Дисертації з теми "Hemodynamic Simulations"

This thesis addresses the solution of the steady and unsteady incompressible Navier-Stokes (INS) equations employing finite element discretizations based on Galerkin variational formulations. The goal is the simulation of blood flow (hemodynamics) in realistic geometries reconstructed in-vivo. Advection-dominated incompressible flows, occurring at physiologic conditions in large arteries, constitute a challenging class of problems both in terms of numerical stability and computational cost. In the context of unsteady incompressible fluid flow simulations a new formulation based on the pressure-correction algorithm featuring discontinuous velocity and continuous pressure a is proposed and validated with numerical experiments. In this configuration we are able exploit the ability of dG to deal with convection-dominated flows maintaining a less expensive Galerkin discretization for the pressure projection step and, therefore, obtaining an effective solution process. The ability to simulate the blood flow behaviour in complex geometries reconstructed in-vivo employing high-order finite element discretizations has been demonstrated. In this context, discontinuous Galerkin (dG) methods offer many advantages: LBB stable equal-order discretizations can be devised, the extension to arbitrary unstructured and nonconforming grids is straightforward, and the resulting discretization displays an increased stability in the high Reynolds regimes. Flexibility, however, comes at a price. In particular, memory requirements as well as the increased computational cost have discouraged wide adoption of these methods up to now. In this thesis we consider effective strategies to overcome these limitations and make available to CFD practioners the flexibility and the good properties previously described. Coupled variables dG discretization of the INS equations are combined with efficient pseudo-transient continuation methods in order to exploit fully implicit discretizations of the non-linear term in the achievement of steady state solutions. Trivial implementation of hp-adaptivity on non-conforming meshes is one of the most attractive and documented dG formulations pros. The benefits of future based adaptive mesh refinement are investigated on simple two-dimensional test cases.

Cette thèse se concentre sur une pathologie spécifique affectant la section abdominale de l'aorte, connue sous le nom d'anévrisme de l'aorte abdominale (AAA). Un anévrisme implique un affaiblissement persistant et localisé de la paroi du vaisseau, entraînant des élargissements et des renflements, provoquant une recirculation et une turbulence du flux sanguin.Notre thèse expose une méthodologie pour la modélisation géométrique des anévrismes abdominaux. Le processus comprend l'acquisition d'images de scanners CT, la reconstruction de la géométrie 3D de l'aorte et l'isolation de l'anévrisme. La phase de modélisation commence par l'identification et l'approximation de la ligne médiane du vaisseau aortique à l'aide de fonctions B-spline. La paroi aortique est ensuite partitionnée et profilée à l'aide de séries de Fourier.Pour évaluer son efficacité, la technique développée est appliquée à un ensemble de données de scanners CT de patients. Les reconstructions obtenues à partir des scans sont également présentées comme des exemples détaillant chaque étape de la procédure. De plus, une évaluation quantitative et la logique derrière les paramètres de modélisation sont expliquées. Ensuite, en tant que première application, la modélisation est intégrée à un processus de registration pour le diagnostic clinique et le suivi.La procédure de modélisation géométrique développée est utilisée dans un pipeline pour des simulations hémodynamiques et une évaluation des risques, en utilisant une approche de modélisation d'ordre réduit pour construire un espace de solution. Des simulations, utilisant des géométries paramétrées, sont réalisées dans des conditions réalistes, et des indicateurs de risque sont calculés et liés à la représentation géométrique à l'aide d'une fonction interpolante à base radiale. Enfin, des prédictions sur les indicateurs de risque sont obtenues pour une géométrie inconnue. Les résultats, bien que prometteurs, pourront être améliorés en augmentant de manière appropriée l'ensemble de données initial.Pour remédier à la pénurie mentionnée de données cliniques, nous avons élaboré un flux de travail automatisé pour générer des géométries synthétiques. Cette approche permet l'identification de paramètres géométriques pertinents et implique l'apprentissage automatique pour générer une population virtuelle de patients cohérente avec les données d'origine. En plus d'améliorer la capacité prédictive des modèles réduits, la méthode peut également être appliquée de manière prospective pour des essais in silico et des études impliquant des populations virtuelles de patients
