Reuben Dorent

Reuben Dorent, Nazim Haouchine, Fryderyk Kögl et al. · harvard

We introduce MHVAE, a deep hierarchical variational auto-encoder (VAE) that synthesizes missing images from various modalities. Extending multi-modal VAEs with a hierarchical latent structure, we introduce a probabilistic formulation for fusing multi-modal images in a common latent representation while having the flexibility to handle incomplete image sets as input. Moreover, adversarial learning is employed to generate sharper images. Extensive experiments are performed on the challenging problem of joint intra-operative ultrasound (iUS) and Magnetic Resonance (MR) synthesis. Our model outperformed multi-modal VAEs, conditional GANs, and the current state-of-the-art unified method (ResViT) for synthesizing missing images, demonstrating the advantage of using a hierarchical latent representation and a principled probabilistic fusion operation. Our code is publicly available \url{https://github.com/ReubenDo/MHVAE}.

Jianning Li, Zongwei Zhou, Jiancheng Yang et al.

Prior to the deep learning era, shape was commonly used to describe the objects. Nowadays, state-of-the-art (SOTA) algorithms in medical imaging are predominantly diverging from computer vision, where voxel grids, meshes, point clouds, and implicit surface models are used. This is seen from numerous shape-related publications in premier vision conferences as well as the growing popularity of ShapeNet (about 51,300 models) and Princeton ModelNet (127,915 models). For the medical domain, we present a large collection of anatomical shapes (e.g., bones, organs, vessels) and 3D models of surgical instrument, called MedShapeNet, created to facilitate the translation of data-driven vision algorithms to medical applications and to adapt SOTA vision algorithms to medical problems. As a unique feature, we directly model the majority of shapes on the imaging data of real patients. As of today, MedShapeNet includes 23 dataset with more than 100,000 shapes that are paired with annotations (ground truth). Our data is freely accessible via a web interface and a Python application programming interface (API) and can be used for discriminative, reconstructive, and variational benchmarks as well as various applications in virtual, augmented, or mixed reality, and 3D printing. Exemplary, we present use cases in the fields of classification of brain tumors, facial and skull reconstructions, multi-class anatomy completion, education, and 3D printing. In future, we will extend the data and improve the interfaces. The project pages are: https://medshapenet.ikim.nrw/ and https://github.com/Jianningli/medshapenet-feedback

Muhammad Asad, Reuben Dorent, Tom Vercauteren

The FastGeodis package provides an efficient implementation for computing Geodesic and Euclidean distance transforms (or a mixture of both), targeting efficient utilisation of CPU and GPU hardware. In particular, it implements the paralellisable raster scan method from Criminisi et al. (2009), where elements in a row (2D) or plane (3D) can be computed with parallel threads. This package is able to handle 2D as well as 3D data, where it achieves up to a 20x speedup on a CPU and up to a 74x speedup on a GPU as compared to an existing open-source library (Wang, 2020) that uses a non-parallelisable single-thread CPU implementation. The performance speedups reported here were evaluated using 3D volume data on an Nvidia GeForce Titan X (12 GB) with a 6-Core Intel Xeon E5-1650 CPU. Further in-depth comparison of performance improvements are discussed in the FastGeodis documentation: https://fastgeodis.readthedocs.io

Matthias Eisenmann, Annika Reinke, Vivienn Weru et al. · utoronto

The number of international benchmarking competitions is steadily increasing in various fields of machine learning (ML) research and practice. So far, however, little is known about the common practice as well as bottlenecks faced by the community in tackling the research questions posed. To shed light on the status quo of algorithm development in the specific field of biomedical imaging analysis, we designed an international survey that was issued to all participants of challenges conducted in conjunction with the IEEE ISBI 2021 and MICCAI 2021 conferences (80 competitions in total). The survey covered participants' expertise and working environments, their chosen strategies, as well as algorithm characteristics. A median of 72% challenge participants took part in the survey. According to our results, knowledge exchange was the primary incentive (70%) for participation, while the reception of prize money played only a minor role (16%). While a median of 80 working hours was spent on method development, a large portion of participants stated that they did not have enough time for method development (32%). 25% perceived the infrastructure to be a bottleneck. Overall, 94% of all solutions were deep learning-based. Of these, 84% were based on standard architectures. 43% of the respondents reported that the data samples (e.g., images) were too large to be processed at once. This was most commonly addressed by patch-based training (69%), downsampling (37%), and solving 3D analysis tasks as a series of 2D tasks. K-fold cross-validation on the training set was performed by only 37% of the participants and only 50% of the participants performed ensembling based on multiple identical models (61%) or heterogeneous models (39%). 48% of the respondents applied postprocessing steps.

