascular risk prediction, underscoring the importance of multimodal integration, model calibration, and domain adaptation for clinical translation.

Sofiène Boutaj, Marin Scalbert, Pierre Marza et al.

Whole slide image (WSI) analysis in digital pathology presents unique challenges due to the gigapixel resolution of WSIs and the scarcity of dense supervision signals. While Multiple Instance Learning (MIL) is a natural fit for slide-level tasks, training robust models requires large and diverse datasets. Even though image augmentation techniques could be utilized to increase data variability and reduce overfitting, implementing them effectively is not a trivial task. Traditional patch-level augmentation is prohibitively expensive due to the large number of patches extracted from each WSI, and existing feature-level augmentation methods lack control over transformation semantics. We introduce HistAug, a fast and efficient generative model for controllable augmentations in the latent space for digital pathology. By conditioning on explicit patch-level transformations (e.g., hue, erosion), HistAug generates realistic augmented embeddings while preserving initial semantic information. Our method allows the processing of a large number of patches in a single forward pass efficiently, while at the same time consistently improving MIL model performance. Experiments across multiple slide-level tasks and diverse organs show that HistAug outperforms existing methods, particularly in low-data regimes. Ablation studies confirm the benefits of learned transformations over noise-based perturbations and highlight the importance of uniform WSI-wise augmentation. Code is available at https://github.com/MICS-Lab/HistAug.

David Restrepo, Ira Ktena, Maria Vakalopoulou et al.

Clinical decision-making relies on the integrated analysis of medical images and the associated clinical reports. While Vision-Language Models (VLMs) can offer a unified framework for such tasks, they can exhibit strong biases toward one modality, frequently overlooking critical visual cues in favor of textual information. In this work, we introduce Selective Modality Shifting (SMS), a perturbation-based approach to quantify a model's reliance on each modality in binary classification tasks. By systematically swapping images or text between samples with opposing labels, we expose modality-specific biases. We assess six open-source VLMs-four generalist models and two fine-tuned for medical data-on two medical imaging datasets with distinct modalities: MIMIC-CXR (chest X-ray) and FairVLMed (scanning laser ophthalmoscopy). By assessing model performance and the calibration of every model in both unperturbed and perturbed settings, we reveal a marked dependency on text input, which persists despite the presence of complementary visual information. We also perform a qualitative attention-based analysis which further confirms that image content is often overshadowed by text details. Our findings highlight the importance of designing and evaluating multimodal medical models that genuinely integrate visual and textual cues, rather than relying on single-modality signals.

Théo Sourget, David Restrepo, Céline Hudelot et al.

Motivated by the strong performance of CLIP-based models in natural image-text domains, recent efforts have adapted these architectures to medical tasks, particularly in radiology, where large paired datasets of images and reports, such as chest X-rays, are available. While these models have shown encouraging results in terms of accuracy and discriminative performance, their fairness and robustness in the different clinical tasks remain largely underexplored. In this study, we extensively evaluate six widely used CLIP-based models on chest X-ray classification using three publicly available datasets: MIMIC-CXR, NIH-CXR14, and NEATX. We assess the models fairness across six conditions and patient subgroups based on age, sex, and race. Additionally, we assess the robustness to shortcut learning by evaluating performance on pneumothorax cases with and without chest drains. Our results indicate performance gaps between patients of different ages, but more equitable results for the other attributes. Moreover, all models exhibit lower performance on images without chest drains, suggesting reliance on spurious correlations. We further complement the performance analysis with a study of the embeddings generated by the models. While the sensitive attributes could be classified from the embeddings, we do not see such patterns using PCA, showing the limitations of these visualisation techniques when assessing models. Our code is available at https://github.com/TheoSourget/clip_cxr_fairness

Andreas Lolos, Stergios Christodoulidis, Maria Vakalopoulou et al.

