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Early identification of patients at risk of cardiovascular diseases (CVD) is crucial for effective preventive care, reducing healthcare burden, and improving patients' quality of life. This study demonstrates the potential of retinal optical coherence tomography (OCT) imaging combined with fundus photographs for identifying future adverse cardiac events. We used data from 977 patients who experienced CVD within a 5-year interval post-image acquisition, alongside 1,877 control participants without CVD, totaling 2,854 subjects. We propose a novel binary classification network based on a Multi-channel Variational Autoencoder (MCVAE), which learns a latent embedding of patients' fundus and OCT images to classify individuals into two groups: those likely to develop CVD in the future and those who are not. Our model, trained on both imaging modalities, achieved promising results (AUROC 0.78 +/- 0.02, accuracy 0.68 +/- 0.002, precision 0.74 +/- 0.02, sensitivity 0.73 +/- 0.02, and specificity 0.68 +/- 0.01), demonstrating its efficacy in identifying patients at risk of future CVD events based on their retinal images. This study highlights the potential of retinal OCT imaging and fundus photographs as cost-effective, non-invasive alternatives for predicting cardiovascular disease risk. The widespread availability of these imaging techniques in optometry practices and hospitals further enhances their potential for large-scale CVD risk screening. Our findings contribute to the development of standardized, accessible methods for early CVD risk identification, potentially improving preventive care strategies and patient outcomes., Comment: Part of the book series: Lecture Notes in Computer Science ((LNCS,volume 15155))

This study proposes an attention-based statistical distance-guided unsupervised domain adaptation model for multi-class cardiovascular magnetic resonance (CMR) image quality assessment. The proposed model consists of a feature extractor, a label predictor and a statistical distance estimator. An annotated dataset as the source set and an unlabeled dataset as the target set with different statistical distributions are considered inputs. The statistical distance estimator approximates the Wasserstein distance between the extracted feature vectors from the source and target data in a mini-batch. The label predictor predicts data labels of source data and uses a combinational loss function for training, which includes cross entropy and centre loss functions plus the estimated value of the distance estimator. Four datasets, including imaging and k-space data, were used to evaluate the proposed model in identifying four common CMR imaging artefacts: respiratory and cardiac motions, Gibbs ringing and Aliasing. The results of the extensive experiments showed that the proposed model, both in image and k-space analysis, has an acceptable performance in covering the domain shift between the source and target sets. The model explainability evaluations and the ablation studies confirmed the proper functioning and effectiveness of all the model's modules. The proposed model outperformed the previous studies regarding performance and the number of examined artefacts. The proposed model can be used for CMR post-imaging quality control or in large-scale cohort studies for image and k-space quality assessment due to the appropriate performance in domain shift coverage without a tedious data-labelling process.

We investigated the potential of optical coherence tomography (OCT) as an additional imaging technique to predict future cardiovascular disease (CVD). We utilised a self-supervised deep learning approach based on Variational Autoencoders (VAE) to learn low-dimensional representations of high-dimensional 3D OCT images and to capture distinct characteristics of different retinal layers within the OCT image. A Random Forest (RF) classifier was subsequently trained using the learned latent features and participant demographic and clinical data, to differentiate between patients at risk of CVD events (MI or stroke) and non-CVD cases. Our predictive model, trained on multimodal data, was assessed based on its ability to correctly identify individuals likely to suffer from a CVD event(MI or stroke), within a 5-year interval after image acquisition. Our self-supervised VAE feature selection and multimodal Random Forest classifier differentiate between patients at risk of future CVD events and the control group with an AUC of 0.75, outperforming the clinically established QRISK3 score (AUC= 0.597). The choroidal layer visible in OCT images was identified as an important predictor of future CVD events using a novel approach to model explanability. Retinal OCT imaging provides a cost-effective and non-invasive alternative to predict the risk of cardiovascular disease and is readily accessible in optometry practices and hospitals., Comment: 18 pages for main manuscript, 7 figures, 2 pages for appendix and preprint for a journal

Background: Image classification can be considered one of the key pillars of medical image analysis. Deep learning (DL) faces challenges that prevent its practical applications despite the remarkable improvement in medical image classification. The data distribution differences can lead to a drop in the efficiency of DL, known as the domain shift problem. Besides, requiring bulk annotated data for model training, the large size of models, and the privacy-preserving of patients are other challenges of using DL in medical image classification. This study presents a strategy that can address the mentioned issues simultaneously. Method: The proposed domain adaptive model based on knowledge distillation can classify images by receiving limited annotated data of different distributions. The designed multiple teachers-meticulous student model trains a student network that tries to solve the challenges by receiving the parameters of several teacher networks. The proposed model was evaluated using six available datasets of different distributions by defining the respiratory motion artefact detection task. Results: The results of extensive experiments using several datasets show the superiority of the proposed model in addressing the domain shift problem and lack of access to bulk annotated data. Besides, the privacy preservation of patients by receiving only the teacher network parameters instead of the original data and consolidating the knowledge of several DL models into a model with almost similar performance are other advantages of the proposed model. Conclusions: The proposed model can pave the way for practical clinical applications of deep classification methods by achieving the mentioned objectives simultaneously.

