Registration of medical image data requires methods that can align anatomical structures precisely while applying smooth and plausible transformations. Ideally, these methods should furthermore operate quickly and apply to a wide variety of tasks. Deep learning-based image registration methods usually entail an elaborate learning procedure with the need for extensive training data. However, they often struggle with versatility when aiming to apply the same approach across various anatomical regions and different imaging modalities. In this work, we present a method that extracts semantic or hand-crafted image features and uses a coupled convex optimisation followed by Adam-based instance optimisation for multitask medical image registration. We make use of pre-trained semantic feature extraction models for the individual datasets and combine them with our fast dual optimisation procedure for deformation field computation. Furthermore, we propose a very fast automatic hyperparameter selection procedure that explores many settings and ranks them on validation data to provide a self-configuring image registration framework. With our approach, we can align image data for various tasks with little learning. We conduct experiments on all available Learn2Reg challenge datasets and obtain results that are to be positioned in the upper ranks of the challenge leaderboards. http://github.com/multimodallearning/convexAdam.

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 multicenter 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 post-processing (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.

Learning-based registration for large-scale 3D point clouds has been shown to improve robustness and accuracy compared to classical methods and can be trained without supervision for locally rigid problems. However, for tasks with highly deformable structures, such as alignment of pulmonary vascular trees for medical diagnostics, previous approaches of self-supervision with regularisation and point distance losses have failed to succeed, leading to the need for complex synthetic augmentation strategies to obtain reliably strong supervision. In this work, we introduce a novel Differentiable Volumetric Rasterisation of point Clouds (DiVRoC) that overcomes those limitations and offers a highly efficient and accurate loss for large-scale deformable 3D registration. DiVRoC drastically reduces the computational complexity for measuring point cloud distances for high-resolution data with over 100k 3D points and can also be employed to extrapolate and regularise sparse motion fields, as loss in a self-training setting and as objective function in instance optimisation. DiVRoC can be successfully embedded into geometric registration networks, including PointPWC-Net and other graph CNNs. Our approach yields new state-of-the-art accuracy on the challenging PVT dataset in three different settings without training with manual ground truth: 1) unsupervised metric-based learning 2) self-supervised learning with pseudo labels generated by self-training and 3) optimisation based alignment without learning. https://github.com/mattiaspaul/ChasingClouds

A popular benchmark for intra-patient lung registration is provided by the DIR-LAB COPDgene dataset consisting of large-motion in- and expiratory breath-hold CT pairs. This dataset alone, however, does not provide enough samples to properly train state-of-the-art deep learning methods. Other public datasets often also provide only small sample sizes or include primarily small motions between scans that do not translate well to larger deformations. For point-based geometric registration, the PVT1010 dataset provides a large number of vessel point clouds without any correspondences and a labeled test set corresponding to the COPDgene cases. However, the absence of correspondences for supervision complicates training, and a fair comparison with image-based algorithms is infeasible, since CT scans for the training data are not publicly available.We here provide a combined benchmark for image- and point-based registration approaches. We curated a total of 248 public multi-centric in- and expiratory lung CT scans from 124 patients, which show large motion between scans, processed them to ensure sufficient homogeneity between the data and generated vessel point clouds that are well distributed even deeper inside the lungs. For supervised training, we provide vein and artery segmentations of the vessels and multiple thousand image-derived keypoint correspondences for each pair. For validation, we provide multiple scan pairs with manual landmark annotations. Finally, as first baselines on our new benchmark, we evaluate several image and point cloud registration methods on the dataset.

Flow estimation on 3D point clouds is a challenging problem in the field of computer vision, which has great significance in many areas, such as autonomous driving and human interaction applications. Within the last years, the field of motion analysis has made great progress. The evaluation of the existing approaches mostly focuses on scenarios where objects are affected by rigid transformations. However, in many application areas such as gesture recognition or pose tracking, the detection of shape changes is essential and breaking them down to local rigid transformations is accompanied by loss of information. One component of our contributions is that we specifically prepared existing datasets for scene flow estimation on deformable objects. Additionally, we benchmark existing methods and analyze their behavior on various subtasks. The results show that already close to 80% of correct correspondences can be found on synthetic hand data, while only around 50% are found on real hand data. Our experimental validation and analysis help to build an understanding of new possibilities in broader areas. Furthermore, they should help to inspire possible further research directions.

