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  • Journal article
    Meyer H, Dawes T, Serrani M, Bai W, Tokarczuk P, Cai J, Simoes Monteiro de Marvao A, Henry A, Lumbers T, Gierten J, Thumberger T, Wittbrodt J, Ware J, Rueckert D, Matthews P, Prasad S, Costantino M, Cook S, Birney E, O'Regan Det al., 2020,

    Genetic and functional insights into the fractal structure of the heart

    , Nature, Vol: 584, Pages: 589-594, ISSN: 0028-0836

    The 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

  • Journal article
    Balaban G, Halliday B, Bradley P, Bai W, Nygaard S, Owen R, Hatipoglu S, Ferreira ND, Izgi C, Tayal U, Corden B, Ware J, Pennell D, Rueckert D, Plank G, Rinaldi CA, Prasad SK, Bishop Met al.,

    Late-gadolinium enhancement interface area and electrophysiological simulations predict arrhythmic events in non-ischemic dilated cardiomyopathy patients

    , JACC: Clinical Electrophysiology, ISSN: 2405-5018

    BACKGROUND: 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.

  • Conference paper
    Chen C, Qin C, Qiu H, Ouyang C, Wang S, Chen L, Tarroni G, Bai W, Rueckert Det 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.

  • Journal article
    Biffi C, Cerrolaza Martinez JJ, Tarroni G, Bai W, Simoes Monteiro de Marvao A, Oktay O, Ledig C, Le Folgoc L, Kamnitsas K, Doumou G, Duan J, Prasad S, Cook S, O'Regan D, Rueckert Det al., 2020,

    Explainable anatomical shape analysis through deep hierarchical generative models

    , IEEE Transactions on Medical Imaging, Vol: 39, Pages: 2088-2099, ISSN: 0278-0062

    Quantification 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.

  • Journal article
    Chen C, Bai W, Davies R, Bhuva A, Manisty C, Moon J, Aung N, Lee A, Sanghvi M, Fung K, Paiva J, Petersen S, Lukaschuk E, Piechnik S, Neubauer S, Rueckert Det al.,

    Improving the generalizability of convolutional neural network-based segmentation on CMR images

    , Frontiers in Cardiovascular Medicine, ISSN: 2297-055X
  • Journal article
    Bhuva AN, Treibel TA, De Marvao A, Biffi C, Dawes TJW, Doumou G, Bai W, Patel K, Boubertakh R, Rueckert D, O'Regan DP, Hughes AD, Moon JC, Manisty CHet 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
  • Journal article
    Chen C, Qin C, Qiu H, Tarroni G, Duan J, Bai W, Rueckert Det al., 2020,

    Deep learning for cardiac image segmentation: A review

    , Frontiers in Cardiovascular Medicine, Vol: 7, Pages: 1-33, ISSN: 2297-055X

    Deep 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.

  • Journal article
    Ruijsink B, Puyol-Antón E, Oksuz I, Sinclair M, Bai W, Schnabel JA, Razavi R, King APet 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: 1876-7591

    OBJECTIVES: 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.

  • Journal article
    Dewey M, Siebes M, Kachelrieß M, Kofoed KF, Maurovich-Horvat P, Nikolaou K, Bai W, Kofler A, Manka R, Kozerke S, Chiribiri A, Schaeffter T, Michallek F, Bengel F, Nekolla S, Knaapen P, Lubberink M, Senior R, Tang M-X, Piek JJ, van de Hoef T, Martens J, Schreiber L, Quantitative Cardiac Imaging Study Groupet al., 2020,

    Clinical quantitative cardiac imaging for the assessment of myocardial ischaemia

    , Nature Reviews Cardiology, Vol: 17, Pages: 427-450, ISSN: 1759-5002

    Cardiac imaging has a pivotal role in the prevention, diagnosis and treatment of ischaemic heart disease. SPECT is most commonly used for clinical myocardial perfusion imaging, whereas PET is the clinical reference standard for the quantification of myocardial perfusion. MRI does not involve exposure to ionizing radiation, similar to echocardiography, which can be performed at the bedside. CT perfusion imaging is not frequently used but CT offers coronary angiography data, and invasive catheter-based methods can measure coronary flow and pressure. Technical improvements to the quantification of pathophysiological parameters of myocardial ischaemia can be achieved. Clinical consensus recommendations on the appropriateness of each technique were derived following a European quantitative cardiac imaging meeting and using a real-time Delphi process. SPECT using new detectors allows the quantification of myocardial blood flow and is now also suited to patients with a high BMI. PET is well suited to patients with multivessel disease to confirm or exclude balanced ischaemia. MRI allows the evaluation of patients with complex disease who would benefit from imaging of function and fibrosis in addition to perfusion. Echocardiography remains the preferred technique for assessing ischaemia in bedside situations, whereas CT has the greatest value for combined quantification of stenosis and characterization of atherosclerosis in relation to myocardial ischaemia. In patients with a high probability of needing invasive treatment, invasive coronary flow and pressure measurement is well suited to guide treatment decisions. In this Consensus Statement, we summarize the strengths and weaknesses as well as the future technological potential of each imaging modality.

  • Journal article
    Kariholu U, Montaldo P, Markati T, Lally PJ, Teiserskas J, Liow N, Oliveira V, Soe A, Shankaran S, Thayyil Set al., 2020,

    Therapeutic hypothermia for mild neonatal encephalopathy: A systematic review and meta-analysis

    , Archives of Disease in Childhood. Fetal and Neonatal Edition, Vol: 105, Pages: 225-228, ISSN: 1359-2998

    Objectives To examine if therapeutic hypothermia reduces the composite outcome of death, moderate or severe disability at 18 months or more after mild neonatal encephalopathy (NE).Data source MEDLINE, Cochrane database, Scopus and ISI Web of Knowledge databases, using ‘hypoxic ischaemic encephalopathy’, ‘newborn’ and ‘hypothermia’, and ‘clinical trials’ as medical subject headings and terms. Manual search of the reference lists of all eligible articles and major review articles and additional data from the corresponding authors of selected articles.Study selection Randomised and quasirandomised controlled trials comparing therapeutic hypothermia with usual care.Data extraction Safety and efficacy data extracted independently by two reviewers and analysed.Results We included the data on 117 babies with mild NE inadvertently recruited to five cooling trials (two whole-body cooling and three selective head cooling) of moderate and severe NE, in the meta-analysis. Adverse outcomes occurred in 11/56 (19.6%) of the cooled babies and 12/61 (19.7%) of the usual care babies (risk ratio 1.11 (95% CIs 0.55 to 2.25)).Conclusions Current evidence is insufficient to recommend routine therapeutic hypothermia for babies with mild encephalopathy and significant benefits or harm cannot be excluded.

This data is extracted from the Web of Science and reproduced under a licence from Thomson Reuters. You may not copy or re-distribute this data in whole or in part without the written consent of the Science business of Thomson Reuters.

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