Generative modelling for shapes is a prerequisite for In-Silico Clinical Trials (ISCTs), which aim to cost-effectively validate medical device interventions using synthetic anatomical shapes, often represented as 3D surface meshes. However, constructing AI models to generate shapes closely resembling the real mesh samples is challenging due to variable vertex counts, connectivities, and the lack of dense vertex-wise correspondences across the training data. Employing graph representations for meshes, we develop a novel unsupervised geometric deep-learning model to establish refinable shape correspondences in a latent space, construct a population-derived atlas and generate realistic synthetic shapes. We additionally extend our proposed base model to a joint shape generative-clustering multi-atlas framework to incorporate further variability and preserve more details in the generated shapes. Experimental results using liver and left-ventricular models demonstrate the approach's applicability to computational medicine, highlighting its suitability for ISCTs through a comparative analysis.

The automated segmentation of cerebral aneurysms is pivotal for accurate diagnosis and treatment planning. Confronted with significant domain shifts and class imbalance in 3D Rotational Angiography (3DRA) data from various medical institutions, the task becomes challenging. These shifts include differences in image appearance, intensity distribution, resolution, and aneurysm size, all of which complicate the segmentation process. To tackle these issues, we propose a novel domain generalization strategy that employs gradient surgery exponential moving average (GS-EMA) optimization technique coupled with boundary-aware contrastive learning (BACL). Our approach is distinct in its ability to adapt to new, unseen domains by learning domain-invariant features, thereby improving the robustness and accuracy of aneurysm segmentation across diverse clinical datasets. The results demonstrate that our proposed approach can extract more domain-invariant features, minimizing over-segmentation and capturing more complete aneurysm structures., Comment: Accepted by ISBI 2024

Unsupervised domain adaptation (UDA) aims to align the labelled source distribution with the unlabelled target distribution to obtain domain-invariant predictive models. Since cross-modality medical data exhibit significant intra and inter-domain shifts and most are unlabelled, UDA is more important while challenging in medical image analysis. This paper proposes a simple yet potent contrastive learning framework for UDA to narrow the inter-domain gap between labelled source and unlabelled target distribution. Our method is validated on cerebral vessel datasets. Experimental results show that our approach can learn latent features from labelled 3DRA modality data and improve vessel segmentation performance in unlabelled MRA modality data., Comment: Accepted by ISBI 2024

Cardiovascular magnetic resonance imaging is emerging as a crucial tool to examine cardiac morphology and function. Essential to this endeavour are anatomical 3D surface and volumetric meshes derived from CMR images, which facilitate computational anatomy studies, biomarker discovery, and in-silico simulations. However, conventional surface mesh generation methods, such as active shape models and multi-atlas segmentation, are highly time-consuming and require complex processing pipelines to generate simulation-ready 3D meshes. In response, we introduce HybridVNet, a novel architecture for direct image-to-mesh extraction seamlessly integrating standard convolutional neural networks with graph convolutions, which we prove can efficiently handle surface and volumetric meshes by encoding them as graph structures. To further enhance accuracy, we propose a multiview HybridVNet architecture which processes both long axis and short axis CMR, showing that it can increase the performance of cardiac MR mesh generation. Our model combines traditional convolutional networks with variational graph generative models, deep supervision and mesh-specific regularisation. Experiments on a comprehensive dataset from the UK Biobank confirm the potential of HybridVNet to significantly advance cardiac imaging and computational cardiology by efficiently generating high-fidelity and simulation ready meshes from CMR images.

Medical image interpretation is central to most clinical applications such as disease diagnosis, treatment planning, and prognostication. In clinical practice, radiologists examine medical images and manually compile their findings into reports, which can be a time-consuming process. Automated approaches to radiology report generation, therefore, can reduce radiologist workload and improve efficiency in the clinical pathway. While recent deep-learning approaches for automated report generation from medical images have seen some success, most studies have relied on image-derived features alone, ignoring non-imaging patient data. Although a few studies have included the word-level contexts along with the image, the use of patient demographics is still unexplored. This paper proposes a novel multi-modal transformer network that integrates chest x-ray (CXR) images and associated patient demographic information, to synthesise patient-specific radiology reports. The proposed network uses a convolutional neural network to extract visual features from CXRs and a transformer-based encoder-decoder network that combines the visual features with semantic text embeddings of patient demographic information, to synthesise full-text radiology reports. Data from two public databases were used to train and evaluate the proposed approach. CXRs and reports were extracted from the MIMIC-CXR database and combined with corresponding patients' data MIMIC-IV. Based on the evaluation metrics used including patient demographic information was found to improve the quality of reports generated using the proposed approach, relative to a baseline network trained using CXRs alone. The proposed approach shows potential for enhancing radiology report generation by leveraging rich patient metadata and combining semantic text embeddings derived thereof, with medical image-derived visual features.

Image-to-text radiology report generation aims to automatically produce radiology reports that describe the findings in medical images. Most existing methods focus solely on the image data, disregarding the other patient information accessible to radiologists. In this paper, we present a novel multi-modal deep neural network framework for generating chest X-rays reports by integrating structured patient data, such as vital signs and symptoms, alongside unstructured clinical notes.We introduce a conditioned cross-multi-head attention module to fuse these heterogeneous data modalities, bridging the semantic gap between visual and textual data. Experiments demonstrate substantial improvements from using additional modalities compared to relying on images alone. Notably, our model achieves the highest reported performance on the ROUGE-L metric compared to relevant state-of-the-art models in the literature. Furthermore, we employed both human evaluation and clinical semantic similarity measurement alongside word-overlap metrics to improve the depth of quantitative analysis. A human evaluation, conducted by a board-certified radiologist, confirms the model's accuracy in identifying high-level findings, however, it also highlights that more improvement is needed to capture nuanced details and clinical context.

