Diseases of the aorta rank as the 20th leading cause of mortality in the US, contributing to 10,000 deaths annually. Thoracic aortic aneurysms are typically asymptomatic, often undetected until life-threatening aortic dissection or rupture occurs. Familial cases constitute one in five instances of thoracic aortic aneurysm and dissection (TAAD), with genetic causes being heterogeneous and known risk genes explaining only a small fraction of cases. We hypothesized that additional TAAD risk genes remain undiscovered. This thesis aims to investigate the genetic etiology of TAAD using genetic and genomic approaches. Our methodological approach included: 1) exome sequencing of DNA from TAAD patients with subsequent genomic analysis, integrating clinical data, and 2) single-cell RNA sequencing (scRNA-seq) of the developing (embryonic) mouse aorta. We sequenced 1650 DNA samples from 1429 TAAD patients and, after quality control, analyzed genomic data from 1278 unrelated TAAD patients of European ancestry. For controls, we used 145,103 unrelated individuals of European ancestry from the UK BioBank. We conducted a per-gene and per-domain burden analysis using a binomial test. To improve the power of detection of novel risk genes, we integrated case-control association of rare damaging variants with cell-type specific gene expression data from scRNA-seq of the ascending and descending aorta of 17 mouse embryos (harvested at the E15 stage) with the hypothesis that true risk genes are highly expressed early in development. Our analysis of known TAAD risk genes identified 52 pathogenic or likely pathogenic variants, explaining 4.1% of TAAD cases, and 75 variants of uncertain significance (5.9%). Next, two potential novel candidate genes emerged from the unbiased case-control analysis, which utilized AlphaFold domain-based annotation of protein structure: β-propeller domain of VPS8 (p = 8.8 × 10-9) and UTP11 (p = 3.9 × 10-8). scRNA-seq of the developing mouse aorta revealed significant cell-type-specific expression differences between the ascending and descending aorta, identifying five subtypes of vascular smooth muscle cells in the ascending aorta and four in the descending aorta. Differentially expressed genes between major aortic cell types were also identified. Both, VPS8 and UTP11 were found to expressed in all three major aortic cell types – vascular smooth muscle cells, fibroblasts, and endothelial cells. In conclusion, our case-control association analysis identified two promising candidate risk genes for TAAD (VPS8 and UTP11), warranting further investigation and confirmation in additional cohorts of patients with aortopathy.

An estimated 85% of haemorrhagic strokes are secondary to the rupture of an intracranial aneurysm (IA), a localised, blood-filled dilation of the artery wall. The clinically observed rupture of occluded IAs has led to hypothesise that the presence of thrombus may restrict the transport of nutrients, most notably oxygen, to the aneurysmal wall, thus heightening the risk of rupture through the deleterious effects of hypoxia on cellular functionality. The limited research into O2 transport within IAs demonstrate the need for further exploration into the possible detrimental hypoxic conditions as a result of intrasaccular haemodynamics and thrombusformation in untreated, treated and evolving IAs, with the ultimate goal of further understanding disease evolution and developing prognostic decision support models for clinical intervention. Preliminary computational fluid dynamic simulations conducted on a 2Daxisymmetric model of a thrombosed artery highlighted the relative importance of wall-side versus the fluid-side mass transport of oxygen. A sensitivity analysis demonstrated that variations in thrombus thickness, and arterial wall cellular respiration rates have the greatest influence on the oxygen distribution to the portion of wall in direct contact with the thrombus. The results of the coupled flow-mass transport computational fluid dynamic simulations within patient-specific IA show that a reduction in intrasaccular flow as a consequence of stent deployment affects the rate at which oxygenated blood reaches the entirety of the dome. Nonetheless, the distribution ofO2 to the aneurysmal wall itself does not differ from the observed oxygen distribution across the wall when the same IA is left untreated. Conversely, the low velocity recirculations observed in an IA presenting with a very high aspect ratio (i.e a narrow neck and high sack height) limited the transport of oxygen to such an extent as to completely deprive the delivery of oxygen to the fundus. The presence of thrombus within the IA dome results in a dramatic reduction in oxygen delivery to the wall, the extent of which is dependent on the local thrombus thickness. Finally, a novel fluid-solid-growth-mass transport (FSGT) mathematical model is conceived to explore the biochemical role of thrombus on the evolution of an IA. The shear-regulate propagation of a thrombus layer during membrane expansion leads to the gradual decrease in oxygen tension within the wall. Moreover, as a consequence of coupling this oxygen deficiency to fibroblast functionality, the collagen fibre mass density was shown to increase at an insufficient rate to compensate for the transfer in load from the degrading elastinous consitituents to the collagenous constituents, thus resulting in the increased stretch of collagen fibres in order to maintain mechanical equilibrium. Moreover this over-expansion results in the gradual unstable evolution of the IA. The observed obstruction to oxygen delivery as a result of intrasaccular haemodynamics and thrombosis compounds the need for further development of more comprehensive chemo-mechano-biological models of IAs so as to better ascertain the level of rupture risk posed by a hypoxic environment. Refinement to the models proposed within this work would prove invaluable to creating a fully integrated multi-physics, multi-scale in silico framework in aid to patient diagnostics and individual treatment planning of IAs.

