Lasse Hansen

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.

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.

Ron Keuth, Lasse Hansen, Maren Balks et al.

Semantic segmentation is a crucial task in medical imaging. Although supervised learning techniques have proven to be effective in performing this task, they heavily depend on large amounts of annotated training data. The recently introduced Segment Anything Model (SAM) enables prompt-based segmentation and offers zero-shot generalization to unfamiliar objects. In our work, we leverage SAM's abstract object understanding for medical image segmentation to provide pseudo labels for semi-supervised learning, thereby mitigating the need for extensive annotated training data. Our approach refines initial segmentations that are derived from a limited amount of annotated data (comprising up to 43 cases) by extracting bounding boxes and seed points as prompts forwarded to SAM. Thus, it enables the generation of dense segmentation masks as pseudo labels for unlabelled data. The results show that training with our pseudo labels yields an improvement in Dice score from $74.29\,\%$ to $84.17\,\%$ and from $66.63\,\%$ to $74.87\,\%$ for the segmentation of bones of the paediatric wrist and teeth in dental radiographs, respectively. As a result, our method outperforms intensity-based post-processing methods, state-of-the-art supervised learning for segmentation (nnU-Net), and the semi-supervised mean teacher approach. Our Code is available on GitHub.

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.

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.

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.

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.

Mattias P Heinrich, Lasse Hansen

Multimodal image registration is a very challenging problem for deep learning approaches. Most current work focuses on either supervised learning that requires labelled training scans and may yield models that bias towards annotated structures or unsupervised approaches that are based on hand-crafted similarity metrics and may therefore not outperform their classical non-trained counterparts. We believe that unsupervised domain adaptation can be beneficial in overcoming the current limitations for multimodal registration, where good metrics are hard to define. Domain adaptation has so far been mainly limited to classification problems. We propose the first use of unsupervised domain adaptation for discrete multimodal registration. Based on a source domain for which quantised displacement labels are available as supervision, we transfer the output distribution of the network to better resemble the target domain (other modality) using classifier discrepancies. To improve upon the sliced Wasserstein metric for 2D histograms, we present a novel approximation that projects predictions into 1D and computes the L1 distance of their cumulative sums. Our proof-of-concept demonstrates the applicability of domain transfer from mono- to multimodal (multi-contrast) 2D registration of canine MRI scans and improves the registration accuracy from 33% (using sliced Wasserstein) to 44%.

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).

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.

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.