On Learning and Generalization to Solve Inverse Problem of Electrophysiological Imaging

In this dissertation, we are interested in solving a linear inverse problem: inverse electrophysiological (EP) imaging, where our objective is to computationally reconstruct personalized cardiac electrical signals based on body surface electrocardiogram (ECG) signals. EP imaging has shown promise in the diagnosis and treatment planning of cardiac dysfunctions such as atrial flutter, atrial fibrillation, ischemia, infarction and ventricular arrhythmia. Towards this goal, we frame it as a problem of learning a function from the domain of measurements to signals. Depending upon the assumptions, we present two classes of solutions: 1) Bayesian inference in a probabilistic graphical model, 2) Learning from samples using deep networks. In both of these approaches, we emphasize on learning the inverse function with good generalization ability, which becomes a main theme of the dissertation. In a Bayesian framework, we argue that this translates to appropriately integrating different sources of knowledge into a common probabilistic graphical model framework and using it for patient specific signal estimation through Bayesian inference. In learning from samples setting, this translates to designing a deep network with good generalization ability, where good generalization refers to the ability to reconstruct inverse EP signals in a distribution of interest (which could very well be outside the sample distribution used during training). By drawing ideas from different areas like functional analysis (e.g. Fenchel duality), variational inference (e.g. Variational Bayes) and deep generative modeling (e.g. variational autoencoder), we show how we can incorporate different prior knowledge in a principled manner in a probabilistic graphical model framework to obtain a good inverse solution with generalization ability. Similarly, to improve generalization of deep networks learning from samples, we use ideas from information theory (e.g. information bottleneck), learning theory (e.g. analytical learning theory), adversarial training, complexity theory and functional analysis (e.g. RKHS). We test our algorithms on synthetic data and real data of the patients who had undergone through catheter ablation in clinics and show that our approach yields significant improvement over existing methods. Towards the end of the dissertation, we investigate general questions on generalization and stabilization of adversarial training of deep networks and try to understand the role of smoothness and function space complexity in answering those questions. We conclude by identifying limitations of the proposed methods, areas of further improvement and open questions that are specific to inverse electrophysiological imaging as well as broader, encompassing theory of learning and generalization

Artificial Intelligence in the Differential Diagnosis of Cardiomyopathy Phenotypes

Artificial intelligence (AI) is rapidly being applied to the medical field, especially in the cardiovascular domain. AI approaches have demonstrated their applicability in the detection, diagnosis, and management of several cardiovascular diseases, enhancing disease stratification and typing. Cardiomyopathies are a leading cause of heart failure and life-threatening ventricular arrhythmias. Identifying the etiologies is fundamental for the management and diagnostic pathway of these heart muscle diseases, requiring the integration of various data, including personal and family history, clinical examination, electrocardiography, and laboratory investigations, as well as multimodality imaging, making the clinical diagnosis challenging. In this scenario, AI has demonstrated its capability to capture subtle connections from a multitude of multiparametric datasets, enabling the discovery of hidden relationships in data and handling more complex tasks than traditional methods. This review aims to present a comprehensive overview of the main concepts related to AI and its subset. Additionally, we review the existing literature on AI-based models in the differential diagnosis of cardiomyopathy phenotypes, and we finally examine the advantages and limitations of these AI approaches

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

Thirty years of artificial intelligence in medicine (AIME) conferences: A review of research themes

Over the past 30 years, the international conference on Artificial Intelligence in MEdicine (AIME) has been organized at different venues across Europe every 2 years, establishing a forum for scientific exchange and creating an active research community. The Artificial Intelligence in Medicine journal has published theme issues with extended versions of selected AIME papers since 1998

Computer-Assisted Electroanatomical Guidance for Cardiac Electrophysiology Procedures