Orientador: José Luiz Gasche / Resumo: Aneurismas são anormalidades formadas em algumas partes do sistema vascular humano e se caracterizam por regiões dilatadas e finas da parede arterial. Um dos tipos mais comuns ocorre no interior das artérias que chegam ao cérebro, no chamado círculo de Willis. Estes casos de aneurismas intracranianos são extremamente perigosos, pois em caso de rompimento podem ocasionar hemorragia cerebral, com consequente morte ou presença de sequelas permanentes no paciente. As causas dos aneurismas vêm sendo investigadas há tempos, e os pesquisadores concordam que os fenômenos hemodinâmicos têm papel fundamental na formação, crescimento e ruptura do aneurisma cerebral. Entretanto, os procedimentos experimentais para se conhecer melhor as características do escoamento de sangue no interior do aneurisma ainda são de difícil realização. A partir do desenvolvimento de técnicas de mapeamento do sistema vascular cerebral, pôde-se obter a geometria de aneurismas de modo que métodos numéricos na solução de problemas de escoamento passaram a ser utilizados. A partir de então, diversas pesquisas vêm sendo feitas visando a investigação da influência das variáveis biológicas e hemodinâmicas na ruptura do aneurisma. Entretanto, apenas recentemente foi dado foco na influência da interação fluido-estrutura que existe neste problema, devido a flexibilidade da parede da artéria. Assim, usando geometrias de aneurismas específicos de pacientes, simulamos o escoamento sanguíneo utilizando o pacote open-source... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Aneurysms are abnormalities formed in some regions of the human vascular system and are characterized by dilated and thin regions of the arterial wall. One of the most common types occurs inside the brain arteries in the so-called circle of Willis. These intracranial aneurysms are extremely dangerous, because in case of rupture they can cause sub-arachnoid hemorrhage, with consequent death or presence of permanent damage to the patient. Causes of aneurysms have been investigated for a long time, and researchers agree that hemodynamic effects play a key role in the formation, growth, and rupture of brain aneurysms. However, the experimental procedures to better understand the characteristics of blood flow within the aneurysm are still difficult to perform. With the development of scanning techniques of the cerebral vascular system, it has been possible to obtain the geometry of aneurysms and then with that numerical methods for the solution of blood flow have begun to be used. Since then, several researchers have been investigating the influence of biological and hemodynamic variables on aneurysms rupture. However, it has been only in the last decade that the influence of fluid-structure interaction, due to the flexibility of the artery wall, on those variables has been investigated. In this context and using patient-specific aneurysm geometries, we simulated the blood flow using the opensource library foam-extend, which uses a partitioned methodology to numerically solve the ... (Complete abstract click electronic access below) / Résumé: Les anévrismes sont des anomalies formées sur certaines régions du système vasculaire humain et sont caractérisés par des régions dilatées de la paroi artérielle, avec une petite épaisseur. L’un des types les plus communs se produit à l’intérieur des artères de la base du cerveau, dans le cercle de Willis. Ces cas d’anévrismes intracrâniens sont extrêmement dangereux car ils peuvent provoquer une hémorragie sous-arachnoïdienne en cas de rupture, avec la mort ou la présence d’un dommage définitif pour le patient. Les causes d’anévrismes sont étudiées depuis longtemps et des recherches reconnaissent que les effets hémodynamiques jouent un rôle clé dans la formation, la croissance, et la rupture des anévrismes intracrâniens. Cependant, les procédures expérimentales pour mieux comprendre les caractéristiques de l’écoulement du sang dans l’anévrisme sont