Mattias P. Heinrich

Alexander Bigalke, Lasse Hansen, Jasper Diesel et al.

3D human pose estimation is a key component of clinical monitoring systems. The clinical applicability of deep pose estimation models, however, is limited by their poor generalization under domain shifts along with their need for sufficient labeled training data. As a remedy, we present a novel domain adaptation method, adapting a model from a labeled source to a shifted unlabeled target domain. Our method comprises two complementary adaptation strategies based on prior knowledge about human anatomy. First, we guide the learning process in the target domain by constraining predictions to the space of anatomically plausible poses. To this end, we embed the prior knowledge into an anatomical loss function that penalizes asymmetric limb lengths, implausible bone lengths, and implausible joint angles. Second, we propose to filter pseudo labels for self-training according to their anatomical plausibility and incorporate the concept into the Mean Teacher paradigm. We unify both strategies in a point cloud-based framework applicable to unsupervised and source-free domain adaptation. Evaluation is performed for in-bed pose estimation under two adaptation scenarios, using the public SLP dataset and a newly created dataset. Our method consistently outperforms various state-of-the-art domain adaptation methods, surpasses the baseline model by 31%/66%, and reduces the domain gap by 65%/82%. Source code is available at https://github.com/multimodallearning/da-3dhpe-anatomy.

Alexander Bigalke, Lasse Hansen, Mattias P. Heinrich

Recent deep learning-based methods for medical image registration achieve results that are competitive with conventional optimization algorithms at reduced run times. However, deep neural networks generally require plenty of labeled training data and are vulnerable to domain shifts between training and test data. While typical intensity shifts can be mitigated by keypoint-based registration, these methods still suffer from geometric domain shifts, for instance, due to different fields of view. As a remedy, in this work, we present a novel approach to geometric domain adaptation for image registration, adapting a model from a labeled source to an unlabeled target domain. We build on a keypoint-based registration model, combining graph convolutions for geometric feature learning with loopy belief optimization, and propose to reduce the domain shift through self-ensembling. To this end, we embed the model into the Mean Teacher paradigm. We extend the Mean Teacher to this context by 1) adapting the stochastic augmentation scheme and 2) combining learned feature extraction with differentiable optimization. This enables us to guide the learning process in the unlabeled target domain by enforcing consistent predictions of the learning student and the temporally averaged teacher model. We evaluate the method for exhale-to-inhale lung CT registration under two challenging adaptation scenarios (DIR-Lab 4D CT to COPD, COPD to Learn2Reg). Our method consistently improves on the baseline model by 50%/47% while even matching the accuracy of models trained on target data. Source code is available at https://github.com/multimodallearning/registration-da-mean-teacher.

Alexander Bigalke, Lasse Hansen, Tony C. W. Mok et al.

State-of-the-art deep learning-based registration methods employ three different learning strategies: supervised learning, which requires costly manual annotations, unsupervised learning, which heavily relies on hand-crafted similarity metrics designed by domain experts, or learning from synthetic data, which introduces a domain shift. To overcome the limitations of these strategies, we propose a novel self-supervised learning paradigm for unsupervised registration, relying on self-training. Our idea is based on two key insights. Feature-based differentiable optimizers 1) perform reasonable registration even from random features and 2) stabilize the training of the preceding feature extraction network on noisy labels. Consequently, we propose cyclical self-training, where pseudo labels are initialized as the displacement fields inferred from random features and cyclically updated based on more and more expressive features from the learning feature extractor, yielding a self-reinforcement effect. We evaluate the method for abdomen and lung registration, consistently surpassing metric-based supervision and outperforming diverse state-of-the-art competitors. Source code is available at https://github.com/multimodallearning/reg-cyclical-self-train.

Alexander Bigalke, Mattias P. Heinrich

Point cloud-based medical registration promises increased computational efficiency, robustness to intensity shifts, and anonymity preservation but is limited by the inefficacy of unsupervised learning with similarity metrics. Supervised training on synthetic deformations is an alternative but, in turn, suffers from the domain gap to the real domain. In this work, we aim to tackle this gap through domain adaptation. Self-training with the Mean Teacher is an established approach to this problem but is impaired by the inherent noise of the pseudo labels from the teacher. As a remedy, we present a denoised teacher-student paradigm for point cloud registration, comprising two complementary denoising strategies. First, we propose to filter pseudo labels based on the Chamfer distances of teacher and student registrations, thus preventing detrimental supervision by the teacher. Second, we make the teacher dynamically synthesize novel training pairs with noise-free labels by warping its moving inputs with the predicted deformations. Evaluation is performed for inhale-to-exhale registration of lung vessel trees on the public PVT dataset under two domain shifts. Our method surpasses the baseline Mean Teacher by 13.5/62.8%, consistently outperforms diverse competitors, and sets a new state-of-the-art accuracy (TRE=2.31mm). Code is available at https://github.com/multimodallearning/denoised_mt_pcd_reg.

