Computational Fluid Dynamic Simulation of Intracranial Aneurysms Analysis of time-dependent changes of hemodynamic parameters - the road the clinical use Hemodynamics are involved in the genesis of intracranial aneurysms and time- dependent changes of their parameters lead to aneurysm growth, stabilization or rupture. Definition of these changes using computational fluid hemodynamics could significantly contribute to the understanding of aneurysmal development and rupture and could enable the routine use of mathematical simulations. In this study, computational fluid dynamics were performed for nine incidental aneurysms. Five aneurysms were monitored throughout time and factors leading to aneurysm rupture were analyzed. In four aneurysms the influence of the hemodynamics on the growth was defined. Major growth occurred in areas of low wall shear stress and oscillatory index. These areas increased in size during growth time. Contrary to this, neck shape remodeling occurred in areas with large wall shear stress and pressure. Throughout the follow-up of ruptured aneurysms, the minimal wall shear stress decreased, and the area of low wall shear stress increased significantly. The results indicate that decreasing values of minimal wall shear stress and increasing values of low wall shear stress area...

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Animal cells are often cultured in stirred tank reactors. Having no cell wall, these animal cells are very sensitive to the fluid mechanical stresses that result from agitation by the impeller and from the rising and bursting of bubbles, which are generated within the culture medium in the stirred tank to supply oxygen by mass transfer to the cells. If excessive, these fluid mechanical stresses can result in damage/death of animal cells. Stress due to the rising and bursting of bubbles can be avoided by using a gas-permeable membrane, in the form of a long coiled tube (with air passing through it) within the stirred tank, instead of air-bubbles to oxygenate the culture medium. Fluid mechanical stress due to impeller agitation can be controlled using appropriate impeller rotational speeds. The aim of this study was to lay the foundations for future work in which a correlation would be developed between cell damage/death and the fluid mechanical stresses that result from impeller agitation and bubbling. Such a correlation could be used to design stirred-tank reactors at any scale and to determine appropriate operating conditions that minimise cell damage/death due to fluid mechanical stresses. Firstly, a validated CFD model of a baffled tank stirred with a Rushton turbine was developed to allow fluid mechanical stresses due to impeller agitation to be estimated. In these simulations, special attention was paid to the turbulence energy dissipation rate, which has been closely linked to cell damage/death in the literature. Different turbulence models, including the k-ε, SST, SSG-RSM and the SAS-SST models, were investigated. All the turbulence models tested predicted the mean axial and tangential velocities reasonably well, but under-predicted the decay of mean radial velocity away from the impeller. The k-ε model predicted poorly the generation and dissipation of turbulence in the vicinity of the impeller. This contrasts with the SST model, which properly predicted the appearance of maxima in the turbulence kinetic energy and turbulence energy dissipation rate just off the impeller blades. Curvature correction improved the SST model by allowing a more accurate prediction of the magnitude and location of these maxima. However, neither the k-ε nor the SST models were able to properly capture the chaotic and three-dimensional nature of the trailing vortices that form downstream of the blades of the impeller. In this sense, the SAS-SST model produced more physical predictions. However,this model has some drawbacks for modelling stirred tanks, such as the large number of modelled revolutions required to obtain good statistical averaging for calculating turbulence quantities. Taking into consideration both accuracy and solution time, the SSG-RSM model was the least satisfactory model tested for predicting turbulent flow in a baffled stirred tank with a Rushton turbine. In the second part of the work, experiments to determine suitable oxygen transfer rates for culturing cells were carried out in a stirred tank oxygenated using either a sparger to bubble air through the culture medium or a gas-permeable membrane. Results showed that the oxygen transfer rates for both methods of oxygenation were always above the minimum oxygen requirements for culturing animal cells commonly produced in industry, although the oxygen transfer rate for air-bubbling was at-least 10 times higher compared with using a gas-permeable membrane. These results pave the way for future experiments, in which animal cells would be cultured in the stirred tank using bubbling and (separately) a gas-permeable membrane for oxygenation so that the effect of rising and bursting bubbles on cell damage/death rates can be quantified. The effect of impeller agitation on cell damage/death would be quantified by using the gas permeable membrane for oxygenation (to remove the detrimental effects of bubbling), and changing the impeller speed to observe