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Image registration is fundamental in medical imaging applications, such as disease progression analysis or radiation therapy planning. The primary objective of image registration is to precisely capture the deformation between two or more images, typically achieved by minimizing an optimization problem. Due to its inherent ill-posedness, regularization is a key component in driving the solution toward anatomically meaningful deformations. A wide range of regularization methods has been proposed for both conventional and deep learning-based registration. However, the appropriate application of regularization techniques often depends on the specific registration problem, and no one-fits-all method exists. Despite its importance, regularization is often overlooked or addressed with default approaches, assuming existing methods are sufficient. A comprehensive and structured review remains missing. This review addresses this gap by introducing a novel taxonomy that systematically categorizes the diverse range of proposed regularization methods. It highlights the emerging field of learned regularization, which leverages data-driven techniques to automatically derive deformation properties from the data. Moreover, this review examines the transfer of regularization methods from conventional to learning-based registration, identifies open challenges, and outlines future research directions. By emphasizing the critical role of regularization in image registration, we hope to inspire the research community to reconsider regularization strategies in modern registration algorithms and to explore this rapidly evolving field further., Comment: Submitted to Medical Image Analysis

Ultrasonography is an essential tool in mid-pregnancy for assessing fetal development, appreciated for its non-invasive and real-time imaging capabilities. Yet, the interpretation of ultrasound images is often complicated by acoustic shadows, speckle noise, and other artifacts that obscure crucial diagnostic details. To address these challenges, our study presents a novel unsupervised anomaly detection framework specifically designed for fetal ultrasound imaging. This framework incorporates gestational age filtering, precise identification of fetal standard planes, and targeted segmentation of brain regions to enhance diagnostic accuracy. Furthermore, we introduce the use of denoising diffusion probabilistic models in this context, marking a significant innovation in detecting previously unrecognized anomalies. We rigorously evaluated the framework using various diffusion-based anomaly detection methods, noise types, and noise levels. Notably, AutoDDPM emerged as the most effective, achieving an area under the precision-recall curve of 79.8\% in detecting anomalies. This advancement holds promise for improving the tools available for nuanced and effective prenatal diagnostics., Comment: ASMUS 2024: 5th International Workshop on Advances in Simplifying Medical Ultrasound

General vision encoders like DINOv2 and SAM have recently transformed computer vision. Even though they are trained on natural images, such encoder models have excelled in medical imaging, e.g., in classification, segmentation, and registration. However, no in-depth comparison of different state-of-the-art general vision encoders for medical registration is available. In this work, we investigate how well general vision encoder features can be used in the dissimilarity metrics for medical image registration. We explore two encoders that were trained on natural images as well as one that was fine-tuned on medical data. We apply the features within the well-established B-spline FFD registration framework. In extensive experiments on cardiac cine MRI data, we find that using features as additional guidance for conventional metrics improves the registration quality. The code is available at github.com/compai-lab/2024-miccai-koegl., Comment: Accepted at WBIR MICCAI 2024

Physics-inspired regularization is desired for intra-patient image registration since it can effectively capture the biomechanical characteristics of anatomical structures. However, a major challenge lies in the reliance on physical parameters: Parameter estimations vary widely across the literature, and the physical properties themselves are inherently subject-specific. In this work, we introduce a novel data-driven method that leverages hypernetworks to learn the tissue-dependent elasticity parameters of an elastic regularizer. Notably, our approach facilitates the estimation of patient-specific parameters without the need to retrain the network. We evaluate our method on three publicly available 2D and 3D lung CT and cardiac MR datasets. We find that with our proposed subject-specific tissue-dependent regularization, a higher registration quality is achieved across all datasets compared to using a global regularizer. The code is available at https://github.com/compai-lab/2024-miccai-reithmeir., Comment: Accepted at MICCAI 2024

With the increasing incidence of neurodegenerative diseases such as Alzheimer's Disease (AD), there is a need for further research that enhances detection and monitoring of the diseases. We present MORPHADE (Morphological Autoencoders for Alzheimer's Disease Detection), a novel unsupervised learning approach which uses deformations to allow the analysis of 3D T1-weighted brain images. To the best of our knowledge, this is the first use of deformations with deep unsupervised learning to not only detect, but also localize and assess the severity of structural changes in the brain due to AD. We obtain markedly higher anomaly scores in clinically important areas of the brain in subjects with AD compared to healthy controls, showcasing that our method is able to effectively locate AD-related atrophy. We additionally observe a visual correlation between the severity of atrophy highlighted in our anomaly maps and medial temporal lobe atrophy scores evaluated by a clinical expert. Finally, our method achieves an AUROC of 0.80 in detecting AD, out-performing several supervised and unsupervised baselines. We believe our framework shows promise as a tool towards improved understanding, monitoring and detection of AD. To support further research and application, we have made our code publicly available at github.com/ci-ber/MORPHADE., Comment: 11 pages, 5 figures