encore difficiles à réaliser. Avec le développement de techniques des images du système vasculaire cérébral, il a été possible d’obtenir la géométrie des anévrismes, donc des méthodes numériques ont commencé à être utilisées pour la solution de l’écoulement dans les anévrismes, et alors plusieurs recherches ont étudié l’influence des variables biologiques et hémodynamiques sur la rupture de l’anévrisme. Cependant, ce n’est que dans la dernière décennie que l’influence de l’interaction fluide-structure, due à la flexibilité de la paroi de l’artère, sur ces variables a été étudiée. Dans ce contexte et à l’aide de géométries d’anévri... (Résumé complet accès életronique ci-dessous) / Mestre

Orientador: José Luiz Gasche / Resumo: Originalmente, stents foram projetados para agir como barreiras mecânicas, impedindo a herniação de coils para a artéria-mãe. Recentemente, estudos mostraram que a atual geração de stents intracranianos auto-expansíveis altera a geometria local das artérias: um fenômeno com efeitos hemodinâmicos em parte incompreendidos. Nós realizamos simulações numéricas para avaliar a influência da remodelagem arterial induzida por stent sobre a hemodinâmica em aneurismas intracranianos. As simulações foram realizadas utilizando o software open-source OpenFOAM. O sangue foi modelado como fluido Newtoniano incompressível e as paredes arteriais foram consideradas rígidas. Para quantificar as alterações hemodinâmicas, avaliamos os parâmetros wall shear stress, WSS, e oscillatory shear index, OSI. Quatro geometrias reais de aneurismas intracranianos em bifurcações foram utilizadas. Em um aneurisma na bifurcação da artéria comunicante anterior (ACoA), um stent foi implantando, levando ao endireitamento das artérias que o receberam. Após o procedimento, os níveis de WSS e OSI aumentaram aproximadamente 60% e 25%, respectivamente. Em dois aneurismas em bifurcações da artéria cerebral média (MCA), dois stents foram implantados em uma configuração em “Y”, resultando em um endireitamento de ambas as artérias-filhas. O WSS máximo na superfície do aneurisma aumentou aproximadamente 5% em um dos casos e 22% no outro. Em outro aneurisma em uma bifurcação da MCA, um stent foi implantado, resultando no en... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Stents were first designed to act as mechanical barriers, preventing coil herniation into the parent artery. The current generation of self-expanding intracranial stents has recently been shown to change the local vascular geometry, a phenomenon with unclear hemodynamic effects. We carried out numerical simulations to assess the role of stent-induced vascular remodeling in modifying intraaneurysmal hemodynamics. Simulations were performed using the open-source software OpenFOAM. Blood was assumed to behave as an incompressible Newtonian fluid; vessel walls were assumed to be rigid. Wall shear stress, WSS, and oscillatory shear index, OSI, were evaluated to quantify the hemodynamic changes in the aneurysm sac. Four pre- and post-stent patient-specific geometries of intracranial bifurcation aneurysm were used. In one aneurysm at the anterior communicating artery (ACoA) bifurcation, a single stent was deployed, resulting in straightening of the host vessels. After stenting, WSS and OSI increased by approximately 60% and 25%, respectively. In two aneurysms at middle cerebral artery (MCA) bifurcations, two stents in a “Y” configuration were deployed, resulting in straightening of both daughter arteries. The maximum WSS on the aneurysm surface increased by approximately 5% in one case and 22% in the other. In another aneurysm at a bifurcation of the MCA, a single stent was deployed, resulting in straightening of the host vessels. After stenting, WSS and OSI reduced by approximately... (Complete abstract click electronic access below) / Mestre

