Inverse estimation of the cardiac purkinje system from electroanatomical maps

Las enfermedades cardiovasculares son la primera causa de mortalidad en el mundo, con 17.7 millones de muertes cada año, aproximadamente el 31% de las muertes en todo el mundo (Organización Mundial de la Salud (OMS) 2018). Las arritmias ventriculares son una causa importante de muerte súbita, que representa aproximadamente la mitad de la mortalidad cardíaca. Algunas de esas arritmias se atribuyen a la red de Purkinje (PKN), que bajo ciertas condiciones puede generar ritmos focales automáticos, y su configuración de red puede sostener circuitos eléctricos reentrantes. Los ritmos focales originados desde la red de Purkinje pueden servir como puntos de inicio en casos de fibrilación ventricular en un amplio espectro de pacientes. El manejo de las enfermedades eléctricas cardíacas es un área clínica en expansión. Las nuevas tecnologías de imágenes y mapeo no invasivas, permiten adquirir imágenes clínicas de alta resolución (MRI, CT) que se pueden utilizar para localizar y caracterizar el tejido cardíaco patológico. Además, los sistemas de navegación electroanatómica (EAM) pueden ayudar al electrofisiólogo a encontrar las fuentes de actividad o circuitos arritmogénicos que mantienen la arritmia y eliminarlos mediante ablación por radiofrecuencia (RFA). A pesar de todos los avances técnicos, los tratamientos clínicos para esas enfermedades todavía se perciben como subóptimos, con tasas de éxito del tratamiento a largo plazo en el rango de 60 a 65%. Por lo tanto, existe una necesidad imperiosa de mejorar los resultados clínicos en beneficio de los pacientes y el sistema de salud. El área del modelado biofísico computacional ha comenzado a penetrar en entornos clínicos en unos pocos hospitales tecnológicamente avanzados y orientados a la investigación en el mundo. El objetivo principal de estas técnicas es el desarrollo de modelos 3D realistas de diferentes órganos, como el corazón, que incluyen, con un alto grado de detalle, características genéticas de las corrientes iónicas, sus mutaciones, las características electrofisiológicas de los diferentes tipos de células cardíacas, la estructura anatómica de los tejidos cardíacos y, en general, del cuerpo humano. A continuación, los modelos se utilizan para simular la función cardíaca, por ejemplo, electrofisiología, para tratar de estratificar a los pacientes o mejorar la planificación y ejecución de la terapia. Los enfoques por computador aún se enfrentan a varios desafíos que impiden su penetración completa en entornos clínicos. Podría decirse que uno de los obstáculos más importantes es el tiempo y la experiencia necesarios para construir un modelo del corazón personalizado a paciente, incluso si todos los datos clínicos necesarios están disponibles. En ese sentido, uno de los componentes del modelo que se ha mantenido elusivo a los modeladores ha sido la PKN, que es clave para la electrofisiología cardíaca. La razón principal es que debido a sus pequeñas dimensiones no existe una técnica clínica con resolución suficiente para permitir su visualización in vivo. El objetivo principal de esta tesis es desarrollar una metodología capaz de estimar inversamente un PKN reducido de paciente a partir de su EAM. Eso implica, primero encontrar en el EAM las fuentes de activación eléctrica, llamadas uniones de Purkinje-miocardio (PMJ), y seguir la estructura que interconecta esos PMJ y reproduce la secuencia de activación del paciente. En resumen, las principales contribuciones de esta tesis son: - Metodología para estimar los PMJ, o las fuentes de actividad eléctrica, sobre una representación 3D del endocardio ventricular, proporcionada por un EAM. El método desarrollado puede procesar directamente los datos adquiridos por un electrofisiólogo en el Cathlab, volver a anotar los tiempos en las muestras adquiridas y obtener las ubicaciones de los PMJs y los tiempos de activación, considerando explicitamente ruido en las muestras. - Metodología para estimar el PKN del paciente a partir de los PMJ estimados, que es capaz de reproducir la secuencia de activación eléctrica del paciente con un error mínimo. El método ha sido validado tanto en EAM sintéticos como en 28 EAM reales, mostrando errores de unos pocos milisegundos. Además, se ha utilizado un PKN estimado para simular el ECG virtual de un paciente, donse se observa coincidencia entre el ECG real y el simulado. En conclusión, he desarrollado y validado una metodología que permite