Personalized noninvasive imaging of volumetric cardiac electrophysiology

Three-dimensionally distributed electrical functioning is the trigger of mechanical contraction of the heart. Disturbance of this electrical flow is known to predispose to mechanical catastrophe but, due to its amenability to certain intervention techniques, a detailed understanding of subject-specific cardiac electrophysiological conditions is of great medical interest. In current clinical practice, body surface potential recording is the standard tool for diagnosing cardiac electrical dysfunctions. However, successful treatments normally require invasive catheter mapping for a more detailed observation of these dysfunctions. In this dissertation, we take a system approach to pursue personalized noninvasive imaging of volumetric cardiac electrophysiology. Under the guidance of existing scientific knowledge of the cardiac electrophysiological system, we extract the subject specific cardiac electrical information from noninvasive body surface potential mapping and tomographic imaging data of individual subjects. In this way, a priori knowledge of system physiology leads the physiologically meaningful interpretation of personal data; at the same time, subject-specific information contained in the data identifies parameters in individual systems that differ from prior knowledge. Based on this perspective, we develop a physiological model-constrained statistical framework for the quantitative reconstruction of the electrical dynamics and inherent electrophysiological property of each individual cardiac system. To accomplish this, we first develop a coupled meshfree-BE (boundary element) modeling approach to represent existing physiological knowledge of the cardiac electrophysiological system on personalized heart-torso structures. Through a state space system approach and sequential data assimilation techniques, we then develop statistical model-data coupling algorithms for quantitative reconstruction of volumetric transmembrane potential dynamics and tissue property of 3D myocardium from body surface potential recoding of individual subjects. We also introduce a data integration component to build personalized cardiac electrophysiology by fusing tomographic image and BSP sequence of the same subject. In addition, we develop a computational reduction strategy that improves the efficiency and stability of the framework. Phantom experiments and real-data human studies are performed for validating each of the framework’s major components. These experiments demonstrate the potential of our framework in providing quantitative understanding of volumetric cardiac electrophysiology for individual subjects and in identifying latent threats in individual’s heart. This may aid in personalized diagnose, treatment planning, and fundamentally, prevention of fatal cardiac arrhythmia

Validation and Opportunities of Electrocardiographic Imaging: From Technical chievements to Clinical Applications

[EN] Electrocardiographic imaging (ECGI) reconstructs the electrical activity of the heart from a dense array of body-surface electrocardiograms and a patient-specific heart-torso geometry. Depending on how it is formulated, ECGI allows the reconstruction of the activation and recovery sequence of the heart, the origin of premature beats or tachycardia, the anchors/hotspots of re-entrant arrhythmias and other electrophysiological quantities of interest. Importantly, these quantities are directly and non-invasively reconstructed in a digitized model of the patient's three-dimensional heart, which has led to clinical interest in ECGI's ability to personalize diagnosis and guide therapy. Despite considerable development over the last decades, validation of ECGI is challenging. Firstly, results depend considerably on implementation choices, which are necessary to deal with ECGI's ill-posed character. Secondly, it is challenging to obtain (invasive) ground truth data of high quality. In this review, we discuss the current status of ECGI validation as well as the major challenges remaining for complete adoption of ECGI in clinical practice. Specifically, showing clinical benefit is essential for the adoption of ECGI. Such benefit may lie in patient outcome improvement, workflow improvement, or cost reduction. Future studies should focus on these aspects to achieve broad adoption of ECGI, but only after the technical challenges have been solved for that specific application/pathology. We propose 'best' practices for technical validation and highlight collaborative efforts recently organized in this field. Continued interaction between engineers, basic scientists, and physicians remains essential to find a hybrid between technical achievements, pathological mechanisms insights, and clinical benefit, to evolve this powerful technique toward a useful role in clinical practice.This study received financial support from the Hein Wellens Fonds, the Cardiovascular Research and Training Institute (CVRTI), the Nora Eccles Treadwell Foundation, the National Institute of General Medical Sciences of the National Institutes of Health (P41GM103545), the National Institutes of Health (NIH HL080093), the French government as part of the Investments of the Future program managed by the National Research Agency (ANR-10-IAHU-04), from the VEGA Grant Agency in Slovakia (2/0071/16), from the Slovak Research and Development Agency (APVV-14-0875), the Fondo Europeo de Desarrollo Regional (FEDER), the Instituto de Salud Carlos III (PI17/01106) and from Conselleria d'Educacio, Investigacio, Cultura i Esport de la Generalitat Valenciana (AICO/2018/267) and NIH grant (HL125998) and National Science Foundation (ACI-1350374).Cluitmans, M.; Brooks, D.; Macleod, RS.; Dossel, O.; Guillem Sánchez, MS.; Van Dam, P.; Svehlikova, J.... 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Uncertainty Quantification and Reduction in Cardiac Electrophysiological Imaging

