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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., Comment: Presented at MICCAI Workshop on Advancing Data Solutions in Medical Imaging AI 2024; Code and data: https://github.com/multimodallearning/SamCarriesTheBurden

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., Comment: Accepted as full paper to MICCAI 2024

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., Comment: Submitted to MICCAI 2024 (Before peer review version)

Purpose: Semantic segmentation and landmark detection are fundamental tasks of medical image processing, facilitating further analysis of anatomical objects. Although deep learning-based pixel-wise classification has set a new-state-of-the-art for segmentation, it falls short in landmark detection, a strength of shape-based approaches. Methods: In this work, we propose a dense image-to-shape representation that enables the joint learning of landmarks and semantic segmentation by employing a fully convolutional architecture. Our method intuitively allows the extraction of arbitrary landmarks due to its representation of anatomical correspondences. We benchmark our method against the state-of-the-art for semantic segmentation (nnUNet), a shape-based approach employing geometric deep learning and a CNN-based method for landmark detection. Results: We evaluate our method on two medical dataset: one common benchmark featuring the lungs, heart, and clavicle from thorax X-rays, and another with 17 different bones in the paediatric wrist. While our method is on pair with the landmark detection baseline in the thorax setting (error in mm of $2.6\pm0.9$ vs $2.7\pm0.9$), it substantially surpassed it in the more complex wrist setting ($1.1\pm0.6$ vs $1.9\pm0.5$). Conclusion: We demonstrate that dense geometric shape representation is beneficial for challenging landmark detection tasks and outperforms previous state-of-the-art using heatmap regression. While it does not require explicit training on the landmarks themselves, allowing for the addition of new landmarks without necessitating retraining.}

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.

When solving a segmentation task, shaped-base methods can be beneficial compared to pixelwise classification due to geometric understanding of the target object as shape, preventing the generation of anatomical implausible predictions in particular for corrupted data. In this work, we propose a novel hybrid method that combines a lightweight CNN backbone with a geometric neural network (Point Transformer) for shape regression. Using the same CNN encoder, the Point Transformer reaches segmentation quality on per with current state-of-the-art convolutional decoders ($4\pm1.9$ vs $3.9\pm2.9$ error in mm and $85\pm13$ vs $88\pm10$ Dice), but crucially, is more stable w.r.t image distortion, starting to outperform them at a corruption level of 30%. Furthermore, we include the nnU-Net as an upper baseline, which has $3.7\times$ more trainable parameters than our proposed method., Comment: Submitted to German Conference on Medical Image Computing 2024

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., Comment: Accepted for International Symposium on Biomedical Imaging 2024 (ISBI 2024)

Applying pre-trained medical segmentation models on out-of-domain images often yields predictions of insufficient quality. Several strategies have been proposed to maintain model performance, such as finetuning or unsupervised- and source-free domain adaptation. These strategies set restrictive requirements for data availability. In this study, we propose to combine domain generalization and test-time adaptation to create a highly effective approach for reusing pre-trained models in unseen target domains. Domain-generalized pre-training on source data is used to obtain the best initial performance in the target domain. We introduce the MIND descriptor previously used in image registration tasks as a further technique to achieve generalization and present superior performance for small-scale datasets compared to existing approaches. At test-time, high-quality segmentation for every single unseen scan is ensured by optimizing the model weights for consistency given different image augmentations. That way, our method enables separate use of source and target data and thus removes current data availability barriers. Moreover, the presented method is highly modular as it does not require specific model architectures or prior knowledge of involved domains and labels. We demonstrate this by integrating it into the nnUNet, which is currently the most popular and accurate framework for medical image segmentation. We employ multiple datasets covering abdominal, cardiac, and lumbar spine scans and compose several out-of-domain scenarios in this study. We demonstrate that our method, combined with pre-trained whole-body CT models, can effectively segment MR images with high accuracy in all of the aforementioned scenarios. Open-source code can be found here: https://github.com/multimodallearning/DG-TTA

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.