Nazim Haouchine, Reuben Dorent, Parikshit Juvekar et al. · harvard

We present a novel method for intraoperative patient-to-image registration by learning Expected Appearances. Our method uses preoperative imaging to synthesize patient-specific expected views through a surgical microscope for a predicted range of transformations. Our method estimates the camera pose by minimizing the dissimilarity between the intraoperative 2D view through the optical microscope and the synthesized expected texture. In contrast to conventional methods, our approach transfers the processing tasks to the preoperative stage, reducing thereby the impact of low-resolution, distorted, and noisy intraoperative images, that often degrade the registration accuracy. We applied our method in the context of neuronavigation during brain surgery. We evaluated our approach on synthetic data and on retrospective data from 6 clinical cases. Our method outperformed state-of-the-art methods and achieved accuracies that met current clinical standards.

Matthias Eisenmann, Annika Reinke, Vivienn Weru et al.

International benchmarking competitions have become fundamental for the comparative performance assessment of image analysis methods. However, little attention has been given to investigating what can be learnt from these competitions. Do they really generate scientific progress? What are common and successful participation strategies? What makes a solution superior to a competing method? To address this gap in the literature, we performed a multi-center study with all 80 competitions that were conducted in the scope of IEEE ISBI 2021 and MICCAI 2021. Statistical analyses performed based on comprehensive descriptions of the submitted algorithms linked to their rank as well as the underlying participation strategies revealed common characteristics of winning solutions. These typically include the use of multi-task learning (63%) and/or multi-stage pipelines (61%), and a focus on augmentation (100%), image preprocessing (97%), data curation (79%), and postprocessing (66%). The "typical" lead of a winning team is a computer scientist with a doctoral degree, five years of experience in biomedical image analysis, and four years of experience in deep learning. Two core general development strategies stood out for highly-ranked teams: the reflection of the metrics in the method design and the focus on analyzing and handling failure cases. According to the organizers, 43% of the winning algorithms exceeded the state of the art but only 11% completely solved the respective domain problem. The insights of our study could help researchers (1) improve algorithm development strategies when approaching new problems, and (2) focus on open research questions revealed by this work.

Samuel Joutard, Reuben Dorent, Sebastien Ourselin et al.

Inter-patient abdominal registration has various applications, from pharmakinematic studies to anatomy modeling. Yet, it remains a challenging application due to the morphological heterogeneity and variability of the human abdomen. Among the various registration methods proposed for this task, probabilistic displacement registration models estimate displacement distribution for a subset of points by comparing feature vectors of points from the two images. These probabilistic models are informative and robust while allowing large displacements by design. As the displacement distributions are typically estimated on a subset of points (which we refer to as driving points), due to computational requirements, we propose in this work to learn a driving points predictor. Compared to previously proposed methods, the driving points predictor is optimized in an end-to-end fashion to infer driving points tailored for a specific registration pipeline. We evaluate the impact of our contribution on two different datasets corresponding to different modalities. Specifically, we compared the performances of 6 different probabilistic displacement registration models when using a driving points predictor or one of 2 other standard driving points selection methods. The proposed method improved performances in 11 out of 12 experiments.

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.

Meng Wei, Charlie Budd, Luis C. Garcia-Peraza-Herrera et al.

Surgical instrument segmentation is recognised as a key enabler in providing advanced surgical assistance and improving computer-assisted interventions. In this work, we propose SegMatch, a semi-supervised learning method to reduce the need for expensive annotation for laparoscopic and robotic surgical images. SegMatch builds on FixMatch, a widespread semi supervised classification pipeline combining consistency regularization and pseudo-labelling, and adapts it for the purpose of segmentation. In our proposed SegMatch, the unlabelled images are first weakly augmented and fed to the segmentation model to generate pseudo-labels. In parallel, images are fed to a strong augmentation branch and consistency between the branches is used as an unsupervised loss. To increase the relevance of our strong augmentations, we depart from using only handcrafted augmentations and introduce a trainable adversarial augmentation strategy. Our FixMatch adaptation for segmentation tasks further includes carefully considering the equivariance and invariance properties of the augmentation functions we rely on. For binary segmentation tasks, our algorithm was evaluated on the MICCAI Instrument Segmentation Challenge datasets, Robust-MIS 2019 and EndoVis 2017. For multi-class segmentation tasks, we relied on the recent CholecInstanceSeg dataset. Our results show that SegMatch outperforms fully-supervised approaches by incorporating unlabelled data, and surpasses a range of state-of-the-art semi-supervised models across different labelled to unlabelled data ratios.

Samuel Joutard, Thomas Pheiffer, Chloe Audigier et al.

