Implementación y estudio de métodos numéricos para la resolución del problema directo e inverso de la electrocardiografía: modelado de la actividad eléctrica en la superficie del torso

El comportamiento del corazón se rige por su actividad eléctrica, el conocimiento de la cual es indispensable para el correcto diagnóstico de diversas patologías cardiacas. Los sistemas de cartografía eléctrica de superficie permiten estudiar de forma no invasiva los potenciales generados por el corazón. Para ello, es necesaria la correcta resolución del problema inverso de la electrocardiografía. En el presente trabajo, se propone el uso de un nuevo algoritmo iterativo para la resolución del problema inverso en términos de múltiples dipolos móviles. Dicho algoritmo ha sido presentado, testeado y validado.Pedrón Torrecilla, J. (2010). Implementación y estudio de métodos numéricos para la resolución del problema directo e inverso de la electrocardiografía: modelado de la actividad eléctrica en la superficie del torso. http://hdl.handle.net/10251/12804Archivo delegad

Non-invasive Reconstruction of the Myocardial Electrical Activity from Body Surface Potential Recordings

[EN] The behavior of the heart is governed by electrical currents generated in the myocardium, and therefore, the study of the cardiac electrical activity is essential for the diagnosis of cardiac diseases. The forward problem of the electrocardiography (FP) entails the calculation of the torso potentials from the electrical activity of the heart and the 3D body model, while the inverse problem (IP) resolution allows the noninvasive reconstruction of the electrical activity of the heart from surface potentials. The IP is of great importance in clinical applications since it allows estimating the electrical activity of the myocardium with only noninvasive recordings. However, IP resolution is still a big challenge in electrocardiography since it is ill-posed, very unstable and has multiple solutions. In this thesis different algorithms and strategies based on the IP resolution were developed and applied in the noninvasive diagnosis of ventricular and atrial arrhythmias and evaluated with mathematical cellular models and clinical data bases. The thesis focuses on the IP resolution for the noninvasive reconstruction of the myocardial electrical activity for different diseases and propagation patterns, implementing a novel system for complex propagation patterns. The obtained results and propagation patterns were evaluated and classified with the corresponding optimal resolution strategy that minimizes the error and increases the stability of the system, proving its advantages and disadvantages depending on the different diseases and their activation pattern. A novel iterative method was implemented for the IP dipolar resolution optimized for representing simple propagation patterns, achieving a high stability and robustness against noise by constraining the solution to a limited number of dipoles. However, propagation patterns not representable by few dipoles need to be computed with the IP in terms of epicardial solutions which provide a more detailed estimation of the myocardial activity. IP resolution in the voltage and phase domains showed a good accuracy for simple and organized propagation patterns. This method allowed the noninvasive diagnosis of the Brugada syndrome or the location of ectopic focus in atrial arrhythmias by performing a parametric analysis of the electrograms morphology or the activation map reconstruction. However, mathematical and patient results presented in this thesis proved that, for complex propagation patterns like atrial fibrillation (AF), inverse solutions in the voltage and phase domains are over-smoothed and over-optimistic, simplifying the complex AF activity, leading to non-physiological results that do not match with the complex intracardiac electrograms recorded in AF patients. In this thesis, we proposed a novel technique for the noninvasive identification and location of high dominant frequency AF sources, based on the assumption that in many cases atrial drivers present the highest activation rate with an intermittent propagation to the rest of the tissue that activates at a slower rate. Although, voltage and phase inverse solutions for AF complex propagation patterns were over smoothed and inaccurate, the noninvasive estimation of frequency maps was significantly more accurate, allowing the identification of the AF frequency gradient and location of high frequency sources. This technique may help in planning ablation procedures, avoiding unnecessary interseptal punctures for right-to-left frequency gradients cases and facilitating the targeting of the AF drivers, reducing risk and time of the clinical procedure.