Ron Keuth, Christoph Großbröhmer, Franziska Halm et al.

Measuring the angle between bone structures is a routine task in medical image analysis and provides a key quantitative parameter for diagnosis and treatment planning. Automated methods can reduce time and cost while improving reproducibility. In this work, we address automatic bone pose estimation using a learning-based point candidate proposal followed by a line model to extract axis parameters. Since conventional line models such as least squares are sensitive to outliers, we incorporate false-positive reduction strategies and robust fitting techniques, such as RANSAC and Hough transforms, to improve robustness. We evaluate our method on three clinically relevant paediatric angle estimation tasks: fracture fragment assessment in radiographs and ultrasound and developmental dysplasia of the hip evaluation in ultrasound using the Graf method. Our approach achieves mean errors of $4.1^\circ$, $5.4^\circ$, and $5.51^\circ$, respectively, not only remaining within the expected clinical observer variability, but also significantly outperforming landmark-based methods. Our code and annotations for fracture angle assessment in radiographs are publicly available on GitHub.

Cassandra Krause, Mattias P. Heinrich, Ron Keuth

Between $15\,\%$ and $45\,\%$ of children experience a fracture during their growth years, making accurate diagnosis essential. Fracture morphology, alongside location and fragment angle, is a key diagnostic feature. In this work, we propose a method to extract fracture morphology by assigning automatically global AO codes to corresponding fracture bounding boxes. This approach enables the use of public datasets and reformulates the global multilabel task into a local multiclass one, improving the average F1 score by $7.89\,\%$. However, performance declines when using imperfect fracture detectors, highlighting challenges for real-world deployment. Our code is available on GitHub.

Leonard Siegert, Paul Fischer, Mattias P. Heinrich et al.

Deformable image registration is fundamental to many medical imaging applications. Registration is an inherently ambiguous task often admitting many viable solutions. While neural network-based registration techniques enable fast and accurate registration, the majority of existing approaches are not able to estimate uncertainty. Here, we present PULPo, a method for probabilistic deformable registration capable of uncertainty quantification. PULPo probabilistically models the distribution of deformation fields on different hierarchical levels combining them using Laplacian pyramids. This allows our method to model global as well as local aspects of the deformation field. We evaluate our method on two widely used neuroimaging datasets and find that it achieves high registration performance as well as substantially better calibrated uncertainty quantification compared to the current state-of-the-art.

Ziad Al-Haj Hemidi, Christian Weihsbach, Mattias P. Heinrich

Motion artifacts in Magnetic Resonance Imaging (MRI) arise due to relatively long acquisition times and can compromise the clinical utility of acquired images. Traditional motion correction methods often fail to address severe motion, leading to distorted and unreliable results. Deep Learning (DL) alleviated such pitfalls through generalization with the cost of vanishing structures and hallucinations, making it challenging to apply in the medical field where hallucinated structures can tremendously impact the diagnostic outcome. In this work, we present an instance-wise motion correction pipeline that leverages motion-guided Implicit Neural Representations (INRs) to mitigate the impact of motion artifacts while retaining anatomical structure. Our method is evaluated using the NYU fastMRI dataset with different degrees of simulated motion severity. For the correction alone, we can improve over state-of-the-art image reconstruction methods by $+5\%$ SSIM, $+5\:db$ PSNR, and $+14\%$ HaarPSI. Clinical relevance is demonstrated by a subsequent experiment, where our method improves classification outcomes by at least $+1.5$ accuracy percentage points compared to motion-corrupted images.