Submitted by Iago Lessa de Oliveira null (iago.42lessa@gmail.com) on 2017-08-30T17:33:54Z No. of bitstreams: 1 Master_Dissertation_iago_lessa_de_oliveira.pdf: 29141101 bytes, checksum: ffe8861f2f133bd987d688271ac0ef4b (MD5) / Approved for entry into archive by Luiz Galeffi (luizgaleffi@gmail.com) on 2017-08-30T18:14:48Z (GMT) No. of bitstreams: 1 oliveira_il_me_ilha.pdf: 29141101 bytes, checksum: ffe8861f2f133bd987d688271ac0ef4b (MD5) / Made available in DSpace on 2017-08-30T18:14:48Z (GMT). No. of bitstreams: 1 oliveira_il_me_ilha.pdf: 29141101 bytes, checksum: ffe8861f2f133bd987d688271ac0ef4b (MD5) Previous issue date: 2017-08-24 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Les anévrismes sont des anomalies formées sur certaines régions du système vasculaire humain et sont caractérisés par des régions dilatées de la paroi artérielle, avec une petite épaisseur. L’un des types les plus communs se produit à l’intérieur des artères de la base du cerveau, dans le cercle de Willis. Ces cas d’anévrismes intracrâniens sont extrêmement dangereux car ils peuvent provoquer une hémorragie sous-arachnoïdienne en cas de rupture, avec la mort ou la présence d’un dommage définitif pour le patient. Les causes d’anévrismes sont étudiées depuis longtemps et des recherches reconnaissent que les effets hémodynamiques jouent un rôle clé dans la formation, la croissance, et la rupture des anévrismes intracrâniens. Cependant, les procédures expérimentales pour mieux comprendre les caractéristiques de l’écoulement du sang dans l’anévrisme sont encore difficiles à réaliser. Avec le développement de techniques des images du système vasculaire cérébral, il a été possible d’obtenir la géométrie des anévrismes, donc des méthodes numériques ont commencé à être utilisées pour la solution de l’écoulement dans les anévrismes, et alors plusieurs recherches ont étudié l’influence des variables biologiques et hémodynamiques sur la rupture de l’anévrisme. Cependant, ce n’est que dans la dernière décennie que l’influence de l’interaction fluide-structure, due à la flexibilité de la paroi de l’artère, sur ces variables a été étudiée. Dans ce contexte et à l’aide de géométries d’anévrismes spécifiques des patients, des simulations numériques ont été effectuées avec le logiciel open-source foam-extend, qui utilise une méthodologie partitionnée pour résoudre numériquement le problème d’interaction fluide-structure. En comparant les paramètres qui peuvent conduire à la rupture – tels que le cisaillement sur la paroi et l’indice d’oscillation du cisaillement – entre les résultats des simulations avec l’hypothèse de la paroi rigide et élastique, nous avons évalué l’influence de la flexibilité de la paroi de l’anévrisme sur ces paramètres, en concluant que cette flexibilité change les valeurs de ces paramètres, donc l’option de traitement peut changer si le médecin les utilise pour décider de traiter le patient. / Aneurismas são anormalidades formadas em algumas partes do sistema vascular humano e se caracterizam por regiões dilatadas e finas da parede arterial. Um dos tipos mais comuns ocorre no interior das artérias que chegam ao cérebro, no chamado círculo de Willis. Estes casos de aneurismas intracranianos são extremamente perigosos, pois em caso de rompimento podem ocasionar hemorragia cerebral, com consequente morte ou presença de sequelas permanentes no paciente. As causas dos aneurismas vêm sendo investigadas há tempos, e os pesquisadores concordam que os fenômenos hemodinâmicos têm papel fundamental na formação, crescimento e ruptura do aneurisma cerebral. Entretanto, os procedimentos experimentais para se conhecer melhor as características do escoamento de sangue no interior do aneurisma ainda são de difícil realização. A partir do desenvolvimento de técnicas de mapeamento do sistema vascular cerebral, pôde-se obter a geometria de aneurismas de modo que métodos numéricos na solução de problemas de escoamento passaram a ser utilizados. A partir de então, diversas pesquisas vêm sendo feitas visando a investigação da influência das variáveis biológicas e hemodinâmicas na ruptura do aneurisma. Entretanto, apenas recentemente foi dado