Magnetic resonance angiography (MRA) is an imaging modality for visualising blood vessels. It is useful for several diagnostic applications and for assessing the risk of adverse events such as haemorrhagic stroke (resulting from the rupture of aneurysms in blood vessels). However, MRAs are not acquired routinely, hence, an approach to synthesise blood vessel segmentations from more routinely acquired MR contrasts such as T1 and T2, would be useful. We present an encoder-decoder model for synthesising segmentations of the main cerebral arteries in the circle of Willis (CoW) from only T2 MRI. We propose a two-phase multi-objective learning approach, which captures both global and local features. It uses learned local attention maps generated by dilating the segmentation labels, which forces the network to only extract information from the T2 MRI relevant to synthesising the CoW. Our synthetic vessel segmentations generated from only T2 MRI achieved a mean Dice score of $0.79 \pm 0.03$ in testing, compared to state-of-the-art segmentation networks such as transformer U-Net ($0.71 \pm 0.04$) and nnU-net($0.68 \pm 0.05$), while using only a fraction of the parameters. The main qualitative difference between our synthetic vessel segmentations and the comparative models was in the sharper resolution of the CoW vessel segments, especially in the posterior circulation.

The Circle of Willis (CoW) is the part of cerebral vasculature responsible for delivering blood to the brain. Understanding the diverse anatomical variations and configurations of the CoW is paramount to advance research on cerebrovascular diseases and refine clinical interventions. However, comprehensive investigation of less prevalent CoW variations remains challenging because of the dominance of a few commonly occurring configurations. We propose a novel generative approach utilising a conditional latent diffusion model with shape and anatomical guidance to generate realistic 3D CoW segmentations, including different phenotypical variations. Our conditional latent diffusion model incorporates shape guidance to better preserve vessel continuity and demonstrates superior performance when compared to alternative generative models, including conditional variants of 3D GAN and 3D VAE. We observed that our model generated CoW variants that are more realistic and demonstrate higher visual fidelity than competing approaches with an FID score 53\% better than the best-performing GAN-based model.

Despite major advances in artificial intelligence (AI) for medicine and healthcare, the deployment and adoption of AI technologies remain limited in real-world clinical practice. In recent years, concerns have been raised about the technical, clinical, ethical and legal risks associated with medical AI. To increase real world adoption, it is essential that medical AI tools are trusted and accepted by patients, clinicians, health organisations and authorities. This work describes the FUTURE-AI guideline as the first international consensus framework for guiding the development and deployment of trustworthy AI tools in healthcare. The FUTURE-AI consortium was founded in 2021 and currently comprises 118 inter-disciplinary experts from 51 countries representing all continents, including AI scientists, clinicians, ethicists, and social scientists. Over a two-year period, the consortium defined guiding principles and best practices for trustworthy AI through an iterative process comprising an in-depth literature review, a modified Delphi survey, and online consensus meetings. The FUTURE-AI framework was established based on 6 guiding principles for trustworthy AI in healthcare, i.e. Fairness, Universality, Traceability, Usability, Robustness and Explainability. Through consensus, a set of 28 best practices were defined, addressing technical, clinical, legal and socio-ethical dimensions. The recommendations cover the entire lifecycle of medical AI, from design, development and validation to regulation, deployment, and monitoring. FUTURE-AI is a risk-informed, assumption-free guideline which provides a structured approach for constructing medical AI tools that will be trusted, deployed and adopted in real-world practice. Researchers are encouraged to take the recommendations into account in proof-of-concept stages to facilitate future translation towards clinical practice of medical AI.

Accurate segmentation of brain vessels is crucial for cerebrovascular disease diagnosis and treatment. However, existing methods face challenges in capturing small vessels and handling datasets that are partially or ambiguously annotated. In this paper, we propose an adaptive semi-supervised approach to address these challenges. Our approach incorporates innovative techniques including progressive semi-supervised learning, adaptative training strategy, and boundary enhancement. Experimental results on 3DRA datasets demonstrate the superiority of our method in terms of mesh-based segmentation metrics. By leveraging the partially and ambiguously labeled data, which only annotates the main vessels, our method achieves impressive segmentation performance on mislabeled fine vessels, showcasing its potential for clinical applications., Comment: Accepted by DALI MICCAI 2023

Deep learning-based deformable registration methods have been widely investigated in diverse medical applications. Learning-based deformable registration relies on weighted objective functions trading off registration accuracy and smoothness of the deformation field. Therefore, they inevitably require tuning the hyperparameter for optimal registration performance. Tuning the hyperparameters is highly computationally expensive and introduces undesired dependencies on domain knowledge. In this study, we construct a registration model based on the gradient surgery mechanism, named GSMorph, to achieve a hyperparameter-free balance on multiple losses. In GSMorph, we reformulate the optimization procedure by projecting the gradient of similarity loss orthogonally to the plane associated with the smoothness constraint, rather than additionally introducing a hyperparameter to balance these two competing terms. Furthermore, our method is model-agnostic and can be merged into any deep registration network without introducing extra parameters or slowing down inference. In this study, We compared our method with state-of-the-art (SOTA) deformable registration approaches over two publicly available cardiac MRI datasets. GSMorph proves superior to five SOTA learning-based registration models and two conventional registration techniques, SyN and Demons, on both registration accuracy and smoothness., Comment: Accepted at MICCAI 2023