This thesis focuses on a specific pathology affecting the abdominal section of the aorta, known as abdominal aortic aneurysm (AAA). An aneurysm involves a persistent and localized weakening of the vessel wall, leading to enlargements and bulges, causing recirculation and turbulence of blood flow.Our thesis outlines a methodology for geometric modeling of abdominal aneurysms. The process involves acquiring CT images, reconstructing the aorta 3D geometry, and isolating the aneurysm. The modeling phase begins by identifying and approximating the centerline of the aortic vessel using B-spline functions. The aortic wall is then partitioned and profiled using Fourier series.To evaluate its effectiveness, the developed technique is applied to a dataset of CT scans from patients. Reconstructions obtained from the scans are also presented as examples to detail each step of the procedure. In addition, a quantitative evaluation and rationale behind modeling parameters are explained. Then, as a first application, the modeling is integrated into a registration process for clinical diagnosis and follow-up.The geometrical modeling procedure developed is used in a pipeline for hemodynamic simulations and risk assessment, employing a reduced-order modeling approach to construct a reduced solution space. Simulations, utilizing parameterized geometries, are conducted under realistic conditions, and risk indicators are computed and linked to the geometrical representation using Radial Basis Functions interpolant. Finally, predictions on risk indicators are obtained for an unknown geometry. The results, despite being promising, can be further improved by appropriately augmenting the initial dataset.To address the aforementioned scarcity of clinical data, we devised an automated workflow for generating synthetic geometries. This approach allows for the identification of relevant geometry parameters and involves machine learning to generate a virtual patient population consistent with the original data. In addition to improving the predictive capability of reduced models, the method can also be applied prospectively for in-silico trials and studies involving virtual patient populations

La structure de l’oeil permet d’observer la microcirculation, grâce aux caméras de fond d’oeil. Ces appareils sont bon marché et couramment utilisés dans la pratique clinique, permettant le dépistage de maladies oculaires. La capacité des vaisseaux à adapter leur diamètre (autorégulation) afin de réguler le débit sanguin est importante dans la microcirculation. L’hémodynamique de l’oeil est impactée par la pression à l’intérieur du globe oculaire (IOP), qui est à son tour influencée par le flux sanguin oculaire. Les altérations de l’autorégulation et l’IOP jouent un rôle dans les maladies oculaires. La modélisation mathématique peut aider à interpréter l’interaction entre ces phénomènes et à mieux exploiter les données médicales disponibles. Dans la première partie, nous présentons un modèle simplifié d’interaction fluidestructure qui inclut l’autorégulation, appliqué à un reseau 3D obtenu par imagerie médicale. Les cellules musculaires lisses regulant le diamètre du vaisseau sont modélisés dans la structure. Ensuite, nous utilisons des équations de poroélasticité pour décrire le flux sanguin dans la choroïde, dans un modèle multi-compartiments de l’oeil. Cette approche permet de rendre compte de la transmission de la pulsatilité de la choroïde à la chambre antérieure, où l’IOP est mesurée. Nous présentons des résultats préliminaires sur la choroïde, l’humeur aqueuse et sur la choroïde couplée avec la vitrée. Enfin, nous présentons un modèle d’ordre réduit pour accélérer des simulations multi-physique. Des modèles de haute précision sont utilisés pour les compartiments d’intérêt et une représentation réduite de l’opérateur de Steklov-Poincaré est utilisée pour les autres compartiments
The structure of the eye offers a unique opportunity to directly observe the microcirculation, by means, for instance, of fundus camera, which are cheap devices commonly used in the clinical practice. This can facilitate the screening of systemic deseases such as diabetes and hypertension, or eye diseases such as glaucoma. A key phenomenon in the microcirculation is the autoregulation, which is the ability of certain vessels to adapt their diameter to regulate the blood flow rate in response to changes in the systemic pressure or metabolic needs. Impairments in autoregulation are strongly correlated with pathological states. The hemodynamics in the eye is influenced by the intraocular pressure (IOP), the pressure inside the eye globe, which is in turn influenced by the ocular blood flow. The interest in the IOP stems from the