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

Transferring Generalized Knowledge from Physics-based Simulation to Clinical Domain

A primary factor for the success of machine learning is the quality of labeled training data. However, in many fields, labeled data can be costly, difficult, or even impossible to acquire. In comparison, computer simulation data can now be generated at a much higher abundance with a much lower cost. These simulation data could potentially solve the problem of data deficiency in many machine learning tasks. Nevertheless, due to model assumptions, simplifications and possible errors, there is always a discrepancy between simulated and real data. This discrepancy needs to be addressed when transferring the knowledge from simulation to real data. Furthermore, simulation data is always tied to specific settings of models parameters, many of which have a considerable range of variations yet not necessarily relevant to the machine learning task of interest. The knowledge extracted from simulation data must thus be generalizable across these parameter variations before being transferred. In this dissertation, we address the two outlined challenges in leveraging simulation data to overcome the shortage of labeled real data, . We do so in a clinical task of localizing the origin of ventricular activation from 12 lead electrocardiograms (ECGs), where the clinical ECG data with labeled sites of origin in the heart can only be invasively available. By adopting the concept of domain adaptation, we address the discrepancy between simulated and clinical ECG data by learning the shift between the two domains using a large amount of simulation data and a small amount of clinical data. By adopting the concept of domain generalization, we then address the reliance of simulated ECG data on patient-specific geometrical models by learning to generalize simulated ECG data across subjects, before transferring them to clinical data. Evaluated on in-vivo premature ventricular contraction (PVC) patients, we demonstrate the feasibility of utilizing a large number of offline simulated ECG datasets to enable the prediction of the origin of arrhythmia with only a small number of clinical ECG data on a new patient

Feasibility of improving risk stratification in the inherited cardiac conditions

Fatal ventricular arrhythmias can occur in patients with Hypertrophic Cardiomyopathy, Brugada Syndrome and rarely in patients with normal cardiac investigations. Despite very different pathogeneses, we hypothesised that a common electrophysiological substrate precipitates these arrhythmias and could be used as a marker for risk stratification. In Chapter 3 of this thesis, we found that fewer than half the cardiac arrest survivors with Brugada Syndrome would have been offered prophylactic defibrillators based on current risk scoring, highlighting the need for better risk stratification. Our group previously used a commercially available 252-electrode vest which constructs ventricular electrograms onto a CT image of the heart to show exercise related differences in high-risk patients. In Chapter 4, we applied this method to Brugada patients, but could not reproduce prior results. Further investigation revealed periodic changes in activation patterns after exercise that could explain this discrepancy. An alternative matrix approach was developed to overcome this problem. Exercise induced conduction heterogeneity differentiated Brugada patients from unaffected controls, but not those surviving cardiac arrest. However, if considered alongside spontaneous type 1 ECG and syncope, inducible conduction heterogeneity markedly improved identification of Brugada cardiac arrest survivors. In Chapter 5 the method was shown to differentiate idiopathic ventricular fibrillation patients from those fully recovered from acute ischaemic cardiac arrest, implying a permanent electrophysiological abnormality. In Chapter 8, we showed prolonged mean local activation times and activation-recovery intervals in hypertrophic cardiomyopathy cardiac arrest survivors compared to those without previous ventricular arrhythmia. These metrics were combined into both logistic regression and support vector machine models to strongly differentiate the groups. We concluded that electrophysiological changes could identify cardiac arrest survivors in various cardiac conditions, but a single factor common pathway was not established. Prospective studies are required to determine if using these parameters could enhance current risk stratification for sudden death.Open Acces

Personnalisation basée sur l'imagerie de modèles cardiaques électrophysiologiques pour la planification du traitement de la tachycardie ventriculaire