the effect of agitation intensity. In the third and final part of this work, the turbulent flow in the stirred tank used in the oxygenation experiments was simulated using CFD. The SST turbulence model with curvature correction was used in these simulations, since it was found to be the most accurate model for predicting turbulence energy dissipation rate in a stirred tank. The predicted local maximum turbulence energy dissipation rate of 8.9x10¹ m2/s3 at a rotational speed of 900 rpm was found to be substantially less than the value of 1.98x10⁵ m2/s3 quoted in the literature as a critical value above which cell damage/death becomes significant. However, the critical value for the turbulence energy dissipation rate quoted in the literature was determined in a single-pass flow device, whereas animal cells in a stirred tank experience frequent exposure to high turbulence energy dissipation rates (in the vicinity of the impeller) due to circulation within the stirred tank and long culture times. Future cell-culturing experiments carried out in the stirred tank of this work would aim to determine a more appropriate critical value for the turbulence energy dissipation rate in a stirred tank, above which cell damage/death becomes a problem.

A case study is considered in which data produced by different techniques have been gathered in various locations within a rock mass in which topography effects are most likely significant. Measurements were performed for the design of a re-powering scheme that includes a new hydraulic conduit and an underground cavern that will primarily be excavated in granite. An integrated approach for extrapolating the results from the various in situ tests to the rock mass volume of interest for the hydroelectric power scheme is presented. This approach includes the development of an equivalent continuum mechanics model. The integration of in situ tests and numerical modelling enables to determine the stress spatial variation which helps ascertain the loading mechanism at the origin of the measured stress field as well as the long-term rheological behavior of the equivalent geomaterial under consideration.

Les développements d'algues benthiques dans les canaux de transport d'eau induisent d'importantes contraintes pour la gestion des canaux de distri bution d'eau. Les nuisances physiques et chimiques associées à ces développements nécessitent des stratégies de gestion alternatives. La thèse étudie des méthodes pour la gestion de ces populations algale basées sur le contrôle hydraulique du système: les chasses hydrauliques. Ces opérations consistent à détacher une partie de la biomasse algale fixée en augmentant les contraintes de cisaillement exercées par le courant sur ces algues fixées au substrat. Leur remise en suspension, entraînant un pic de turbidité, doit également être maîtrisée. L'approche proposée vise à caractériser et modéliser les processus de développement, de détachement et de transport des algues lors de ces chasses hydrauliques. Des suivis expérimentaux de la croissance sont réalisés en mésocosme (à l'échelle de canaux réduits). Les suivis de biomasse permettent de caler un modèle de croissance de la couverture algale intégrant l'effet de l'hydrodynamique et de la s ensibilité des algues aux perturbations hydrodynamiques. Des stratégies de chasses sont ensuite expérimentées sur deux canaux de distribution d'eau en zone méditérannéenne. Un modèle de la dynamique des algues fixées et en dérive en réponse à une chasse hydraulique est ensuite élaboré sur la base de ces expérimentations, et calé sur les nuages de turbidité observés. Finalement, un cadre méthodologique basé sur un modèle linéaire est proposé pour des applications à la gestion en temps réel d'une variable de qualité : la turbidité. Deux approches de contrôle sont présentées : la commande en boucle ouverte et la commande adaptative qui permet de recaler les paramètres inconnus comme la biomasse initiale. / Algae developments in open-channel networks induce strong constraints for the network management. The physical and chemical nuisances linked to these developments require alternative management strategies. The thesis proposes an original method for these algae management based on the hydraulic control of the system using flushing-flows. These flushes consist in detaching a part of the fixed algae by increasing the hydraulic shear stress exerted on the biomass fixed on the substratum. The re-suspension of algae in the water column induces a turbidity peak which also has to be controlled. The proposed approach aims at characterizing and modelling the processes of algae development, detachment and transport during the flushes. Experimental monitoring of the growth phase is conducted in experimental flumes. The biomass samples are used to calibrate a model of algal growth which integrates the hydrodynamic effect and the algae sensitivity in the Med iterranean region. A model of the fixed and drift algae dynamics in response to a flush is then developed and calibrated on the observerd turbidity plumes. Finally, a control framework based on a linear model is proposed for the turbidity control during a flush. An open-loop control is first developed, then an adaptative feedback controller is tested to estimate unknown parameters such as initial biomass.