Domain Adaptation (DA) has recently been of strong interest in the medical imaging community. While a large variety of DA techniques have 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 Domain Adaptation. The goal of the challenge 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 commonly performed using contrast-enhanced T1 (ceT1) MR imaging. However, there is growing interest in using non-contrast imaging sequences such as high-resolution T2 (hrT2) imaging. For this reason, we established an unsupervised cross-modality segmentation benchmark. The training dataset provides annotated ceT1 scans (N=105) and unpaired non-annotated hrT2 scans (N=105). The aim was to automatically perform unilateral VS and bilateral cochlea segmentation on hrT2 scans as provided in the testing set (N=137). This problem is particularly challenging given the large intensity distribution gap across the modalities and the small volume of the structures. A total of 55 teams from 16 countries submitted predictions to the validation leaderboard. Among them, 16 teams from 9 different countries submitted their algorithm for the evaluation phase. The level of performance reached by the top-performing teams is strikingly high (best median Dice score — VS: 88.4%; Cochleas: 85.7%) and close to full supervision (median Dice score — 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.

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.

Hand gesture recognition can benefit from directly processing 3D point cloud sequences, which carry rich geometric information and enable the learning of expressive spatio-temporal features. However, currently employed single-stream models cannot sufficiently capture multi-scale features that include both fine-grained local posture variations and global hand movements. We therefore propose a novel dual-stream model, which decouples the learning of local and global features. These are eventually fused in an LSTM for temporal modelling. To induce the global and local stream to capture complementary position and posture features, we propose the use of different 3D learning architectures in both streams. Specifically, state-of-the-art point cloud networks excel at capturing fine posture variations from raw point clouds in the local stream. To track hand movements in the global stream, we combine an encoding with residual basis point sets and a fully-connected DenseNet. We evaluate the method on the Shrec'17 and DHG dataset and report state-of-the-art results at a reduced computational cost. Source code is available at https://github.com/multimodallearning/hand-gesture-posture-position.

In the last two years learning-based methods have started to show encouraging results in different supervised and unsupervised medical image registration tasks. Deep neural networks enable (near) real time applications through fast inference times and have tremendous potential for increased registration accuracies by task-specific learning. However, estimation of large 3D deformations, for example present in inhale to exhale lung CT or interpatient abdominal MRI registration, is still a major challenge for the widely adopted U-Net-like network architectures. Even when using multi-level strategies, current state-of-the-art DL registration results do not yet reach the high accuracy of conventional frameworks. To overcome the problem of large deformations for deep learning approaches, in this work, we present GraphRegNet, a sparse keypoint-based geometric network for dense deformable medical image registration. Similar to the successful 2D optical flow estimation of FlowNet or PWC-Net we leverage discrete dense displacement maps to facilitate the registration process. In order to cope with enormously increasing memory requirements when working with displacement maps in 3D medical volumes and to obtain a well-regularised and accurate deformation field we 1) formulate the registration task as the prediction of displacement vectors on a sparse irregular grid of distinctive keypoints and 2) introduce our efficient GraphRegNet for displacement regularisation, a combination of convolutional and graph neural network layers in a unified architecture. In our experiments on exhale to inhale lung CT registration we demonstrate substantial improvements (TRE below 1.4 mm) over other deep learning methods. Our code is publicly available at https://github.com/multimodallearning/graphregnet.

In brain tumor surgery, the quality and safety of the procedure can be impacted by intra-operative tissue deformation, called brain shift. Brain shift can move the surgical targets and other vital structures such as blood vessels, thus invalidating the pre-surgical plan. Intra-operative ultrasound (iUS) is a convenient and cost-effective imaging tool to track brain shift and tumor resection. Accurate image registration techniques that update pre-surgical MRI based on iUS are crucial but challenging. The MICCAI Challenge 2018 for Correction of Brain shift with Intra-Operative UltraSound (CuRIOUS2018) provided a public platform to benchmark MRI-iUS registration algorithms on newly released clinical datasets. In this work, we present the data, setup, evaluation, and results of CuRIOUS 2018, which received 6 fully automated algorithms from leading academic and industrial research groups. All algorithms were first trained with the public RESECT database, and then ranked based on a test dataset of 10 additional cases with identical data curation and annotation protocols as the RESECT database. The article compares the results of all participating teams and discusses the insights gained from the challenge, as well as future work.