Ziad Al-Haj Hemidi, Eytan Kats, Mattias P. Heinrich

Accelerating Magnetic Resonance Imaging (MRI) reduces scan time but often degrades image quality. While Implicit Neural Representations (INRs) show promise for MRI reconstruction, they struggle at high acceleration factors due to weak prior constraints, leading to structural loss and aliasing artefacts. To address this, we propose PrIINeR, an INR-based MRI reconstruction method that integrates prior knowledge from pre-trained deep learning models into the INR framework. By combining population-level knowledge with instance-based optimization and enforcing dual data consistency, PrIINeR aligns both with the acquired k-space data and the prior-informed reconstruction. Evaluated on the NYU fastMRI dataset, our method not only outperforms state-of-the-art INR-based approaches but also improves upon several learning-based state-of-the-art methods, significantly improving structural preservation and fidelity while effectively removing aliasing artefacts.PrIINeR bridges deep learning and INR-based techniques, offering a more reliable solution for high-quality, accelerated MRI reconstruction. The code is publicly available on https://github.com/multimodallearning/PrIINeR.

Christian Weihsbach, Christian N. Kruse, Alexander Bigalke et al.

Purpose: Applying pre-trained medical deep learning segmentation models on out-of-domain images often yields predictions of insufficient quality. In this study, we propose to use a powerful generalizing descriptor along with augmentation to enable domain-generalized pre-training and test-time adaptation, achieving high-quality segmentation in unseen domains. Materials and Methods: In this retrospective study five different publicly available datasets (2012 to 2022) including 3D CT and MRI images are used to evaluate segmentation performance in out-of-domain scenarios. The settings include abdominal, spine, and cardiac imaging. The data is randomly split into training and test samples. Domain-generalized pre-training on source data is used to obtain the best initial performance in the target domain. We introduce the combination of the generalizing SSC descriptor and GIN intensity augmentation for optimal generalization. Segmentation results are subsequently optimized at test time, where we propose to adapt the pre-trained models for every unseen scan with a consistency scheme using the same augmentation-descriptor combination. The segmentation is evaluated using Dice similarity and Hausdorff distance and the significance of improvements is tested with the Wilcoxon signed-rank test. Results: The proposed generalized pre-training and subsequent test-time adaptation improves model performance significantly in CT to MRI cross-domain prediction for abdominal (+46.2% and +28.2% Dice), spine (+72.9%), and cardiac (+14.2% and +55.7% Dice) scenarios (p<0.001). Conclusion: Our method enables optimal, independent usage of medical image source and target data and bridges domain gaps successfully with a compact and efficient methodology. Open-source code available at: https://github.com/multimodallearning/DG-TTA

Lasse Hansen, Mattias P. Heinrich

As in other areas of medical image analysis, e.g. semantic segmentation, deep learning is currently driving the development of new approaches for image registration. Multi-scale encoder-decoder network architectures achieve state-of-the-art accuracy on tasks such as intra-patient alignment of abdominal CT or brain MRI registration, especially when additional supervision, such as anatomical labels, is available. The success of these methods relies to a large extent on the outstanding ability of deep CNNs to extract descriptive visual features from the input images. In contrast to conventional methods, the explicit inclusion of geometric information plays only a minor role, if at all. In this work we take a look at an exactly opposite approach by investigating a deep learning framework for registration based solely on geometric features and optimisation. We combine graph convolutions with loopy belief message passing to enable highly accurate 3D point cloud registration. Our experimental validation is conducted on complex key-point graphs of inner lung structures, strongly outperforming dense encoder-decoder networks and other point set registration methods. Our code is publicly available at https://github.com/multimodallearning/deep-geo-reg.

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

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

Eytan Kats, Christoph Grossbroehmer, Ziad Al-Haj Hemidi et al.

Medical image registration is a fundamental task in medical image analysis, enabling the alignment of images from different modalities or time points. However, intensity inconsistencies and nonlinear tissue deformations pose significant challenges to the robustness of registration methods. Recent approaches leveraging self-supervised representation learning show promise by pre-training feature extractors to generate robust anatomical embeddings, that farther used for the registration. In this work, we propose a novel framework that integrates equivariant contrastive learning directly into the registration model. Our approach leverages the power of contrastive learning to learn robust feature representations that are invariant to tissue deformations. By jointly optimizing the contrastive and registration objectives, we ensure that the learned representations are not only informative but also suitable for the registration task. We evaluate our method on abdominal and thoracic image registration tasks, including both intra-patient and inter-patient scenarios. Experimental results demonstrate that the integration of contrastive learning directly into the registration framework significantly improves performance, surpassing strong baseline methods.