Purpose: Navigation guidance is a key requirement for a multitude of lung interventions using video bronchoscopy. State-of-the-art solutions focus on lung biopsies using electromagnetic tracking and intraoperative image registration w.r.t. preoperative CT scans for guidance. The requirement of patient-specific CT scans hampers the utilisation of navigation guidance for other applications such as intensive care units. Methods: This paper addresses navigation guidance solely incorporating bronchosopy video data. In contrast to state-of-the-art approaches we entirely omit the use of electromagnetic tracking and patient-specific CT scans. Guidance is enabled by means of topological bronchoscope localization w.r.t. an interpatient airway model. Particularly, we take maximally advantage of anatomical constraints of airway trees being sequentially traversed. This is realized by incorporating sequences of CNN-based airway likelihoods into a Hidden Markov Model. Results: Our approach is evaluated based on multiple experiments inside a lung phantom model. With the consideration of temporal context and use of anatomical knowledge for regularization, we are able to improve the accuracy up to to 0.98 compared to 0.81 (weighted F1: 0.98 compared to 0.81) for a classification based on individual frames. Conclusion: We combine CNN-based single image classification of airway segments with anatomical constraints and temporal HMM-based inference for the first time. Our approach renders vision-only guidance for bronchoscopy interventions in the absence of electromagnetic tracking and patient-specific CT scans possible., Comment: Submitted to International Journal of Computer Assisted Radiology and Surgery

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., Comment: accepted at MICCAI 2023

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., Comment: early accepted at MICCAI 2023; corrected confused reference

International benchmarking competitions have become fundamental for the comparative performance assessment of image analysis methods. However, little attention has been given to investigating what can be learnt from these competitions. Do they really generate scientific progress? What are common and successful participation strategies? What makes a solution superior to a competing method? To address this gap in the literature, we performed a multi-center study with all 80 competitions that were conducted in the scope of IEEE ISBI 2021 and MICCAI 2021. Statistical analyses performed based on comprehensive descriptions of the submitted algorithms linked to their rank as well as the underlying participation strategies revealed common characteristics of winning solutions. These typically include the use of multi-task learning (63%) and/or multi-stage pipelines (61%), and a focus on augmentation (100%), image preprocessing (97%), data curation (79%), and postprocessing (66%). The "typical" lead of a winning team is a computer scientist with a doctoral degree, five years of experience in biomedical image analysis, and four years of experience in deep learning. Two core general development strategies stood out for highly-ranked teams: the reflection of the metrics in the method design and the focus on analyzing and handling failure cases. According to the organizers, 43% of the winning algorithms exceeded the state of the art but only 11% completely solved the respective domain problem. The insights of our study could help researchers (1) improve algorithm development strategies when approaching new problems, and (2) focus on open research questions revealed by this work., Comment: accepted to CVPR 2023

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.

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., Comment: accepted at Medical Image Analysis

Video bronchoscopy is routinely conducted for biopsies of lung tissue suspected for cancer, monitoring of COPD patients and clarification of acute respiratory problems at intensive care units. The navigation within complex bronchial trees is particularly challenging and physically demanding, requiring long-term experiences of physicians. This paper addresses the automatic segmentation of bronchial orifices in bronchoscopy videos. Deep learning-based approaches to this task are currently hampered due to the lack of readily-available ground truth segmentation data. Thus, we present a data-driven pipeline consisting of a k-means followed by a compact marker-based watershed algorithm which enables to generate airway instance segmentation maps from given depth images. In this way, these traditional algorithms serve as weak supervision for training a shallow CNN directly on RGB images solely based on a phantom dataset. We evaluate generalization capabilities of this model on two in-vivo datasets covering 250 frames on 21 different bronchoscopies. We demonstrate that its performance is comparable to those models being directly trained on in-vivo data, reaching an average error of 11 vs 5 pixels for the detected centers of the airway segmentation by an image resolution of 128x128. Our quantitative and qualitative results indicate that in the context of video bronchoscopy, phantom data and weak supervision using non-learning-based approaches enable to gain a semantic understanding of airway structures., Comment: 5 Pages, 2 figures, only supplemental file, submitted to SPIE MI