Registering CT images of the chest is a crucial step for several tasks such as disease progression tracking or surgical planning. It is also a challenging step because of the heterogeneous content of the human abdomen which implies complex deformations. In this work, we focus on accurately registering a subset of organs of interest. We register organ surface point clouds, as may typically be extracted from an automatic segmentation pipeline, by expanding the Bayesian Coherent Point Drift algorithm (BCPD). We introduce MO-BCPD, a multi-organ version of the BCPD algorithm which explicitly models three important aspects of this task: organ individual elastic properties, inter-organ motion coherence and segmentation inaccuracy. This model also provides an interpolation framework to estimate the deformation of the entire volume. We demonstrate the efficiency of our method by registering different patients from the LITS challenge dataset. The target registration error on anatomical landmarks is almost twice as small for MO-BCPD compared to standard BCPD while imposing the same constraints on individual organs deformation.

Navodini Wijethilake, Aaron Kujawa, Reuben Dorent et al.

Vestibular Schwannoma (VS) typically grows from the inner ear to the brain. It can be separated into two regions, intrameatal and extrameatal respectively corresponding to being inside or outside the inner ear canal. The growth of the extrameatal regions is a key factor that determines the disease management followed by the clinicians. In this work, a VS segmentation approach with subdivision into intra-/extra-meatal parts is presented. We annotated a dataset consisting of 227 T2 MRI instances, acquired longitudinally on 137 patients, excluding post-operative instances. We propose a staged approach, with the first stage performing the whole tumour segmentation and the second stage performing the intra-/extra-meatal segmentation using the T2 MRI along with the mask obtained from the first stage. To improve on the accuracy of the predicted meatal boundary, we introduce a task-specific loss which we call Boundary Distance Loss. The performance is evaluated in contrast to the direct intrameatal extrameatal segmentation task performance, i.e. the Baseline. Our proposed method, with the two-stage approach and the Boundary Distance Loss, achieved a Dice score of 0.8279+-0.2050 and 0.7744+-0.1352 for extrameatal and intrameatal regions respectively, significantly improving over the Baseline, which gave Dice score of 0.7939+-0.2325 and 0.7475+-0.1346 for the extrameatal and intrameatal regions respectively.

Maximilian Fehrentz, Mohammad Farid Azampour, Reuben Dorent et al.

We present in this paper a novel approach for 3D/2D intraoperative registration during neurosurgery via cross-modal inverse neural rendering. Our approach separates implicit neural representation into two components, handling anatomical structure preoperatively and appearance intraoperatively. This disentanglement is achieved by controlling a Neural Radiance Field's appearance with a multi-style hypernetwork. Once trained, the implicit neural representation serves as a differentiable rendering engine, which can be used to estimate the surgical camera pose by minimizing the dissimilarity between its rendered images and the target intraoperative image. We tested our method on retrospective patients' data from clinical cases, showing that our method outperforms state-of-the-art while meeting current clinical standards for registration. Code and additional resources can be found at https://maxfehrentz.github.io/style-ngp/.

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.

Romain Valabregue, Ines Khemir, Eric Badinet et al.

Synthetic training has recently advanced brain MRI segmentation by enabling contrast-agnostic models trained entirely on generated data. However, most existing approaches rely on hundreds of automatically labeled templates, introducing systematic biases and limiting their flexibility to incorporate new anatomical structures. We present the Segment It All Model (SIAM), a 3D whole-head segmentation framework for 16 anatomical structures, trained using only six high-quality, manually annotated templates. SIAM extends domain randomization to both intensity and shape domains: synthetic image generation ensures contrast variability, while high-resolution spatial transformations model anatomical differences in cortical thickness and deep nuclei morphology. Unlike prior synthetic models, SIAM simultaneously segments brain as well as extra-cerebral tissues, including cerebrospinal fluid, vessels, dura mater, skull, and skin, enabling fully automated, preprocessing-free analysis. Evaluation across eight heterogeneous datasets (N=301), that include multiple contrasts (T1-weighted, T2-weighted, CT) and span a wide range of ages, demonstrates that SIAM matches or outperforms state-of-the-art methods for brain structures, in addition to extending automated segmentation to non-brain structures. The model also exhibits superior consistency across contrasts and repeated acquisitions, together with improved sensitivity to subtle gray matter atrophy. We openly release the model and the label templates at https://github.com/romainVala/SIAM.

Reuben Dorent, Erickson Torio, Nazim Haouchine et al.