Medical image registration aims at identifying the spatial deformation between images of the same anatomical region and is fundamental to image-based diagnostics and therapy. To date, the majority of the deep learning-based registration methods employ regularizers that enforce global spatial smoothness, e.g., the diffusion regularizer. However, such regularizers are not tailored to the data and might not be capable of reflecting the complex underlying deformation. In contrast, physics-inspired regularizers promote physically plausible deformations. One such regularizer is the linear elastic regularizer which models the deformation of elastic material. These regularizers are driven by parameters that define the material's physical properties. For biological tissue, a wide range of estimations of such parameters can be found in the literature and it remains an open challenge to identify suitable parameter values for successful registration. To overcome this problem and to incorporate physical properties into learning-based registration, we propose to use a hypernetwork that learns the effect of the physical parameters of a physics-inspired regularizer on the resulting spatial deformation field. In particular, we adapt the HyperMorph framework to learn the effect of the two elasticity parameters of the linear elastic regularizer. Our approach enables the efficient discovery of suitable, data-specific physical parameters at test time., Comment: Manuscript accepted at SPIE Medical Imaging 2024

Automated segmentation of the blood vessels in 3D volumes is an essential step for the quantitative diagnosis and treatment of many vascular diseases. 3D vessel segmentation is being actively investigated in existing works, mostly in deep learning approaches. However, training 3D deep networks requires large amounts of manual 3D annotations from experts, which are laborious to obtain. This is especially the case for 3D vessel segmentation, as vessels are sparse yet spread out over many slices and disconnected when visualized in 2D slices. In this work, we propose a novel method to segment the 3D peripancreatic arteries solely from one annotated 2D projection per training image with depth supervision. We perform extensive experiments on the segmentation of peripancreatic arteries on 3D contrast-enhanced CT images and demonstrate how well we capture the rich depth information from 2D projections. We demonstrate that by annotating a single, randomly chosen projection for each training sample, we obtain comparable performance to annotating multiple 2D projections, thereby reducing the annotation effort. Furthermore, by mapping the 2D labels to the 3D space using depth information and incorporating this into training, we almost close the performance gap between 3D supervision and 2D supervision. Our code is available at: https://github.com/alinafdima/3Dseg-mip-depth.

Multi-modal image registration is a crucial pre-processing step in many medical applications. However, it is a challenging task due to the complex intensity relationships between different imaging modalities, which can result in large discrepancy in image appearance. The success of multi-modal image registration, whether it is conventional or learning based, is predicated upon the choice of an appropriate distance (or similarity) measure. Particularly, deep learning registration algorithms lack in accuracy or even fail completely when attempting to register data from an "unseen" modality. In this work, we present Modality Agnostic Distance (MAD), a deep image distance}] measure that utilises random convolutions to learn the inherent geometry of the images while being robust to large appearance changes. Random convolutions are geometry-preserving modules which we use to simulate an infinite number of synthetic modalities alleviating the need for aligned paired data during training. We can therefore train MAD on a mono-modal dataset and successfully apply it to a multi-modal dataset. We demonstrate that not only can MAD affinely register multi-modal images successfully, but it has also a larger capture range than traditional measures such as Mutual Information and Normalised Gradient Fields.

The skeleton of a digital image is a compact representation of its topology, geometry, and scale. It has utility in many computer vision applications, such as image description, segmentation, and registration. However, skeletonization has only seen limited use in contemporary deep learning solutions. Most existing skeletonization algorithms are not differentiable, making it impossible to integrate them with gradient-based optimization. Compatible algorithms based on morphological operations and neural networks have been proposed, but their results often deviate from the geometry and topology of the true medial axis. This work introduces the first three-dimensional skeletonization algorithm that is both compatible with gradient-based optimization and preserves an object's topology. Our method is exclusively based on matrix additions and multiplications, convolutional operations, basic non-linear functions, and sampling from a uniform probability distribution, allowing it to be easily implemented in any major deep learning library. In benchmarking experiments, we prove the advantages of our skeletonization algorithm compared to non-differentiable, morphological, and neural-network-based baselines. Finally, we demonstrate the utility of our algorithm by integrating it with two medical image processing applications that use gradient-based optimization: deep-learning-based blood vessel segmentation, and multimodal registration of the mandible in computed tomography and magnetic resonance images., Comment: Accepted at ICCV 2023