foco na influência da interação fluido-estrutura que existe neste problema, devido a flexibilidade da parede da artéria. Assim, usando geometrias de aneurismas específicos de pacientes, simulamos o escoamento sanguíneo utilizando o pacote open-source foam-extend, que possui uma metodologia particionada implementada para resolver numericamente o problema de interação fluido-estrutura. Através de comparação dos parâmetros que podem levar a ruptura -- tensão de cisalhamento na parede e índice de oscilação do cisalhamento -- entre os resultados das simulações considerando as hipóteses de parede rígida e flexível, avaliamos a influência da flexibilidade da parede em tais parâmetros, concluindo que tal flexibilidade tem influência nos parâmetros que podem levar à ruptura do aneurisma a ponto de alterar a decisão de tratamento, caso ela fosse feita baseada em tais parâmetros. / Aneurysms are abnormalities formed in some regions of the human vascular system and are characterized by dilated and thin regions of the arterial wall. One of the most common types occurs inside the brain arteries in the so-called circle of Willis. These intracranial aneurysms are extremely dangerous, because in case of rupture they can cause sub-arachnoid hemorrhage, with consequent death or presence of permanent damage to the patient. Causes of aneurysms have been investigated for a long time, and researchers agree that hemodynamic effects play a key role in the formation, growth, and rupture of brain aneurysms. However, the experimental procedures to better understand the characteristics of blood flow within the aneurysm are still difficult to perform. With the development of scanning techniques of the cerebral vascular system, it has been possible to obtain the geometry of aneurysms and then with that numerical methods for the solution of blood flow have begun to be used. Since then, several researchers have been investigating the influence of biological and hemodynamic variables on aneurysms rupture. However, it has been only in the last decade that the influence of fluid-structure interaction, due to the flexibility of the artery wall, on those variables has been investigated. In this context and using patient-specific aneurysm geometries, we simulated the blood flow using the opensource library foam-extend, which uses a partitioned methodology to numerically solve the fluid-structure interaction problem. By comparing the parameters that can lead to rupture – wall shear stress and oscillatory shear index – between the results of the simulations considering the rigid and flexible walls hypotheses, we evaluated the influence of wall flexibility on such parameters, concluding that the flexibility influences the parameters that can lead to rupture, changing the decision of treatment if made using those parameters.

Approximately 7000 rare disorders exist, affecting 2 percent of Canadians and millions of people worldwide. Given that for many rare diseases only one allele is mutated, we hypothesize inducing expression of the remaining wild-type allele may have a therapeutic effect. SMAD3 heterozygosity results in Aneurysms-Osteoarthritis Syndrome (AOS) – an aortic aneurysm disorder also known as Loeys-Dietz Syndrome Type 3. We conducted a screen of FDA-approved compounds and found that 13-cis-retinoic acid (13-CRA) induces SMAD3 in normal human fibroblast cultures. Treatment with therapeutic concentrations of 13-CRA increased SMAD3 mRNA in normal human fibroblasts, patient fibroblasts, wild-type murine vascular smooth muscle cells and Smad3+/- murine vascular smooth muscle cells. Increases in SMAD3 protein were also observed in normal human fibroblasts, patient fibroblasts, and wild-type murine vascular smooth muscle cells. Immunofluorescent imaging revealed the primary site of protein induction to be nuclear. We report here the in vitro induction of SMAD3 mRNA and protein by therapeutic levels of 13-CRA and suggest further investigation of this modality for the treatment of AOS.