We propose a novel attention gate (AG) model for medical image analysis that automatically learns to focus on target structures of varying shapes and sizes. Models trained with AGs implicitly learn to suppress irrelevant regions in an input image while highlighting salient features useful for a specific task. This enables us to eliminate the necessity of using explicit external tissue/organ localisation modules when using convolutional neural networks (CNNs). AGs can be easily integrated into standard CNN models such as VGG or U-Net architectures with minimal computational overhead while increasing the model sensitivity and prediction accuracy. The proposed AG models are evaluated on a variety of tasks, including medical image classification and segmentation. For classification, we demonstrate the use case of AGs in scan plane detection for fetal ultrasound screening. We show that the proposed attention mechanism can provide efficient object localisation while improving the overall prediction performance by reducing false positives. For segmentation, the proposed architecture is evaluated on two large 3D CT abdominal datasets with manual annotations for multiple organs. Experimental results show that AG models consistently improve the prediction performance of the base architectures across different datasets and training sizes while preserving computational efficiency. Moreover, AGs guide the model activations to be focused around salient regions, which provides better insights into how model predictions are made. The source code for the proposed AG models is publicly available.

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 challenging due to the large variation of the heart shape, and different image qualities of the clinical data. To achieve this goal, an initial set of training data is generally needed for constructing priors or for training. Furthermore, 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 provided 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 showed that the performance of CT WHS was generally better than that of MRI WHS. The segmentation of the substructures for different categories of patients could present different levels of challenge due to the difference in imaging and variations of heart shapes. The deep learning (DL)-based methods demonstrated great potential, though several of them reported poor results in the blinded evaluation. Their performance could vary greatly across different network structures and training strategies. The conventional algorithms, mainly based on multi-atlas segmentation, demonstrated good performance, though the accuracy and computational efficiency could be limited. The challenge, including 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 (www.sdspeople.fudan.edu.cn/zhuangxiahai/0/mmwhs/).

Incorporation of prior knowledge about organ shape and location is key to improve performance of image analysis approaches. In particular, priors can be useful in cases where images are corrupted and contain artefacts due to limitations in image acquisition. The highly constrained nature of anatomical objects can be well captured with learning-based techniques. However, in most recent and promising techniques such as CNN-based segmentation it is not obvious how to incorporate such prior knowledge. State-of-the-art methods operate as pixel-wise classifiers where the training objectives do not incorporate the structure and inter-dependencies of the output. To overcome this limitation, we propose a generic training strategy that incorporates anatomical prior knowledge into CNNs through a new regularisation model, which is trained end-to-end. The new framework encourages models to follow the global anatomical properties of the underlying anatomy (e.g. shape, label structure) via learnt non-linear representations of the shape. We show that the proposed approach can be easily adapted to different analysis tasks (e.g. image enhancement, segmentation) and improve the prediction accuracy of the state-of-the-art models. The applicability of our approach is shown on multi-modal cardiac data sets and public benchmarks. In addition, we demonstrate how the learnt deep models of 3-D shapes can be interpreted and used as biomarkers for classification of cardiac pathologies.

Accurate localization of anatomical landmarks is an important step in medical imaging, as it provides useful prior information for subsequent image analysis and acquisition methods. It is particularly useful for initialization of automatic image analysis tools (e.g. segmentation and registration) and detection of scan planes for automated image acquisition. Landmark localization has been commonly performed using learning based approaches, such as classifier and/or regressor models. However, trained models may not generalize well in heterogeneous datasets when the images contain large differences due to size, pose and shape variations of organs. To learn more data-adaptive and patient specific models, we propose a novel stratification based training model, and demonstrate its use in a decision forest. The proposed approach does not require any additional training information compared to the standard model training procedure and can be easily integrated into any decision tree framework. The proposed method is evaluated on 1080 3D high-resolution and 90 multi-stack 2D cardiac cine MR images. The experiments show that the proposed method achieves state-of-the-art landmark localization accuracy and outperforms standard regression and classification based approaches. Additionally, the proposed method is used in a multi-atlas segmentation to create a fully automatic segmentation pipeline, and the results show that it achieves state-of-the-art segmentation accuracy.

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.