Cardiac arrhythmias are serious life-threatening episodes affecting both the aging population and younger patients with pre-existing heart conditions. One of the most effective therapeutic procedures is the minimally-invasive catheter-driven endovascular electrophysiology study, whereby electrical potentials and activation patterns in the affected cardiac chambers are measured and subsequent ablation of arrhythmogenic tissue is performed. Despite emerging technologies such as electroanatomical mapping and remote intraoperative navigation systems for improved catheter manipulation and stability, successful ablation of arrhythmias is still highly-dependent on the operator’s skills and experience. This thesis proposes a framework towards standardisation in the electroanatomical mapping and ablation planning by merging knowledge transfer from previous cases and patient-specific data. In particular, contributions towards four different procedural aspects were made: optimal electroanatomical mapping, arrhythmia path computation, catheter tip stability analysis, and ablation simulation and optimisation. In order to improve the intraoperative electroanatomical map, anatomical areas of high mapping interest were proposed, as learned from previous electrophysiology studies. Subsequently, the arrhythmic wave propagation on the endocardial surface and potential ablation points were computed. The ablation planning is further enhanced, firstly by the analysis of the catheter tip stability and the probability of slippage at sparse locations on the endocardium and, secondly, by the simulation of the ablation result from the computation of convolutional matrices which model mathematically the ablation process. The methods proposed by this thesis were validated on data from patients with complex congenital heart disease, who present unusual cardiac anatomy and consequently atypical arrhythmias. The proposed methods also build a generic framework for computer guidance of electrophysiology, with results showing complementary information that can be easily integrated into the clinical workflow.Open Acces

A review of ECG-based diagnosis support systems for obstructive sleep apnea

Humans need sleep. It is important for physical and psychological recreation. During sleep our consciousness is suspended or least altered. Hence, our ability to avoid or react to disturbances is reduced. These disturbances can come from external sources or from disorders within the body. Obstructive Sleep Apnea (OSA) is such a disorder. It is caused by obstruction of the upper airways which causes periods where the breathing ceases. In many cases, periods of reduced breathing, known as hypopnea, precede OSA events. The medical background of OSA is well understood, but the traditional diagnosis is expensive, as it requires sophisticated measurements and human interpretation of potentially large amounts of physiological data. Electrocardiogram (ECG) measurements have the potential to reduce the cost of OSA diagnosis by simplifying the measurement process. On the down side, detecting OSA events based on ECG data is a complex task which requires highly skilled practitioners. Computer algorithms can help to detect the subtle signal changes which indicate the presence of a disorder. That approach has the following advantages: computers never tire, processing resources are economical and progress, in the form of better algorithms, can be easily disseminated as updates over the internet. Furthermore, Computer-Aided Diagnosis (CAD) reduces intra- and inter-observer variability. In this review, we adopt and support the position that computer based ECG signal interpretation is able to diagnose OSA with a high degree of accuracy

Novel Methods to Incorporate Physiological Prior Knowledge into the Inverse Problem of Electrocardiography - Application to Localization of Ventricular Excitation Origins

17 Millionen Todesfälle jedes Jahr werden auf kardiovaskuläre Erkankungen zurückgeführt. Plötzlicher Herztod tritt bei ca. 25% der Patienten mit kardiovaskulären Erkrankungen auf und kann mit ventrikulärer Tachykardie in Verbindung gebracht werden. Ein wichtiger Schritt für die Behandlung von ventrikulärer Tachykardie ist die Detektion sogenannter Exit-Points, d.h. des räumlichen Ursprungs der Erregung. Da dieser Prozess sehr zeitaufwändig ist und nur von fähigen Kardiologen durchgeführt werden kann, gibt es eine Notwendigkeit für assistierende Lokalisationsmöglichkeiten, idealerweise automatisch und nichtinvasiv. Elektrokardiographische Bildgebung versucht, diesen klinischen Anforderungen zu genügen, indem die elektrische Aktivität des Herzens aus Messungen der Potentiale auf der Körperoberfläche rekonstruiert wird. Die resultierenden Informationen können verwendet werden, um den Erregungsursprung zu detektieren. Aktuelle Methoden um das inverse Problem zu lösen weisen jedoch entweder eine geringe Genauigkeit oder Robustheit auf, was ihren klinischen Nutzen einschränkt. Diese Arbeit analysiert zunächst das Vorwärtsproblem im Zusammenhang mit zwei Quellmodellen: Transmembranspannungen und extrazelluläre Potentiale. Die mathematischen Eigenschaften der Relation zwischen den Quellen des Herzens und der Körperoberflächenpotentiale werden systematisch analysiert und der Einfluss auf das inverse Problem verdeutlicht. Dieses Wissen wird anschließend zur Lösung des inversen Problems genutzt. Hierzu werden drei neue Methoden eingeführt: eine verzögerungsbasierte Regularisierung, eine Methode basierend auf einer Regression von Körperoberflächenpotentialen und eine Deep-Learning-basierte Lokalisierungsmethode. Diese drei Methoden werden in einem simulierten und zwei klinischen Setups vier etablierten Methoden gegenübergestellt und bewertet. Auf dem simulierten Datensatz und auf einem der beiden klinischen Datensätze erzielte eine der neuen Methoden bessere Ergebnisse als die konventionellen Ansätze, während Tikhonov-Regularisierung auf dem verbleibenden klinischen Datensatz die besten Ergebnisse erzielte. Potentielle Ursachen für diese Ergebnisse werden diskutiert und mit Eigenschaften des Vorwärtsproblems in Verbindung gebracht