Eytan Kats, Mattias P. Heinrich

Medical image registration is a critical component of clinical imaging workflows, enabling accurate longitudinal assessment, multi-modal data fusion, and image-guided interventions. Intensity-based approaches often struggle with interscanner variability and complex anatomical deformations, whereas feature-based methods offer improved robustness by leveraging semantically informed representations. In this work, we investigate DINO-style self-supervised pretraining directly on 3D medical imaging data, aiming to learn dense volumetric features well suited for deformable registration. We assess the resulting representations on challenging interpatient abdominal registration task across both MRI and CT modalities. Our domain-specialized pretraining outperforms the DINOv2 model trained on a large-scale collection of natural images, while requiring substantially lower computational resources at inference time. Moreover, it surpasses established registration models under out-of-domain evaluation, demonstrating the value of task-agnostic yet medical imaging-focused pretraining for robust and efficient 3D image registration.

Eytan Kats, Kai Geissler, Daniel Mensing et al.

Automated patient positioning plays an important role in optimizing scanning procedure and improving patient throughput. Leveraging depth information captured by RGB-D cameras presents a promising approach for estimating internal organ positions, thereby enabling more accurate and efficient positioning. In this work, we propose a learning-based framework that directly predicts the 3D locations and shapes of multiple internal organs from single 2D depth images of the body surface. Utilizing a large-scale dataset of full-body MRI scans, we synthesize depth images paired with corresponding anatomical segmentations to train a unified convolutional neural network architecture. Our method accurately localizes a diverse set of anatomical structures, including bones and soft tissues, without requiring explicit surface reconstruction. Experimental results demonstrate the potential of integrating depth sensors into radiology workflows to streamline scanning procedures and enhance patient experience through automated patient positioning.

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.

Hellena Hempe, Alexander Bigalke, Mattias P. Heinrich

Degenerative spinal pathologies are highly prevalent among the elderly population. Timely diagnosis of osteoporotic fractures and other degenerative deformities facilitates proactive measures to mitigate the risk of severe back pain and disability. In this study, we specifically explore the use of shape auto-encoders for vertebrae, taking advantage of advancements in automated multi-label segmentation and the availability of large datasets for unsupervised learning. Our shape auto-encoders are trained on a large set of vertebrae surface patches, leveraging the vast amount of available data for vertebra segmentation. This addresses the label scarcity problem faced when learning shape information of vertebrae from image intensities. Based on the learned shape features we train an MLP to detect vertebral body fractures. Using segmentation masks that were automatically generated using the TotalSegmentator, our proposed method achieves an AUC of 0.901 on the VerSe19 testset. This outperforms image-based and surface-based end-to-end trained models. Additionally, our results demonstrate that pre-training the models in an unsupervised manner enhances geometric methods like PointNet and DGCNN. Our findings emphasise the advantages of explicitly learning shape features for diagnosing osteoporotic vertebrae fractures. This approach improves the reliability of classification results and reduces the need for annotated labels. This study provides novel insights into the effectiveness of various encoder-decoder models for shape analysis of vertebrae and proposes a new decoder architecture: the point-based shape decoder.

Alessa Hering, Sarah de Boer, Anindo Saha et al.

The PI-CAI (Prostate Imaging: Cancer AI) challenge led to expert-level diagnostic algorithms for clinically significant prostate cancer detection. The algorithms receive biparametric MRI scans as input, which consist of T2-weighted and diffusion-weighted scans. These scans can be misaligned due to multiple factors in the scanning process. Image registration can alleviate this issue by predicting the deformation between the sequences. We investigate the effect of image registration on the diagnostic performance of AI-based prostate cancer diagnosis. First, the image registration algorithm, developed in MeVisLab, is analyzed using a dataset with paired lesion annotations. Second, the effect on diagnosis is evaluated by comparing case-level cancer diagnosis performance between using the original dataset, rigidly aligned diffusion-weighted scans, or deformably aligned diffusion-weighted scans. Rigid registration showed no improvement. Deformable registration demonstrated a substantial improvement in lesion overlap (+10% median Dice score) and a positive yet non-significant improvement in diagnostic performance (+0.3% AUROC, p=0.18). Our investigation shows that a substantial improvement in lesion alignment does not directly lead to a significant improvement in diagnostic performance. Qualitative analysis indicated that jointly developing image registration methods and diagnostic AI algorithms could enhance diagnostic accuracy and patient outcomes.