In this paper a novel Large Deformation Diffeomorphic Metric Mapping (LDDMM) scheme is presented which has significantly lower computational and memory demands than standard LDDMM but achieves the same accuracy. We exploit the smoothness of velocities and transformations by using a coarser discretization compared to the image resolution. This reduces required memory and accelerates numerical optimization as well as solution of transport equations. Accuracy is essentially unchanged as the mismatch of transformed moving and fixed image is incorporated into the model at high resolution. Reductions in memory consumption and runtime are demonstrated for registration of lung CT images. State-of-the-art accuracy is shown for the challenging DIR-Lab chronic obstructive pulmonary disease (COPD) lung CT data sets obtaining a mean landmark distance after registration of 1.03 mm and the best average results so far. These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Intra-interventional respiratory motion estimation has become vital for image-guided interventions, especially radiation therapy. While real-time tracking of highly discriminative landmarks like tumours and markers is possible with classic approaches (e.g. template matching), their robustness decreases when used with non-ionising imaging (4D MRI or US). Furthermore, they ignore the motion of neighbouring structures. We address these challenges by dividing the computation of dense deformable registration in two phases: First, a low-parametric full domain patient-specific motion model is learnt. Second, a sparse subset of feature locations is used to track motion locally, while the global motion patterns are constrained by the learnt model. In contrast to previous work, we optimise both objectives (local similarity and globally smooth motion) jointly using a coupled convex energy minimisation. This improves the tracking robustness and leads to a more accurate global motion estimation. The algorithm is computationally efficient and significantly outperforms classic template matching-based dense field estimation in 12 of 14 challenging 4D MRI and 4D ultrasound sequences. These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Variations in the shape and appearance of anatomical structures in medical images are often relevant radiological signs of disease. Automatic tools can help automate parts of this manual process. A cloud-based evaluation framework is presented in this paper including results of benchmarking current state-of-the-art medical imaging algorithms for anatomical structure segmentation and landmark detection: the VISCERAL Anatomy benchmarks. The algorithms are implemented in virtual machines in the cloud where participants can only access the training data and can be run privately by the benchmark administrators to objectively compare their performance in an unseen common test set. Overall, 120 computed tomography and magnetic resonance patient volumes were manually annotated to create a standard Gold Corpus containing a total of 1295 structures and 1760 landmarks. Ten participants contributed with automatic algorithms for the organ segmentation task, and three for the landmark localization task. Different algorithms obtained the best scores in the four available imaging modalities and for subsets of anatomical structures. The annotation framework, resulting data set, evaluation setup, results and performance analysis from the three VISCERAL Anatomy benchmarks are presented in this article. Both the VISCERAL data set and Silver Corpus generated with the fusion of the participant algorithms on a larger set of non-manually-annotated medical images are available to the research community.

Deformable image registration is an important tool in medical image analysis. In the case of lung computed tomography (CT) registration there are three major challenges: large motion of small features, sliding motions between organs, and changing image contrast due to compression. Recently, Markov random field (MRF)-based discrete optimization strategies have been proposed to overcome problems involved with continuous optimization for registration, in particular its susceptibility to local minima. However, to date the simplifications made to obtain tractable computational complexity reduced the registration accuracy. We address these challenges and preserve the potentially higher quality of discrete approaches with three novel contributions. First, we use an image-derived minimum spanning tree as a simplified graph structure, which copes well with the complex sliding motion and allows us to find the global optimum very efficiently. Second, a stochastic sampling approach for the similarity cost between images is introduced within a symmetric, diffeomorphic B-spline transformation model with diffusion regularization. The complexity is reduced by orders of magnitude and enables the minimization of much larger label spaces. In addition to the geometric transform labels, hyper-labels are introduced, which represent local intensity variations in this task, and allow for the direct estimation of lung ventilation. We validate the improvements in accuracy and performance on exhale-inhale CT volume pairs using a large number of expert landmarks.

EMPIRE10 (Evaluation of Methods for Pulmonary Image REgistration 2010) is a public platform for fair and meaningful comparison of registration algorithms which are applied to a database of intrapatient thoracic CT image pairs. Evaluation of nonrigid registration techniques is a nontrivial task. This is compounded by the fact that researchers typically test only on their own data, which varies widely. For this reason, reliable assessment and comparison of different registration algorithms has been virtually impossible in the past. In this work we present the results of the launch phase of EMPIRE10, which comprised the comprehensive evaluation and comparison of 20 individual algorithms from leading academic and industrial research groups. All algorithms are applied to the same set of 30 thoracic CT pairs. Algorithm settings and parameters are chosen by researchers expert in the configuration of their own method and the evaluation is independent, using the same criteria for all participants. All results are published on the EMPIRE10 website (http://empire10.isi.uu.nl). The challenge remains ongoing and open to new participants. Full results from 24 algorithms have been published at the time of writing. This paper details the organization of the challenge, the data and evaluation methods and the outcome of the initial launch with 20 algorithms. The gain in knowledge and future work are discussed.