la estimación de la PKN de un paciente con errores mínimos en la secuencia de activación, y que puede usarse para personalizar simulaciones biofísicas del corazón o ayudar al electrofisiólogo en la planificación de intervenciones de RFA.Cardiovascular disease is the number one cause of mortality in the world, accounting for 17.7 million deaths each year, an estimated 31% of all deaths worldwide (World Health Organization (WHO) 2018). Ventricular arrhythmias are a major cause of sudden death, which accounts for approximately half of cardiac mortality. Some of those arrhythmias are attributed to the Purkinje network (PKN), which under certain conditions can generate both automatic and triggered focal rhythms, and its network configuration can sustain re‑entrant circuits. Focal Purkinje triggers can serve as initial points of ventricular fibrillation in a wide spectrum of patients. The management of cardiac electrical diseases is an expanding clinical activity. New non-invasive imaging and mapping technologies, allow to acquire high resolution clinical images (MRI, CT) that can be used to localize and characterize pathological cardiac tissue. Furthermore, electroanatomical navigating (EAM) systems, can aid electrophysiologist to find the sources of arrhythmogenic activity or circuits maintaining arrhythmia, and eliminate them by radio-frequency ablation (RFA). Despite all the technical advances, overall clinical outcome for those diseases is still perceived as suboptimal, with long-term treatment success rates in the range of 60 to 65%. Therefore, there is a compelling need to improve clinical outcomes for the benefit of the patients and the healthcare system. The area of computational biophysical modeling has already started to penetrate in clinical environments in a few technologically advanced research oriented hospitals in the world. The main objective of these techniques is the development of realistic 3D models of different organs, such as the heart, that include, with a high degree of detail, genetic characteristics of the ionic currents, their mutations, the electrophysiological characteristics of the different cardiac cell types, the anatomical structure of cardiac tissues, and in general of the human body. Following, the models are used to simulate the heart function, e.g., electrophysiology, to try to stratify patients or improve therapy planning and delivery. Computer-based approaches are still facing several challenges that prevent their complete penetration into clinical environments. Arguably, one of the most important obstacles is the time and expertise required to build a patient-specific model of the heart, even if all necessary clinical data are available. In that sense, one of the model components that has remained largely elusive to modelers has been the PKN, which is key for cardiac electrophysiology. The main reason is that due to its small dimensions there is no clinical technique with enough resolution to allow its visualization in vivo. The main purpose of this thesis is to develop a methodology able to inversely estimate a reduced PKN of patient from his EAM. That involves, first, finding in the EAM the sources of electrical activation, so called Purkinje-myocardial junctions (PMJs), and, following, finding the structure that interconnects those PMJs and reproduces the patient sequence of activation. In summary, the main contributions of this thesis are: - Methodology to estimate the PMJs, or the sources of electrical activity, from a 3D representation of the ventricular endocardium provided by an EAM. The method developed can process directly the data acquired by an electrophysiologist in the Cathlab, re-annotate the time samples, and obtain the PMJ locations and activation times, explicitly considering noise in the samples. - Methodology to estimate the patient PKN from the estimated PMJs, that is able to reproduce the patient's sequence of electrical activation with a minimal error. The method has been validated on synthetic EAMs as well as in 28 real EAMs, showing errors of a few milliseconds. In addition, an estimated PKN has been used to simulate the virtual ECG of a patient, showing a good match with the clinical one. In conclusion, I have developed and validated a methodology that permits the estimation of a patient's PKN with small errors in the sequence of activation, that can be used to personalize biophysical simulations of the heart or aid electrophysiologist in the planning of RFA interventions

