Recent evidence suggests that cardiac mechanics (e.g. cardiac strains) are better measures of heart function compared to common clinical metrics like ejection fraction. However, commonly-used parameters of cardiac mechanics remain limited to just a few measurements averaged over the whole left ventricle. We hypothesized that recent advances in cardiac magnetic resonance imaging (MRI) could be extended to provide measures of cardiac mechanics throughout the left and right ventricles (LV and RV, respectively). Displacement Encoding with Stimulated Echoes (DENSE) is a cardiac MRI technique that has been validated for measuring LV mechanics at a magnetic field strength of 1.5 T but not at higher field strengths such as 3.0 T. However, it is desirable to perform DENSE at 3.0 T, which would yield a better signal to noise ratio for imaging the thin RV wall. Results in Chapter 2 support the hypothesis that DENSE has similar accuracy at 1.5 and 3.0 T. Compared to standard, clinical cardiac MRI, DENSE requires more expertise to perform and is not as widely used. If accurate mechanics could be measured from standard MRI, the need for DENSE would be reduced. However, results from Chapter 3 support the hypothesis that measured cardiac mechanics from standard MRI do not agree with, and thus cannot be used in place of, measurements from DENSE. Imaging the thin RV wall with its complex contraction pattern requires both three-dimensional (3D) measures of myocardial motion and higher resolution imaging. Results from Chapter 4 support the hypothesis that a lower displacement-encoding frequency can be used to allow for easier processing of 3D DENSE images. Results from Chapter 5 support the hypothesis that images with higher resolution (decreased blurring) can be achieved by using more spiral interleaves during the DENSE image acquisition. Finally, processing DENSE images to yield measures of cardiac mechanics in the LV is relatively simple due to the LV’s mostly cylindrical geometry. Results from Chapter 6 support the hypothesis that a local coordinate system can be adapted to the geometry of the RV to quantify mechanics in an equivalent manner as the LV. In summary, cardiac mechanics can now be quantified throughout the left and right ventricles using DENSE cardiac MRI.

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La compréhension clinique et le traitement des maladies cardiovasculaires est extrêmement complexe. Pour chaque patient, les cardiologues sont confrontés à des difficultés pour déterminer la pathologie, choisir une thérapie ou encore sélectionner les patients susceptibles de bien répondre à un traitement donné. Afin de fournir une aide additionnelle aux cardiologues, de nombreuses équipes de recherche étudient la possibilité de planifier de telles thérapies grâce à des modèles biophysiques du cœur. Ils formulent l'hypothèse que l'on peut combiner les données fonctionnelles et anatomiques afin de créer des modèles cardiaques personnalisés à chaque patient qui auraient le potentiel de prédire les bénéfices des différentes thérapies. Les simulations électromécaniques du cœur sont basées sur des modèles informatiques qui peuvent représenter la géométrie, le mouvement et la propagation d'ondes électriques pendant un cycle cardiaque avec suffisamment de précision. L'intégration d'information anatomique, mécanique et électrophysiologique pour un patient donné est essentielle pour construire ce type de modèle.Dans cette thèse, nous présentons tout d'abord les méthodes de personnalisations géométriques, cinématiques et électrophysiologiques nécessaires à toutes modélisations mécaniques. Nous utilisons ensuite le modèle électromécanique de Bestel-Clément-Sorine qui a déjà prouvé avoir un bon réalisme sans être trop complexe au vu des données disponibles. Nous commençons par détailler la nouvelle implémentation de ce modèle dans une plateforme efficace de simulation médicale ayant l'avantage d'être libre et interactive, puis nous analysons les résultats de la simulation par une étude de sensibilité complète.Dans un deuxième temps, nous étudions la possibilité de personnaliser les paramètres mécaniques de ce modèle à partir d'images médicales (IRM). Pour cela, nous proposons en premier lieu une méthode automatique de calibration qui estime les paramètres mécaniques globaux à partir de courbes de pressions et volumes. Cette technique testée sur 6 volontaires et 2 cas pathologiques nous a permis de faire une étude de spécificité qui consiste à déterminer les paramètres pertinents capables de différencier les cas pathologiques des cas sains.Une fois initialisés à ces valeurs calibrées, les paramètres sont personnalisés localement avec un algorithme d'optimisation plus complexe. Le « Reduced Order Unscented Kalman Filtering » est utilisé pour estimer les contractilités de toutes les zones AHA du ventricule gauche à partir des volumes régionaux extraits des séquences d'images IRM. Cette stratégie de personnalisation a été validée et testée sur plusieurs cas pathologiques et volontaires. Ces différentes contributions ont montré des résultats prometteurs tout au long de cette thèse et certains sont déjà utilisés pour quelques études de recherche. / The clinical understanding and treatment of cardiovascular diseases is highly complex. For each patient, cardiologists face