fact that it plays a role in several eye-diseases, such as glaucoma. Mathematical modelling can help in interpreting the interplay between these phenomena and better exploit the available data. In the first part of the thesis we present a simplified fluid-structure interaction model that includes autoregulation. A layer of fibers in the vessel wall models the smooth muscle cells that regulate the diameter of the vessel. The model is applied to a 3D image-based network of retinal arterioles. In the second part, we propose a multi-compartments model of the eye. We use the equations of poroelasticity to model the blood flow in the choroid. The model includes other compartments that transmit the pulsatility from the choroid to the anterior chamber, where the measurements of the IOP are actually performed. We present some preliminary results on the choroid, the aqueous humor and on the choroid coupled with the vitreous. Finally, we present a reduced order modelling technique to speed up multiphysics simulations. We use high fidelity models for the compartments of particular interest from the modelling point of view. The other compartments are instead replaced by a reduced representation of the corresponding Steklov-Poincaré operator

L’ablation partielle du foie est une chirurgie qui intervient dans le traitement des lésions du foie et lors d’une transplantation partielle de foie. Les relations entre l’hémodynamique du foie, son volume et ses fonctions restent à élucider pour mieux comprendre les causes des complications de ces chirurgies. Lors de la chirurgie, l’hémodynamique du foie est altérée suite à l’augmentation de la résistance au flux sanguin de l’organe. La régénération du foie semble dépendante des changements de débit et de pression dans la veine porte. D’autre part, comme le foie reçoit 25% du débit cardiaque, la chirurgie impacte la circulation sanguine globale. Dans ce contexte, le premier objectif est de mieux comprendre, grâce à des modèles mathématiques, l’influence de l’hépatectomie sur l’hémodynamique. Le second objectif est l’analyse de la perfusion et de la fonction du foie. Premièrement, la procédure chirurgicale, les conditions expérimentales ainsi que les mesures obtenues sont détaillées. Ensuite, les valeurs moyennes mesurées lors de douze chirurgies sont reproduites par un modèle de circulation entière, basé sur des équations différentielles ordinaires. Lors des différentes hépatectomies, des changements de forme de courbe sont observés. Un modèle de circulation entière, basée sur des équations 1D et 0D est proposé pour analyser ces changements. Ce travail pourrait permettre une meilleure compréhension des changements d’architecture du foie induits par l’hépatectomie. Puis, le transport dans le sang d’un composé ainsi que son traitement par le foie sont modélisés. Un modèle pharmacocinétique est développé et grâce aux mesures, les paramètres du modèle sont estimés
Major liver resection is being performed to treat liver lesions or for adult-to-adult living donor liver transplantation. Complications of these surgeries are related to a poor liver function. The links between liver hemodynamics, liver volume and liver function remain unclear and are important to better understand these complications. The surgery increases the resistance to blood flow in the organ, therefore it modifies liver hemodynamics. Large modifications of the portal vein hemodynamics have been associated with poor liver regeneration. Moreover the liver receives 25% of the cardiac outflow, therefore liver surgery may impact the whole blood circulation. In this context, the first goal is to investigate with mathematical models the impact of liver surgery on liver hemodynamics. The second goal is to study the liver perfusion and function with mathematical models. The first part describes the experimental conditions and reports the measurements recorded. Then, the second part focuses on the liver hemodynamics during partial hepatectomy. On one hand, the hemodynamics during several surgeries is quantitatively reproduced and explained by a closed-loop model based on ODE. On the other hand, the change of waveforms observed after different levels of liver resection is reproduced with a model of the global circulation, including 0D and 1D equations. This may contribute to a better understanding of the change of liver architecture induced by hepatectomy. Next, the transport in blood of a compound is studied. And a pharmacokinetics model and its parameter identification are developed to quantitatively analyze indocyanine green fluorescence dynamics in the liver tissue

