Deep Learning in Cardiology

The medical field is creating large amount of data that physicians are unable to decipher and use efficiently. Moreover, rule-based expert systems are inefficient in solving complicated medical tasks or for creating insights using big data. Deep learning has emerged as a more accurate and effective technology in a wide range of medical problems such as diagnosis, prediction and intervention. Deep learning is a representation learning method that consists of layers that transform the data non-linearly, thus, revealing hierarchical relationships and structures. In this review we survey deep learning application papers that use structured data, signal and imaging modalities from cardiology. We discuss the advantages and limitations of applying deep learning in cardiology that also apply in medicine in general, while proposing certain directions as the most viable for clinical use.Comment: 27 pages, 2 figures, 10 table

A COMPUTATIONAL FRAMEWORK FOR NEONATAL BRAIN MRI STRUCTURE SEGMENTATION AND CLASSIFICATION

Deep Learning is increasingly being used in both supervised and unsupervised learning to derive complex patterns from data. However, the successful implementation of deep learning using medical imaging requires careful consideration for the quality and availability of data. Infants diagnosed with CHD are at a higher risk for neurodevelopmental impairment. Many of these deficits may be attenuated by early detection and intervention. However, we currently lack effective diagnostic tools for the reliable detection of these disorders at the neonatal period. We believe that the structural correlates of the cognitive deficits associated with developmental abnormalities can be measured within the first few months of life. Based on this assumption, we hypothesize that we can use an atlas registration based structural segmentation pipeline to sufficiently reduce the search space of neonatal structural brain MRI to viably implement convolutional neural networks for dysplasia classification. Secondly, we hypothesize that convolutional neural networks can successfully identify morphological biomarkers capable of detecting structurally abnormal brain substructures. In this study, we develop a computational framework for the automated classification of dysplastic substructures from neonatal MRI. We validate our implementation on a dataset of neonates born with CHD, as this is a vulnerable population for structural dysmaturation. We chose the cerebellum as the initial test substructure because of its relatively simple structure and known vulnerability to structural dysplasia in infants born with CHD. We then apply the same method to the hippocampus, a more challenging substructure due to its complex morphological properties. We attempt to overcome the limited availability of clinical data in neonatal populations by first extracting each brain substructure of interest and individually registering them into a standard space. This greatly reduces the search space required to learn the subtle abnormalities associated with a given pathology, making it feasible to implement a 3-D CNN as the classification algorithm. We achieved excellent classification accuracy in detecting dysplastic cerebelli, and demonstrate a viable computational framework for search space reduction using limited clinical datasets. All methods developed in this work are designed to be extensible, reproducible, and generalizable diagnostic tools for future neuroimaging problems

Machine learning approaches to model cardiac shape in large-scale imaging studies

Recent improvements in non-invasive imaging, together with the introduction of fully-automated segmentation algorithms and big data analytics, has paved the way for large-scale population-based imaging studies. These studies promise to increase our understanding of a large number of medical conditions, including cardiovascular diseases. However, analysis of cardiac shape in such studies is often limited to simple morphometric indices, ignoring large part of the information available in medical images. Discovery of new biomarkers by machine learning has recently gained traction, but often lacks interpretability. The research presented in this thesis aimed at developing novel explainable machine learning and computational methods capable of better summarizing shape variability, to better inform association and predictive clinical models in large-scale imaging studies. A powerful and flexible framework to model the relationship between three-dimensional (3D) cardiac atlases, encoding multiple phenotypic traits, and genetic variables is first presented. The proposed approach enables the detection of regional phenotype-genotype associations that would be otherwise neglected by conventional association analysis. Three learning-based systems based on deep generative models are then proposed. In the first model, I propose a classifier of cardiac shapes which exploits task-specific generative shape features, and it is designed to enable the visualisation of the anatomical effect these features encode in 3D, making the classification task transparent. The second approach models a database of anatomical shapes via a hierarchy of conditional latent variables and it is capable of detecting, quantifying and visualising onto a template shape the most discriminative anatomical features that characterize distinct clinical conditions. Finally, a preliminary analysis of a deep learning system capable of reconstructing 3D high-resolution cardiac segmentations from a sparse set of 2D views segmentations is reported. This thesis demonstrates that machine learning approaches can facilitate high-throughput analysis of normal and pathological anatomy and of its determinants without losing clinical interpretability.Open Acces