In order to be able to use artificial intelligence (AI) in medicine without scepticism and to recognise and assess its growing potential, a basic understanding of this topic is necessary among current and future medical staff. Under the premise of "trust through understanding", we developed an innovative online course as a learning opportunity within the framework of the German KI Campus (AI campus) project, which is a self-guided course that teaches the basics of AI for the analysis of medical image data. The main goal is to provide a learning environment for a sufficient understanding of AI in medical image analysis so that further interest in this topic is stimulated and inhibitions towards its use can be overcome by means of positive application experience. The focus was on medical applications and the fundamentals of machine learning. The online course was divided into consecutive lessons, which include theory in the form of explanatory videos, practical exercises in the form of Streamlit and practical exercises and/or quizzes to check learning progress. A survey among the participating medical students in the first run of the course was used to analyse our research hypotheses quantitatively., Comment: 5 pages

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., Comment: 11 pages, accepted at MICCAI 2022

An increasing number of colonoscopic guidance and assistance systems rely on machine learning algorithms which require a large amount of high-quality training data. In order to ensure high performance, the latter has to resemble a substantial portion of possible configurations. This particularly addresses varying anatomy, mucosa appearance and image sensor characteristics which are likely deteriorated by motion blur and inadequate illumination. The limited amount of readily available training data hampers to account for all of these possible configurations which results in reduced generalization capabilities of machine learning models. We propose an exemplary solution for synthesizing colonoscopy videos with substantial appearance and anatomical variations which enables to learn discriminative domain-randomized representations of the interior colon while mimicking real-world settings., Comment: 4 pages, 5 figures

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., Comment: 10 pages, accepted at WBIR 2022

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., Comment: In Medical Image Analysis

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/.

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.

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.

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., Comment: accepted at IPMI 2021

The construction of three-dimensional multi-modal tissue maps provides an opportunity to spur interdisciplinary innovations across temporal and spatial scales through information integration. While the preponderance of effort is allocated to the cellular level and explore the changes in cell interactions and organizations, contextualizing findings within organs and systems is essential to visualize and interpret higher resolution linkage across scales. There is a substantial normal variation of kidney morphometry and appearance across body size, sex, and imaging protocols in abdominal computed tomography (CT). A volumetric atlas framework is needed to integrate and visualize the variability across scales. However, there is no abdominal and retroperitoneal organs atlas framework for multi-contrast CT. Hence, we proposed a high-resolution CT retroperitoneal atlas specifically optimized for the kidney across non-contrast CT and early arterial, late arterial, venous and delayed contrast enhanced CT. Briefly, we introduce a deep learning-based volume of interest extraction method and an automated two-stage hierarchal registration pipeline to register abdominal volumes to a high-resolution CT atlas template. To generate and evaluate the atlas, multi-contrast modality CT scans of 500 subjects (without reported history of renal disease, age: 15-50 years, 250 males & 250 females) were processed. We demonstrate a stable generalizability of the atlas template for integrating the normal kidney variation from small to large, across contrast modalities and populations with great variability of demographics. The linkage of atlas and demographics provided a better understanding of the variation of kidney anatomy across populations., Comment: 8 pages, 5 figures

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)., Comment: Accepted by SPIE2021 Medical Imaging (oral)

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%., Comment: Medical Imaging with Deep Learning (accepted short paper) https://openreview.net/forum?id=wbZM-DcJB9

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).

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.