Intraoperative ultrasound (iUS) imaging has the potential to improve surgical outcomes in brain surgery. However, its interpretation is challenging, even for expert neurosurgeons. In this work, we designed the first patient-specific framework that performs brain tumor segmentation in trackerless iUS. To disambiguate ultrasound imaging and adapt to the neurosurgeon's surgical objective, a patient-specific real-time network is trained using synthetic ultrasound data generated by simulating virtual iUS sweep acquisitions in pre-operative MR data. Extensive experiments performed in real ultrasound data demonstrate the effectiveness of the proposed approach, allowing for adapting to the surgeon's definition of surgical targets and outperforming non-patient-specific models, neurosurgeon experts, and high-end tracking systems. Our code is available at: \url{https://github.com/ReubenDo/MHVAE-Seg}.

Tiago Assis, Ines P. Machado, Benjamin Zwick et al.

Accurate compensation of brain shift is critical for maintaining the reliability of neuronavigation during neurosurgery. While keypoint-based registration methods offer robustness to large deformations and topological changes, they typically rely on simple geometric interpolators that ignore tissue biomechanics to create dense displacement fields. In this work, we propose a novel deep learning framework that estimates dense, physically plausible brain deformations from sparse matched keypoints. We first generate a large dataset of synthetic brain deformations using biomechanical simulations. Then, a residual 3D U-Net is trained to refine standard interpolation estimates into biomechanically guided deformations. Experiments on a large set of simulated displacement fields demonstrate that our method significantly outperforms classical interpolators, reducing by half the mean square error while introducing negligible computational overhead at inference time. Code available at: \href{https://github.com/tiago-assis/Deep-Biomechanical-Interpolator}{https://github.com/tiago-assis/Deep-Biomechanical-Interpolator}.

Daniil Morozov, Reuben Dorent, Nazim Haouchine

Intraoperative registration of real-time ultrasound (iUS) to preoperative Magnetic Resonance Imaging (MRI) remains an unsolved problem due to severe modality-specific differences in appearance, resolution, and field-of-view. To address this, we propose a novel 3D cross-modal keypoint descriptor for MRI-iUS matching and registration. Our approach employs a patient-specific matching-by-synthesis approach, generating synthetic iUS volumes from preoperative MRI. This enables supervised contrastive training to learn a shared descriptor space. A probabilistic keypoint detection strategy is then employed to identify anatomically salient and modality-consistent locations. During training, a curriculum-based triplet loss with dynamic hard negative mining is used to learn descriptors that are i) robust to iUS artifacts such as speckle noise and limited coverage, and ii) rotation-invariant . At inference, the method detects keypoints in MR and real iUS images and identifies sparse matches, which are then used to perform rigid registration. Our approach is evaluated using 3D MRI-iUS pairs from the ReMIND dataset. Experiments show that our approach outperforms state-of-the-art keypoint matching methods across 11 patients, with an average precision of $69.8\%$. For image registration, our method achieves a competitive mean Target Registration Error of 2.39 mm on the ReMIND2Reg benchmark. Compared to existing iUS-MR registration approach, our framework is interpretable, requires no manual initialization, and shows robustness to iUS field-of-view variation. Code is available at https://github.com/morozovdd/CrossKEY.

Fernando Pérez-García, Reuben Dorent, Michele Rizzi et al.

Accurate segmentation of brain resection cavities (RCs) aids in postoperative analysis and determining follow-up treatment. Convolutional neural networks (CNNs) are the state-of-the-art image segmentation technique, but require large annotated datasets for training. Annotation of 3D medical images is time-consuming, requires highly-trained raters, and may suffer from high inter-rater variability. Self-supervised learning strategies can leverage unlabeled data for training. We developed an algorithm to simulate resections from preoperative magnetic resonance images (MRIs). We performed self-supervised training of a 3D CNN for RC segmentation using our simulation method. We curated EPISURG, a dataset comprising 430 postoperative and 268 preoperative MRIs from 430 refractory epilepsy patients who underwent resective neurosurgery. We fine-tuned our model on three small annotated datasets from different institutions and on the annotated images in EPISURG, comprising 20, 33, 19 and 133 subjects. The model trained on data with simulated resections obtained median (interquartile range) Dice score coefficients (DSCs) of 81.7 (16.4), 82.4 (36.4), 74.9 (24.2) and 80.5 (18.7) for each of the four datasets. After fine-tuning, DSCs were 89.2 (13.3), 84.1 (19.8), 80.2 (20.1) and 85.2 (10.8). For comparison, inter-rater agreement between human annotators from our previous study was 84.0 (9.9). We present a self-supervised learning strategy for 3D CNNs using simulated RCs to accurately segment real RCs on postoperative MRI. Our method generalizes well to data from different institutions, pathologies and modalities. Source code, segmentation models and the EPISURG dataset are available at https://github.com/fepegar/ressegijcars .

Junyu Chen, Shuwen Wei, Joel Honkamaa et al.