Cardiac electrophysiological (EP) imaging involves solving an inverse problem that infers cardiac electrical activity from body-surface electrocardiography data on a physical domain defined by the body torso. To avoid unreasonable solutions that may fit the data, this inference is often guided by data-independent prior assumptions about different properties of cardiac electrical sources as well as the physical domain. However, these prior assumptions may involve errors and uncertainties that could affect the inference accuracy. For example, common prior assumptions on the source properties, such as fixed spatial and/or temporal smoothness or sparseness assumptions, may not necessarily match the true source property at different conditions, leading to uncertainties in the inference. Furthermore, prior assumptions on the physical domain, such as the anatomy and tissue conductivity of different organs in the thorax model, represent an approximation of the physical domain, introducing errors to the inference. To determine the robustness of the EP imaging systems for future clinical practice, it is important to identify these errors/uncertainties and assess their impact on the solution. This dissertation focuses on the quantification and reduction of the impact of uncertainties caused by prior assumptions/models on cardiac source properties as well as anatomical modeling uncertainties on the EP imaging solution. To assess the effect of fixed prior assumptions/models about cardiac source properties on the solution of EP imaging, we propose a novel yet simple Lp-norm regularization method for volumetric cardiac EP imaging. This study reports the necessity of an adaptive prior model (rather than fixed model) for constraining the complex spatiotemporally changing properties of the cardiac sources. We then propose a multiple-model Bayesian approach to cardiac EP imaging that employs a continuous combination of prior models, each re-effecting a specific spatial property for volumetric sources. The 3D source estimation is then obtained as a weighted combination of solutions across all models. Including a continuous combination of prior models, our proposed method reduces the chance of mismatch between prior models and true source properties, which in turn enhances the robustness of the EP imaging solution. To quantify the impact of anatomical modeling uncertainties on the EP imaging solution, we propose a systematic statistical framework. Founded based on statistical shape modeling and unscented transform, our method quantifies anatomical modeling uncertainties and establish their relation to the EP imaging solution. Applied on anatomical models generated from different image resolutions and different segmentations, it reports the robustness of EP imaging solution to these anatomical shape-detail variations. We then propose a simplified anatomical model for the heart that only incorporates certain subject-specific anatomical parameters, while discarding local shape details. Exploiting less resources and processing for successful EP imaging, this simplified model provides a simple clinically-compatible anatomical modeling experience for EP imaging systems. Different components of our proposed methods are validated through a comprehensive set of synthetic and real-data experiments, including various typical pathological conditions and/or diagnostic procedures, such as myocardial infarction and pacing. Overall, the methods presented in this dissertation for the quantification and reduction of uncertainties in cardiac EP imaging enhance the robustness of EP imaging, helping to close the gap between EP imaging in research and its clinical application

The Application of Computer Techniques to ECG Interpretation

This book presents some of the latest available information on automated ECG analysis written by many of the leading researchers in the field. It contains a historical introduction, an outline of the latest international standards for signal processing and communications and then an exciting variety of studies on electrophysiological modelling, ECG Imaging, artificial intelligence applied to resting and ambulatory ECGs, body surface mapping, big data in ECG based prediction, enhanced reliability of patient monitoring, and atrial abnormalities on the ECG. It provides an extremely valuable contribution to the field

Doctor of Philosophy

dissertationInverse Electrocardiography (ECG) aims to noninvasively estimate the electrophysiological activity of the heart from the voltages measured at the body surface, with promising clinical applications in diagnosis and therapy. The main challenge of this emerging technique lies in its mathematical foundation: an inverse source problem governed by partial differential equations (PDEs) which is severely ill-conditioned. Essential to the success of inverse ECG are computational methods that reliably achieve accurate inverse solutions while harnessing the ever-growing complexity and realism of the bioelectric simulation. This dissertation focuses on the formulation, optimization, and solution of the inverse ECG problem based on finite element methods, consisting of two research thrusts. The first thrust explores the optimal finite element discretization specifically oriented towards the inverse ECG problem. In contrast, most existing discretization strategies are designed for forward problems and may become inappropriate for the corresponding inverse problems. Based on a Fourier analysis of how discretization relates to ill-conditioning, this work proposes refinement strategies that optimize approximation accuracy o f the inverse ECG problem while mitigating its ill-conditioning. To fulfill these strategies, two refinement techniques are developed: one uses hybrid-shaped finite elements whereas the other adapts high-order finite elements. The second research thrust involves a new methodology for inverse ECG solutions called PDE-constrained optimization, an optimization framework that flexibly allows convex objectives and various physically-based constraints. This work features three contributions: (1) fulfilling optimization in the continuous space, (2) formulating rigorous finite element solutions, and (3) fulfilling subsequent numerical optimization by a primal-dual interiorpoint method tailored to the given optimization problem's specific algebraic structure. The efficacy o f this new method is shown by its application to localization o f cardiac ischemic disease, in which the method, under realistic settings, achieves promising solutions to a previously intractable inverse ECG problem involving the bidomain heart model. In summary, this dissertation advances the computational research of inverse ECG, making it evolve toward an image-based, patient-specific modality for biomedical research