Motion-resolved reconstruction for abdominal magnetic resonance imaging (MRI) remains a challenge due to the trade-off between residual motion blurring caused by discretized motion states and undersampling artefacts. In this work, we propose to generate blurring-free motion-resolved abdominal reconstructions by learning a neural implicit representation directly in k-space (NIK). Using measured sampling points and a data-derived respiratory navigator signal, we train a network to generate continuous signal values. To aid the regularization of sparsely sampled regions, we introduce an additional informed correction layer (ICo), which leverages information from neighboring regions to correct NIK's prediction. Our proposed generative reconstruction methods, NIK and ICoNIK, outperform standard motion-resolved reconstruction techniques and provide a promising solution to address motion artefacts in abdominal MRI.

Automatic segmentation of the placenta in fetal ultrasound (US) is challenging due to the (i) high diversity of placenta appearance, (ii) the restricted quality in US resulting in highly variable reference annotations, and (iii) the limited field-of-view of US prohibiting whole placenta assessment at late gestation. In this work, we address these three challenges with a multi-task learning approach that combines the classification of placental location (e.g., anterior, posterior) and semantic placenta segmentation in a single convolutional neural network. Through the classification task the model can learn from larger and more diverse datasets while improving the accuracy of the segmentation task in particular in limited training set conditions. With this approach we investigate the variability in annotations from multiple raters and show that our automatic segmentations (Dice of 0.86 for anterior and 0.83 for posterior placentas) achieve human-level performance as compared to intra- and inter-observer variability. Lastly, our approach can deliver whole placenta segmentation using a multi-view US acquisition pipeline consisting of three stages: multi-probe image acquisition, image fusion and image segmentation. This results in high quality segmentation of larger structures such as the placenta in US with reduced image artifacts which are beyond the field-of-view of single probes., Comment: 21 pages (18 + appendix), 13 figures (9 + appendix)

We present PRETUS -a Plugin-based Real Time UltraSound software platform for live ultrasound image analysis and operator support. The software is lightweight; functionality is brought in via independent plug-ins that can be arranged in sequence. The software allows to capture the real-time stream of ultrasound images from virtually any ultrasound machine, applies computational methods and visualises the results on-the-fly. Plug-ins can run concurrently without blocking each other. They can be implemented in C ++ and Python. A graphical user interface can be implemented for each plug-in, and presented to the user in a compact way. The software is free and open source, and allows for rapid prototyping and testing of real-time ultrasound imaging methods in a manufacturer-agnostic fashion. The software is provided with input, output and processing plug-ins, as well as with tutorials to illustrate how to develop new plug-ins for PRETUS.

Late gadolinium enhancement magnetic resonance imaging (LGE MRI) is commonly used to visualize and quantify left atrial (LA) scars. The position and extent of scars provide important information of the pathophysiology and progression of atrial fibrillation (AF). Hence, LA scar segmentation and quantification from LGE MRI can be useful in computer-assisted diagnosis and treatment stratification of AF patients. Since manual delineation can be time-consuming and subject to intra- and inter-expert variability, automating this computing is highly desired, which nevertheless is still challenging and under-researched. This paper aims to provide a systematic review on computing methods for LA cavity, wall, scar and ablation gap segmentation and quantification from LGE MRI, and the related literature for AF studies. Specifically, we first summarize AF-related imaging techniques, particularly LGE MRI. Then, we review the methodologies of the four computing tasks in detail, and summarize the validation strategies applied in each task. Finally, the possible future developments are outlined, with a brief survey on the potential clinical applications of the aforementioned methods. The review shows that the research into this topic is still in early stages. Although several methods have been proposed, especially for LA segmentation, there is still large scope for further algorithmic developments due to performance issues related to the high variability of enhancement appearance and differences in image acquisition., Comment: 30 pages