Automated deep phenotyping of the cardiovascular system using magnetic resonance imaging

Across a lifetime, the cardiovascular system must adapt to a great range of demands from the body. The individual changes in the cardiovascular system that occur in response to loading conditions are influenced by genetic susceptibility, and the pattern and extent of these changes have prognostic value. Brachial blood pressure (BP) and left ventricular ejection fraction (LVEF) are important biomarkers that capture this response, and their measurements are made at high resolution. Relatively, clinical analysis is crude, and may result in lost information and the introduction of noise. Digital information storage enables efficient extraction of information from a dataset, and this strategy may provide more precise and deeper measures to breakdown current phenotypes into their component parts. The aim of this thesis was to develop automated analysis of cardiovascular magnetic resonance (CMR) imaging for more detailed phenotyping, and apply these techniques for new biological insights into the cardiovascular response to different loading conditions. I therefore tested the feasibility and clinical utility of computational approaches for image and waveform analysis, recruiting and acquiring additional patient cohorts where necessary, and then applied these approaches prospectively to participants before and after six-months of exercise training for a first-time marathon. First, a multi-centre, multi-vendor, multi-field strength, multi-disease CMR resource of 110 patients undergoing repeat imaging in a short time-frame was assembled. The resource was used to assess whether automated analysis of LV structure and function is feasible on real-world data, and if it can improve upon human precision. This showed that clinicians can be confident in detecting a 9% change in EF or a 20g change in LV mass. This will be difficult to improve by clinicians because the greatest source of human error was attributable to the observer rather than modifiable factors. Having understood these errors, a convolutional neural network was trained on separate multi-centre data for automated analysis and was successfully generalizable to the real-world CMR data. Precision was similar to human analysis, and performance was 186 times faster. This real-world benchmarking resource has been made freely available (thevolumesresource.com). Precise automated segmentations were then used as a platform to delve further into the LV phenotype. Global LVEFs measured from CMR imaging in 116 patients with severe aortic stenosis were broken down into ~10 million regional measurements of structure and function, represented by computational three-dimensional LV models for each individual. A cardiac atlas approach was used to compile, label, segment and represent these data. Models were compared with healthy matched controls, and co-registered with follow-up one year after aortic valve replacement (AVR). This showed that there is a tendency to asymmetric septal hypertrophy in all patients with severe aortic stenosis (AS), rather than a characteristic specific to predisposed patients. This response to AS was more unfavourable in males than females (associated with higher NT-proBNP, and lower blood pressure), but was more modifiable with AVR. This was not detected using conventional analysis. Because cardiac function is coupled with the vasculature, a novel integrated assessment of the cardiovascular system was developed. Wave intensity theory was used to combine central blood pressure and CMR aortic blood flow-velocity waveforms to represent the interaction of the heart with the vessels in terms of traveling energy waves. This was performed and then validated in 206 individuals (the largest cohort to date), demonstrating inefficient ventriculo-arterial coupling in female sex and healthy ageing. CMR imaging was performed in 236 individuals before training for a first-time marathon and 138 individuals were followed-up after marathon completion. After training, systolic/diastolic blood pressure reduced by 4/3mmHg, descending aortic stiffness decreased by 16%, and ventriculo-arterial coupling improved by 14%. LV mass increased slightly, with a tendency to more symmetrical hypertrophy. The reduction in aortic stiffness was equivalent to a 4-year reduction in estimated biological aortic age, and the benefit was greater in older, male, and slower individuals. In conclusion, this thesis demonstrates that automating analysis of clinical cardiovascular phenotypes is precise with significant time-saving. Complex data that is usually discarded can be used efficiently to identify new biology. Deeper phenotypes developed in this work inform risk reduction behaviour in healthy individuals, and demonstrably deliver a more sensitive marker of LV remodelling, potentially enhancing risk prediction in severe aortic stenosis