Medical image challenges have played a transformative role in advancing the field, catalyzing algorithmic innovation and establishing new performance standards across diverse clinical applications. Image registration, a foundational task in neuroimaging pipelines, has similarly benefited from the Learn2Reg initiative. Building on this foundation, we introduce the Large-scale Unsupervised Brain MRI Image Registration (LUMIR) challenge, a next-generation benchmark designed to assess and advance unsupervised brain MRI registration. Distinct from prior challenges that leveraged anatomical label maps for supervision, LUMIR removes this dependency by providing over 4,000 preprocessed T1-weighted brain MRIs for training without any label maps, encouraging biologically plausible deformation modeling through self-supervision. In addition to evaluating performance on 590 held-out test subjects, LUMIR introduces a rigorous suite of zero-shot generalization tasks, spanning out-of-domain imaging modalities (e.g., FLAIR, T2-weighted, T2*-weighted), disease populations (e.g., Alzheimer's disease), acquisition protocols (e.g., 9.4T MRI), and species (e.g., macaque brains). A total of 1,158 subjects and over 4,000 image pairs were included for evaluation. Performance was assessed using both segmentation-based metrics (Dice coefficient, 95th percentile Hausdorff distance) and landmark-based registration accuracy (target registration error). Across both in-domain and zero-shot tasks, deep learning-based methods consistently achieved state-of-the-art accuracy while producing anatomically plausible deformation fields. The top-performing deep learning-based models demonstrated diffeomorphic properties and inverse consistency, outperforming several leading optimization-based methods, and showing strong robustness to most domain shifts, the exception being a drop in performance on out-of-domain contrasts.

Aaron Kujawa, Reuben Dorent, Sebastien Ourselin et al.

Whole brain parcellation requires inferring hundreds of segmentation labels in large image volumes and thus presents significant practical challenges for deep learning approaches. We introduce label merge-and-split, a method that first greatly reduces the effective number of labels required for learning-based whole brain parcellation and then recovers original labels. Using a greedy graph colouring algorithm, our method automatically groups and merges multiple spatially separate labels prior to model training and inference. The merged labels may be semantically unrelated. A deep learning model is trained to predict merged labels. At inference time, original labels are restored using atlas-based influence regions. In our experiments, the proposed approach reduces the number of labels by up to 68% while achieving segmentation accuracy comparable to the baseline method without label merging and splitting. Moreover, model training and inference times as well as GPU memory requirements were reduced significantly. The proposed method can be applied to all semantic segmentation tasks with a large number of spatially separate classes within an atlas-based prior.

Reuben Dorent, Nazim Haouchine, Alexandra Golby et al.

We propose a deep mixture of multimodal hierarchical variational auto-encoders called MMHVAE that synthesizes missing images from observed images in different modalities. MMHVAE's design focuses on tackling four challenges: (i) creating a complex latent representation of multimodal data to generate high-resolution images; (ii) encouraging the variational distributions to estimate the missing information needed for cross-modal image synthesis; (iii) learning to fuse multimodal information in the context of missing data; (iv) leveraging dataset-level information to handle incomplete data sets at training time. Extensive experiments are performed on the challenging problem of pre-operative brain multi-parametric magnetic resonance and intra-operative ultrasound imaging.

Kathleen Baur, Xin Xiong, Erickson Torio et al. · harvard

Although Digital Subtraction Angiography (DSA) is the most important imaging for visualizing cerebrovascular anatomy, its interpretation by clinicians remains difficult. This is particularly true when treating arteriovenous malformations (AVMs), where entangled vasculature connecting arteries and veins needs to be carefully identified.The presented method aims to enhance DSA image series by highlighting critical information via automatic classification of vessels using a combination of two learning models: An unsupervised machine learning method based on Independent Component Analysis that decomposes the phases of flow and a convolutional neural network that automatically delineates the vessels in image space. The proposed method was tested on clinical DSA images series and demonstrated efficient differentiation between arteries and veins that provides a viable solution to enhance visualizations for clinical use.

Reuben Dorent, Polina Golland, William Wells

Mutual Information (MI) is a fundamental measure of statistical dependence widely used in representation learning. While direct optimization of MI via its definition as a Kullback-Leibler divergence (KLD) is often intractable, many recent methods have instead maximized alternative dependence measures, most notably, the Jensen-Shannon divergence (JSD) between joint and product of marginal distributions via discriminative losses. However, the connection between these surrogate objectives and MI remains poorly understood. In this work, we bridge this gap by deriving a new, tight, and tractable lower bound on KLD as a function of JSD in the general case. By specializing this bound to joint and marginal distributions, we demonstrate that maximizing the JSD-based information increases a guaranteed lower bound on mutual information. Furthermore, we revisit the practical implementation of JSD-based objectives and observe that minimizing the cross-entropy loss of a binary classifier trained to distinguish joint from marginal pairs recovers a known variational lower bound on the JSD. Extensive experiments demonstrate that our lower bound is tight when applied to MI estimation. We compared our lower bound to state-of-the-art neural estimators of variational lower bound across a range of established reference scenarios. Our lower bound estimator consistently provides a stable, low-variance estimate of a tight lower bound on MI. We also demonstrate its practical usefulness in the context of the Information Bottleneck framework. Taken together, our results provide new theoretical justifications and strong empirical evidence for using discriminative learning in MI-based representation learning.