This thesis reports on investigations carried out to study of the effect of horizontal wall jets on rough, fixed and mobile beds in open channel flow. Experimental tests were carried out, using fixed and mobile sediment beds. Computer simulation models for the flow within the jet and resulting sediment transport were developed and their results analysed in this study. In the experimental phase, tests were carried out with both fixed and mobile sediment beds. The shape of the water surface, numerous point velocity measurements and measurements of the evolving scour hole shape were made. Detailed descriptions of the turbulent flow field over a fixed rough bed and for scour holes at equilibrium were obtained for a range of initial jet conditions. Fully turbulent, multiphase flow was modelled using the Fluent Computational Fluid Dynamics software. This was used to analyze the flow caused by a jet in a rectangle open-channel with a rough bed, and also the flow pattern in a channel with a local scour hole. The volume of fluid (VOF) multiphase method and K- model was used to model the fluid flow in both cases. The model predictions of velocity and shear stress were compared against experimental observations. The experimental data was used to develop new empirical relationships to describe the pattern of boundary shear stress caused by a wall jet over fixed beds and in equilibrium scour holes. These relationships were linked with existing bed-load transport rate models in order to predict the temporal evolution of scour holes. An analytical model describing the relationship between the wall jet flow and the development of a local scour hole shape was reported and its predictions compared with experimental data.

L’incidence des maladies cardiovasculaires d’origine athéromateuse demeure un problème majeur en santé publique et malgré le développement de techniques curatives endovasculaires, la chirurgie demeure nécessaire chez de nombreux patients. Le remplacement vasculaire se fait par une veine autologue qui reste le « gold standard » ou, lorsque les patients n’ont pas le capital vasculaire suffisant, par une prothèse. Actuellement, si les techniques utilisant des prothèses synthétiques sont satisfaisantes pour le remplacement d’artères de gros calibre, celui des artères de petit calibre demeure toujours un défi du fait du caractère thrombogène des biomatériaux utilisés et de leurs mauvaises propriétés mécaniques. Depuis quelques années, le concept d’ingénierie tissulaire a émergé et évolué. Il pourrait permettre de proposer de nouveaux types de substituts vasculaires hybrides et/ou biologiques, grâce en particulier à l’utilisation de cellules souches et de leurs progéniteurs, ouvrant d’intéressantes perspectives dans le domaine de l’ingénierie vasculaire. Le but de ce travail a été d’obtenir de manière fiable et reproductible des cellules à phénotype endothélial mature à partir de progéniteurs endothéliaux issus de moelle osseuse et sang périphérique humains et de définir leurs réponses dans des conditions proches de celles observées dans un vaisseau natif. Des cellules (PDECs : Progenitor Derived Endothelial Cells) ont pu être amplifiées à partir de progéniteurs, elles présentent les marqueurs membranaires classiquement utilisés pour définir des cellules endothéliales matures. Elles sont capables, sur différents revêtements utilisés cliniquement tels le collagène de type I et la colle de fibrine ainsi que sur un revêtement plus expérimental (Multicouches de PolyElectrolytes), de former une monocouche confluente. Ces PDECs résistent à des contraintes mécaniques de cisaillement de type artériel et l’analyse de gènes et protéines impliqués dans la biologie de l’endothélium a montré qu’elles répondent à ces stimulations par l’expression d’un phénotype en lien avec une activité antithrombogène. De plus, les travaux préliminaires réalisés sur ces PDECs cocultivés avec des progéniteurs ostéoblastiques, ouvrent d’intéressantes perspectives concernant leur utilisation dans le cadre de l’ingénierie du tissu osseux vascularisé. / The incidence of atherosclerotic arterial disease is still a major public health problem and despite endovascular surgery therapies, surgical treatment is necessary for many patients. Vascular bypass is performed with an autologous vein which remains the gold standard, or when patients do not have appropriate blood vessels to be used as replacement, with a synthetic prosthesis. Nowadays, synthetic vascular grafts have been successfully used in the treatment of the pathology of large arteries, but the replacement of the smaller sized arteries is still a challenge because synthetic vascular grafts are known to be highly thrombogenic