Right ventricular biomechanics in pulmonary hypertension

As outcome in pulmonary hypertension is strongly associated with progressive right ventricular dysfunction, the work in this thesis seeks to determine the regional distribution of forces on the right ventricle, its geometry, and deformations subsequent to load. This thesis contributes to the understanding of how circulating biomarkers of energy metabolism and stress-response pathways are related to adverse cardiac remodelling and functional decompensation. A numerical model of the heart was used to derive a three-dimensional representation of right ventricular morphology, function and wall stress in pulmonary hypertension patients. This approach was tested by modelling the effect of pulmonary endarterectomy in patients with chronic thromboembolic disease. The relationship between the cardiac phenotype and 10 circulating metabolites, known to be associated with all-cause mortality, was assessed using mass univariate regression. Increasing afterload (mean pulmonary artery pressure) was significantly associated with hypertrophy of the right ventricular inlet and dilatation, indicative of global eccentric remodelling, and decreased systolic excursion. Right ventricular ejection fraction was found to be negatively associated with 3-hydroxy-3-methylglutarate, N-formylmethionine, and fumarate. Wall stress was related to all-cause mortality and its decrease after pulmonary endarterectomy was associated with a fall in brain natriuretic peptide. Six metabolites were associated with elevated end-systolic wall stress: dehydroepiandrosterone sulfate, N2,N2-dimethylguanosine, N1-methylinosine, 3-hydroxy-3-methylglutarate, N-acetylmethionine, and N-formylmethionine. Metabolic profiles related to energy metabolism and stress-response are associated with elevations in right ventricular end-systolic wall stress that have prognostic significance in pulmonary hypertension patients. These results show that statistical parametric mapping can give regional information on the right ventricle and that metabolic phenotyping, as well as predicting outcomes, provides markers informative of the biomechanical status of the right ventricle in pulmonary hypertension.Open Acces

Foetal echocardiographic segmentation

Congenital heart disease affects just under one percentage of all live births [1]. Those defects that manifest themselves as changes to the cardiac chamber volumes are the motivation for the research presented in this thesis. Blood volume measurements in vivo require delineation of the cardiac chambers and manual tracing of foetal cardiac chambers is very time consuming and operator dependent. This thesis presents a multi region based level set snake deformable model applied in both 2D and 3D which can automatically adapt to some extent towards ultrasound noise such as attenuation, speckle and partial occlusion artefacts. The algorithm presented is named Mumford Shah Sarti Collision Detection (MSSCD). The level set methods presented in this thesis have an optional shape prior term for constraining the segmentation by a template registered to the image in the presence of shadowing and heavy noise. When applied to real data in the absence of the template the MSSCD algorithm is initialised from seed primitives placed at the centre of each cardiac chamber. The voxel statistics inside the chamber is determined before evolution. The MSSCD stops at open boundaries between two chambers as the two approaching level set fronts meet. This has significance when determining volumes for all cardiac compartments since cardiac indices assume that each chamber is treated in isolation. Comparison of the segmentation results from the implemented snakes including a previous level set method in the foetal cardiac literature show that in both 2D and 3D on both real and synthetic data, the MSSCD formulation is better suited to these types of data. All the algorithms tested in this thesis are within 2mm error to manually traced segmentation of the foetal cardiac datasets. This corresponds to less than 10% of the length of a foetal heart. In addition to comparison with manual tracings all the amorphous deformable model segmentations in this thesis are validated using a physical phantom. The volume estimation of the phantom by the MSSCD segmentation is to within 13% of the physically determined volume