Lasse Hansen, Wiebke Heyer, Christoph Großbröhmer et al.

Medical image registration is critical for clinical applications, and fair benchmarking of different methods is essential for monitoring ongoing progress. To date, the Learn2Reg 2020-2023 challenges have released several complementary datasets and established metrics for evaluations. However, these editions did not capture all aspects of the registration problem, particularly in terms of modality diversity and task complexity. To address these limitations, the 2024 edition introduces three new tasks, including large-scale multi-modal registration and unsupervised inter-subject brain registration, as well as the first microscopy-focused benchmark within Learn2Reg. The new datasets also inspired new method developments, including invertibility constraints, pyramid features, keypoints alignment and instance optimisation.

Reuben Dorent, Laura Rigolo, Colin P. Galvin et al.

Accurate intraoperative image guidance is critical for achieving maximal safe resection in brain tumor surgery, yet neuronavigation systems based on preoperative MRI lose accuracy during the procedure due to brain shift. Aligning post-resection intraoperative ultrasound (iUS) with preoperative MRI can restore spatial accuracy by estimating brain shift deformations, but it remains a challenging problem given the large anatomical and topological changes and substantial modality intensity gap. The ReMIND2Reg 2025 Challenge provides the largest public benchmark for this task, built upon the ReMIND dataset. It offers 99 training cases, 5 validation cases, and 10 private test cases comprising paired 3D ceT1 MRI, T2 MRI, and post-resection 3D iUS volumes. Data are provided without annotations for training, while validation and test performance are evaluated on manually annotated anatomical landmarks. Metrics include target registration error (TRE), robustness to worst-case landmark misalignment (TRE30), and runtime. By establishing a standardized evaluation framework for this clinically critical and technically complex problem, ReMIND2Reg aims to accelerate the development of robust, generalizable, and clinically deployable multimodal registration algorithms for image-guided neurosurgery.

Hugues Roy, Reuben Dorent, Ninon Burgos

Unsupervised anomaly detection (UAD) plays a crucial role in neuroimaging for identifying deviations from healthy subject data and thus facilitating the diagnosis of neurological disorders. In this work, we focus on Bayesian flow networks (BFNs), a novel class of generative models, which have not yet been applied to medical imaging or anomaly detection. BFNs combine the strength of diffusion frameworks and Bayesian inference. We introduce AnoBFN, an extension of BFNs for UAD, designed to: i) perform conditional image generation under high levels of spatially correlated noise, and ii) preserve subject specificity by incorporating a recursive feedback from the input image throughout the generative process. We evaluate AnoBFN on the challenging task of Alzheimer's disease-related anomaly detection in FDG PET images. Our approach outperforms other state-of-the-art methods based on VAEs (beta-VAE), GANs (f-AnoGAN), and diffusion models (AnoDDPM), demonstrating its effectiveness at detecting anomalies while reducing false positive rates.

Navodini Wijethilake, Reuben Dorent, Marina Ivory et al.

The cross-Modality Domain Adaptation (crossMoDA) challenge series, initiated in 2021 in conjunction with the International Conference on Medical Image Computing and Computer Assisted Intervention (MICCAI), focuses on unsupervised cross-modality segmentation, learning from contrast-enhanced T1 (ceT1) and transferring to T2 MRI. The task is an extreme example of domain shift chosen to serve as a meaningful and illustrative benchmark. From a clinical application perspective, it aims to automate Vestibular Schwannoma (VS) and cochlea segmentation on T2 scans for more cost-effective VS management. Over time, the challenge objectives have evolved to enhance its clinical relevance. The challenge evolved from using single-institutional data and basic segmentation in 2021 to incorporating multi-institutional data and Koos grading in 2022, and by 2023, it included heterogeneous routine data and sub-segmentation of intra- and extra-meatal tumour components. In this work, we report the findings of the 2022 and 2023 editions and perform a retrospective analysis of the challenge progression over the years. The observations from the successive challenge contributions indicate that the number of outliers decreases with an expanding dataset. This is notable since the diversity of scanning protocols of the datasets concurrently increased. The winning approach of the 2023 edition reduced the number of outliers on the 2021 and 2022 testing data, demonstrating how increased data heterogeneity can enhance segmentation performance even on homogeneous data. However, the cochlea Dice score declined in 2023, likely due to the added complexity from tumour sub-annotations affecting overall segmentation performance. While progress is still needed for clinically acceptable VS segmentation, the plateauing performance suggests that a more challenging cross-modal task may better serve future benchmarking.