and have poor mechanical properties. Recently, the tissue engineering concept has emerged and advances. It can allow to propose development of new hybrid or biologic vascular substitutes, using stem cells and progenitor cells, holding great promise for vascular tissue engineering. The aim of the present study was to obtain reliably and reproducibly, cells with mature endothelial phenotype from endothelial progenitor cells isolated from human bone marrow and peripheral blood and investigate cell response in conditions similar to those observed in a native vessel. We were able to expand cells (PDECs: Progenitor Derived Endothelial Cells) from progenitors which exhibit markers conventionally used to define mature endothelial cells. They were able, on scaffolds currently used in clinic like collagen type I and fibrin glue or on more experimental scaffold (Polyelectrolytes multilayers films), to form a confluent monolayer. These PDECs are able to withstand arterial shear stress and analysis of genes and proteins implicated in endothelium biology shows that these cells respond to shear stress stimulation with a phenotype connected to an anti-thrombogenic activity. Moreover, preliminary studies using co-cultures of PDECs and osteoblastic progenitors, open interesting perspectives concerning PDECs to be used in the field of vascularized bone tissue engineering.

O presente estudo foi realizado para investigar a relação entre forças hemodinâmicas locais e remodelamento intimal e medial nos segmentos pré-estenose e pós-estenose da parede da aorta abdominal de ratos submetidos à estenose acentuada. Foram utilizados ratos Wistar machos divididos em dois grupos: sham-operado, grupo controle em que a aorta foi apenas manipulada, e grupo estenosado, animais submetidos à cirurgia de estenose da aorta abdominal. As aortas demonstraram duas respostas remodeladoras distintas e diferentes ao estímulo hemodinâmico induzido pela coarctação infra-diafragmática. A primeira é o remodelamento no segmento pré-estenótico hipertensivo com tensão circunferencial da parede aumentada associada com estresse tensional normal, fluxo laminar e tensão de cisalhamento normal. As células endoteliais eram heterogêneas, aumentadas em tamanho e alongadas em direção ao fluxo. Além disso, observou-se conspícuas placas neointimais difusamente distribuídas e espessamento medial. Nossos achados sugerem que a tensão circunferencial da parede aumentada devido a hipertensão tem papel fundamental no remodelamento desse segmento através de efeitos biomecânicos sobre o estresse oxidativo e expressão aumentada de TGF-?. A segunda é o remodelamento no segmento pós-estenótico normotenso com fluxo turbilhonar e baixa tensão de cisalhamento na parede associados a tensão circunferencial da parede e estresse tensional normais. As células endoteliais apresentavam-se semelhantes aos controles, exceto por alterações fenotípicas focais associadas à presença de conspícuas placas neointimais focalmente distribuídas, similares mas muito maiores que as encontradas no segmento pré-estenose. Mais estudos são necessários para se determinar como as forças mecânicas do fluxo turbilhonar e da baixa tensão de cisalhamento na parede são detectadas e traduzidas em sinais bioquímicos para as células e convertidas em alterações fenotípicas patofisiologicamente relevantes. / The present investigation was carried out to evaluate the relationship between local hemodynamic forces and intimal and medial remodeling in the proximal and distal segments of the arterial walls of rats in relation to severe stenosis of the aorta. Male Wistar young rats were divided randomly into: operated group, animals submitted to surgical abdominal aorta stenosis, and sham-operated group, a control group of animals submitted to sham operation to simulate abdominal aorta stenosis. Constricted aortas showed two distinct adaptive remodeling responses to hemodynamic stimuli induced by coarctation. The first is remodeling in the hypertensive prestenotic segment with increased circumferential wall tension associated with normal tensile stress, laminar flow/normal wall shear stress. The remodeling in this segment is characterized by enlarged heterogeneous endothelial cells, elongated in the direction of the blood flow, diffusely distributed neointimal plaques, appearing as discrete bulging toward the vascular lumen, and medial thickening. Our findings suggest that increased circumferential wall tension due to hypertension play a pivotal role in the remodeling of the prestenotic segment through biomechanical effects on oxidative stress and increased TGF-? expression. The second is remodeling in the normotensive poststenotic segment with turbulent flow/low wall shear stress and normal circumferential wall tension and tensile stress. The remodeling in this segment is characterized by groups of endothelial cells with phenotypic alterations and focally distributed neointimal plaques, similar but many of them larger than those found in the prestenotic segments. Further studies are needed to determine how the mechanical forces of turbulent flow/low shear stress are detected and transduced into biochemical signaling by the cells of the artery walls and then converted into pathophysiologic relevant phenotypic changes.