[ES] El comportamiento del corazón se rige por corrientes eléctricas generadas en el miocardio y, por lo tanto, el estudio de su actividad eléctrica es esencial para el diagnóstico de enfermedades cardíacas. El problema directo (PD) de la electrocardiografía implica el cálculo de los potenciales del torso a partir de la actividad eléctrica del corazón y el modelo 3D del cuerpo, mientras que la resolución del problema inverso (PI) permite la reconstrucción no invasiva de la actividad eléctrica del corazón a partir de los potenciales de superficie, cobrando una gran importancia en la práctica clínica. Sin embargo, sigue siendo un gran desafío para la electrocardiografía ya que está mal planteado, es muy inestable y tiene múltiples soluciones. A lo largo de esta tesis se han desarrollado diferentes estrategias para la resolución del PI, aplicándolas en el diagnóstico no invasivo de arritmias ventriculares y auriculares, verificándolas mediante modelos celulares matemáticos y bases de datos clínicas. La tesis se centra en la resolución del PI para la reconstrucción no invasiva de la actividad eléctrica del miocardio para diferentes enfermedades cardiacas con diferentes patrones de propagación, implementando un novedoso sistema para patrones de propagación complejos. Además, se han validado los resultados obtenidos y se han clasificado los diferentes patrones de propagación con la estrategia de resolución del PI óptima que minimice el error y aumente la estabilidad del sistema. Un nuevo método iterativo fue implementado para la resolución del PI para fuentes dipolares, siendo óptimo para representar patrones de propagación simples, logrando una alta estabilidad e inmunidad al ruido al restringir la solución a un número limitado de dipolos. Sin embargo, los patrones de propagación que no pueden ser representados por un número limitado de dipolos deben calcularse mediante la resolución del PI en términos de potenciales epicárdicos, proporcionando una estimación más detallada de la actividad del miocardio. La resolución del PI en el dominio de la tensión y fase mostró ser muy preciso para patrones de propagación simples y organizados. Este método permite el diagnóstico no invasivo del síndrome de Brugada o la ubicación de focos ectópicos en arritmias auriculares mediante un análisis paramétrico de la morfología de los electrogramas o la reconstrucción de los mapas de activación. Sin embargo, los resultados matemáticos y clínicos presentados en esta tesis demostraron que, para patrones de propagación complejos como la fibrilación auricular (FA), los resultados obtenidos mediante la resolución del PI en el dominio de la tensión y fase son demasiado suaves y optimistas, simplificando enormemente la complejidad de la FA, llevando a resultados no fisiológicos que no coinciden con la actividad compleja de los electrogramas intracardiacos registrados en pacientes con FA. En esta tesis, se ha propuesto una novedosa técnica para la identificación y localización no invasiva de fuentes con una frecuencia dominante alta, basado en la suposición de que en muchos casos las fuentes eléctricas que generan y mantienen la FA presentan una tasa de activación más alta, con una propagación intermitente hacia el resto del tejido auricular cuya frecuencia de activación es más lenta. Aunque las soluciones en el dominio de la tensión y fase para patrones de propagación complejos fueron más suaves y menos precisas, la estimación no invasiva de los mapas de frecuencia fue significativamente más precisa, permitiendo la identificación del gradiente de frecuencia y ubicación de las fuentes de FA de alta frecuencia. Esta técnica puede ser de gran ayuda en la planificación de los procedimientos de ablación, evitando punciones