issues in determining the pathology, choosing a therapy or selecting suitable patients for the therapy. In order to provide additional guidance to cardiologists, many research groups are investigating the possibility to plan such therapies based on biophysical models of the heart. The hypothesis is that one may combine anatomical and functional data to build patient-specific cardiac models that could have the potential to predict the benefits of different therapies. Cardiac electromechanical simulations are based on computational models that can represent the heart geometry, motion and electrophysiology patterns during a cardiac cycle with sufficient accuracy. Integration of anatomical, mechanical and electrophysiological information for a given subject is essential to build such models.In this thesis, we first introduce the geometry, kinematics and electrophysiology personalizations that are necessary inputs to mechanical modeling. We propose to use the Bestel-Cl'ement-Sorine electromechanical model of the heart, which is sufficiently accurate without being over-parametrized for the available data. We start by presenting a new implementation of this model in an efficient opensource framework for interactive medical simulation and we analyze the resulting simulations through a complete sensitivity analysis.In a second step, the goal is to personalize the mechanical parameters from medical images (MRI data). To this end, we first propose an automatic calibration algorithm that estimates global mechanical parameters from volume and pressure curves. This technique was tested on 7 volunteers and 2 heart failure cases and allowed to perform a preliminary specificity study that intends to determine the relevant parameters able to differentiate the pathological cases from the control cases.Once initialized with the calibrated values, the parameters are then locally personalized with a more complex optimization algorithm. Reduced Order Unscented Kalman Filtering is used to estimate the contractilities on all of the AHA zones of the Left Ventricle, matching the regional volumes extracted from cine MRI data. This personalization strategy was validated and tested on several pathological and healthy cases. These contributions have led to promising results through this thesis and some are already used for various research studies.

Cardiac magnetic resonance (MR) imaging can non-invasively assess heart function. Displacement encoding with stimulated echoes (DENSE) is an advanced cardiac MR imaging technique that measures tissue displacement and can be used to quantify cardiac mechanics (e.g. strain and torsion). When combined with clinical risk factors, cardiac mechanics have been shown to be better predictors of mortality than traditional measures of heart function. End-expiratory breath-holds are typically used to minimize respiratory motion artifacts. Unfortunately, requiring subjects to breath-hold introduces limitations with the duration of image acquisition and quality of data acquired, especially in patients with limited ability to hold their breath. Thus, DENSE acquisitions often require respiratory navigator gating, which works by measuring the diaphragm during normal breathing and only acquiring data when the diaphragm is within a pre-defined acceptance window. Unfortunately, navigator gating results in long scan durations due to inconsistent breathing patterns. Also, the navigator echo can be used in different ways to accept or reject image data, which creates several navigator configuration options. Each respiratory navigator configuration has distinct advantages and disadvantages that directly affect scan duration and image quality, which can affect derived cardiac mechanics. Scan duration and image quality need to be optimized to improve the clinical utility of DENSE. Thus, the goal of this project was to optimize those parameters. To accomplish this goal, we set out to complete 3 aims: 1) understand how respiratory gating affects the reproducibility of measures of cardiac mechanics, 2) determine the optimal respiratory navigator configuration, and 3) reduce scan duration by developing and using an interactive videogame to optimize navigator efficiency. Aim 1 of this project demonstrated that the variability in torsion, but not strain, could be significantly reduced through the use of a respiratory navigator compared to traditional breath-holds. Aim 2 demonstrated that, among the configuration options, the dual-navigator configuration resulted in the best image quality compared to the reference standard (traditional breath-holds), but also resulted in the longest scan duration. In Aim 3, we developed an interactive breathing-controlled videogame and demonstrated that its use during cardiac MR can significantly reduce scan duration compared to traditional free-breathing and also led to a small improvement in signal-to-noise ratio of the acquired images. In summary, respiratory navigator gating with DENSE 1) reduces the variability in measured LV torsion, 2) results in the best image quality with the dual-navigator configuration, and 3) results in significantly shorter scan durations through the use of an interactive videogame. Selecting the optimal navigator configuration and using an interactive videogame can improve the clinical utility of DENSE.