Left atrial (LA) segmentation from late gadolinium enhanced magnetic resonance imaging (LGE MRI) is a crucial step needed for planning the treatment of atrial fibrillation. However, automatic LA segmentation from LGE MRI is still challenging, due to the poor image quality, high variability in LA shapes, and unclear LA boundary. Though deep learning-based methods can provide promising LA segmentation results, they often generalize poorly to unseen domains, such as data from different scanners and/or sites. In this work, we collect 210 LGE MRIs from different centers with different levels of image quality. To evaluate the domain generalization ability of models on the LA segmentation task, we employ four commonly used semantic segmentation networks for the LA segmentation from multi-center LGE MRIs. Besides, we investigate three domain generalization strategies, i.e., histogram matching, mutual information based disentangled representation, and random style transfer, where a simple histogram matching is proved to be most effective., Comment: 10 pages, 4 figures, MICCAI2021

Deep neural networks exhibit limited generalizability across images with different entangled domain features and categorical features. Learning generalizable features that can form universal categorical decision boundaries across domains is an interesting and difficult challenge. This problem occurs frequently in medical imaging applications when attempts are made to deploy and improve deep learning models across different image acquisition devices, across acquisition parameters or if some classes are unavailable in new training databases. To address this problem, we propose Mutual Information-based Disentangled Neural Networks (MIDNet), which extract generalizable categorical features to transfer knowledge to unseen categories in a target domain. The proposed MIDNet adopts a semi-supervised learning paradigm to alleviate the dependency on labeled data. This is important for real-world applications where data annotation is time-consuming, costly and requires training and expertise. We extensively evaluate the proposed method on fetal ultrasound datasets for two different image classification tasks where domain features are respectively defined by shadow artifacts and image acquisition devices. Experimental results show that the proposed method outperforms the state-of-the-art on the classification of unseen categories in a target domain with sparsely labeled training data., Comment: arXiv admin note: substantial text overlap with arXiv:2003.00321

Deep learning (DL)-based models have demonstrated good performance in medical image segmentation. However, the models trained on a known dataset often fail when performed on an unseen dataset collected from different centers, vendors and disease populations. In this work, we present a random style transfer network to tackle the domain generalization problem for multi-vendor and center cardiac image segmentation. Style transfer is used to generate training data with a wider distribution/ heterogeneity, namely domain augmentation. As the target domain could be unknown, we randomly generate a modality vector for the target modality in the style transfer stage, to simulate the domain shift for unknown domains. The model can be trained in a semi-supervised manner by simultaneously optimizing a supervised segmentation and an unsupervised style translation objective. Besides, the framework incorporates the spatial information and shape prior of the target by introducing two regularization terms. We evaluated the proposed framework on 40 subjects from the M\&Ms challenge2020, and obtained promising performance in the segmentation for data from unknown vendors and centers., Comment: 11 pages

Left atrial (LA) and atrial scar segmentation from late gadolinium enhanced magnetic resonance imaging (LGE MRI) is an important task in clinical practice. %, to guide ablation therapy and predict treatment results for atrial fibrillation (AF) patients. The automatic segmentation is however still challenging, due to the poor image quality, the various LA shapes, the thin wall, and the surrounding enhanced regions. Previous methods normally solved the two tasks independently and ignored the intrinsic spatial relationship between LA and scars. In this work, we develop a new framework, namely AtrialJSQnet, where LA segmentation, scar projection onto the LA surface, and scar quantification are performed simultaneously in an end-to-end style. We propose a mechanism of shape attention (SA) via an explicit surface projection, to utilize the inherent correlation between LA and LA scars. In specific, the SA scheme is embedded into a multi-task architecture to perform joint LA segmentation and scar quantification. Besides, a spatial encoding (SE) loss is introduced to incorporate continuous spatial information of the target, in order to reduce noisy patches in the predicted segmentation. We evaluated the proposed framework on 60 LGE MRIs from the MICCAI2018 LA challenge. Extensive experiments on a public dataset demonstrated the effect of the proposed AtrialJSQnet, which achieved competitive performance over the state-of-the-art. The relatedness between LA segmentation and scar quantification was explicitly explored and has shown significant performance improvements for both tasks. The code and results will be released publicly once the manuscript is accepted for publication via https://zmiclab.github.io/projects.html., Comment: 12 pages

We present a computational method for real-time, patient-specific simulation of 2D ultrasound (US) images. The method uses a large number of tracked ultrasound images to learn a function that maps position and orientation of the transducer to ultrasound images. This is a first step towards realistic patient-specific simulations that will enable improved training and retrospective examination of complex cases. Our models can simulate a 2D image in under 4ms (well within real-time constraints), and produce simulated images that preserve the content (anatomical structures and artefacts) of real ultrasound images., Comment: Accepted for presentation at MIUA 2020