Measurement of the inclusive and dijet cross-sections of b-jets in pp collisions at sqrt(s) = 7 TeV with the ATLAS detector

The inclusive and dijet production cross-sections have been measured for jets containing b-hadrons (b-jets) in proton-proton collisions at a centre-of-mass energy of sqrt(s) = 7 TeV, using the ATLAS detector at the LHC. The measurements use data corresponding to an integrated luminosity of 34 pb^-1. The b-jets are identified using either a lifetime-based method, where secondary decay vertices of b-hadrons in jets are reconstructed using information from the tracking detectors, or a muon-based method where the presence of a muon is used to identify semileptonic decays of b-hadrons inside jets. The inclusive b-jet cross-section is measured as a function of transverse momentum in the range 20 < pT < 400 GeV and rapidity in the range |y| < 2.1. The bbbar-dijet cross-section is measured as a function of the dijet invariant mass in the range 110 < m_jj < 760 GeV, the azimuthal angle difference between the two jets and the angular variable chi in two dijet mass regions. The results are compared with next-to-leading-order QCD predictions. Good agreement is observed between the measured cross-sections and the predictions obtained using POWHEG + Pythia. MC@NLO + Herwig shows good agreement with the measured bbbar-dijet cross-section. However, it does not reproduce the measured inclusive cross-section well, particularly for central b-jets with large transverse momenta.Comment: 10 pages plus author list (21 pages total), 8 figures, 1 table, final version published in European Physical Journal

Search for displaced vertices arising from decays of new heavy particles in 7 TeV pp collisions at ATLAS

We present the results of a search for new, heavy particles that decay at a significant distance from their production point into a final state containing charged hadrons in association with a high-momentum muon. The search is conducted in a pp-collision data sample with a center-of-mass energy of 7 TeV and an integrated luminosity of 33 pb^-1 collected in 2010 by the ATLAS detector operating at the Large Hadron Collider. Production of such particles is expected in various scenarios of physics beyond the standard model. We observe no signal and place limits on the production cross-section of supersymmetric particles in an R-parity-violating scenario as a function of the neutralino lifetime. Limits are presented for different squark and neutralino masses, enabling extension of the limits to a variety of other models.Comment: 8 pages plus author list (20 pages total), 8 figures, 1 table, final version to appear in Physics Letters

Single hadron response measurement and calorimeter jet energy scale uncertainty with the ATLAS detector at the LHC

The uncertainty on the calorimeter energy response to jets of particles is derived for the ATLAS experiment at the Large Hadron Collider (LHC). First, the calorimeter response to single isolated charged hadrons is measured and compared to the Monte Carlo simulation using proton-proton collisions at centre-of-mass energies of sqrt(s) = 900 GeV and 7 TeV collected during 2009 and 2010. Then, using the decay of K_s and Lambda particles, the calorimeter response to specific types of particles (positively and negatively charged pions, protons, and anti-protons) is measured and compared to the Monte Carlo predictions. Finally, the jet energy scale uncertainty is determined by propagating the response uncertainty for single charged and neutral particles to jets. The response uncertainty is 2-5% for central isolated hadrons and 1-3% for the final calorimeter jet energy scale.Comment: 24 pages plus author list (36 pages total), 23 figures, 1 table, submitted to European Physical Journal

Measurement of the polarisation of W bosons produced with large transverse momentum in pp collisions at sqrt(s) = 7 TeV with the ATLAS experiment

This paper describes an analysis of the angular distribution of W->enu and W->munu decays, using data from pp collisions at sqrt(s) = 7 TeV recorded with the ATLAS detector at the LHC in 2010, corresponding to an integrated luminosity of about 35 pb^-1. Using the decay lepton transverse momentum and the missing transverse energy, the W decay angular distribution projected onto the transverse plane is obtained and analysed in terms of helicity fractions f0, fL and fR over two ranges of W transverse momentum (ptw): 35 < ptw < 50 GeV and ptw > 50 GeV. Good agreement is found with theoretical predictions. For ptw > 50 GeV, the values of f0 and fL-fR, averaged over charge and lepton flavour, are measured to be : f0 = 0.127 +/- 0.030 +/- 0.108 and fL-fR = 0.252 +/- 0.017 +/- 0.030, where the first uncertainties are statistical, and the second include all systematic effects.Comment: 19 pages plus author list (34 pages total), 9 figures, 11 tables, revised author list, matches European Journal of Physics C versio

Observation of a new chi_b state in radiative transitions to Upsilon(1S) and Upsilon(2S) at ATLAS