The generation of virtual populations (VPs) of anatomy is essential for conducting in silico trials of medical devices. Typically, the generated VP should capture sufficient variability while remaining plausible and should reflect the specific characteristics and demographics of the patients observed in real populations. In several applications, it is desirable to synthesise virtual populations in a \textit{controlled} manner, where relevant covariates are used to conditionally synthesise virtual populations that fit a specific target population/characteristics. We propose to equip a conditional variational autoencoder (cVAE) with normalising flows to boost the flexibility and complexity of the approximate posterior learnt, leading to enhanced flexibility for controllable synthesis of VPs of anatomical structures. We demonstrate the performance of our conditional flow VAE using a data set of cardiac left ventricles acquired from 2360 patients, with associated demographic information and clinical measurements (used as covariates/conditional information). The results obtained indicate the superiority of the proposed method for conditional synthesis of virtual populations of cardiac left ventricles relative to a cVAE. Conditional synthesis performance was evaluated in terms of generalisation and specificity errors and in terms of the ability to preserve clinically relevant biomarkers in synthesised VPs, that is, the left ventricular blood pool and myocardial volume, relative to the real observed population., Comment: Accepted at MICCAI 2023

Background and Objectives: Cardiovascular magnetic resonance (CMR) imaging is a powerful modality in functional and anatomical assessment for various cardiovascular diseases. Sufficient image quality is essential to achieve proper diagnosis and treatment. A large number of medical images, the variety of imaging artefacts, and the workload of imaging centres are among the things that reveal the necessity of automatic image quality assessment (IQA). However, automated IQA requires access to bulk annotated datasets for training deep learning (DL) models. Labelling medical images is a tedious, costly and time-consuming process, which creates a fundamental challenge in proposing DL-based methods for medical applications. This study aims to present a new method for CMR IQA when there is limited access to annotated datasets. Methods: The proposed generalised deep meta-learning model can evaluate the quality by learning tasks in the prior stage and then fine-tuning the resulting model on a small labelled dataset of the desired tasks. This model was evaluated on the data of over 6,000 subjects from the UK Biobank for five defined tasks, including detecting respiratory motion, cardiac motion, Aliasing and Gibbs ringing artefacts and images without artefacts. Results: The results of extensive experiments show the superiority of the proposed model. Besides, comparing the model's accuracy with the domain adaptation model indicates a significant difference by using only 64 annotated images related to the desired tasks. Conclusion: The proposed model can identify unknown artefacts in images with acceptable accuracy, which makes it suitable for medical applications and quality assessment of large cohorts., Comment: 16 pages, 1 figure, 2 tables

This study explores the use of the Dirichlet Variational Autoencoder (DirVAE) for learning disentangled latent representations of chest X-ray (CXR) images. Our working hypothesis is that distributional sparsity, as facilitated by the Dirichlet prior, will encourage disentangled feature learning for the complex task of multi-label classification of CXR images. The DirVAE is trained using CXR images from the CheXpert database, and the predictive capacity of multi-modal latent representations learned by DirVAE models is investigated through implementation of an auxiliary multi-label classification task, with a view to enforce separation of latent factors according to class-specific features. The predictive performance and explainability of the latent space learned using the DirVAE were quantitatively and qualitatively assessed, respectively, and compared with a standard Gaussian prior-VAE (GVAE). We introduce a new approach for explainable multi-label classification in which we conduct gradient-guided latent traversals for each class of interest. Study findings indicate that the DirVAE is able to disentangle latent factors into class-specific visual features, a property not afforded by the GVAE, and achieve a marginal increase in predictive performance relative to GVAE. We generate visual examples to show that our explainability method, when applied to the trained DirVAE, is able to highlight regions in CXR images that are clinically relevant to the class(es) of interest and additionally, can identify cases where classification relies on spurious feature correlations., Comment: 13 pages, 8 figures, to be published in SPIE Medical Imaging 2023

Recent genome-wide association studies (GWAS) have been successful in identifying associations between genetic variants and simple cardiac parameters derived from cardiac magnetic resonance (CMR) images. However, the emergence of big databases including genetic data linked to CMR, facilitates investigation of more nuanced patterns of shape variability. Here, we propose a new framework for gene discovery entitled Unsupervised Phenotype Ensembles (UPE). UPE builds a redundant yet highly expressive representation by pooling a set of phenotypes learned in an unsupervised manner, using deep learning models trained with different hyperparameters. These phenotypes are then analyzed via (GWAS), retaining only highly confident and stable associations across the ensemble. We apply our approach to the UK Biobank database to extract left-ventricular (LV) geometric features from image-derived three-dimensional meshes. We demonstrate that our approach greatly improves the discoverability of genes influencing LV shape, identifying 11 loci with study-wide significance and 8 with suggestive significance. We argue that our approach would enable more extensive discovery of gene associations with image-derived phenotypes for other organs or image modalities., Comment: 14 pages of main text, 22 pages of supplemental information