This thesis presents a finite element methodology for simulating fluid–solid interactions in the left ventricle (LV) under LVAD support. The developed model was utilised to study the passive and active characteristics of ventricular function in anatomically accurate LV geometries constructed from normal and patient image data. A non–conforming ALE Navier–Stokes/finite–elasticity fluid–solid coupling system formed the core of the numerical scheme, onto which several novel numerical additions were made. These included a fictitious domain (FD) Lagrange multiplier method to capture the interactions between immersed rigid bodies and encasing elastic solids (required for the LVAD cannula), as well as modifications to the Newton–Raphson/line search algorithm (which provided a 2 to 10 fold reduction in simulation time). Additional developments involved methods for extending the model to ventricular simulations. This required the creation of coupling methods, for both fluid and solid problems, to enable the integration of a lumped parameter representation of the systemic and pulmonary circulatory networks; the implementation and tuning of models of passive and active myocardial behaviour; as well as the testing of appropriate element types for coupling non–conforming fluid– solid finite element models under high interface tractions (finding that curvilinear spatial interpolations of the fluid geometry perform best). The behaviour of the resulting numerical scheme was investigated in a series of canonical test problems and found to be convergent and stable. The FD convergence studies also found that discontinuous pressure elements were better at capturing pressure gradients across FD boundaries. The ventricular simulations focused firstly on studying the passive diastolic behaviour of the LV both with and without LVAD support. Substantially different vortical flow features were observed when LVAD outflow was included. Additionally, a study of LVAD cannula lengths, using a particle tracking algorithm to determine recirculation rates of blood within the LV, found that shorter cannulas improved the recirculation of blood from the LV apex. Incorporating myocardial contraction, the model was extended to simulate the full cardiac cycle, converging on a repeating pressure–volume loop over 2 heart beats. Studies on the normal LV geometry found that LVAD implementation restricts the recirculation of early diastolic inflow, and that fluid–solid coupled models introduce greater heterogeneity of myocardial work than was observed in equivalent solid only models. A patient study was undertaken using a myocardial geometry constructed using image data from an LVAD implant recipient. A series of different LVAD flow regimes were tested. It was found that the opening of the aortic valve had a homogenising effect on the spatial variation of work, indicating that the synchronisation of LVAD outflow with the cardiac cycle is more important if the valve remains shut. Additionally, increasing LVAD outflow during systole and decreasing it during diastole led to improved mixing of blood in the ventricular cavity – compared with either the inverse, or holding outflow constant. Validation of these findings has the potential to impact the treatment protocols of LVAD patients.

