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Journal articleBalaban G, Halliday B, Bradley P, et al., 2021,
Late-gadolinium enhancement interface area and electrophysiological simulations predict arrhythmic events in non-ischemic dilated cardiomyopathy patients
, JACC: Clinical Electrophysiology, Vol: 7, Pages: 238-249, ISSN: 2405-5018BACKGROUND: The presence of late-gadolinium enhancement (LGE) predicts life threatening ventricular arrhythmias in non-ischemic dilated cardiomyopathy (NIDCM); however, risk stratification remains imprecise. LGE shape and simulations of electrical activity may be able to provide additional prognostic information.OBJECTIVE: This study sought to investigate whether shape-based LGE metrics and simulations of reentrant electrical activity are associated with arrhythmic events in NIDCM patients.METHODS: CMR-LGE shape metrics were computed for a cohort of 156 NIDCM patients with visible LGE and tested retrospectively for an association with an arrhythmic composite end-point of sudden cardiac death and ventricular tachycardia. Computational models were created from images and used in conjunction with simulated stimulation protocols to assess the potential for reentry induction in each patient’s scar morphology. A mechanistic analysis of the simulations was carried out to explain the associations. RESULTS: During a median follow-up of 1611 [IQR 881-2341] days, 16 patients (10.3%) met the primary endpoint. In an inverse probability weighted Cox regression, the LGE-myocardial interface area (HR:1.75; 95% CI:1.24-2.47; p=0.001), number of simulated reentries (HR: 1.4; 95% CI: 1.23-1.59; p<0.01) and LGE volume (HR:1.44; 95% CI:1.07-1.94; p=0.02) were associated with arrhythmic events. Computational modeling revealed repolarisation heterogeneity and rate-dependent block of electrical wavefronts at the LGE-myocardial interface as putative arrhythmogenic mechanisms directly related to LGE interface area.CONCLUSION: The area of interface between scar and surviving myocardium, as well as simulated reentrant activity, are associated with an elevated risk of major arrhythmic events in NIDCM patients with LGE and represent novel risk predictors.
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Journal articleXiong Z, Xia Q, Hu Z, et al., 2021,
A global benchmark of algorithms for segmenting the left atrium from late gadolinium-enhanced cardiac magnetic resonance imaging
, Medical Image Analysis, Vol: 67, Pages: 1-14, ISSN: 1361-8415Segmentation of medical images, particularly late gadolinium-enhanced magnetic resonance imaging (LGE-MRI) used for visualizing diseased atrial structures, is a crucial first step for ablation treatment of atrial fibrillation. However, direct segmentation of LGE-MRIs is challenging due to the varying intensities caused by contrast agents. Since most clinical studies have relied on manual, labor-intensive approaches, automatic methods are of high interest, particularly optimized machine learning approaches. To address this, we organized the 2018 Left Atrium Segmentation Challenge using 154 3D LGE-MRIs, currently the world's largest atrial LGE-MRI dataset, and associated labels of the left atrium segmented by three medical experts, ultimately attracting the participation of 27 international teams. In this paper, extensive analysis of the submitted algorithms using technical and biological metrics was performed by undergoing subgroup analysis and conducting hyper-parameter analysis, offering an overall picture of the major design choices of convolutional neural networks (CNNs) and practical considerations for achieving state-of-the-art left atrium segmentation. Results show that the top method achieved a Dice score of 93.2% and a mean surface to surface distance of 0.7 mm, significantly outperforming prior state-of-the-art. Particularly, our analysis demonstrated that double sequentially used CNNs, in which a first CNN is used for automatic region-of-interest localization and a subsequent CNN is used for refined regional segmentation, achieved superior results than traditional methods and machine learning approaches containing single CNNs. This large-scale benchmarking study makes a significant step towards much-improved segmentation methods for atrial LGE-MRIs, and will serve as an important benchmark for evaluating and comparing the future works in the field. Furthermore, the findings from this study can potentially be extended to other imaging datasets and modalitie
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Journal articleBai W, Suzuki H, Huang J, et al., 2020,
A population-based phenome-wide association study of cardiac and aortic structure and function
, Nature Medicine, Vol: 26, Pages: 1654-1662, ISSN: 1078-8956Differences in cardiac and aortic structure and function are associated with cardiovascular diseases and a wide range of other types of disease. Here we analyzed cardiovascular magnetic resonance images from a population-based study, the UK Biobank, using an automated machine-learning-based analysis pipeline. We report a comprehensive range of structural and functional phenotypes for the heart and aorta across 26,893 participants, and explore how these phenotypes vary according to sex, age and major cardiovascular risk factors. We extended this analysis with a phenome-wide association study, in which we tested for correlations of a wide range of non-imaging phenotypes of the participants with imaging phenotypes. We further explored the associations of imaging phenotypes with early-life factors, mental health and cognitive function using both observational analysis and Mendelian randomization. Our study illustrates how population-based cardiac and aortic imaging phenotypes can be used to better define cardiovascular disease risks as well as heart–brain health interactions, highlighting new opportunities for studying disease mechanisms and developing image-based biomarkers.