Les simulations numériques des écoulements sanguins cardiovasculaires peuvent combler d’importantes lacunes dans les capacités actuelles de traitement clinique. En effet, elles offrent des moyens non invasifs pour quantifier l’hémodynamique dans le cœur et les principaux vaisseaux sanguins chez les patients atteints de maladies cardiovasculaires. Ainsi, elles permettent de recouvrer les caractéristiques des écoulements sanguins qui ne peuvent pas être obtenues directement à partir de l’imagerie médicale. Dans ce sens, des simulations personnalisées utilisant des informations propres aux patients aideraient à une prévision individualisée des risques. Nous pourrions en effet, disposer des informations clés sur la progression éventuelle d’une maladie ou détecter de possibles anomalies physiologiques. Les modèles numériques peuvent fournir également des moyens pour concevoir et tester de nouveaux dispositifs médicaux et peuvent être utilisés comme outils prédictifs pour la planification de traitement chirurgical personnalisé. Ils aideront ainsi à la prise de décision clinique. Cependant, une difficulté dans cette approche est que, pour être fiables, les simulations prédictives spécifiques aux patients nécessitent une assimilation efficace de leurs données médicales. Ceci nécessite la solution d’un problème hémodynamique inverse, où les paramètres du modèle sont incertains et sont estimés à l’aide des techniques d’assimilation de données.Dans cette thèse, le problème inverse pour l’estimation des paramètres est résolu par une méthode d’assimilation de données basée sur un filtre de Kalman d’ensemble (EnKF). Connaissant les incertitudes sur les mesures, un tel filtre permet la quantification des incertitudes liées aux paramètres estimés. Un algorithme d’estimation de paramètres, basé sur un filtre de Kalman d’ensemble, est proposé dans cette thèse pour des calculs hémodynamiques spécifiques à un patient, dans un réseau artériel schématique et à partir de mesures cliniques incertaines. La méthodologie est validée à travers plusieurs scenarii in silico utilisant des données synthétiques. La performance de l’algorithme d’estimation de paramètres est également évaluée sur des données expérimentales pour plusieurs réseaux artériels et dans un cas provenant d’un banc d’essai in vitro et des données cliniques réelles d’un volontaire (cas spécifique du patient). Le but principal de cette thèse est l’analyse hémodynamique spécifique du patient dans le polygone de Willis, appelé aussi cercle artériel du cerveau. Les propriétés hémodynamiques communes, comme celles de la paroi artérielle (module de Young, épaisseur de la paroi et coefficient viscoélastique), et les paramètres des conditions aux limites (coefficients de réflexion et paramètres du modèle de Windkessel) sont estimés. Il est également démontré qu’un modèle appelé compartiment d’ordre réduit (ou modèle dimension zéro) permet une estimation simple et fiable des caractéristiques du flux sanguin dans le polygone de Willis. De plus, il est ressorti que les simulations avec les paramètres estimés capturent les formes attendues pour les ondes de pression et de débit aux emplacements prescrits par le clinicien
Cardiovascular blood flow simulations can fill several critical gaps in current clinical capabilities. They offer non-invasive ways to quantify hemodynamics in the heart and major blood vessels for patients with cardiovascular diseases, that cannot be directly obtained from medical imaging. Patient-specific simulations (incorporating data unique to the individual) enable individualised risk prediction, provide key insights into disease progression and/or abnormal physiologic detection. They also provide means to systematically design and test new medical devices, and are used as predictive tools to surgical and personalize treatment planning and, thus aid in clinical decision-making. Patient-specific predictive simulations require effective assimilation of medical data for reliable simulated predictions. This is usually achieved by the solution of an inverse hemodynamic problem, where uncertain model parameters are estimated using the techniques for merging data and numerical models known as data assimilation methods.In this thesis, the inverse problem is solved through a data assimilation method using an ensemble Kalman filter (EnKF) for parameter estimation. By using an ensemble Kalman filter, the solution also comes with a quantification of the uncertainties for the estimated parameters. An ensemble Kalman filter-based parameter estimation algorithm is proposed for patient-specific hemodynamic computations in a schematic arterial network from uncertain clinical measurements. Several in silico scenarii (using synthetic data) are considered to investigate the efficiency of the parameter estimation algorithm using EnKF. The usefulness of the parameter estimation algorithm is also assessed using experimental data from an in vitro test rig and actual real clinical data from a volunteer (patient-specific case). The proposed algorithm is