Ischaemic heart disease remains the single leading cause of death throughout the world. Rupture of an advanced atheromatous coronary plaque precipitates the majority of these clinical events, resulting in thrombosis and myocardial infarction. Post-mortem studies have identified thin-cap fibroatheroma (TCFA) as the plaque subtype most prone to rupture with prospective virtual-histology intravascular ultrasound (VH-IVUS) studies linking VH-TCFA to future adverse clinical events. VH-TCFA are however common along the coronary tree with the majority remaining clinically silent, suggesting that factors other than plaque phenotype play an important role in determining rupture and future plaque behaviour. Rupture is thought to occur when the structural stress within the plaque exceeds the material strength of the overlying fibrous cap. Previous histological work has demonstrated that ruptured plaques are associated with higher stress compared to non-ruptured controls, with in vivo VH-IVUS studies linking higher plaque structural stress (PSS) with the presentation of acute coronary syndrome. Wall shear stress (WSS) on the other hand has been implicated in early plaque development and plaque growth suggesting that both PSS and WSS can influence future plaque behaviour. The work presented in this thesis is associated with a number of novel findings. First, it is the only work to demonstrate that in vivo PSS is higher in coronary atherosclerotic plaques with rupture vs. no rupture across a range of plaque subtypes and irrespective of whether analysis of the entire plaque or of regions close to the minimal luminal area is performed. Second, it shows that the pattern and extent of plaque progression and regression defined as an increase and decrease in plaque area, respectively, are associated with specific biomechanical environments at baseline, in the only study that examines the role of both PSS and WSS in this process. More specifically, high PSS is associated with changes consistent with increased vulnerability both in areas of progression and regression. On the other hand, lower WSS at baseline is associated with greater increases in plaque area and burden in areas that progress and with smaller decreases in areas that regress largely due to changes in fibrous tissue. Although the role of WSS in determining future plaque behaviour has been previously examined, this is the first time that this is assessed specifically in areas of progression and regression, particularly important in view of the dynamic nature of atherosclerotic plaques. More importantly, the work presented in this thesis demonstrates that the interplay of these biomechanical forces is associated with specific patterns of plaque progression and regression despite the fact that PSS and WSS are independent of each other. This has never been previously demonstrated and further suggests that incorporation of biomechanical analysis can play role in the identification of plaques that lead to future clinical events. Finally, the ability of PSS to identify plaques that lead to adverse clinical events was assessed through a propensity core matched analysis of the PROSPECT (A Prospective Natural-History Study of Coronary Atherosclerosis) study. The analysis presented here is the largest, most extensive and thus most significant work to ever examine this with results suggesting that incorporation of PSS and associated parameters can improve the capability of VH-IVUS to identify plaques that lead to such events. In summary, the results of this thesis suggest that coronary PSS plays an important role in the pathophysiology of plaque rupture, and that its incorporation in routine plaque assessment may improve our current ability to identifying coronary plaques that lead to future adverse clinical events. The interplay between PSS and WSS may also affect future plaque behaviour and in particular progression and regression. Prospective studies are now required to fully evaluate the role of these biomechanical forces in plaque development, and whether their incorporation in plaque evaluation can be of clinical significance.