Reuben Dorent, Aaron Kujawa, Marina Ivory et al.

Domain Adaptation (DA) has recently raised strong interests in the medical imaging community. While a large variety of DA techniques has been proposed for image segmentation, most of these techniques have been validated either on private datasets or on small publicly available datasets. Moreover, these datasets mostly addressed single-class problems. To tackle these limitations, the Cross-Modality Domain Adaptation (crossMoDA) challenge was organised in conjunction with the 24th International Conference on Medical Image Computing and Computer Assisted Intervention (MICCAI 2021). CrossMoDA is the first large and multi-class benchmark for unsupervised cross-modality DA. The challenge's goal is to segment two key brain structures involved in the follow-up and treatment planning of vestibular schwannoma (VS): the VS and the cochleas. Currently, the diagnosis and surveillance in patients with VS are performed using contrast-enhanced T1 (ceT1) MRI. However, there is growing interest in using non-contrast sequences such as high-resolution T2 (hrT2) MRI. Therefore, we created an unsupervised cross-modality segmentation benchmark. The training set provides annotated ceT1 (N=105) and unpaired non-annotated hrT2 (N=105). The aim was to automatically perform unilateral VS and bilateral cochlea segmentation on hrT2 as provided in the testing set (N=137). A total of 16 teams submitted their algorithm for the evaluation phase. The level of performance reached by the top-performing teams is strikingly high (best median Dice - VS:88.4%; Cochleas:85.7%) and close to full supervision (median Dice - VS:92.5%; Cochleas:87.7%). All top-performing methods made use of an image-to-image translation approach to transform the source-domain images into pseudo-target-domain images. A segmentation network was then trained using these generated images and the manual annotations provided for the source image.

Reuben Dorent, Samuel Joutard, Jonathan Shapey et al.

We introduce $\textit{InExtremIS}$, a weakly supervised 3D approach to train a deep image segmentation network using particularly weak train-time annotations: only 6 extreme clicks at the boundary of the objects of interest. Our fully-automatic method is trained end-to-end and does not require any test-time annotations. From the extreme points, 3D bounding boxes are extracted around objects of interest. Then, deep geodesics connecting extreme points are generated to increase the amount of "annotated" voxels within the bounding boxes. Finally, a weakly supervised regularised loss derived from a Conditional Random Field formulation is used to encourage prediction consistency over homogeneous regions. Extensive experiments are performed on a large open dataset for Vestibular Schwannoma segmentation. $\textit{InExtremIS}$ obtained competitive performance, approaching full supervision and outperforming significantly other weakly supervised techniques based on bounding boxes. Moreover, given a fixed annotation time budget, $\textit{InExtremIS}$ outperforms full supervision. Our code and data are available online.

Reuben Dorent, Thomas Booth, Wenqi Li et al.

Brain tissue segmentation from multimodal MRI is a key building block of many neuroimaging analysis pipelines. Established tissue segmentation approaches have, however, not been developed to cope with large anatomical changes resulting from pathology, such as white matter lesions or tumours, and often fail in these cases. In the meantime, with the advent of deep neural networks (DNNs), segmentation of brain lesions has matured significantly. However, few existing approaches allow for the joint segmentation of normal tissue and brain lesions. Developing a DNN for such a joint task is currently hampered by the fact that annotated datasets typically address only one specific task and rely on task-specific imaging protocols including a task-specific set of imaging modalities. In this work, we propose a novel approach to build a joint tissue and lesion segmentation model from aggregated task-specific hetero-modal domain-shifted and partially-annotated datasets. Starting from a variational formulation of the joint problem, we show how the expected risk can be decomposed and optimised empirically. We exploit an upper bound of the risk to deal with heterogeneous imaging modalities across datasets. To deal with potential domain shift, we integrated and tested three conventional techniques based on data augmentation, adversarial learning and pseudo-healthy generation. For each individual task, our joint approach reaches comparable performance to task-specific and fully-supervised models. The proposed framework is assessed on two different types of brain lesions: White matter lesions and gliomas. In the latter case, lacking a joint ground-truth for quantitative assessment purposes, we propose and use a novel clinically-relevant qualitative assessment methodology.

Reuben Dorent, Samuel Joutard, Jonathan Shapey et al.