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Journal articleMeyer H, Dawes T, Serrani M, et al., 2020,
Genetic and functional insights into the fractal structure of the heart
, Nature, Vol: 584, Pages: 589-594, ISSN: 0028-0836The inner surfaces of the human heart are covered by a complex network of muscular strands that is thought to be a vestigeof embryonic development.1,2 The function of these trabeculae in adults and their genetic architecture are unknown. Toinvestigate this we performed a genome-wide association study using fractal analysis of trabecular morphology as animage-derived phenotype in 18,096 UK Biobank participants. We identified 16 significant loci containing genes associatedwith haemodynamic phenotypes and regulation of cytoskeletal arborisation.3,4 Using biomechanical simulations and humanobservational data, we demonstrate that trabecular morphology is an important determinant of cardiac performance. Throughgenetic association studies with cardiac disease phenotypes and Mendelian randomisation, we find a causal relationshipbetween trabecular morphology and cardiovascular disease risk. These findings suggest an unexpected role for myocardialtrabeculae in the function of the adult heart, identify conserved pathways that regulate structural complexity, and reveal theirinfluence on susceptibility to disease
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Conference paperChen C, Qin C, Qiu H, et al., 2020,
Realistic adversarial data augmentation for MR image segmentation
, International Conference on Medical Image Computing and Computer-Assisted Intervention (MICCAI)Neural network-based approaches can achieve high accuracy in various medicalimage segmentation tasks. However, they generally require large labelleddatasets for supervised learning. Acquiring and manually labelling a largemedical dataset is expensive and sometimes impractical due to data sharing andprivacy issues. In this work, we propose an adversarial data augmentationmethod for training neural networks for medical image segmentation. Instead ofgenerating pixel-wise adversarial attacks, our model generates plausible andrealistic signal corruptions, which models the intensity inhomogeneities causedby a common type of artefacts in MR imaging: bias field. The proposed methoddoes not rely on generative networks, and can be used as a plug-in module forgeneral segmentation networks in both supervised and semi-supervised learning.Using cardiac MR imaging we show that such an approach can improve thegeneralization ability and robustness of models as well as provide significantimprovements in low-data scenarios.
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Journal articleBiffi C, Cerrolaza Martinez JJ, Tarroni G, et al., 2020,
Explainable anatomical shape analysis through deep hierarchical generative models
, IEEE Transactions on Medical Imaging, Vol: 39, Pages: 2088-2099, ISSN: 0278-0062Quantification of anatomical shape changes currently relies on scalar global indexes which are largely insensitive to regional or asymmetric modifications. Accurate assessment of pathology-driven anatomical remodeling is a crucial step for the diagnosis and treatment of many conditions. Deep learning approaches have recently achieved wide success in the analysis of medical images, but they lack interpretability in the feature extraction and decision processes. In this work, we propose a new interpretable deep learning model for shape analysis. In particular, we exploit deep generative networks to model a population of anatomical segmentations through a hierarchy of conditional latent variables. At the highest level of this hierarchy, a two-dimensional latent space is simultaneously optimised to discriminate distinct clinical conditions, enabling the direct visualisation of the classification space. Moreover, the anatomical variability encoded by this discriminative latent space can be visualised in the segmentation space thanks to the generative properties of the model, making the classification task transparent. This approach yielded high accuracy in the categorisation of healthy and remodelled left ventricles when tested on unseen segmentations from our own multi-centre dataset as well as in an external validation set, and on hippocampi from healthy controls and patients with Alzheimer’s disease when tested on ADNI data. More importantly, it enabled the visualisation in three-dimensions of both global and regional anatomical features which better discriminate between the conditions under exam. The proposed approach scales effectively to large populations, facilitating highthroughput analysis of normal anatomy and pathology in largescale studies of volumetric imaging.