Medical image registration is a challenging task involving the estimation of spatial transformations to establish anatomical correspondence between pairs or groups of images. Recently, deep learning-based image registration methods have been widely explored, and demonstrated to enable fast and accurate image registration in a variety of applications. However, most deep learning-based registration methods assume that the deformation fields are smooth and continuous everywhere in the image domain, which is not always true, especially when registering images whose fields of view contain discontinuities at tissue/organ boundaries. In such scenarios, enforcing smooth, globally continuous deformation fields leads to incorrect/implausible registration results. We propose a novel discontinuity-preserving image registration method to tackle this challenge, which ensures globally discontinuous and locally smooth deformation fields, leading to more accurate and realistic registration results. The proposed method leverages the complementary nature of image segmentation and registration and enables joint segmentation and pair-wise registration of images. A co-attention block is proposed in the segmentation component of the network to learn the structural correlations in the input images, while a discontinuity-preserving registration strategy is employed in the registration component of the network to ensure plausibility in the estimated deformation fields at tissue/organ interfaces. We evaluate our method on the task of intra-subject spatio-temporal image registration using large-scale cinematic cardiac magnetic resonance image sequences, and demonstrate that our method achieves significant improvements over the state-of-the-art for medical image registration, and produces high-quality segmentation masks for the regions of interest.

Data-driven methods have become increasingly more prominent for musculoskeletal modelling due to their conceptually intuitive simple and fast implementation. However, the performance of a pre-trained data-driven model using the data from specific subject(s) may be seriously degraded when validated using the data from a new subject, hindering the utility of the personalised musculoskeletal model in clinical applications. This paper develops an active physics-informed deep transfer learning framework to enhance the dynamic tracking capability of the musculoskeletal model on the unseen data. The salient advantages of the proposed framework are twofold: 1) For the generic model, physics-based domain knowledge is embedded into the loss function of the data-driven model as soft constraints to penalise/regularise the data-driven model. 2) For the personalised model, the parameters relating to the feature extraction will be directly inherited from the generic model, and only the parameters relating to the subject-specific inference will be finetuned by jointly minimising the conventional data prediction loss and the modified physics-based loss. In this paper, we use the synchronous muscle forces and joint kinematics prediction from surface electromyogram (sEMG) as the exemplar to illustrate the proposed framework. Moreover, convolutional neural network (CNN) is employed as the deep neural network to implement the proposed framework, and the physics law between muscle forces and joint kinematics is utilised as the soft constraints. Results of comprehensive experiments on a self-collected dataset from eight healthy subjects indicate the effectiveness and great generalization of the proposed framework., Comment: arXiv admin note: text overlap with arXiv:2207.01435

Generating virtual populations of anatomy that capture sufficient variability while remaining plausible is essential for conducting in-silico trials of medical devices. However, not all anatomical shapes of interest are always available for each individual in a population. Hence, missing/partially-overlapping anatomical information is often available across individuals in a population. We introduce a generative shape model for complex anatomical structures, learnable from datasets of unpaired datasets. The proposed generative model can synthesise complete whole complex shape assemblies coined virtual chimaeras, as opposed to natural human chimaeras. We applied this framework to build virtual chimaeras from databases of whole-heart shape assemblies that each contribute samples for heart substructures. Specifically, we propose a generative shape compositional framework which comprises two components - a part-aware generative shape model which captures the variability in shape observed for each structure of interest in the training population; and a spatial composition network which assembles/composes the structures synthesised by the former into multi-part shape assemblies (viz. virtual chimaeras). We also propose a novel self supervised learning scheme that enables the spatial composition network to be trained with partially overlapping data and weak labels. We trained and validated our approach using shapes of cardiac structures derived from cardiac magnetic resonance images available in the UK Biobank. Our approach significantly outperforms a PCA-based shape model (trained with complete data) in terms of generalisability and specificity. This demonstrates the superiority of the proposed approach as the synthesised cardiac virtual populations are more plausible and capture a greater degree of variability in shape than those generated by the PCA-based shape model., Comment: 15 pages, 4 figures, 4 tables. Accepted by IEEE Transactions on Neural Networks and Learning Systems

In silico tissue models enable evaluating quantitative models of magnetic resonance imaging. This includes validating and sensitivity analysis of imaging biomarkers and tissue microstructure parameters. We propose a novel method to generate a realistic numerical phantom of myocardial microstructure. We extend previous studies accounting for the cardiomyocyte shape variability, water exchange between the cardiomyocytes (intercalated discs), myocardial microstructure disarray, and four sheetlet orientations. In the first stage of the method, cardiomyocytes and sheetlets are generated by considering the shape variability and intercalated discs in cardiomyocyte-to-cardiomyocyte connections. Sheetlets are then aggregated and oriented in the directions of interest. Our morphometric study demonstrates no significant difference ($p>0.01$) between the distribution of volume, length, and primary and secondary axes of the numerical and real (literature) cardiomyocyte data. Structural correlation analysis validates that the in-silico tissue is in the same class of disorderliness as the real tissue. Additionally, the absolute angle differences between the simulated helical angle (HA) and input HA (reference value) of the cardiomyocytes ($4.3^\circ\pm 3.1^\circ$) demonstrate a good agreement with the absolute angle difference between the measured HA using experimental cardiac diffusion tensor imaging (cDTI) and histology (reference value) reported by (Holmes et al., 2000) ($3.7^\circ\pm6.4^\circ$) and (Scollan et al., 1998) ($4.9^\circ\pm 14.6^\circ$). The angular distance between eigenvectors and sheetlet angles of the input and simulated cDTI is smaller than those between measured angles using structural tensor imaging (gold standard) and experimental cDTI. These results confirm that the proposed method can generate richer numerical phantoms for the myocardium than previous studies., Comment: Medical Image Analysis, in press