evaluated on arterial networks which include single arteries, cases of bifurcation, a simple human arterial network and a complex arterial network including the circle of Willis.The ultimate aim is to perform patient-specific hemodynamic analysis in the network of the circle of Willis. Common hemodynamic properties (parameters), like arterial wall properties (Young’s modulus, wall thickness, and viscoelastic coefficient) and terminal boundary parameters (reflection coefficient and Windkessel model parameters) are estimated as the solution to an inverse problem using time series pressure values and blood flow rate as measurements. It is also demonstrated that a proper reduced order zero-dimensional compartment model can lead to a simple and reliable estimation of blood flow features in the circle of Willis. The simulations with the estimated parameters capture target pressure or flow rate waveforms at given specific locations

Proper functioning of brain critically depends on cerebral blood inflow and outflow. Moreover, the venous contribution in auto-regulation function and maintaining pressure and blood flow balance in body organs such as brain has been highlighted. Auto-regulating mechanism and cerebral circulation are influenced by many biophysical factors such as aging, posture and gravitational pressure change, and vessel stenosis. Therefore, it is important to gain a satisfactory understanding of physiological and biomechanical properties of the venous system and the interaction between intra- and extracranial compartments under different physiological conditions. For what concerns congenital vascular disease is one of the known leading causes of death in paediatric age. Despite the importance of paediatric haemodynamics, large investigations have been devoted to the evaluation of circulation in adults. The novelties of this study consist in the development of a well calibrated mathematical model of cardiovascular circulation in paediatric subjects as well as adults, simulating the full range posture change effects on hemodynamic physiology from head down tilt to supine and upright, predicting the flow rate change in main neck arteries and veins in microgravity environment, and the IJV asymmetric stenosis (followed by head rotation) effects on the head and neck hemodynamic alteration. The model consists of two parts that simulates the arterial (1D) and brain and venous (0D) vascular tree. The cardiovascular system is built as a network of hydraulic resistances and capacitances to properly model physiological parameters like total peripheral resistance, and to calculate vascular pressure and the related flow rate at any branch of the tree. This dissertation presents the results of the scientific work developed in collaboration with the paediatric hospital of Sant Joan de Déu ,Spain. A data set was provided including information about human vessels network anatomy, blood rheology (blood velocity and flow), vessel status, venous biomechanics factors (inner pressure and wall shear stress) and also volunteers characteristics (age, respiratory rate, bloop pressure and clinical reason of their MRI scan). The model presented here was tuned by using two different MRI datasets. We benefited from the use of 2D and 4D PC-MRI techniques. Results show that the model is able to reproduce the physiological behavior of IJVs and other collateral veins, with average values in good agreement with experimental data of supine paediatric and adult subjects. Physiological age-related parameters were used to adjust left ventricle pressure pulse and cerebral blood flow for paediatrics. Every simulated data fell inside the standard error from the corresponding average experimental value. The model outcomes indicated about 88% correlation with MRI data. Concerning the head rotation effects simulation, the conductance of left IJV was decreased to model the imposed stenosis influenced by torsion-compression force. MR image acquisition and numerical simulation were performed in two situations: the neutral and 80 degree left head rotation. Flow rate and wall shear stress analysis within IJVs demonstrated a strong interindividual dependency. Concerning the posture change and microgravity study, the model in line with literature confirmed the role of peripheral veins in regional blood redistribution during posture change from supine to upright and microgravity environment as hypothesized in literature. Therefore, model outcomes are in excellent agreement with experimental average flows and literature. The methods presented can be used to predict the response of the hemodynamic system in many other physiological and pathological conditions in both paediatric and adult cases. It also provides a virtual laboratory to examine the consequence of a wide range of orthostatic stresses on haemodynamics.