Acute infarct survival rates have drastically improved over the last decades, mechanically increasing chronic infarct related affections.Among these affections, ischaemic ventricular tachycardia (VT) is a particularly serious arrhythmia that can lead to the often lethal ventricular fibrillation. VT can be treated by radio frequency ablation of the arrhythmogenic substrate.The first phase of this long and risky interventional cardiology procedure is an electrophysiological (EP) exploration of the heart.This phase aims at localising the ablation targets, notably by inducing the arrhythmia in a controlled setting. In this work we propose to re-create this exploration phase in silico, by personalising cardiac EP models.We show that key information about infarct scar location and heterogeneity can be automatically obtained by a deep learning-based automated segmentation of the myocardium on computed tomography (CT) images.Our goal is to use this information to run patient-specific simulations of depolarisation wave propagation in the myocardium, mimicking the interventional cardiology exploration phase.We start by studying the relationship between the depolarisation wave propagation velocity and the left ventricular wall thickness to personalise an Eikonal model, an approach that can successfully reproduce periodic activation maps of the left ventricle recorded during VT.We then propose efficient algorithms to detect the repolarisation wave on unipolar electrograms (UEG), that we use to analyse the UEGs embedded in such intra-cardiac recordings.Thanks to a multimodal registration between these recordings and CT images, we establish relationships between action potential durations/restitution properties and left ventricular wall thickness.These relationships are finally used to parametrise a reaction-diffusion model able to reproduce interventional cardiologists' induction protocols that trigger realistic and documented VTs. inteinterventional cardiologists' induction protocols that trigger realistic and documented VTs.La survie lors de la phase aiguë de l'infarctus du myocarde a énormément progressé au cours des dernières décennies, augmentant ainsi la mortalité des affections liées à l'infarctus chronique.Parmi ces pathologies, la tachycardie ventriculaire (TV) est une arythmie particulièrement grave qui peut conduire à la fibrillation ventriculaire, souvent fatale.La TV peut être traitée par ablation par radio-fréquences du substrat arythmogène.La première phase de cette procédure, longue et risquée, est une exploration électrophysiologique (EP) du cœur consistant à déterminer les cibles de cette ablation, notamment en provoquant l'arythmie dans un environnement contrôléDans cette thèse, nous proposons de re-créer in silico cette phase exploratoire, en personnalisation des modèles cardiaques EP.Nous montrons que des informations clefs à propos de la localisation et de l'hétérogénéité de la cicatrice d'infarctus peuvent être obtenues automatiquement par une segmentation d'images tomodensitométriques (TDM) utilisant un réseau de neurones artificiels.Notre but est alors d'utiliser ces informations pour réaliser des simulations spécifiques à un patient de la propagation de l'onde de dépolarisation dans le myocarde, reproduisant la phase exploratoire décrite plus haut.Nous commençons par étudier la relation entre la vitesse de l'onde de dépolarisation et l'épaisseur du ventricule gauche, relation qui permet de personnaliser un modèle EP Eikonal; cette approche permet fr reproduire des cartes d'activations périodiques du ventricule gauche obtenues durant des TV.Nous proposons ensuite des algorithmes efficaces pour détecter l'onde de repolarisation sur les électrogrammes unipolaires (EGU), que nous utilisons pour analyser les EGU contenus dans les enregistrements intra-cardiaques à notre disposition.Grâce à un recalage multimodal entre ces enregistrements et des images TDM, nous établissons des relations entre durées de potentiels d'action (DPA)/propriétés de restitutions de DPA et épaisseur du ventricule gauche.Enfin, ces relations sont utilisés pour paramétrer un modèle de réaction-diffusion capable de reproduire fidèlement les protocoles d'induction des cardiologues interventionnels qui provoquent des TV réalistes et documentées

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

Electrophysiology

The outstanding evolution of recording techniques paved the way for better understanding of electrophysiological phenomena within the human organs, including the cardiovascular, ophthalmologic and neural systems. In the field of cardiac electrophysiology, the development of more and more sophisticated recording and mapping techniques made it possible to elucidate the mechanism of various cardiac arrhythmias. This has even led to the evolution of techniques to ablate and cure most complex cardiac arrhythmias. Nevertheless, there is still a long way ahead and this book can be considered a valuable addition to the current knowledge in subjects related to bioelectricity from plants to the human heart

Knowledge discovery on the integrative analysis of electrical and mechanical dyssynchrony to improve cardiac resynchronization therapy