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Journal articleChen C, Bai W, Davies R, et al., 2020,
Improving the generalizability of convolutional neural network-based segmentation on CMR images
, Frontiers in Cardiovascular Medicine, ISSN: 2297-055X -
Journal articleBhuva AN, Treibel TA, De Marvao A, et al., 2020,
Sex and regional differences inmyocardial plasticity in aortic stenosis are revealed by 3D modelmachine learning
, EUROPEAN HEART JOURNAL-CARDIOVASCULAR IMAGING, Vol: 21, Pages: 417-427, ISSN: 2047-2404- Author Web Link
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Journal articleChen C, Qin C, Qiu H, et al., 2020,
Deep learning for cardiac image segmentation: A review
, Frontiers in Cardiovascular Medicine, Vol: 7, Pages: 1-33, ISSN: 2297-055XDeep learning has become the most widely used approach for cardiac imagesegmentation in recent years. In this paper, we provide a review of over 100cardiac image segmentation papers using deep learning, which covers commonimaging modalities including magnetic resonance imaging (MRI), computedtomography (CT), and ultrasound (US) and major anatomical structures ofinterest (ventricles, atria and vessels). In addition, a summary of publiclyavailable cardiac image datasets and code repositories are included to providea base for encouraging reproducible research. Finally, we discuss thechallenges and limitations with current deep learning-based approaches(scarcity of labels, model generalizability across different domains,interpretability) and suggest potential directions for future research.
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Journal articleRuijsink B, Puyol-Antón E, Oksuz I, et al., 2020,
Fully automated, quality-controlled cardiac analysis from CMR: Validation and large-scale application to characterize cardiac function
, JACC: Cardiovascular Imaging, Vol: 13, Pages: 684-695, ISSN: 1876-7591OBJECTIVES: This study sought to develop a fully automated framework for cardiac function analysis from cardiac magnetic resonance (CMR), including comprehensive quality control (QC) algorithms to detect erroneous output. BACKGROUND: Analysis of cine CMR imaging using deep learning (DL) algorithms could automate ventricular function assessment. However, variable image quality, variability in phenotypes of disease, and unavoidable weaknesses in training of DL algorithms currently prevent their use in clinical practice. METHODS: The framework consists of a pre-analysis DL image QC, followed by a DL algorithm for biventricular segmentation in long-axis and short-axis views, myocardial feature-tracking (FT), and a post-analysis QC to detect erroneous results. The study validated the framework in healthy subjects and cardiac patients by comparison against manual analysis (n = 100) and evaluation of the QC steps' ability to detect erroneous results (n = 700). Next, this method was used to obtain reference values for cardiac function metrics from the UK Biobank. RESULTS: Automated analysis correlated highly with manual analysis for left and right ventricular volumes (all r > 0.95), strain (circumferential r = 0.89, longitudinal r > 0.89), and filling and ejection rates (all r ≥ 0.93). There was no significant bias for cardiac volumes and filling and ejection rates, except for right ventricular end-systolic volume (bias +1.80 ml; p = 0.01). The bias for FT strain was <1.3%. The sensitivity of detection of erroneous output was 95% for volume-derived parameters and 93% for FT strain. Finally, reference values were automatically derived from 2,029 CMR exams in healthy subjects. CONCLUSIONS: The study demonstrates a DL-based framework for automated, quality-controlled characterization of cardiac function from cine CMR, without the need for direct clinician oversight.
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