interseptales innecesarias para casos con un gradiente de frecuencia de derecha a izquierda y facilitando la localización de las fuentes de alta frecuencia[CA] El comportament del cor es regeix per corrents elèctrics generades en el miocardi i, per tant, l'estudi de la seua activitat elèctrica és essencial per al diagnòstic de malalties cardíaques. El problema directe (PD) de l'electrocardiografia implica el càlcul dels potencials del tors a partir de l'activitat elèctrica del cor i el model 3D del cos, mentre que la resolució del problema invers (PI) permet la reconstrucció no invasiva de l'activitat elèctrica del cor a partir de els potencials de superfície. La resolució del PI de l'electrocardiografia té una gran importància en la pràctica clínica atès que fa possible una estimació de l'activitat elèctrica del miocardi únicament a partir de registres no invasius. No obstant això, la resolució del PI segueix sent un gran desafiament per a la electrocardiografia ja que està mal plantejat, és molt inestable i té múltiples solucions. Al llarg d'aquesta tesi s'han desenvolupat diferents estratègies basades en la resolució PI, aplicant-les en el diagnòstic no invasiu d'arítmies ventriculars i auriculars, verificant mitjançant models cel·lulars matemàtics i bases de dades clíniques. La tesi se centra en la resolució del PI per a la reconstrucció no invasiva de l'activitat elèctrica del miocardi per a diferents malalties cardíaques amb diferents patrons de propagació, implementant un nou sistema per a patrons de propagació complexos. A més se han validat els resultats obtinguts i se han classificat els diferents patrons de propagació amb l'estratègia de resolució del PI òptima que minimitze l'error i augmente l'estabilitat del sistema. Un nou mètode iteratiu va ser implementat per a la resolució del PI per fonts dipolars, sent òptim per representar patrons de propagació simples, aconseguint una alta estabilitat i immunitat al soroll en restringir la solució a un nombre limitat de dipols. No obstant això, els patrons de propagació que no poden ser representats per un nombre limitat de dipols s'han de calcular mitjançant la resolució del PI en termes de potencials epicàrdics, proporcionant una estimació més detallada de l'activitat del miocardi. La resolució del PI en el domini de la tensió i fase va mostrar ser molt precís per a patrons de propagació simples i organitzats. Aquest mètode permet el diagnòstic no invasiu de la síndrome de Brugada o la ubicació de focus ectòpics en arítmies auriculars mitjançant una anàlisi paramètric de la morfologia dels electrogrames o la reconstrucció dels mapes d'activació. No obstant això, els resultats matemàtics i clínics presentats en aquesta tesi van demostrar que, per patrons de propagació complexos com la fibril·lació auricular (FA), els resultats obtinguts mitjançant la resolució del PI en el domini de la tensió i fase són massa suaus i optimistes, simplificant enormement la complexitat de la FA, obtenint resultats no fisiològics que no coincideixen amb l'activitat complexa dels electrogrames intracardiacos registrats en pacients amb FA. En aquesta tesi, s'ha proposat una nova tècnica per a la identificació i localització no invasiva de fonts amb una freqüència dominant alta, basat en la suposició que en molts casos les fonts elèctriques que generen i mantenen la FA presenten una taxa d'activació més alta, amb una propagació intermitent cap a la resta del teixit auricular on la freqüència d'activació és més lenta. Encara que, les solucions en el domini de la tensió i fase per patrons de propagació complexos van ser més suaus i menys precises, l'estimació no invasiva dels mapes de freqüència va ser significativament més precisa, permetent la identificació del gradient de freqüència i ubicació de les fonts de FA d'alta freqüència. Aquesta tècnica pot ser de gran ajuda en la planificació dels procediments d'ablació, evitant puncions interseptales innecessaris per a casos amb un gradient de freqüència de dreta a esquerra i facilitant laPedrón Torrecilla, J. (2015). Non-invasive Reconstruction of the Myocardial Electrical Activity from Body Surface Potential Recordings [Tesis doctoral no publicada]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/58268TESI