Submitted by Renata Lopes (renatasil82@gmail.com) on 2017-05-15T14:59:59Z No. of bitstreams: 1 marcoshenriquefonsecaribeiro.pdf: 12873424 bytes, checksum: 2b2b91fd2a9726856a0486afa760fe2c (MD5) / Approved for entry into archive by Adriana Oliveira (adriana.oliveira@ufjf.edu.br) on 2017-05-17T16:01:12Z (GMT) No. of bitstreams: 1 marcoshenriquefonsecaribeiro.pdf: 12873424 bytes, checksum: 2b2b91fd2a9726856a0486afa760fe2c (MD5) / Made available in DSpace on 2017-05-17T16:01:12Z (GMT). No. of bitstreams: 1 marcoshenriquefonsecaribeiro.pdf: 12873424 bytes, checksum: 2b2b91fd2a9726856a0486afa760fe2c (MD5) Previous issue date: 2016-10-03 / A Tomografia por Impedância Elétrica (TIE) consiste em uma técnica onde imagens são construídas a partir da injeção de uma corrente elétrica em determinado meios, seguida da leitura de valores de potencial elétrico em pontos do contorno externo de tal domínio. Desta maneira, conhecendo-se ou estimando-se a condutividade elétrica de regiões internas ao meio, pode-se inferir aspectos geométricos da composição do mesmo. Trabalhos na literatura aplicam esta técnica ao contexto de obtenção de imagens do tórax humano, com objetivo de estimar a geometria das cavidades cardíacas de um determinado paciente. O objetivo final de estudo deste trabalho, dentro do contexto de aplicação da TIE à obtenção de cavidades cardíacas, é propor uma metodologia para a estimação da Fração de Ejeção Cardíaca, ou simplesmente Fração de Ejeção (FE), que consiste em medir o percentual de volume de sangue expulso dos ventrículos ao final de um ciclo de batimento do coração. Este trabalho visa evoluir outros trabalhos já existentes que modelam o problema acima descrito como sendo um problema inverso, de otimização, onde se pretende minimizar a diferença entre valores de potencial elétrico medidos e valores simulados por modelos computacionais. A evolução se dá em níveis diferentes. No primeiro nível, é feito um avanço sobre as técnicas de otimização para a resolução do problema inverso, em sua formulaçãobidimensional. Paratal, épropostaumametaheurísticaqueauxiliamétodosde buscanaobtençãodevaloresmaisacurados. Estametaheurísticaéapresentadaemversões sequencial e paralela. São apresentados resultados computacionais de testes realizados para este primeiro nível. Em um segundo nível, é feita a modelagem em três dimensões das mesmas abordagens já encontradas na literatura, que, para a aplicação específica da determinação da FE, até então estão limitadas a modelos bidimensionais. Assim, todo o problema é revisto para uma nova proposta de modelagem, que inclui a criação de modelos geométricos tridimensionais para as regiões de interesse do problema. Como principal contribuição do trabalho neste segundo nível, encontra-se um esquema de parametrização das malhas de polígonos que modelam ventrículos do coração, de forma que se tenha uma maneira compacta de representar as mesmas e, ao mesmo tempo, diminuindo o custo computacional do método de otimização por meio de drástica redução do número de variáveis do problema. Por fim, também é realizado um estudo preliminar da sensibilidade da técnica à presença de ruídos nos dados de entrada. / The Electrical Impedance Tomography (EIT) consists in a technique where images are constructed from the measurements of the electrical potential in some points on the external boundary of some specific domain, caused by the injection of an electrical current in such domain. This way, knowing or estimating the electrical conductivity of some regions inside the domain, geometric aspects of the composition of that domain can be inferred. Works in literature apply this technique to the context of obtaining images from the human thorax, with the objective of estimating the geometry of some cardiac cavities of a specific patient. The final goal of this work, inside the context of the obtention of cardiac cavities, is to propose a methodology for estimating the Cardiac Ejection Fraction, orsimplyEjectionFraction(EF),whichconsistsinmeasuringthepercentualofthevolume of blood expelled from the ventricles at the end of a heart beat cicle. This work intends to evolute previous works, that models the above mentioned problem as an inverse problem, an optimization problem, where the intention is to minimize the difference between the values of measured electrical potentials and the values obtained through simulation using computational models. This evolution occurs in different levels. In the first level, is performedanimprovementoverthepre-existentoptimizationtechniquesforthesolutionof theinverseproblem,inatwodimensionalversion. Forthis,isproposedametaheuristicthat assistssearchmethodstowardstheobtentionofmoreaccuratedvalues. Suchmetaheuristic is presented in sequential and parallel versions. Computational results for performed tests for this level are presented. In a second level, a three dimensional modeling of the same approaches found in literature is done. Those approaches, for the specific application of determining the EF, are so far limited to two dimensional models. Therefore, the whole problem is reviewed in order to propose a new model, which includes the creation of three dimensional geometric models for the regions of interest of the problem. As the main contribution of this work in that second level, there is a parameterization schema of the polygon meshes that model heart ventricles, so that it provides a compact way of representing such meshes, and, at the same time, a way of reducing the computational cost of the optimization method by means of a drastic reduction of the number of variables of the problem. Finally, a preliminary study of the sensibility of the technique to the presence of noise in the input data is also performed.