<p>An abdominal aortic aneurysm (AAA), defined as a pathological expansion of the largest artery in the abdomen, is a relatively common disease that frequently leads to death if rupture occurs. Once diagnosed, clinicians often evaluate the rupture risk based on the maximum diameter of the aneurysm, a limited metric that is not accurate for all patients. In this study, we worked to provide additional distinguishing factors between growing and stable AAAs to aid in clinical rupture risk assessment. We utilized a relatively new murine model that uses surgical application of topical elastase to cause initial aortic expansion, and a lysyl oxidase inhibitor, β-aminopropionitrile (BAPN), in the drinking water to promote AAA growth. We further sought to develop and demonstrate applications of advanced imaging approaches, including four-dimensional ultrasound (4DUS), to obtain and evaluate alternative geometric and biomechanical parameters between 1) growing AAAs, 2) stable AAAs, and 3) non-aneurysmal control mice. Our study confirmed the reproducibility of the model and found reduced strain values, greater tortuosity, and decreased elastin health in mice with aneurysms. We also found expanding murine AAAs to have increased peak wall stress and surface area per length compared to stable aneurysms. The results from this work help provide a better understanding of the growth patterns associated with elastase-BAPN murine aneurysms and demonstrate the capabilities of high-frequency ultrasound. Eventually these data could help lay the groundwork for improving insight into clinical prediction of AAA expansion.</p>

Les anévrysmes de l'aorte abdominale (AAAs) sont des dilatations artérielles qui exposent le patient au décès par rupture. Ils sont caractérisés notamment par la perte de la monocouche de cellules endothéliales et son remplacement par un épais thrombus mural. Cependant, le lienentre l'accroissement du diamètre anévrysmal, la présence d'un thrombus et la perte en cellules endothéliales reste inexploré. Notre hypothèse est que la perte de l'endothélium contribue au développement des AAAs et que sa restauration par thérapie cellulaire permettrait de stabiliser les AAAs. In vivo, la réparation endothéliale implique le recrutement des cellules endothéliales adjacentes mais également des cellules progénitrices endothéliales (EPCs). Chez l'homme, le nombre et l’activité fonctionnelle des EPCs sont inversement corrélés aux facteurs de risque cardiovasculaire, et très peu de données sont disponibles sur l’activité fonctionnelle des EPCs issues de patients porteurs d'AAA. La présence du thrombus pourrait ainsi diminuer le nombre et les propriétés cicatricielles des EPCs issues de patients porteurs d'AAA. / Summary not transmitted

Les perspectives d'évolution des techniques chirurgicales sont de plus en plus demandeuses de modèles permettant de prédire déplacements et contraintes au sein des tissus. De tels modèles permettent par exemple de mieux focaliser un traitement sur une zone de tissu affectée par une pathologie. L'un des principaux obstacles posés par la plupart des modèles existants adaptés à la description du comportement mécanique des tissus vivants concerne la difficulté de mesure de leurs paramètres. Il en résulte une difficulté à les déterminer, ainsi qu'à comprendre leur influence. L'adoption d'une modélisation multiéchelles permet d'apporter une réponse satisfaisante à ce problème. En effet, elle autorise la prise en compte et lacombinaison de phénomènes simples qui ont lieu à différentes échelles, et fait ainsi intervenir des paramètres physiques et mesurables. Dans l'étude proposée, nous nous focalisons sur le comportement mécanique des parois des veines en pont, qui peuvent parvenir à rupture lors d'un choc appliqué à la tête. Nous proposons pour commencer des observations par microscopie optique, microtomographie X et microscopie confocale biphotonique visant à caractériser la structure de la paroi vasculaire à différentes échelles. Un essai mécanique est combiné à l'une des observations. Nous proposons ensuite une nouvelle modélisation multiéchelles du comportement mécanique de cette paroi vasculaire. Cette modélisation combine des modèles simples à trois échelles et reproduit ainsi le comportement mécanique global de la paroi vasculaire. Pour finir, le modèle est intégré à une modélisation par éléments finis afin de permettre l'étude de géométries complexes. / Modeling the mechanical behavior of living tissues gets nowadays more and more importance. Indeed, mechanical models can be integrated within assisted surgery devices to help for example the surgeon to better focus on an area affected by pathology.One of the main drawbacks of existing numerical models for the mechanical behavior of living tissues concerns the difficulty to measure their parameters, which makes their determination difficult. Adopting a multiscale modeling approach seems to be an answer to this issue. It allows taking into account the global complexity of the behavior by considering simple phenomena that occur at each scale. By this way, the parameters of the model deal with physical characteristics and remain measurable.In the present study, we focus on the mechanical behavior of bridging vein walls. These veins can break when the head is submitted to a shock loading. We start by some experimental observations using optical microscopy, X-ray microtomography and multiphoton confocal microscopy. These observations allow getting a detailed knowledge about the vein wall constitution. Additionally a mechanical tensile test is combined with one of these observations. Then we propose a new multiscale approach for the description of the mechanical behavior of vessel walls. It combines simple models associated with three scales and describes in this way the overall mechanical behavior of the vein wall. The evolution of the material structure at different scales is taken into account and contributes to the global hyperelastic mechanical behavior of the tissue. Finally, our model is implemented in a finite element code in order to study complex geometries.

