Patient-specific multi-physics simulations have the potential to improve the diagnosis, treatment, and scientific inquiry of heart valve dynamics. It has been shown that the flow characteristics within the left ventricle are important to correctly capture the aortic and mitral valve motion and corresponding fluid dynamics, motivating the use of patient-specific imaging to describe the aortic and mitral valve geometries as well as the motion of the left ventricle (LV). The LV position can be captured at several time points in the cardiac cycle, such that its motion can be prescribed a priori as a Dirichlet boundary condition during a simulation. Valve leaflet motion, however, should be computed from soft-tissue models and incorporated using fully-coupled Fluid Structure Interaction (FSI) algorithms. While FSI simulations have in part or wholly been achieved by multiple groups, to date, no high-throughput models have been developed, which are needed for use in a clinical environment. This project seeks to enable patient-derived moving LV boundary conditions, and has been developed for use with a previously developed immersed boundary, fixed Cartesian grid FSI framework. One challenge in specifying LV motion from medical images stems from the low temporal resolution available. Typical imaging modalities contain only tens of images during the cardiac cycle to describe the change in position of the left ventricle. This temporal resolution is significantly lower than the time resolution needed to capture fluid dynamics of a highly deforming heart valve, and thus an approach to describe intermediate positions of the LV is necessary. Here, we propose a primarily Eulerian means of representing LV displacement. This is a natural extension, since an Eulerian framework is employed in the CFD model to describe the large displacement of the heart valve leaflets. This approach to using Eulerian interface representation is accomplished by applying “morphing” techniques commonly used in the field of computer graphics. For the approach developed in the current work, morphing is adapted to the unique characteristics of a Cartesian grid flow solver which presents challenges of adaptive mesh refinement, narrow band approach, parallel domain decomposition, and the need to supply a local surface velocity to the flow solver that describes both normal and tangential motion. This is accomplished by first generating a skeleton from the Eulerian interface representation, and deforming the skeleton between image frames to determine bulk displacement. After supplying bulk displacement, local displacement is determined using the Eulerian fields. The skeletons are also utilized to automate the simulation setup to track the locations upstream and downstream where the system inflow/outflow boundary conditions are to be applied, which in the current approach, are not limited to Cartesian domain boundaries.

Submitted by Maria Cristina (library@lncc.br) on 2017-05-04T18:59:46Z No. of bitstreams: 1 ThesisBulant-FrenteVerso.pdf: 28359198 bytes, checksum: 3e4d2806f9cb5049e4739c99aaff7bf4 (MD5) / Approved for entry into archive by Maria Cristina (library@lncc.br) on 2017-05-04T18:59:56Z (GMT) No. of bitstreams: 1 ThesisBulant-FrenteVerso.pdf: 28359198 bytes, checksum: 3e4d2806f9cb5049e4739c99aaff7bf4 (MD5) / Made available in DSpace on 2017-05-04T19:00:06Z (GMT). No. of bitstreams: 1 ThesisBulant-FrenteVerso.pdf: 28359198 bytes, checksum: 3e4d2806f9cb5049e4739c99aaff7bf4 (MD5) Previous issue date: 2017-03-06 / Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) / Coronary heart disease is one of the leading causes of death worldwide. Although several risk factors are well known; many lesions cannot be explained by these factors alone. The hypothesis of arteries developing lesions due to its morphology, known as geometric risk factors and/or due to hemodynamic forces, has been raised more than thirty years ago. Although investigators have found connection between geometric/hemodynamic variables and lesions, there exists no quantifiable index that helps physicians to predict actual risks. Even when a severe lesion is present, recent studies have found that some patients can develop collateral circulation to provide sufficient blood flow to the myocardium, thus avoiding ischemia. In turn, the gold standard for