Eytan Kats, Jochen G. Hirsch, Mattias P. Heinrich

This paper demonstrates a self-supervised framework for learning voxel-wise coarse-to-fine representations tailored for dense downstream tasks. Our approach stems from the observation that existing methods for hierarchical representation learning tend to prioritize global features over local features due to inherent architectural bias. To address this challenge, we devise a training strategy that balances the contributions of features from multiple scales, ensuring that the learned representations capture both coarse and fine-grained details. Our strategy incorporates 3-fold improvements: (1) local data augmentations, (2) a hierarchically balanced architecture, and (3) a hybrid contrastive-restorative loss function. We evaluate our method on CT and MRI data and demonstrate that our new approach particularly beneficial for fine-tuning with limited annotated data and consistently outperforms the baseline counterpart in linear evaluation settings.

Ron Keuth, Paul Kaftan, Mattias P. Heinrich

The generalization of the Transformer architecture via MetaFormer has reshaped our understanding of its success in computer vision. By replacing self-attention with simpler token mixers, MetaFormer provides strong baselines for vision tasks. However, while extensively studied on natural image datasets, its use in medical imaging remains scarce, and existing works rarely compare different token mixers, potentially overlooking more suitable designs choices. In this work, we present the first comprehensive study of token mixers for medical imaging. We systematically analyze pooling-, convolution-, and attention-based token mixers within the MetaFormer architecture on image classification (global prediction task) and semantic segmentation (dense prediction task). Our evaluation spans eight datasets covering diverse modalities and common challenges in the medical domain. Given the prevalence of pretraining from natural images to mitigate medical data scarcity, we also examine transferring pretrained weights to new token mixers. Our results show that, for classification, low-complexity token mixers (e.g. grouped convolution or pooling) are sufficient, aligning with findings on natural images. Pretrained weights remain useful despite the domain gap introduced by the new token mixer. For segmentation, we find that the local inductive bias of convolutional token mixers is essential. Grouped convolutions emerge as the preferred choice, as they reduce runtime and parameter count compared to standard convolutions, while the MetaFormer's channel-MLPs already provide the necessary cross-channel interactions.

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.

Eytan Kats, Kai Geißler, Jochen G. Hirsch et al.

Automated patient positioning is a crucial step in streamlining MRI workflows and enhancing patient throughput. RGB-D camera-based systems offer a promising approach to automate this process by leveraging depth information to estimate internal organ positions. This paper investigates the feasibility of a learning-based framework to infer approximate internal organ positions from the body surface. Our approach utilizes a large-scale dataset of MRI scans to train a deep learning model capable of accurately predicting organ positions and shapes from depth images alone. We demonstrate the effectiveness of our method in localization of multiple internal organs, including bones and soft tissues. Our findings suggest that RGB-D camera-based systems integrated into MRI workflows have the potential to streamline scanning procedures and improve patient experience by enabling accurate and automated patient positioning.

Wiebke Heyer, Yannic Elser, Lennart Berkel et al.

In modern cancer research, the vast volume of medical data generated is often underutilised due to challenges related to patient privacy. The OncoReg Challenge addresses this issue by enabling researchers to develop and validate image registration methods through a two-phase framework that ensures patient privacy while fostering the development of more generalisable AI models. Phase one involves working with a publicly available dataset, while phase two focuses on training models on a private dataset within secure hospital networks. OncoReg builds upon the foundation established by the Learn2Reg Challenge by incorporating the registration of interventional cone-beam computed tomography (CBCT) with standard planning fan-beam CT (FBCT) images in radiotherapy. Accurate image registration is crucial in oncology, particularly for dynamic treatment adjustments in image-guided radiotherapy, where precise alignment is necessary to minimise radiation exposure to healthy tissues while effectively targeting tumours. This work details the methodology and data behind the OncoReg Challenge and provides a comprehensive analysis of the competition entries and results. Findings reveal that feature extraction plays a pivotal role in this registration task. A new method emerging from this challenge demonstrated its versatility, while established approaches continue to perform comparably to newer techniques. Both deep learning and classical approaches still play significant roles in image registration, with the combination of methods, particularly in feature extraction, proving most effective.