Made available in DSpace on 2015-03-04T18:57:36Z (GMT). No. of bitstreams: 1 bulant.pdf: 14030619 bytes, checksum: 7bdeb54a02eeadbb90a53496f04a524c (MD5) Previous issue date: 2013-02-26 / This work focuses on tomographic reconstruction and three-dimensional arterial structures segmentation problems, understanding both as fundamentals modules of patient specific-based cardiovascular modeling. Is in this context where the possibility of improving information quality contained in medical images, by means of more accurate reconstruction methods, is of interest because of its impact on segmentation algorithm precision, allowing the construction of more realistic vessel geometrical models. Specifically, in this work, we study the reconstruction from projection inverse problem based on the classic simplified model for x-ray interaction, using the Radon transform, in two and three dimensions with different acquisition geometries. Then, we present the standard methods, which are based on analytic inversion of the Radon transform in the form of back-projection. An iterative reconstruction method based on sensitivity analysis, was studied and adapted to work in a parallel and matrix-free form. In addition, a novel reconstruction method, with foundations given by the theoretical framework of variational formulations, is developed. In view of the characteristics of the methodology, the computational implementation is carried out following a distributed computing paradigm on top of a matrix-free form version of the method. We perform parameter sensitivity analysis for each method, and a quantitative comparative analysis among them, using the well known Shepp-Logan head phantom, is also presented. Some preliminary reconstruction studies with real data are presented. In the context of medical image segmentation, we explore two alternatives for arterial structures segmentation from three dimension images acquired on three-Dimensional Rotational Angiography and Computed Tomography Angiography clinical studies. The first methodology is based on a simple seeded region growing algorithm, combined with thresholding and anisotropic diffusion techniques. The second pipeline uses a Level Set approach, initialized with the colliding fronts algorithm. Now days, Level Set methods variants are gaining popularity for vessel segmentation problems. In this work, we present a qualitative comparison by segmenting a numerical phantom, as well as segmenting arterial structures on different anatomical regions of the head and neck. At last, we present some recommendations for method and parameter choosing, as a function of the anatomical region. / Este trabalho foca-se nos problemas da reconstrução tomográfica e da segmentação de estruturas arteriais em três dimensões, entendendo ambos como blocos fundamentais na modelagem do sistema cardiovascular humano orientada a pacientes específicos. Dentro deste contexto, a possibilidade de melhorar a qualidade das informações contidas nas imagens médicas realizadas em estudos clínicos via métodos de reconstrução mais precisos torna-se atraente porque impacta diretamente na acurácia das técnicas de segmentação, e permite a construção de modelos geométricos mais próximos à realidade. Especificamente, neste trabalho, o problema inverso de reconstrução a partir de projeções é estudado empregando o modelo simplificado clássico, via a transformada de Radon, para duas e três dimensões com diferentes geometrias de amostragem. Logo, os métodos de resolução padrão baseados na inversão analítica desta transformada em forma de back-projection foram estudados. Um método iterativo baseado em análise de sensibilidade, denominado aqui como método baseado no gradiente topológico, foi estudado e adaptado para funcionar com um esquema matrix-free em paralelo. Em seguida, um novo método com fundamentos na teoria de formulações variacionais é desenvolvido. Devido às características do método, o mesmo é implementado computacionalmente empregando paralelismo e um formato matrix-free. Um estudo quantitativo sobre os parâmetros de cada método é fornecido, assim como também um estudo comparativo entre todos eles usando o amplamente difundido fantasma de Shepp-Logan. Por fim, estudos preliminares com projeções de estudos de angiografias rotacionais tridimensionais são apresentados. No contexto da segmentação de imagens médicas, duas alternativas são apresentadas para segmentar estruturas arteriais a partir de imagens tridimensionais provenientes de estudos de angiografia rotacional e tomográfica. A primeira metodologia baseia-se num enfoque simples de crescimento de região, combinado com thresholding e suavizado anisotrópico. A segunda metodologia utiliza um enfoque de Level Set, inicializado por uma técnica denominada colliding fronts. Na atualidade diversas variantes do método de Level Set têm ganhado popularidade na segmentação de estruturas arteriais. Neste trabalho comparam-se qualitativamente ambas alternativas com um fantasma numérico, e na segmentação de estruturas arteriais presentes em imagens médicas localizadas em diversas regiões anatômicas. Por fim, recomendações sobre o método mais conveniente a ser utilizado em cada região junto com valores para os parâmetros são fornecidos.