Cardiac resynchronization therapy (CRT) is a standard method of treating heart failure by coordinating the function of the left and right ventricles. However, up to 40% of CRT recipients do not experience clinical symptoms or cardiac function improvements. The main reasons for CRT non-response include: (1) suboptimal patient selection based on electrical dyssynchrony measured by electrocardiogram (ECG) in current guidelines; (2) mechanical dyssynchrony has been shown to be effective but has not been fully explored; and (3) inappropriate placement of the CRT left ventricular (LV) lead in a significant number of patients. In terms of mechanical dyssynchrony, we utilize an autoencoder to extract new predictive features from nuclear medicine images, characterizing local mechanical dyssynchrony and improving the CRT response rate. Although machine learning can identify complex patterns and make accurate predictions from large datasets, the low interpretability of these black box methods makes it difficult to integrate them with clinical decisions made by physicians in the healthcare setting. Therefore, we use visualization techniques to enable physicians to understand the physical meaning of new features and the reasoning behind the clinical decisions made by the artificial intelligent model. For electrical dyssynchrony, we use short-time Fourier transform (STFT) to transform one-dimensional waveforms into two-dimensional frequency-time spectra. And transfer learning is used to leverage the knowledge learned from a large arrhythmia ECG dataset of related medical conditions to improve patient selection for CRT with limited data. This improves prediction accuracy, reduces the time and resources required, and potentially leads to better patient outcomes. Furthermore, an innovative approach is proposed for using three-dimensional spatial VCG information to describe the characteristics of electrical dyssynchrony, locate the latest activation site, and combine it with the latest mechanical contraction site to select the optimal LV lead position. In addition, we apply deep reinforcement learning to the decision-making problem of CRT patients. We investigate discrete state space/specific action space models to find the best treatment strategy, improve the reward equation based on the physician\u27s experience, and learn the approximation of the best action-value function that can improve the treatment policy used by clinicians and provide interpretability

Towards end-to-end security in internet of things based healthcare

Healthcare IoT systems are distinguished in that they are designed to serve human beings, which primarily raises the requirements of security, privacy, and reliability. Such systems have to provide real-time notifications and responses concerning the status of patients. Physicians, patients, and other caregivers demand a reliable system in which the results are accurate and timely, and the service is reliable and secure. To guarantee these requirements, the smart components in the system require a secure and efficient end-to-end communication method between the end-points (e.g., patients, caregivers, and medical sensors) of a healthcare IoT system. The main challenge faced by the existing security solutions is a lack of secure end-to-end communication. This thesis addresses this challenge by presenting a novel end-to-end security solution enabling end-points to securely and efficiently communicate with each other. The proposed solution meets the security requirements of a wide range of healthcare IoT systems while minimizing the overall hardware overhead of end-to-end communication. End-to-end communication is enabled by the holistic integration of the following contributions. The first contribution is the implementation of two architectures for remote monitoring of bio-signals. The first architecture is based on a low power IEEE 802.15.4 protocol known as ZigBee. It consists of a set of sensor nodes to read data from various medical sensors, process the data, and send them wirelessly over ZigBee to a server node. The second architecture implements on an IP-based wireless sensor network, using IEEE 802.11 Wireless Local Area Network (WLAN). The system consists of a IEEE 802.11 based sensor module to access bio-signals from patients and send them over to a remote server. In both architectures, the server node collects the health data from several client nodes and updates a remote database. The remote webserver accesses the database and updates the webpage in real-time, which can be accessed remotely. The second contribution is a novel secure mutual authentication scheme for Radio Frequency Identification (RFID) implant systems. The proposed scheme relies on the elliptic curve cryptography and the D-Quark lightweight hash design. The scheme consists of three main phases: (1) reader authentication and verification, (2) tag identification, and (3) tag verification. We show that among the existing public-key crypto-systems, elliptic curve is the optimal choice due to its small key size as well as its efficiency in computations. The D-Quark lightweight hash design has been tailored for resource-constrained devices. The third contribution is proposing a low-latency and secure cryptographic keys generation approach based on Electrocardiogram (ECG) features. This is performed by taking advantage of the uniqueness and randomness properties of ECG's main features comprising of PR, RR, PP, QT, and ST intervals. This approach achieves low latency due to its reliance on reference-free ECG's main features that can be acquired in a short time. The approach is called Several ECG Features (SEF)-based cryptographic key generation. The fourth contribution is devising a novel secure and efficient end-to-end security scheme for mobility enabled healthcare IoT. The proposed scheme consists of: (1) a secure and efficient end-user authentication and authorization architecture based on the certificate based Datagram Transport Layer Security (DTLS) handshake protocol, (2) a secure end-to-end communication method based on DTLS session resumption, and (3) support for robust mobility based on interconnected smart gateways in the fog layer. Finally, the fifth and the last contribution is the analysis of the performance of the state-of-the-art end-to-end security solutions in healthcare IoT systems including our end-to-end security solution. In this regard, we first identify and present the essential requirements of robust security solutions for healthcare IoT systems. We then analyze the performance of the state-of-the-art end-to-end security solutions (including our scheme) by developing a prototype healthcare IoT system