functional stenosis assessment is an invasive medical exam called Fractional Flow Reserve (FFR). Moreover, these studies are expensive, require highly qualify professionals and involve risks to the patient during intervention. In this context, the goals of the proposed thesis are (i) to fully characterize coronary arterial trees from a geometrical perspective, search for hereditary geometric features and correlations between morphology and disease; (ii) to construct a modeling methodology for the estimation of FFR making use of computational fluid dynamic models built on top of patient-specific medical images of coronary arterial networks. Results for goal (i) include the geometric characterization of a patient sample consisting of siblings. Several studies involving standard and non-traditional geometry-based indexes, in which associations between geometry and lesion presence was found, as well as indications of arterial geometry heritability between siblings. Regarding hemodynamic simulations in the context of FFR, i.e. goal (ii), a novel technique to define patient-specific boundary conditions in 3D models was presented and tested; the impact of image modality, i.e. coronary computed tomography (CCTA) and intravascular ultrasound (IVUS), on hemodynamics variables was assessed for the first time, which helps to better assess the results obtained from the combination of numerical simulations and medical images. A comparison of 3D and 1D CFD simulations for coronary blood flow based purely on FFR is presented. Several computational settings are compared to invasive measurements with results comparable to the state of the art. / A doença coronáriana é uma das principais causas de morte em todo o mundo. Embora vários fatores de risco sejam bem conhecidos; muitas lesões não podem ser explicadas apenas por esses fatores. A hipótese das artérias desenvolverem lesões devido à sua morfologia, conhecida como fatores de risco geométricos e/ou devido a forças hemodinâmicas, foi levantada há mais de trinta anos. Embora tenha sido encontrada uma conexão entre variáveis geométricas/hemodinâmicas e lesões, não existe um índice quantificável que ajude os médicos a prever os riscos reais. Mesmo quando uma lesão grave está presente, estudos recentes descobriram que alguns pacientes podem desenvolver circulação colateral para fornecer fluxo sanguíneo suficiente para o miocárdio, evitando assim a isquemia. Por sua vez, o padrão ouro para avaliar a funcionalidade de uma lesão é o exame médico invasivo chamado Reserva de Fluxo Fracionada (FFR por suas siglas em inglês). Além disso, esses estudos são caros, exigem profissionais altamente qualificados e envolvem riscos para o paciente durante a intervenção. Nesse contexto, os objetivos desta tese são (i) caracterizar completamente as artérias coronárias de uma perspectiva geométrica, buscar características geométricas hereditárias e correlações entre morfologia e doença; (ii) construir uma metodologia de modelagem para a estimativa do FFR, utilizando modelos da dinâmica dos fluidos computacional (CFD por suas siglas em inglês) construídos a partir de imagens médicas de artérias coronárias de pacientes específicos. Resultados para meta (i) incluem a caracterização geométrica de uma amostra de pacientes constituída por pares de irmãos. Vários estudos são realizados envolvendo índices padronizados e não tradicionais baseados na geometria, nos quais foram encontradas associações entre geometria e presença de lesão, bem como indicações de herdabilidade de geometria arterial entre irmãos. Em relação às simulações hemodinâmicas no contexto de FFR, isto é, meta (ii), é apresentada e testada uma nova técnica para definir condições de contorno específicas para cada paciente em modelos 3D; ainda, foi avaliado pela primeira vez o impacto da modalidade de imagem, em particular, tomografia computadorizada coronária (CCTA) e ultrassom intravascular (IVUS), sobre variáveis hemodinâmicas, o que ajuda a avaliar melhor os resultados obtidos pela combinação de simulações numéricas e imagens médicas. Também é apresentada uma comparação de simulações de CFD empregando modelos 3D e 1D do fluxo sanguíneo coronário focado puramente na estimação do FFR. Vários cenários são comparados com medidas invasivas com resultados similares aos encontrados no estado de arte da técnica.