Body Surface Potential Propagation Maps During Macroreentrant Atrial Arrhythmias. A Simulation Study

Abstract Atrial flutter (AFL) i

Noninvasive Estimation of Epicardial Dominant High-Frequency Regions During Atrial Fibrillation

[EN] Introduction Ablation of high dominant frequency (DF) sources in patients with atrial fibrillation (AF) is an effective treatment option for paroxysmal AF. The aim of this study was to evaluate the accuracy of noninvasive estimation of DF and electrical patterns determination by solving the inverse problem of the electrocardiography. Methods Four representative AF patients with left-to-right and right-to-left atrial DF patterns were included in the study. For each patient, intracardiac electrograms from both atria were recorded simultaneously together with 67-lead body surface recordings. In addition to clinical recordings, realistic mathematical models of atria and torso anatomy with different DF patterns of AF were used. For both mathematical models and clinical recordings, inverse-computed electrograms were compared to intracardiac electrograms in terms of voltage, phase, and frequency spectrum relative errors. Results Comparison between intracardiac and inverse computed electrograms for AF patients showed 8.8 ± 4.4% errors for DF, 32 ± 4% for voltage, and 65 ± 4% for phase determination. These results were corroborated by mathematical simulations showing that the inverse problem solution was able to reconstruct the frequency spectrum and the DF maps with relative errors of 5.5 ± 4.1%, whereas the reconstruction of the electrograms or the instantaneous phase presented larger relative errors (i.e., 38 ± 15% and 48 ± 14 % respectively, P < 0.01). Conclusions Noninvasive reconstruction of atrial frequency maps can be achieved by solving the inverse problem of electrocardiography with a higher accuracy than temporal distribution patterns.Pedrón-Torrecilla, J.; Rodrigo Bort, M.; M. Climent, A.; Liberos, A.; Pérez-David E; Bermejo, J.; Arenal, A.... (2016). Noninvasive Estimation of Epicardial Dominant High-Frequency Regions During Atrial Fibrillation. Journal of Cardiovascular Electrophysiology. 27(4):435-442. doi:https://doi.org/10.1111/jce.12931S43544227

Body surface localization of left and right atrial high-frequency rotors in atrial fibrillation patients: A clinical-computational study

Background: Ablation is an effective therapy in atrial fibrillation (AF) patients in which an electrical driver can be identified. Objective: The aim of this study is to present and discuss a novel and strictly non-invasive approach to map and identify atrial regions responsible for AF perpetuation. Methods: Surface potential recordings of 14 patients with AF were recorded using a 67-lead recording system. Singularity points (SPs) were identified in surface phase maps after band-pass filtering at the highest dominant frequency (HDF). Mathematical models of combined atria and torso were constructed and used to investigate the ability of surface phase maps to estimate rotor activity in the atrial wall. Results: The simulations show that surface SPs originate at atrial SPs, but not all atrial SPs are reflected at the surface. Stable SPs were found in AF signals during 8.3±5.7% vs. 73.1±16.8% of the time in unfiltered vs. HDF-filtered patient data respectively (p<0.01). The average duration of each rotational pattern was also lower in unfiltered than in HDF-filtered AF signals (160±43 vs. 342±138 ms, p<0.01) resulting in 2.8±0.7 rotations per rotor. Band-pass filtering reduced the apparent meandering of surface HDF rotors by reducing the effect of the atrial electrical activity taking place at different frequencies. Torso surface SPs representing HDF rotors during AF were reflected at specific areas corresponding to the fastest atrial location. Conclusion: Phase analysis of surface potential signals after HDF-filtering during AF shows reentrant drivers localized to either the LA or RA, helping in localizing ablation targetsThis work was supported in part by the Spanish Society of Cardiology (Becas Investigacion Clinica 2009); the Universitat Politecnica de Valencia through its research initiative program; the Generalitat Valenciana grant (ACIF/2013/021); the Ministerio de Economia y Competitividad, Rod RIC; the Centro Nacional de Investigaciones Cardiovasculares (proyecto CNIC-13); the Coulter Foundation from the Biomedical Engineering Department, University of Michigan; the Gelman Award from the Cardiovascular Division, University of Michigan; the National Heart, Lung, and Blood Institute grants (P01411.039707, P01-1111187226, and R01-11L118304); and the Leducq Foundation. Dr Femandez-Aviles served on the advisory board of Medtronic and has received research funding from St Jude Medical Spain. Dr Berenfeld has received research support from Medtronic and St Jude Medical; he is a colbunder and scientific officer of Rhythm Solutions. None of the companies disclosed financed the research described in this article.Rodrigo Bort, M.; Guillem Sánchez, MS.; Climent, AM.; Pedrón Torrecilla, J.; Liberos Mascarell, A.; Millet Roig, J.; Fernandez-Aviles, F.... (2014). Body surface localization of left and right atrial high-frequency rotors in atrial fibrillation patients: A clinical-computational study. Heart Rhythm. 11(9):1584-1591. https://doi.org/10.1016/j.hrthm.2014.05.013S1584159111

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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