Mattias P. Heinrich, Lasse Hansen

The majority of current research in deep learning based image registration addresses inter-patient brain registration with moderate deformation magnitudes. The recent Learn2Reg medical registration benchmark has demonstrated that single-scale U-Net architectures, such as VoxelMorph that directly employ a spatial transformer loss, often do not generalise well beyond the cranial vault and fall short of state-of-the-art performance for abdominal or intra-patient lung registration. Here, we propose two straightforward steps that greatly reduce this gap in accuracy. First, we employ keypoint self-supervision with a novel network head that predicts a discretised heatmap and robustly reduces large deformations for better robustness. Second, we replace multiple learned fine-tuning steps by a single instance optimisation with hand-crafted features and the Adam optimiser. Different to other related work, including FlowNet or PDD-Net, our approach does not require a fully discretised architecture with correlation layer. Our ablation study demonstrates the importance of keypoints in both self-supervised and unsupervised (using only a MIND metric) settings. On a multi-centric inspiration-exhale lung CT dataset, including very challenging COPD scans, our method outperforms VoxelMorph by improving nonlinear alignment by 77% compared to 19% - reaching target registration errors of 2 mm that outperform all but one learning methods published to date. Extending the method to semantic features sets new stat-of-the-art performance on inter-subject abdominal CT registration.

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.

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.

Hanna Siebert, Lasse Hansen, Mattias P. Heinrich

Current approaches for deformable medical image registration often struggle to fulfill all of the following criteria: versatile applicability, small computation or training times, and the being able to estimate large deformations. Furthermore, end-to-end networks for supervised training of registration often become overly complex and difficult to train. For the Learn2Reg2021 challenge, we aim to address these issues by decoupling feature learning and geometric alignment. First, we introduce a new very fast and accurate optimisation method. By using discretised displacements and a coupled convex optimisation procedure, we are able to robustly cope with large deformations. With the help of an Adam-based instance optimisation, we achieve very accurate registration performances and by using regularisation, we obtain smooth and plausible deformation fields. Second, to be versatile for different registration tasks, we extract hand-crafted features that are modality and contrast invariant and complement them with semantic features from a task-specific segmentation U-Net. With our results we were able to achieve the overall Learn2Reg2021 challenge's second place, winning Task 1 and being second and third in the other two tasks.

Kaiwen Xu, Riqiang Gao, Mirza S. Khan et al.

A major goal of lung cancer screening is to identify individuals with particular phenotypes that are associated with high risk of cancer. Identifying relevant phenotypes is complicated by the variation in body position and body composition. In the brain, standardized coordinate systems (e.g., atlases) have enabled separate consideration of local features from gross/global structure. To date, no analogous standard atlas has been presented to enable spatial mapping and harmonization in chest computational tomography (CT). In this paper, we propose a thoracic atlas built upon a large low dose CT (LDCT) database of lung cancer screening program. The study cohort includes 466 male and 387 female subjects with no screening detected malignancy (age 46-79 years, mean 64.9 years). To provide spatial mapping, we optimize a multi-stage inter-subject non-rigid registration pipeline for the entire thoracic space. We evaluate the optimized pipeline relative to two baselines with alternative non-rigid registration module: the same software with default parameters and an alternative software. We achieve a significant improvement in terms of registration success rate based on manual QA. For the entire study cohort, the optimized pipeline achieves a registration success rate of 91.7%. The application validity of the developed atlas is evaluated in terms of discriminative capability for different anatomic phenotypes, including body mass index (BMI), chronic obstructive pulmonary disease (COPD), and coronary artery calcification (CAC).

Lasse Hansen, Mattias P. Heinrich

Though, deep learning based medical image registration is currently starting to show promising advances, often, it still fells behind conventional frameworks in terms of registration accuracy. This is especially true for applications where large deformations exist, such as registration of interpatient abdominal MRI or inhale-to-exhale CT lung registration. Most current works use U-Net-like architectures to predict dense displacement fields from the input images in different supervised and unsupervised settings. We believe that the U-Net architecture itself to some level limits the ability to predict large deformations (even when using multilevel strategies) and therefore propose a novel approach, where the input images are mapped into a displacement space and final registrations are reconstructed from this embedding. Experiments on inhale-to-exhale CT lung registration demonstrate the ability of our architecture to predict large deformations in a single forward path through our network (leading to errors below 2 mm).

Max Blendowski, Mattias P. Heinrich

Current deep learning methods are based on the repeated, expensive application of convolutions with parameter-intensive weight matrices. In this work, we present a novel concept that enables the application of differentiable random ferns in end-to-end networks. It can then be used as multiplication-free convolutional layer alternative in deep network architectures. Our experiments on the binary classification task of the TUPAC'16 challenge demonstrate improved results over the state-of-the-art binary XNOR net and only slightly worse performance than its 2x more parameter intensive floating point CNN counterpart.