We introduce a method for training neural networks to perform image or volume segmentation in which prior knowledge about the topology of the segmented object can be explicitly provided and then incorporated into the training process. By using the differentiable properties of persistent homology, a concept used in topological data analysis, we can specify the desired topology of segmented objects in terms of their Betti numbers and then drive the proposed segmentations to contain the specified topological features. Importantly this process does not require any ground-truth labels, just prior knowledge of the topology of the structure being segmented. We demonstrate our approach in three experiments. Firstly we create a synthetic task in which handwritten MNIST digits are de-noised, and show that using this kind of topological prior knowledge in the training of the network significantly improves the quality of the de-noised digits. Secondly we perform an experiment in which the task is segmenting the myocardium of the left ventricle from cardiac magnetic resonance images. We show that the incorporation of the prior knowledge of the topology of this anatomy improves the resulting segmentations in terms of both the topological accuracy and the Dice coefficient. Thirdly, we extend the method to 3D volumes and demonstrate its performance on the task of segmenting the placenta from ultrasound data, again showing that incorporating topological priors improves performance on this challenging task. We find that embedding explicit prior knowledge in neural network segmentation tasks is most beneficial when the segmentation task is especially challenging and that it can be used in either a semi-supervised or post-processing context to extract a useful training gradient from images without pixelwise labels., Comment: IEEE Transactions on Pattern Analysis and Machine Intelligence, 2020

Motion imaging phantoms are expensive, bulky and difficult to transport and set-up. The purpose of this paper is to demonstrate a simple approach to the design of multi-modality motion imaging phantoms that use mechanically stored energy to produce motion. We propose two phantom designs that use mainsprings and elastic bands to store energy. A rectangular piece was attached to an axle at the end of the transmission chain of each phantom, and underwent a rotary motion upon release of the mechanical motor. The phantoms were imaged with MRI and US, and the image sequences were embedded in a 1D non linear manifold (Laplacian Eigenmap) and the spectrogram of the embedding was used to derive the angular velocity over time. The derived velocities were consistent and reproducible within a small error. The proposed motion phantom concept showed great potential for the construction of simple and affordable motion phantoms, Comment: Accepted for publication at IEEE EMBC (41st International Engineering in Medicine and Biology Conference) 2019

The development of robotic-assisted extracorporeal ultrasound systems has a long history and a number of projects have been proposed since the 1990s focusing on different technical aspects. These aim to resolve the deficiencies of on-site manual manipulation of hand-held ultrasound probes. This paper presents the recent ongoing developments of a series of bespoke robotic systems, including both single-arm and dual-arm versions, for a project known as intelligent Fetal Imaging and Diagnosis (iFIND). After a brief review of the development history of the extracorporeal ultrasound robotic system used for fetal and abdominal examinations, the specific aim of the iFIND robots, the design evolution, the implementation details of each version, and the initial clinical feedback of the iFIND robot series are presented. Based on the preliminary testing of these newly-proposed robots on 42 volunteers, the successful and re-liable working of the mechatronic systems were validated. Analysis of a participant questionnaire indicates a comfortable scanning experience for the volunteers and a good acceptance rate to being scanned by the robots., Comment: 12 pages, 6 figures, TAROS conference 2019

Detecting acoustic shadows in ultrasound images is important in many clinical and engineering applications. Real-time feedback of acoustic shadows can guide sonographers to a standardized diagnostic viewing plane with minimal artifacts and can provide additional information for other automatic image analysis algorithms. However, automatically detecting shadow regions using learning-based algorithms is challenging because pixel-wise ground truth annotation of acoustic shadows is subjective and time consuming. In this paper we propose a weakly supervised method for automatic confidence estimation of acoustic shadow regions. Our method is able to generate a dense shadow-focused confidence map. In our method, a shadow-seg module is built to learn general shadow features for shadow segmentation, based on global image-level annotations as well as a small number of coarse pixel-wise shadow annotations. A transfer function is introduced to extend the obtained binary shadow segmentation to a reference confidence map. Additionally, a confidence estimation network is proposed to learn the mapping between input images and the reference confidence maps. This network is able to predict shadow confidence maps directly from input images during inference. We use evaluation metrics such as DICE, inter-class correlation and etc. to verify the effectiveness of our method. Our method is more consistent than human annotation, and outperforms the state-of-the-art quantitatively in shadow segmentation and qualitatively in confidence estimation of shadow regions. We further demonstrate the applicability of our method by integrating shadow confidence maps into tasks such as ultrasound image classification, multi-view image fusion and automated biometric measurements.