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Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ)
This thesis is concerned with two major problems arising in the modeling of the cardiovascular system. The first topic consists in a comprehensive approach for the simulation of arterial blood flow and its effect on the stress state of the arterial wall, and the second topic is concerned with the in-vivo characterization of residual deformations in arterial wall tissues, based on data provided by medical images. Specifically, regarding the first topic, an original modeling framework is proposed for the treatment of hemodynamic problems with increased realism, featuring a combination of several modeling techniques in order to account for i) the fact that the initial (image-based) geometry corresponds to a configuration which is at equilibrium with an internal pressure acting over the lumen, and with tethering forces located at the artificial (axial) boundaries delimiting the arterial region of interest; ii) the fluid-structure interaction problem; iii) the complex constitutive behavior of the arterial wall; iv) the influence of surrounding tissues; v) the interaction of the vessel with the rest of the cardiovascular system; and iv) the influence of residual stresses. In order to tackle the issues described above, the preload mechanical problem is solved in a first stage, finding the zero-load material configuration which is employed to define suitable constitutive equations. This is performed by finding the solution for the mechanical equilibrium of the given image configuration considering the vessel at this state to be loaded by an internal baseline pressure and an axial traction (caused by tethering forces) at the artificial boundaries. It is worthwhile to mention that this axial traction is such that a previously defined pre-stretch level is considered on the equilibrium image configuration. Once the reference configuration is obtained, the complete 3D fluid-structure interaction simulation is carried out, coupled with a dimensionally reduced 1D model of the rest of the cardiovascular system. Strong coupling via fixed-point iterations is achieved for the fluid-structure interaction, while the dimensionally heterogeneous coupling is achieved through a Broyden method. Regarding the constitutive modeling, a fiber-reinforced hyperelastic constitutive law is considered. Furthermore, through the analysis of several numerical examples, the sensitivity with respect to the existence of the preload stresses is assessed to quantify the importance of this issue. These results indicate that the stress state of the arterial wall is strongly influenced by the existence of preload. Therefore, the consideration of such preload state is mandatory for the prediction of stresses in arterial tissue. For the second topic, a conceptual framework is presented for the in-vivo estimation of residual deformations and stresses. As a given data, a set of known configurations for an arterial segment is considered, which can potentially be obtained from medical imaging techniques. The mechanical equilibrium equations corresponding to such configurations are introduced through a variational approach, highlighting the role of the residual deformations and associated stresses. In this context, a cost functional is proposed to measure the imbalance of the mechanical setting arising from the consideration of inconsistent residual deformations, based on the generalized residuals of the associated variational equations. Then, the characterization of residual deformations becomes an optimization problem, focused on the minimization of this cost functional. For this purpose, a simple gradient descent method and an interior-point algorithm for constrained optimization are explored in this work. The proposed methodology is tested using three numerical examples based on manufactured solutions, a simple clamped bar, a thick-walled cylinder and a three-layered aorta artery. The obtained results are promising and suggest that the present method (or variants based on the present ideas), when coupled with adequate image acquisition techniques, could successfully lead to the in-vivo identification of residual deformations.