Musculoskeletal models have been widely used for detailed biomechanical analysis to characterise various functional impairments given their ability to estimate movement variables (i.e., muscle forces and joint moment) which cannot be readily measured in vivo. Physics-based computational neuromusculoskeletal models can interpret the dynamic interaction between neural drive to muscles, muscle dynamics, body and joint kinematics and kinetics. Still, such set of solutions suffers from slowness, especially for the complex models, hindering the utility in real-time applications. In recent years, data-driven methods has emerged as a promising alternative due to the benefits in speedy and simple implementation, but they cannot reflect the underlying neuromechanical processes. This paper proposes a physics-informed deep learning framework for musculoskeletal modelling, where physics-based domain knowledge is brought into the data-driven model as soft constraints to penalise/regularise the data-driven model. We use the synchronous muscle forces and joint kinematics prediction from surface electromyogram (sEMG) as the exemplar to illustrate the proposed framework. Convolutional neural network (CNN) is employed as the deep neural network to implement the proposed framework. At the same time, the physics law between muscle forces and joint kinematics is used the soft constraint. Experimental validations on two groups of data, including one benchmark dataset and one self-collected dataset from six healthy subjects, are performed. The experimental results demonstrate the effectiveness and robustness of the proposed framework.

Standard plane (SP) localization is essential in routine clinical ultrasound (US) diagnosis. Compared to 2D US, 3D US can acquire multiple view planes in one scan and provide complete anatomy with the addition of coronal plane. However, manually navigating SPs in 3D US is laborious and biased due to the orientation variability and huge search space. In this study, we introduce a novel reinforcement learning (RL) framework for automatic SP localization in 3D US. Our contribution is three-fold. First, we formulate SP localization in 3D US as a tangent-point-based problem in RL to restructure the action space and significantly reduce the search space. Second, we design an auxiliary task learning strategy to enhance the model's ability to recognize subtle differences crossing Non-SPs and SPs in plane search. Finally, we propose a spatial-anatomical reward to effectively guide learning trajectories by exploiting spatial and anatomical information simultaneously. We explore the efficacy of our approach on localizing four SPs on uterus and fetal brain datasets. The experiments indicate that our approach achieves a high localization accuracy as well as robust performance., Comment: Accepted by MICCAI 2022

Tumor infiltration of the recurrent laryngeal nerve (RLN) is a contraindication for robotic thyroidectomy and can be difficult to detect via standard laryngoscopy. Ultrasound (US) is a viable alternative for RLN detection due to its safety and ability to provide real-time feedback. However, the tininess of the RLN, with a diameter typically less than 3mm, poses significant challenges to the accurate localization of the RLN. In this work, we propose a knowledge-driven framework for RLN localization, mimicking the standard approach surgeons take to identify the RLN according to its surrounding organs. We construct a prior anatomical model based on the inherent relative spatial relationships between organs. Through Bayesian shape alignment (BSA), we obtain the candidate coordinates of the center of a region of interest (ROI) that encloses the RLN. The ROI allows a decreased field of view for determining the refined centroid of the RLN using a dual-path identification network, based on multi-scale semantic information. Experimental results indicate that the proposed method achieves superior hit rates and substantially smaller distance errors compared with state-of-the-art methods., Comment: Early Accepted by MICCAI 2022

Cardiovascular magnetic resonance (CMR) imaging has become a modality with superior power for the diagnosis and prognosis of cardiovascular diseases. One of the essential basic quality controls of CMR images is to investigate the complete cardiac coverage, which is necessary for the volumetric and functional assessment. This study examines the full cardiac coverage using a 3D convolutional model and then reduces the number of false predictions using an innovative salient region detection model. Salient regions are extracted from the short-axis cine CMR stacks using a three-step proposed algorithm. Combining the 3D CNN baseline model with the proposed salient region detection model provides a cascade detector that can reduce the number of false negatives of the baseline model. The results obtained on the images of over 6,200 participants of the UK Biobank population cohort study show the superiority of the proposed model over the previous state-of-the-art studies. The dataset is the largest regarding the number of participants to control the cardiac coverage. The accuracy of the baseline model in identifying the presence/absence of basal/apical slices is 96.25\% and 94.51\%, respectively, which increases to 96.88\% and 95.72\% after improving using the proposed salient region detection model. Using the salient region detection model by forcing the baseline model to focus on the most informative areas of the images can help the model correct misclassified samples' predictions. The proposed fully automated model's performance indicates that this model can be used in image quality control in population cohort datasets and also real-time post-imaging quality assessments.