Este trabalho apresenta a avaliação das tensões de cisalhamento nas interfaces verticais de paredes de alvenaria interconectadas em casos onde atuam simultaneamente carregamentos verticais e ações horizontais. Os valores obtidos para as máximas tensões de cisalhamento são comparados com as resistências estabelecidas na norma brasileira em vigor, NBR 10837 (ABNT, 1989), e no texto base para sua revisão. Os valores das referidas normas também são confrontados com valores experimentais, avaliando-se criticamente a aplicação dos limites normativos na prática de projetos de edifícios existentes. Adicionalmente, são avaliadas duas formas distintas de modelagem de edifícios de alvenaria estrutural, quando submetidos às ações horizontais. A primeira consiste em uma abordagem simplificada e bastante usual entre projetistas, a associação plana de paredes isoladas. Sua aferição é importante para fornecer ao projetista uma ferramenta que lhe permita obter resultados de maneira rápida e confiável. A segunda forma de modelagem é uma análise de pórtico tridimensional que permite uma análise mais completa das paredes de contraventamento, incluindo os efeitos das deformações por cisalhamento. Com o intuito de avaliar as diferenças observadas entre os dois modelos, foram empregados testes estatísticos, que permitem analisar se eles são estatisticamente iguais a um nível de significância de 5%. Para aquisição dos dados para as análises são feitos estudos de casos com quatro edifícios residenciais usuais, com diferentes arranjos arquitetônicos, variando-se o número de pavimentos em quatro, oito, doze e dezesseis, de modo a se obter maior representatividade dos resultados. Com os resultados obtidos nas avaliações, concluiu-se que os valores adotados como limites de resistência pelo texto base da revisão da NBR 10837 (ABNT, 1989) parecem ser rigorosos para realidade brasileira. Com relação à comparação dos modelos estudados, os testes estatísticos direcionam a uma conclusão importante, que é a de não haver diferença entre eles, para um nível de 5% de significância. / This work presents the evaluation of the shear stress at the vertical interfaces of interconnected masonry walls simultaneously subjected to vertical and horizontal loads. The obtained maximum shear stress values are compared to the shear strengths prescribed by the current Brazilian code, NBR 10837 (ABNT, 1989), and by its review base text. The prescribed values are also confronted with experimental values, critically evaluating the application of the regulatory limits in the practical design of existing buildings. Additionally, two different ways of modeling the structural masonry buildings when submitted by horizontal actions are evaluated. The first one is a simple approach, largely used by designers, that consists in the two dimensional association of isolated walls. Its evaluation is important to provide the designer with a quick and reliable analytical tool. The second way of modeling is a three dimensional frame analysis, which allows a more complete simulation of the shear walls, including the shear strain effects. In order to evaluate the differences between the two models, statistical tests were employed for examining whether they are statistically equal at a significance level of 5%. Case studies were performed taking into account four residential buildings with different architectural arrangements. The number of floors was also varied considering four, eight, twelve and sixteen, in order to obtain more meaningful results. The developed analysis showed that the strength limits prescribed by the review base text of the NBR 10837 (ABNT, 1989) seem to be very much strict according to the Brazilian common practice. Regarding the comparison of the studied analytical models, the statistical tests showed that there is no difference between them at a significance level of 5%.