Multiple Instance Learning (MIL) offers a natural solution for settings where only coarse, bag-level labels are available, without having access to instance-level annotations. This is usually the case in digital pathology, which consists of gigapixel sized images. While deterministic attention-based MIL approaches achieve strong bag-level performance, they often overlook the uncertainty inherent in instance relevance. In this paper, we address the lack of uncertainty quantification in instance-level attention scores by introducing \textbf{SGPMIL}, a new probabilistic attention-based MIL framework grounded in Sparse Gaussian Processes (SGP). By learning a posterior distribution over attention scores, SGPMIL enables principled uncertainty estimation, resulting in more reliable and calibrated instance relevance maps. Our approach not only preserves competitive bag-level performance but also significantly improves the quality and interpretability of instance-level predictions under uncertainty. SGPMIL extends prior work by introducing feature scaling in the SGP predictive mean function, leading to faster training, improved efficiency, and enhanced instance-level performance. Extensive experiments on multiple well-established digital pathology datasets highlight the effectiveness of our approach across both bag- and instance-level evaluations. Our code will be made publicly available.

Joseph Boyd, Mykola Liashuha, Eric Deutsch et al.

The examination of histopathology images is considered to be the gold standard for the diagnosis and stratification of cancer patients. A key challenge in the analysis of such images is their size, which can run into the gigapixels and can require tedious screening by clinicians. With the recent advances in computational medicine, automatic tools have been proposed to assist clinicians in their everyday practice. Such tools typically process these large images by slicing them into tiles that can then be encoded and utilized for different clinical models. In this study, we propose a novel generative framework that can learn powerful representations for such tiles by learning to plausibly expand their visual field. In particular, we developed a progressively grown generative model with the objective of visual field expansion. Thus trained, our model learns to generate different tissue types with fine details, while simultaneously learning powerful representations that can be used for different clinical endpoints, all in a self-supervised way. To evaluate the performance of our model, we conducted classification experiments on CAMELYON17 and CRC benchmark datasets, comparing favorably to other self-supervised and pre-trained strategies that are commonly used in digital pathology. Our code is available at https://github.com/jcboyd/cdpath21-gan.

Marvin Lerousseau, Maria Vakalopoulou, Eric Deutsch et al.

Multiple instance learning (MIL) is the preferred approach for whole slide image classification. However, most MIL approaches do not exploit the interdependencies of tiles extracted from a whole slide image, which could provide valuable cues for classification. This paper presents a novel MIL approach that exploits the spatial relationship of tiles for classifying whole slide images. To do so, a sparse map is built from tiles embeddings, and is then classified by a sparse-input CNN. It obtained state-of-the-art performance over popular MIL approaches on the classification of cancer subtype involving 10000 whole slide images. Our results suggest that the proposed approach might (i) improve the representation learning of instances and (ii) exploit the context of instance embeddings to enhance the classification performance. The code of this work is open-source at {github censored for review}.

Théo Estienne, Maria Vakalopoulou, Enzo Battistella et al.

Image registration is one of the most challenging problems in medical image analysis. In the recent years, deep learning based approaches became quite popular, providing fast and performing registration strategies. In this short paper, we summarise our work presented on Learn2Reg challenge 2020. The main contributions of our work rely on (i) a symmetric formulation, predicting the transformations from source to target and from target to source simultaneously, enforcing the trained representations to be similar and (ii) integration of variety of publicly available datasets used both for pretraining and for augmenting segmentation labels. Our method reports a mean dice of $0.64$ for task 3 and $0.85$ for task 4 on the test sets, taking third place on the challenge. Our code and models are publicly available at https://github.com/TheoEst/abdominal_registration and \https://github.com/TheoEst/hippocampus_registration.

Marvin Lerousseau, Maria Vakalopoulou, Marion Classe et al.

Histopathological image segmentation is a challenging and important topic in medical imaging with tremendous potential impact in clinical practice. State of the art methods rely on hand-crafted annotations which hinder clinical translation since histology suffers from significant variations between cancer phenotypes. In this paper, we propose a weakly supervised framework for whole slide imaging segmentation that relies on standard clinical annotations, available in most medical systems. In particular, we exploit a multiple instance learning scheme for training models. The proposed framework has been evaluated on multi-locations and multi-centric public data from The Cancer Genome Atlas and the PatchCamelyon dataset. Promising results when compared with experts' annotations demonstrate the potentials of the presented approach. The complete framework, including $6481$ generated tumor maps and data processing, is available at https://github.com/marvinler/tcga_segmentation.