The chi_b(nP) quarkonium states are produced in proton-proton collisions at the Large Hadron Collider (LHC) at sqrt(s) = 7 TeV and recorded by the ATLAS detector. Using a data sample corresponding to an integrated luminosity of 4.4 fb^-1, these states are reconstructed through their radiative decays to Upsilon(1S,2S) with Upsilon->mu+mu-. In addition to the mass peaks corresponding to the decay modes chi_b(1P,2P)->Upsilon(1S)gamma, a new structure centered at a mass of 10.530+/-0.005 (stat.)+/-0.009 (syst.) GeV is also observed, in both the Upsilon(1S)gamma and Upsilon(2S)gamma decay modes. This is interpreted as the chi_b(3P) system.Comment: 5 pages plus author list (18 pages total), 2 figures, 1 table, corrected author list, matches final version in Physical Review Letter

Standalone vertex finding in the ATLAS muon spectrometer

A dedicated reconstruction algorithm to find decay vertices in the ATLAS muon spectrometer is presented. The algorithm searches the region just upstream of or inside the muon spectrometer volume for multi-particle vertices that originate from the decay of particles with long decay paths. The performance of the algorithm is evaluated using both a sample of simulated Higgs boson events, in which the Higgs boson decays to long-lived neutral particles that in turn decay to bbar b final states, and pp collision data at √s = 7 TeV collected with the ATLAS detector at the LHC during 2011

Measurements of Higgs boson production and couplings in diboson final states with the ATLAS detector at the LHC

Measurements are presented of production properties and couplings of the recently discovered Higgs boson using the decays into boson pairs, H →γ γ, H → Z Z∗ →4l and H →W W∗ →lνlν. The results are based on the complete pp collision data sample recorded by the ATLAS experiment at the CERN Large Hadron Collider at centre-of-mass energies of √s = 7 TeV and √s = 8 TeV, corresponding to an integrated luminosity of about 25 fb−1. Evidence for Higgs boson production through vector-boson fusion is reported. Results of combined fits probing Higgs boson couplings to fermions and bosons, as well as anomalous contributions to loop-induced production and decay modes, are presented. All measurements are consistent with expectations for the Standard Model Higgs boson

Measurement of the top quark-pair production cross section with ATLAS in pp collisions at \sqrt{s}=7\TeV

A measurement of the production cross-section for top quark pairs(\ttbar) in $pp$ collisions at \sqrt{s}=7 \TeV is presented using data recorded with the ATLAS detector at the Large Hadron Collider. Events are selected in two different topologies: single lepton (electron $e$ or muon $\mu$) with large missing transverse energy and at least four jets, and dilepton ($ee$, $\mu\mu$ or $e\mu$) with large missing transverse energy and at least two jets. In a data sample of 2.9 pb-1, 37 candidate events are observed in the single-lepton topology and 9 events in the dilepton topology. The corresponding expected backgrounds from non-\ttbar Standard Model processes are estimated using data-driven methods and determined to be $12.2 \pm 3.9$ events and $2.5 \pm 0.6$ events, respectively. The kinematic properties of the selected events are consistent with SM \ttbar production. The inclusive top quark pair production cross-section is measured to be \sigmattbar=145 \pm 31 ^{+42}_{-27} pb where the first uncertainty is statistical and the second systematic. The measurement agrees with perturbative QCD calculations.Comment: 30 pages plus author list (50 pages total), 9 figures, 11 tables, CERN-PH number and final journal adde

Measurement of the top quark pair cross section with ATLAS in pp collisions at √s=7 TeV using final states with an electron or a muon and a hadronically decaying τ lepton

A measurement of the cross section of top quark pair production in proton-proton collisions recorded with the ATLAS detector at the Large Hadron Collider at a centre-of-mass energy of 7 TeV is reported. The data sample used corresponds to an integrated luminosity of 2.05 fb -1. Events with an isolated electron or muon and a τ lepton decaying hadronically are used. In addition, a large missing transverse momentum and two or more energetic jets are required. At least one of the jets must be identified as originating from a b quark. The measured cross section, σtt-=186±13(stat.)±20(syst.)±7(lumi.) pb, is in good agreement with the Standard Model prediction