While computed tomographic angiography (CTA) has emerged as a powerful noninvasive option that allows for direct visualization of arterial stenosis(AS), it cant assess the hemodynamic abnormality caused by an AS. Alternatively, trans-stenotic pressure gradient (TSPG) and fractional flow reserve (FFR) are well-validated hemodynamic indices to assess the ischemic severity of an AS. However, they have significant restriction in practice due to invasiveness and high cost. To fill the gap, a new computational modality, called <i>InVascular</i> has been developed for non-invasive quantification TSPG and/or FFR based on patient's CTA, aiming to quantify the hemodynamic abnormality of the stenosis and help to assess the therapeutic/surgical benefits of treatment for the patient. Such a new capability gives rise to a potential of computation aided diagnostics and therapeutics in a patient-specific environment for ASs, which is expected to contribute to precision planning for cardiovascular disease treatment. <i>InVascular</i> integrates a computational modeling of diseases arteries based on CTA and Doppler ultrasonography data, with cutting-edge Graphic Processing Unit (GPU) parallel-computing technology. Revolutionary fast computing speed enables noninvasive quantification of TSPG and/or FFR for an AS within a clinic permissible time frame. In this work, we focus on the implementation of inlet and outlet boundary condition (BC) based on physiological image date and and 3-element Windkessel model as well as lumped parameter network in volumetric lattice Boltzmann method. The application study in real human coronary and renal arterial system demonstrates the reliability of the in vivo pressure quantification through the comparisons of pressure waves between noninvasive computational and invasive measurement. In addition, parametrization of worsening renal arterial stenosis (RAS) and coronary arterial stenosis (CAS) characterized by volumetric lumen reduction (S) enables establishing the correlation between TSPG/FFR and S, from which the ischemic severity of the AS (mild, moderate, or severe) can be identified. In this study, we quantify TSPG and/or FFR for five patient cases with visualized stenosis in coronary and renal arteries and compare the non-invasive computational results with invasive measurement through catheterization. The ischemic severity of each AS is predicted. The results of this study demonstrate the reliability and clinical applicability of <i>InVascular</i>.

In this project, the inverse problem of determining regional pressure variations from measured blood velocity data in the contect of a cardiovascular setting has been approached. A common esimator, the pressure poisson estimator (PPE) has been implemented in a non-variational setting and evaluated for clinically relevant synthetic flow cases, over dynamically varying domains, mimicking or directly representing the intra-cardiac space: A synthetic dynamic domain benchmark problem and a patient specific model of the left ventricle. The results obtained show under ideal condition the capability of the approach to tackle complex domains successfully and to obtain regional pressure fields to a high degree of accuracy when compared to a locally provided state of the art estimator, the stokes estimator (STE). Under noise, results obtained suggest that divergence may occur with finer temporal resolution. Spatially convergence in a setting mimicking an image scenario is observed with minor exceptions though to stem from the specific composition of the flow field between discretizations. The implementation at hand avoids common problems in the non-variational approaches of this estimator stemming from domain complexity and leads to a simple application of the pure neumann boundary conditions required to compute the relative pressure field while avoiding the need to estimate boundary normals or use an embedded approach. The resulting linear system has desirable properties such as symmetry and compliance with the discrete compatibility condition by construction. / Syftet med följande projekt har varit att undersöka metoder för uppskattning av regionala tryckvariationer från uppmätta flödeshastigheter, med direkt tillämpning för förbättrad kardiovaskulär diagnostik. Mer specifikt har en tillgänglig gold-standardmetod; Pressure Poisson Estimatorn (PPE); implementerats i en icke-variationell miljö och utvärderats över en samling testfall med ökande komplexitet och med ökande relevans för det kliniska problemet med kardiovaskulär tryckmätning i det dynamiskt varierande hjärtutrymmet: ett syntetiskt referensproblem med varierande dynamisk rörelse, och en patientspecifik modell av vänster kammare. De erhållna resultaten visar att den icke-variationella implementeringen av PPE framgångsrikt kan hantera komplexa domäner och erhålla regionala tryckfält med hög noggrannhet. PPE-metoden påvisar också konkurrenskraftig noggrannhet i jamförelse med alternativa referensmetoder så som den s.k. Stokes-estimators (STE). Resultat visar också på tillfredställande beteende under realistiska signal-till-brus-förhallanden, likväl som spatiotemporell konvergens vid upplösningar som motsvarar vad som kan förväntas vid klinisk bildgivning. I summering visar våra resultat att vår implementering av PPE undviker vanliga problem i alterantiva icke-variationella implementeringar som annars kan uppkomma vid analys av komplexa flödesdomaner, och att en förenklad men likväl korrekt implementering av de rena Neumann-gränsvillkor som krävs för att beräkna det relativa tryckfältet kan uppnås utan behovet av att uppskatta icke-triviala gränsnormaler. Utöver detta påvisar det resulterande linjära systemet även önskvarda egenskaper såsom numerisk symmetri och överenstämmelse med diskreta kompatibilitetsvillkor.