Bayesian Active Learning for Personalization and Uncertainty Quantification in Cardiac Electrophysiological Model

Cardiacvascular disease is the top death causing disease worldwide. In recent years, high-fidelity personalized models of the heart have shown an increasing capability to supplement clinical cardiology for improved patient-specific diagnosis, prediction, and treatment planning. In addition, they have shown promise to improve scientific understanding of a variety of disease mechanisms. However, model personalization by estimating the patient-specific tissue properties that are in the form of parameters of a physiological model is challenging. This is because tissue properties, in general, cannot be directly measured and they need to be estimated from measurements that are indirectly related to them through a physiological model. Moreover, these unknown tissue properties are heterogeneous and spatially varying throughout the heart volume presenting a difficulty of high-dimensional (HD) estimation from indirect and limited measurement data. The challenge in model personalization, therefore, summarizes to solving an ill-posed inverse problem where the unknown parameters are HD and the forward model is complex with a non-linear and computationally expensive physiological model. In this dissertation, we address the above challenge with following contributions. First, to address the concern of a complex forward model, we propose the surrogate modeling of the complex target function containing the forward model – an objective function in deterministic estimation or a posterior probability density function in probabilistic estimation – by actively selecting a set of training samples and a Bayesian update of the prior over the target function. The efficient and accurate surrogate of the expensive target function obtained in this manner is then utilized to accelerate either deterministic or probabilistic parameter estimation. Next, within the framework of Bayesian active learning we enable active surrogate learning over a HD parameter space with two novel approaches: 1) a multi-scale optimization that can adaptively allocate higher resolution to heterogeneous tissue regions and lower resolution to homogeneous tissue regions; and 2) a generative model from low-dimensional (LD) latent code to HD tissue properties. Both of these approaches are independently developed and tested within a parameter optimization framework. Furthermore, we devise a novel method that utilizes the surrogate pdf learned on an estimated LD parameter space to improve the proposal distribution of Metropolis Hastings for an accelerated sampling of the exact posterior pdf. We evaluate the presented methods on estimating local tissue excitability of a cardiac electrophysiological model in both synthetic data experiments and real data experiments. Results demonstrate that the presented methods are able to improve the accuracy and efficiency in patient-specific model parameter estimation in comparison to the existing approaches used for model personalization

ALEC: Active learning with ensemble of classifiers for clinical diagnosis of coronary artery disease

Invasive angiography is the reference standard for coronary artery disease (CAD) diagnosis but is expensive and associated with certain risks. Machine learning (ML) using clinical and noninvasive imaging parameters can be used for CAD diagnosis to avoid the side effects and cost of angiography. However, ML methods require labeled samples for efficient training. The labeled data scarcity and high labeling costs can be mitigated by active learning. This is achieved through selective query of challenging samples for labeling. To the best of our knowledge, active learning has not been used for CAD diagnosis yet. An Active Learning with Ensemble of Classifiers (ALEC) method is proposed for CAD diagnosis, consisting of four classifiers. Three of these classifiers determine whether a patient’s three main coronary arteries are stenotic or not. The fourth classifier predicts whether the patient has CAD or not. ALEC is first trained using labeled samples. For each unlabeled sample, if the outputs of the classifiers are consistent, the sample along with its predicted label is added to the pool of labeled samples. Inconsistent samples are manually labeled by medical experts before being added to the pool. The training is performed once more using the samples labeled so far. The interleaved phases of labeling and training are repeated until all samples are labeled. Compared with 19 other active learning algorithms, ALEC combined with a support vector machine classifier attained superior performance with 97.01% accuracy. Our method is justified mathematically as well. We also comprehensively analyze the CAD dataset used in this paper. As part of dataset analysis, features pairwise correlation is computed. The top 15 features contributing to CAD and stenosis of the three main coronary arteries are determined. The relationship between stenosis of the main arteries is presented using conditional probabilities. The effect of considering the number of stenotic arteries on sample discrimination is investigated. The discrimination power over dataset samples is visualized, assuming each of the three main coronary arteries as a sample label and considering the two remaining arteries as sample features