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., Comment: Accepted for SPIE Medical Imaging 2020: Computer-Aided Diagnosis

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., Comment: accepted for MICCAI 2019 Workshop Graph Learning in Medical Imaging

Mask R-CNN is a state-of-the-art network architecture for the detection and segmentation of object instances in the computer vision domain. In this contribution, it is used to localize, label and segment individual ribs in anterior-posterior chest X-ray images. For this purpose, several extensions have been made to the original architecture, in order to address the specific challenges of this application. This includes the use of rib specific networks, facilitating dedicated anchor boxes sampled from a training set, as well as a sequential processing of all ribs. Here, the segmentation result of the upper neighbor rib is used as additional input to the network. This approach is the first addressing both rib segmentation and anatomical labeling in chest radiographs. The results are comparable or even better than existing methods aiming only at segmentation., Comment: MIDL 2019 [arXiv:1907.08612]

Currently, most bone implants used in orthopedics and traumatology are non-degradable and may need to be surgically removed later on e.g. in the case of children. This removal is associated with health risks which could be minimized by using biodegradable implants. Therefore, research on magnesium-based implants is ongoing, which can be objectively quantified through synchrotron radiation microtomography and subsequent image analysis. In order to evaluate the suitability of these materials, e.g. their stability over time, accurate pixelwise segmentations of these high-resolution scans are necessary. The fully-convolutional U-Net architecture achieves a Dice coefficient of 0.750 +/- 0.102 when trained with a small dataset with dense expert annotations. However, extending the learning to larger databases would require prohibitive annotation efforts. Hence, in this work we implemented and compared new training methods that require only a small fraction of manually annotated pixels. While directly training on these scribble annotation deteriorates the segmentation quality by 26.8 percentage points, our new random walk-based semi-automatic target achieves the same Dice overlap as a dense supervision, and thus offers a more promising approach for sparse annotations., Comment: MIDL 2019 [arXiv:1907.08612] Extended Abstract

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., Comment: accepted for publication at MICCAI 2019, open source code available at https://github.com/multimodallearning/pdd_net

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 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., Comment: This work has been submitted to the IEEE for possible publication

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, Comment: There is an ongoing dispute about the presentation of this paper. It will be withdrawn until the dispute is resoved

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/})., Comment: 14 pages, 7 figures, sumitted to Medical Image Analysis

While deep learning has achieved significant advances in accuracy for medical image segmentation, its benefits for deformable image registration have so far remained limited to reduced computation times. Previous work has either focused on replacing the iterative optimization of distance and smoothness terms with CNN-layers or using supervised approaches driven by labels. Our method is the first to combine the complementary strengths of global semantic information (represented by segmentation labels) and local distance metrics that help align surrounding structures. We demonstrate significant higher Dice scores (of 86.5\%) for deformable cardiac image registration compared to classic registration (79.0\%) as well as label-driven deep learning frameworks (83.4\%)., Comment: Accepted at BVM Workshop 2019

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., Comment: accepted for ECCV 2018 Workshop Geometry Meets Deep Learning

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., Comment: Accepted for Medical Image Analysis (Special Issue on Medical Imaging with Deep Learning). arXiv admin note: substantial text overlap with arXiv:1804.03999, arXiv:1804.05338

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., Comment: 12 pages, 7 figures, \c{opyright} 2017 IEEE. Personal use is permitted, but republication/redistribution requires IEEE permission

We propose a novel attention gate (AG) model for medical imaging 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 of cascaded convolutional neural networks (CNNs). AGs can be easily integrated into standard CNN architectures such as the U-Net model with minimal computational overhead while increasing the model sensitivity and prediction accuracy. The proposed Attention U-Net architecture is evaluated on two large CT abdominal datasets for multi-class image segmentation. Experimental results show that AGs consistently improve the prediction performance of U-Net across different datasets and training sizes while preserving computational efficiency. The code for the proposed architecture is publicly available., Comment: Accepted to published in MIDL'18 (Revised Version) / OpenReview link: https://openreview.net/forum?id=Skft7cijM

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.

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 learned 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 datasets and public benchmarks. Additionally, we demonstrate how the learned deep models of 3D shapes can be interpreted and used as biomarkers for classification of cardiac pathologies., Comment: Published in IEEE Transactions on Medical Imaging (Aug 2017)