Population imaging studies rely upon good quality medical imagery before downstream image quantification. This study provides an automated approach to assess image quality from cardiovascular magnetic resonance (CMR) imaging at scale. We identify four common CMR imaging artefacts, including respiratory motion, cardiac motion, Gibbs ringing, and aliasing. The model can deal with images acquired in different views, including two, three, and four-chamber long-axis and short-axis cine CMR images. Two deep learning-based models in spatial and frequency domains are proposed. Besides recognising these artefacts, the proposed models are suitable to the common challenges of not having access to data labels. An unsupervised domain adaptation method and a Fourier-based convolutional neural network are proposed to overcome these challenges. We show that the proposed models reliably allow for CMR image quality assessment. The accuracies obtained for the spatial model in supervised and weakly supervised learning are 99.41+0.24 and 96.37+0.66 for the UK Biobank dataset, respectively. Using unsupervised domain adaptation can somewhat overcome the challenge of not having access to the data labels. The maximum achieved domain gap coverage in unsupervised domain adaptation is 16.86%. Domain adaptation can significantly improve a 5-class classification task and deal with considerable domain shift without data labels. Increasing the speed of training and testing can be achieved with the proposed model in the frequency domain. The frequency-domain model can achieve the same accuracy yet 1.548 times faster than the spatial model. This model can also be used directly on k-space data, and there is no need for image reconstruction., Comment: 21 pages, 9 figures, 7 tables

Since the emergence of COVID-19, deep learning models have been developed to identify COVID-19 from chest X-rays. With little to no direct access to hospital data, the AI community relies heavily on public data comprising numerous data sources. Model performance results have been exceptional when training and testing on open-source data, surpassing the reported capabilities of AI in pneumonia-detection prior to the COVID-19 outbreak. In this study impactful models are trained on a widely used open-source data and tested on an external test set and a hospital dataset, for the task of classifying chest X-rays into one of three classes: COVID-19, non-COVID pneumonia and no-pneumonia. Classification performance of the models investigated is evaluated through ROC curves, confusion matrices and standard classification metrics. Explainability modules are implemented to explore the image features most important to classification. Data analysis and model evaluations show that the popular open-source dataset COVIDx is not representative of the real clinical problem and that results from testing on this are inflated. Dependence on open-source data can leave models vulnerable to bias and confounding variables, requiring careful analysis to develop clinically useful/viable AI tools for COVID-19 detection in chest X-rays., Comment: To be published in MedInfo 21 - 18th World Congress on Medical and Health Informatics; 5 pages, 5 figures

The aortic vessel tree is composed of the aorta and its branching arteries, and plays a key role in supplying the whole body with blood. Aortic diseases, like aneurysms or dissections, can lead to an aortic rupture, whose treatment with open surgery is highly risky. Therefore, patients commonly undergo drug treatment under constant monitoring, which requires regular inspections of the vessels through imaging. The standard imaging modality for diagnosis and monitoring is computed tomography (CT), which can provide a detailed picture of the aorta and its branching vessels if completed with a contrast agent, called CT angiography (CTA). Optimally, the whole aortic vessel tree geometry from consecutive CTAs is overlaid and compared. This allows not only detection of changes in the aorta, but also of its branches, caused by the primary pathology or newly developed. When performed manually, this reconstruction requires slice by slice contouring, which could easily take a whole day for a single aortic vessel tree, and is therefore not feasible in clinical practice. Automatic or semi-automatic vessel tree segmentation algorithms, however, can complete this task in a fraction of the manual execution time and run in parallel to the clinical routine of the clinicians. In this paper, we systematically review computing techniques for the automatic and semi-automatic segmentation of the aortic vessel tree. The review concludes with an in-depth discussion on how close these state-of-the-art approaches are to an application in clinical practice and how active this research field is, taking into account the number of publications, datasets and challenges.

Nodule segmentation from breast ultrasound images is challenging yet essential for the diagnosis. Weakly-supervised segmentation (WSS) can help reduce time-consuming and cumbersome manual annotation. Unlike existing weakly-supervised approaches, in this study, we propose a novel and general WSS framework called Flip Learning, which only needs the box annotation. Specifically, the target in the label box will be erased gradually to flip the classification tag, and the erased region will be considered as the segmentation result finally. Our contribution is three-fold. First, our proposed approach erases on superpixel level using a Multi-agent Reinforcement Learning framework to exploit the prior boundary knowledge and accelerate the learning process. Second, we design two rewards: classification score and intensity distribution reward, to avoid under- and over-segmentation, respectively. Third, we adopt a coarse-to-fine learning strategy to reduce the residual errors and improve the segmentation performance. Extensively validated on a large dataset, our proposed approach achieves competitive performance and shows great potential to narrow the gap between fully-supervised and weakly-supervised learning., Comment: Accepted by MICCAI 2021

The performance of deep segmentation models often degrades due to distribution shifts in image intensities between the training and test data sets. This is particularly pronounced in multi-centre studies involving data acquired using multi-vendor scanners, with variations in acquisition protocols. It is challenging to address this degradation because the shift is often not known \textit{a priori} and hence difficult to model. We propose a novel framework to ensure robust segmentation in the presence of such distribution shifts. Our contribution is three-fold. First, inspired by the spirit of curriculum learning, we design a novel style curriculum to train the segmentation models using an easy-to-hard mode. A style transfer model with style fusion is employed to generate the curriculum samples. Gradually focusing on complex and adversarial style samples can significantly boost the robustness of the models. Second, instead of subjectively defining the curriculum complexity, we adopt an automated gradient manipulation method to control the hard and adversarial sample generation process. Third, we propose the Local Gradient Sign strategy to aggregate the gradient locally and stabilise training during gradient manipulation. The proposed framework can generalise to unknown distribution without using any target data. Extensive experiments on the public M\&Ms Challenge dataset demonstrate that our proposed framework can generalise deep models well to unknown distributions and achieve significant improvements in segmentation accuracy., Comment: Accepted by MICCAI-2021