Ribana Roscher, Marc Rußwurm, Caroline Gevaert et al.

Recent developments and research in modern machine learning have led to substantial improvements in the geospatial field. Although numerous deep learning architectures and models have been proposed, the majority of them have been solely developed on benchmark datasets that lack strong real-world relevance. Furthermore, the performance of many methods has already saturated on these datasets. We argue that a shift from a model-centric view to a complementary data-centric perspective is necessary for further improvements in accuracy, generalization ability, and real impact on end-user applications. Furthermore, considering the entire machine learning cycle-from problem definition to model deployment with feedback-is crucial for enhancing machine learning models that can be reliable in unforeseen situations. This work presents a definition as well as a precise categorization and overview of automated data-centric learning approaches for geospatial data. It highlights the complementary role of data-centric learning with respect to model-centric in the larger machine learning deployment cycle. We review papers across the entire geospatial field and categorize them into different groups. A set of representative experiments shows concrete implementation examples. These examples provide concrete steps to act on geospatial data with data-centric machine learning approaches.

Saarthak Kapse, Pushpak Pati, Srijan Das et al.

Introducing interpretability and reasoning into Multiple Instance Learning (MIL) methods for Whole Slide Image (WSI) analysis is challenging, given the complexity of gigapixel slides. Traditionally, MIL interpretability is limited to identifying salient regions deemed pertinent for downstream tasks, offering little insight to the end-user (pathologist) regarding the rationale behind these selections. To address this, we propose Self-Interpretable MIL (SI-MIL), a method intrinsically designed for interpretability from the very outset. SI-MIL employs a deep MIL framework to guide an interpretable branch grounded on handcrafted pathological features, facilitating linear predictions. Beyond identifying salient regions, SI-MIL uniquely provides feature-level interpretations rooted in pathological insights for WSIs. Notably, SI-MIL, with its linear prediction constraints, challenges the prevalent myth of an inevitable trade-off between model interpretability and performance, demonstrating competitive results compared to state-of-the-art methods on WSI-level prediction tasks across three cancer types. In addition, we thoroughly benchmark the local and global-interpretability of SI-MIL in terms of statistical analysis, a domain expert study, and desiderata of interpretability, namely, user-friendliness and faithfulness.

Théo Moutakanni, Piotr Bojanowski, Guillaume Chassagnon et al.

AI Foundation models are gaining traction in various applications, including medical fields like radiology. However, medical foundation models are often tested on limited tasks, leaving their generalisability and biases unexplored. We present RayDINO, a large visual encoder trained by self-supervision on 873k chest X-rays. We compare RayDINO to previous state-of-the-art models across nine radiology tasks, from classification and dense segmentation to text generation, and provide an in depth analysis of population, age and sex biases of our model. Our findings suggest that self-supervision allows patient-centric AI proving useful in clinical workflows and interpreting X-rays holistically. With RayDINO and small task-specific adapters, we reach state-of-the-art results and improve generalization to unseen populations while mitigating bias, illustrating the true promise of foundation models: versatility and robustness.

Leo Fillioux, Julio Silva-Rodríguez, Ismail Ben Ayed et al.