Timo Kepp, Helge Sudkamp, Claus von der Burchard et al.

The treatment of age-related macular degeneration (AMD) requires continuous eye exams using optical coherence tomography (OCT). The need for treatment is determined by the presence or change of disease-specific OCT-based biomarkers. Therefore, the monitoring frequency has a significant influence on the success of AMD therapy. However, the monitoring frequency of current treatment schemes is not individually adapted to the patient and therefore often insufficient. While a higher monitoring frequency would have a positive effect on the success of treatment, in practice it can only be achieved with a home monitoring solution. One of the key requirements of a home monitoring OCT system is a computer-aided diagnosis to automatically detect and quantify pathological changes using specific OCT-based biomarkers. In this paper, for the first time, retinal scans of a novel self-examination low-cost full-field OCT (SELF-OCT) are segmented using a deep learning-based approach. A convolutional neural network (CNN) is utilized to segment the total retina as well as pigment epithelial detachments (PED). It is shown that the CNN-based approach can segment the retina with high accuracy, whereas the segmentation of the PED proves to be challenging. In addition, a convolutional denoising autoencoder (CDAE) refines the CNN prediction, which has previously learned retinal shape information. It is shown that the CDAE refinement can correct segmentation errors caused by artifacts in the OCT image.

Lasse Hansen, Doris Dittmer, Mattias P. Heinrich

Deformable registration continues to be one of the key challenges in medical image analysis. While iconic registration methods have started to benefit from the recent advances in medical deep learning, the same does not yet apply for the registration of point sets, e.g. registration based on surfaces, keypoints or landmarks. This is mainly due to the restriction of the convolution operator in modern CNNs to densely gridded input. However, with the newly developed methods from the field of geometric deep learning suitable tools are now emerging, which enable powerful analysis of medical data on irregular domains. In this work, we present a new method that enables the learning of regularized feature descriptors with dynamic graph CNNs. By incorporating the learned geometric features as prior probabilities into the well-established coherent point drift (CPD) algorithm, formulated as differentiable network layer, we establish an end-to-end framework for robust registration of two point sets. Our approach is evaluated on the challenging task of aligning keypoints extracted from lung CT scans in inhale and exhale states with large deformations and without any additional intensity information. Our results indicate that the inherent geometric structure of the extracted keypoints is sufficient to establish descriptive point features, which yield a significantly improved performance and robustness of our registration framework.

Mattias P. Heinrich

Nonlinear image registration continues to be a fundamentally important tool in medical image analysis. Diagnostic tasks, image-guided surgery and radiotherapy as well as motion analysis all rely heavily on accurate intra-patient alignment. Furthermore, inter-patient registration enables atlas-based segmentation or landmark localisation and shape analysis. When labelled scans are scarce and anatomical differences large, conventional registration has often remained superior to deep learning methods that have so far mainly dealt with relatively small or low-complexity deformations. We address this shortcoming by leveraging ideas from probabilistic dense displacement optimisation that has excelled in many registration tasks with large deformations. We propose to design a network with approximate min-convolutions and mean field inference for differentiable displacement regularisation within a discrete weakly-supervised registration setting. By employing these meaningful and theoretically proven constraints, our learnable registration algorithm contains very few trainable weights (primarily for feature extraction) and is easier to train with few labelled scans. It is very fast in training and inference and achieves state-of-the-art accuracies for the challenging inter-patient registration of abdominal CT outperforming previous deep learning approaches by 15% Dice overlap.

Xiahai Zhuang, Lei Li, Christian Payer et al.