3D ultrasound (US) is widely used for its rich diagnostic information. However, it is criticized for its limited field of view. 3D freehand US reconstruction is promising in addressing the problem by providing broad range and freeform scan. The existing deep learning based methods only focus on the basic cases of skill sequences, and the model relies on the training data heavily. The sequences in real clinical practice are a mix of diverse skills and have complex scanning paths. Besides, deep models should adapt themselves to the testing cases with prior knowledge for better robustness, rather than only fit to the training cases. In this paper, we propose a novel approach to sensorless freehand 3D US reconstruction considering the complex skill sequences. Our contribution is three-fold. First, we advance a novel online learning framework by designing a differentiable reconstruction algorithm. It realizes an end-to-end optimization from section sequences to the reconstructed volume. Second, a self-supervised learning method is developed to explore the context information that reconstructed by the testing data itself, promoting the perception of the model. Third, inspired by the effectiveness of shape prior, we also introduce adversarial training to strengthen the learning of anatomical shape prior in the reconstructed volume. By mining the context and structural cues of the testing data, our online learning methods can drive the model to handle complex skill sequences. Experimental results on developmental dysplasia of the hip US and fetal US datasets show that, our proposed method can outperform the start-of-the-art methods regarding the shift errors and path similarities., Comment: Early accepted by MICCAI-2021

Image registration aims to establish spatial correspondence across pairs, or groups of images, and is a cornerstone of medical image computing and computer-assisted-interventions. Currently, most deep learning-based registration methods assume that the desired deformation fields are globally smooth and continuous, which is not always valid for real-world scenarios, especially in medical image registration (e.g. cardiac imaging and abdominal imaging). Such a global constraint can lead to artefacts and increased errors at discontinuous tissue interfaces. To tackle this issue, we propose a weakly-supervised Deep Discontinuity-preserving Image Registration network (DDIR), to obtain better registration performance and realistic deformation fields. We demonstrate that our method achieves significant improvements in registration accuracy and predicts more realistic deformations, in registration experiments on cardiac magnetic resonance (MR) images from UK Biobank Imaging Study (UKBB), than state-of-the-art approaches., Comment: Provisional accepted in MICCAI 2021

In large studies involving multi protocol Magnetic Resonance Imaging (MRI), it can occur to miss one or more sub-modalities for a given patient owing to poor quality (e.g. imaging artifacts), failed acquisitions, or hallway interrupted imaging examinations. In some cases, certain protocols are unavailable due to limited scan time or to retrospectively harmonise the imaging protocols of two independent studies. Missing image modalities pose a challenge to segmentation frameworks as complementary information contributed by the missing scans is then lost. In this paper, we propose a novel model, Multi-modal Gaussian Process Prior Variational Autoencoder (MGP-VAE), to impute one or more missing sub-modalities for a patient scan. MGP-VAE can leverage the Gaussian Process (GP) prior on the Variational Autoencoder (VAE) to utilize the subjects/patients and sub-modalities correlations. Instead of designing one network for each possible subset of present sub-modalities or using frameworks to mix feature maps, missing data can be generated from a single model based on all the available samples. We show the applicability of MGP-VAE on brain tumor segmentation where either, two, or three of four sub-modalities may be missing. Our experiments against competitive segmentation baselines with missing sub-modality on BraTS'19 dataset indicate the effectiveness of the MGP-VAE model for segmentation tasks., Comment: Accepted in MICCAI 2021

Image registration is a fundamental building block for various applications in medical image analysis. To better explore the correlation between the fixed and moving images and improve registration performance, we propose a novel deep learning network, Co-Attention guided Registration Network (CAR-Net). CAR-Net employs a co-attention block to learn a new representation of the inputs, which drives the registration of the fixed and moving images. Experiments on UK Biobank cardiac cine-magnetic resonance image data demonstrate that CAR-Net obtains higher registration accuracy and smoother deformation fields than state-of-the-art unsupervised registration methods, while achieving comparable or better registration performance than corresponding weakly-supervised variants. In addition, our approach can provide critical structural information of the input fixed and moving images simultaneously in a completely unsupervised manner.

Deep segmentation models that generalize to images with unknown appearance are important for real-world medical image analysis. Retraining models leads to high latency and complex pipelines, which are impractical in clinical settings. The situation becomes more severe for ultrasound image analysis because of their large appearance shifts. In this paper, we propose a novel method for robust segmentation under unknown appearance shifts. Our contribution is three-fold. First, we advance a one-stage plug-and-play solution by embedding hierarchical style transfer units into a segmentation architecture. Our solution can remove appearance shifts and perform segmentation simultaneously. Second, we adopt Dynamic Instance Normalization to conduct precise and dynamic style transfer in a learnable manner, rather than previously fixed style normalization. Third, our solution is fast and lightweight for routine clinical adoption. Given 400*400 image input, our solution only needs an additional 0.2ms and 1.92M FLOPs to handle appearance shifts compared to the baseline pipeline. Extensive experiments are conducted on a large dataset from three vendors demonstrate our proposed method enhances the robustness of deep segmentation models., Comment: Accepted by IEEE ISBI 2021