Recent advances in self-supervision and contrastive learning have brought the performance of foundation models to unprecedented levels in a variety of tasks. Fueled by this progress, these models are becoming the prevailing approach for a wide array of real-world vision problems, including risk-sensitive and high-stakes applications. However, ensuring safe deployment in these scenarios requires a more comprehensive understanding of their uncertainty modeling capabilities, which has been barely explored. In this work, we delve into the behaviour of vision and vision-language foundation models under Conformal Prediction (CP), a statistical framework that provides theoretical guarantees of marginal coverage of the true class. Across extensive experiments including popular vision classification benchmarks, well-known foundation vision models, and three CP methods, our findings reveal that foundation models are well-suited for conformalization procedures, particularly those integrating Vision Transformers. We also show that calibrating the confidence predictions of these models, a popular strategy to improve their uncertainty quantification, actually leads to efficiency degradation of the conformal set on adaptive CP methods. Furthermore, few-shot adaptation of Vision-Language Models (VLMs) to downstream tasks, whose popularity is surging, enhances conformal scores compared to zero-shot predictions. Last, our empirical study exposes APS as particularly promising in the context of vision foundation models, as it does not violate the marginal coverage guarantees across multiple challenging, yet realistic scenarios.

Varun Belagali, Pierre Marza, Srikar Yellapragada et al.

Learning dense correspondences, critical for application such as video label propagation, is hindered by tedious and unscalable manual annotation. Self-supervised methods address this by using a cross-view pretext task, often modeled with a masked autoencoder, where a masked target view is reconstructed from an anchor view. However, acquiring effective training data remains a challenge - collecting diverse video datasets is difficult and costly, while simple image crops lack necessary pose variations. This paper introduces CDG-MAE, a novel MAE-based self-supervised method that uses diverse synthetic views generated from static images via an image-conditioned diffusion model. These generated views exhibit substantial changes in pose and perspective, providing a rich training signal that overcomes the limitations of video and crop-based anchors. We present a quantitative method to evaluate local and global consistency of generated images, discussing their use for cross-view self-supervised pretraining. Furthermore, we enhance the standard single-anchor MAE setting to a multi-anchor strategy to effectively modulate the difficulty of pretext task. CDG-MAE significantly outperforms state-of-the-art MAE methods reliant only on images and substantially narrows the performance gap to video-based approaches.

Théo Moutakanni, Maxime Oquab, Marc Szafraniec et al.

Self-Supervised learning (SSL) with Joint-Embedding Architectures (JEA) has led to outstanding performances. All instantiations of this paradigm were trained using strong and well-established hand-crafted data augmentations, leading to the general belief that they are required for the proper training and performance of such models. On the other hand, generative reconstruction-based models such as BEIT and MAE or Joint-Embedding Predictive Architectures such as I-JEPA have shown strong performance without using data augmentations except masking. In this work, we challenge the importance of invariance and data-augmentation in JEAs at scale. By running a case-study on a recent SSL foundation model - DINOv2 - we show that strong image representations can be obtained with JEAs and only cropping without resizing provided the training data is large enough, reaching state-of-the-art results and using the least amount of augmentation in the literature. Through this study, we also discuss the impact of compute constraints on the outcomes of experimental deep learning research, showing that they can lead to very different conclusions.

Bhakti Baheti, Satrajit Chakrabarty, Hamed Akbari et al.

Registration of longitudinal brain MRI scans containing pathologies is challenging due to dramatic changes in tissue appearance. Although there has been progress in developing general-purpose medical image registration techniques, they have not yet attained the requisite precision and reliability for this task, highlighting its inherent complexity. Here we describe the Brain Tumor Sequence Registration (BraTS-Reg) challenge, as the first public benchmark environment for deformable registration algorithms focusing on estimating correspondences between pre-operative and follow-up scans of the same patient diagnosed with a diffuse brain glioma. The BraTS-Reg data comprise de-identified multi-institutional multi-parametric MRI (mpMRI) scans, curated for size and resolution according to a canonical anatomical template, and divided into training, validation, and testing sets. Clinical experts annotated ground truth (GT) landmark points of anatomical locations distinct across the temporal domain. Quantitative evaluation and ranking were based on the Median Euclidean Error (MEE), Robustness, and the determinant of the Jacobian of the displacement field. The top-ranked methodologies yielded similar performance across all evaluation metrics and shared several methodological commonalities, including pre-alignment, deep neural networks, inverse consistency analysis, and test-time instance optimization per-case basis as a post-processing step. The top-ranked method attained the MEE at or below that of the inter-rater variability for approximately 60% of the evaluated landmarks, underscoring the scope for further accuracy and robustness improvements, especially relative to human experts. The aim of BraTS-Reg is to continue to serve as an active resource for research, with the data and online evaluation tools accessible at https://bratsreg.github.io/.