Knowledge of whole heart anatomy is a prerequisite for many clinical applications. Whole heart segmentation (WHS), which delineates substructures of the heart, can be very valuable for modeling and analysis of the anatomy and functions of the heart. However, automating this segmentation can be arduous due to the large variation of the heart shape, and different image qualities of the clinical data. To achieve this goal, a set of training data is generally needed for constructing priors or for training. In addition, it is difficult to perform comparisons between different methods, largely due to differences in the datasets and evaluation metrics used. This manuscript presents the methodologies and evaluation results for the WHS algorithms selected from the submissions to the Multi-Modality Whole Heart Segmentation (MM-WHS) challenge, in conjunction with MICCAI 2017. The challenge provides 120 three-dimensional cardiac images covering the whole heart, including 60 CT and 60 MRI volumes, all acquired in clinical environments with manual delineation. Ten algorithms for CT data and eleven algorithms for MRI data, submitted from twelve groups, have been evaluated. The results show that many of the deep learning (DL) based methods achieved high accuracy, even though the number of training datasets was limited. A number of them also reported poor results in the blinded evaluation, probably due to overfitting in their training. The conventional algorithms, mainly based on multi-atlas segmentation, demonstrated robust and stable performance, even though the accuracy is not as good as the best DL method in CT segmentation. The challenge, including the provision of the annotated training data and the blinded evaluation for submitted algorithms on the test data, continues as an ongoing benchmarking resource via its homepage (\url{www.sdspeople.fudan.edu.cn/zhuangxiahai/0/mmwhs/}).

Lasse Hansen, Jasper Diesel, Mattias P. Heinrich

Graph convolutional networks are a new promising learning approach to deal with data on irregular domains. They are predestined to overcome certain limitations of conventional grid-based architectures and will enable efficient handling of point clouds or related graphical data representations, e.g. superpixel graphs. Learning feature extractors and classifiers on 3D point clouds is still an underdeveloped area and has potential restrictions to equal graph topologies. In this work, we derive a new architectural design that combines rotationally and topologically invariant graph diffusion operators and node-wise feature learning through 1x1 convolutions. By combining multiple isotropic diffusion operations based on the Laplace-Beltrami operator, we can learn an optimal linear combination of diffusion kernels for effective feature propagation across nodes on an irregular graph. We validated our approach for learning point descriptors as well as semantic classification on real 3D point clouds of human poses and demonstrate an improvement from 85% to 95% in Dice overlap with our multi-kernel approach.

Jan Rühaak, Thomas Polzin, Stefan Heldmann et al.

We present a novel algorithm for the registration of pulmonary CT scans. Our method is designed for large respiratory motion by integrating sparse keypoint correspondences into a dense continuous optimization framework. The detection of keypoint correspondences enables robustness against large deformations by jointly optimizing over a large number of potential discrete displacements, whereas the dense continuous registration achieves subvoxel alignment with smooth transformations. Both steps are driven by the same normalized gradient fields data term. We employ curvature regularization and a volume change control mechanism to prevent foldings of the deformation grid and restrict the determinant of the Jacobian to physiologically meaningful values. Keypoint correspondences are integrated into the dense registration by a quadratic penalty with adaptively determined weight. Using a parallel matrix-free derivative calculation scheme, a runtime of about 5 min was realized on a standard PC. The proposed algorithm ranks first in the EMPIRE10 challenge on pulmonary image registration. Moreover, it achieves an average landmark distance of 0.82 mm on the DIR-Lab COPD database, thereby improving upon the state of the art in accuracy by 15%. Our algorithm is the first to reach the inter-observer variability in landmark annotation on this dataset.

Mattias P. Heinrich, Max Blendowski, Ozan Oktay

Deep convolutional neural networks (DCNN) are currently ubiquitous in medical imaging. While their versatility and high quality results for common image analysis tasks including segmentation, localisation and prediction is astonishing, the large representational power comes at the cost of highly demanding computational effort. This limits their practical applications for image guided interventions and diagnostic (point-of-care) support using mobile devices without graphics processing units (GPU). We propose a new scheme that approximates both trainable weights and neural activations in deep networks by ternary values and tackles the open question of backpropagation when dealing with non-differentiable functions. Our solution enables the removal of the expensive floating-point matrix multiplications throughout any convolutional neural network and replaces them by energy and time preserving binary operators and population counts. Our approach, which is demonstrated using a fully-convolutional network (FCN) for CT pancreas segmentation leads to more than 10-fold reduced memory requirements and we provide a concept for sub-second inference without GPUs. Our ternary approximation obtains high accuracies (without any post-processing) with a Dice overlap of 71.0% that are statistically equivalent to using networks with high-precision weights and activations. We further demonstrate the significant improvements reached in comparison to binary quantisation and without our proposed ternary hyperbolic tangent continuation. We present a key enabling technique for highly efficient DCNN inference without GPUs that will help to bring the advances of deep learning to practical clinical applications. It has also great promise for improving accuracies in large-scale medical data retrieval.