Although deep convolutional networks have reached state-of-the-art performance in many medical image segmentation tasks, they have typically demonstrated poor generalisation capability. To be able to generalise from one domain (e.g. one imaging modality) to another, domain adaptation has to be performed. While supervised methods may lead to good performance, they require to fully annotate additional data which may not be an option in practice. In contrast, unsupervised methods don't need additional annotations but are usually unstable and hard to train. In this work, we propose a novel weakly-supervised method. Instead of requiring detailed but time-consuming annotations, scribbles on the target domain are used to perform domain adaptation. This paper introduces a new formulation of domain adaptation based on structured learning and co-segmentation. Our method is easy to train, thanks to the introduction of a regularised loss. The framework is validated on Vestibular Schwannoma segmentation (T1 to T2 scans). Our proposed method outperforms unsupervised approaches and achieves comparable performance to a fully-supervised approach.

Reuben Dorent, Samuel Joutard, Marc Modat et al.

We propose a new deep learning method for tumour segmentation when dealing with missing imaging modalities. Instead of producing one network for each possible subset of observed modalities or using arithmetic operations to combine feature maps, our hetero-modal variational 3D encoder-decoder independently embeds all observed modalities into a shared latent representation. Missing data and tumour segmentation can be then generated from this embedding. In our scenario, the input is a random subset of modalities. We demonstrate that the optimisation problem can be seen as a mixture sampling. In addition to this, we introduce a new network architecture building upon both the 3D U-Net and the Multi-Modal Variational Auto-Encoder (MVAE). Finally, we evaluate our method on BraTS2018 using subsets of the imaging modalities as input. Our model outperforms the current state-of-the-art method for dealing with missing modalities and achieves similar performance to the subset-specific equivalent networks.

Reuben Dorent, Wenqi Li, Jinendra Ekanayake et al.

Brain tissue segmentation from multimodal MRI is a key building block of many neuroscience analysis pipelines. It could also play an important role in many clinical imaging scenarios. Established tissue segmentation approaches have however not been developed to cope with large anatomical changes resulting from pathology. The effect of the presence of brain lesions, for example, on their performance is thus currently uncontrolled and practically unpredictable. Contrastingly, with the advent of deep neural networks (DNNs), segmentation of brain lesions has matured significantly and is achieving performance levels making it of interest for clinical use. However, few existing approaches allow for jointly segmenting normal tissue and brain lesions. Developing a DNN for such joint task is currently hampered by the fact that annotated datasets typically address only one specific task and rely on a task-specific hetero-modal imaging protocol. In this work, we propose a novel approach to build a joint tissue and lesion segmentation model from task-specific hetero-modal and partially annotated datasets. Starting from a variational formulation of the joint problem, we show how the expected risk can be decomposed and optimised empirically. We exploit an upper-bound of the risk to deal with missing imaging modalities. For each task, our approach reaches comparable performance than task-specific and fully-supervised models.

Samuel Joutard, Reuben Dorent, Amanda Isaac et al.

Medical image processing tasks such as segmentation often require capturing non-local information. As organs, bones, and tissues share common characteristics such as intensity, shape, and texture, the contextual information plays a critical role in correctly labeling them. Segmentation and labeling is now typically done with convolutional neural networks (CNNs) but the context of the CNN is limited by the receptive field which itself is limited by memory requirements and other properties. In this paper, we propose a new attention module, that we call Permutohedral Attention Module (PAM), to efficiently capture non-local characteristics of the image. The proposed method is both memory and computationally efficient. We provide a GPU implementation of this module suitable for 3D medical imaging problems. We demonstrate the efficiency and scalability of our module with the challenging task of vertebrae segmentation and labeling where context plays a crucial role because of the very similar appearance of different vertebrae.

Guotai Wang, Jonathan Shapey, Wenqi Li et al.

Automatic segmentation of vestibular schwannoma (VS) tumors from magnetic resonance imaging (MRI) would facilitate efficient and accurate volume measurement to guide patient management and improve clinical workflow. The accuracy and robustness is challenged by low contrast, small target region and low through-plane resolution. We introduce a 2.5D convolutional neural network (CNN) able to exploit the different in-plane and through-plane resolutions encountered in standard of care imaging protocols. We use an attention module to enable the CNN to focus on the small target and propose a supervision on the learning of attention maps for more accurate segmentation. Additionally, we propose a hardness-weighted Dice loss function that gives higher weights to harder voxels to boost the training of CNNs. Experiments with ablation studies on the VS tumor segmentation task show that: 1) the proposed 2.5D CNN outperforms its 2D and 3D counterparts, 2) our supervised attention mechanism outperforms unsupervised attention, 3) the voxel-level hardness-weighted Dice loss can improve the performance of CNNs. Our method achieved an average Dice score and ASSD of 0.87 and 0.43~mm respectively. This will facilitate patient management decisions in clinical practice.