Alessa Hering, Lasse Hansen, Tony C. W. Mok et al.

Image registration is a fundamental medical image analysis task, and a wide variety of approaches have been proposed. However, only a few studies have comprehensively compared medical image registration approaches on a wide range of clinically relevant tasks. This limits the development of registration methods, the adoption of research advances into practice, and a fair benchmark across competing approaches. The Learn2Reg challenge addresses these limitations by providing a multi-task medical image registration data set for comprehensive characterisation of deformable registration algorithms. A continuous evaluation will be possible at https://learn2reg.grand-challenge.org. Learn2Reg covers a wide range of anatomies (brain, abdomen, and thorax), modalities (ultrasound, CT, MR), availability of annotations, as well as intra- and inter-patient registration evaluation. We established an easily accessible framework for training and validation of 3D registration methods, which enabled the compilation of results of over 65 individual method submissions from more than 20 unique teams. We used a complementary set of metrics, including robustness, accuracy, plausibility, and runtime, enabling unique insight into the current state-of-the-art of medical image registration. This paper describes datasets, tasks, evaluation methods and results of the challenge, as well as results of further analysis of transferability to new datasets, the importance of label supervision, and resulting bias. While no single approach worked best across all tasks, many methodological aspects could be identified that push the performance of medical image registration to new state-of-the-art performance. Furthermore, we demystified the common belief that conventional registration methods have to be much slower than deep-learning-based methods.

Théo Estienne, Maria Vakalopoulou, Enzo Battistella et al.

Deformable registration consists of finding the best dense correspondence between two different images. Many algorithms have been published, but the clinical application was made difficult by the high calculation time needed to solve the optimisation problem. Deep learning overtook this limitation by taking advantage of GPU calculation and the learning process. However, many deep learning methods do not take into account desirable properties respected by classical algorithms. In this paper, we present MICS, a novel deep learning algorithm for medical imaging registration. As registration is an ill-posed problem, we focused our algorithm on the respect of different properties: inverse consistency, symmetry and orientation conservation. We also combined our algorithm with a multi-step strategy to refine and improve the deformation grid. While many approaches applied registration to brain MRI, we explored a more challenging body localisation: abdominal CT. Finally, we evaluated our method on a dataset used during the Learn2Reg challenge, allowing a fair comparison with published methods.

Othmane Laousy, Guillaume Chassagnon, Edouard Oyallon et al.

Sarcopenia is a medical condition characterized by a reduction in muscle mass and function. A quantitative diagnosis technique consists of localizing the CT slice passing through the middle of the third lumbar area (L3) and segmenting muscles at this level. In this paper, we propose a deep reinforcement learning method for accurate localization of the L3 CT slice. Our method trains a reinforcement learning agent by incentivizing it to discover the right position. Specifically, a Deep Q-Network is trained to find the best policy to follow for this problem. Visualizing the training process shows that the agent mimics the scrolling of an experienced radiologist. Extensive experiments against other state-of-the-art deep learning based methods for L3 localization prove the superiority of our technique which performs well even with a limited amount of data and annotations.

Théo Estienne, Maria Vakalopoulou, Stergios Christodoulidis et al.

Explainability of deep neural networks is one of the most challenging and interesting problems in the field. In this study, we investigate the topic focusing on the interpretability of deep learning-based registration methods. In particular, with the appropriate model architecture and using a simple linear projection, we decompose the encoding space, generating a new basis, and we empirically show that this basis captures various decomposed anatomically aware geometrical transformations. We perform experiments using two different datasets focusing on lungs and hippocampus MRI. We show that such an approach can decompose the highly convoluted latent spaces of registration pipelines in an orthogonal space with several interesting properties. We hope that this work could shed some light on a better understanding of deep learning-based registration methods.