Esta tese aborda dois problemas de relevância na modelagem do sistema cardiovascular humano. O primeiro tema consiste no desenvolvimento de um enfoque abrangente para a simulação do escoamento sanguíneo e sua interação com a parede arterial, e o segundo tópico é a caracterização in-vivo de tensões e deformações residuais na parede arterial baseada em dados fornecidos por imagens médicas. De maneira específica, em relação ao primeiro tópico, um marco de modelagem é proposto para o tratamento de problemas hemodinâmicos com um alto grau de realismo, apresentando uma combinação de diferentes técnicas de modelagem para levar em conta i) o fato que as geometrias iniciais obtidas a partir de imagens médicas são correspondentes a um sistema de carregamentos não nulos, definido pela existência da pressão interna no lumen e de tensões axiais localizadas nos contornos artificiais do segmento arterial; ii) o problema de interação fluido-estrutura; iii) o complexo comportamento constitutivo da parede arterial; iv) a interação do segmento de interesse com o resto do sistema cardiovascular; e v) a influência dos tecidos circundantes; e vi) a existência de tensões residuais. Para a abordagem das questões descritas acima, o problema mecânico de precarregamento é resolvido em uma primeira etapa, encontrando a configuração material de carregamento nulo onde as equações constitutivas são usualmente definidas. Isto é realizado encontrando a solução do problema de equilíbrio mecânico da estrutura arterial dada, considerando que o vaso está submetido a um nível de pressão de base e uma tração axial nos contornos artificiais. Vale a pena ressaltar que esta tração axial é correspondente a um nível de pre-estiramento previamente definido. Uma vez que a configuração de referência é obtida, a simulação fluido-estrutura 3D é realizada, acoplada com um modelo dimensionalmente reduzido do resto do sistema cardiovascular. Um acoplamento forte através de iterações de ponto fixo é empregado para representar a interação fluido-estrutura, equanto o acoplamento entre modelos dimensionalmente heterogêneos é conseguido usando um método tipo Broyden. Em relação à modelagem constitutiva, um modelo hyperelástico reforçado com fibras é considerado. Além disso, através da análise de vários exemplos numéricos, a sensibilidade com relação à existência de precarregamentos é quantificada para remarcar a relevância desta questão. Tais resultados indicam que o estado de tensão da parede arterial é fortemente influenciado pela existência de precarregamentos. Assim sendo, levar em consideração esse estado de precarga é fundamental para a predição de tensões no tecido arterial. Em relação ao segundo tópico, um marco conceptual é apresentado para estimação de tensões e deformações residuais. Consideramos que os dados são um conjunto de configurações de um segmento arterial, as quais poderiam ser obtidas a partir do uso de técnicas de adquisição e , processamento e segmentação de imagens. Utilizando um enfoque variacional, são apresentadas as equações de equilíbrio mecânico para as configurações conhecidas, acentuando o papel desempenhado pelas deformações residuais. Neste contexto, apresenta-se um funcional custo que mede o desbalance mecânico que é originado se um campo de deformações residuais inconsistente é admitido. Este funcional custo está baseado no resíduo generalizado das equações variacionais previamente mencionadas. Como consequência, o problema de estimação de deformações residuais é transformado em um problema de otimização, no qual se procura minimizar o funcional custo proposto. Com este objetivo, neste trabalho de tese são considerados dois métodos, um método de gradiente e um algoritmo de ponto interior para problemas que apresentam restrições. A metodologia proposta é testada em três exemplos numéricos baseados em soluções manufaturadas: um barra engastada, um cilindro de parede grossa, e uma artéria aorta composta por três camadas. Os resultados obtidos são promissores e sugerem que o método apresentado (ou variantes baseadas nas ideias aqui mostradas) junto com técnicas adequadas para a adquisição de imagens podem conduzir à identificação in-vivo de deformações residuais.

In order to simulate cellular blood, a coarse-grained spectrin-link (SL) red blood cell (RBC) membrane model is coupled with a lattice-Boltzmann (LB) based suspension solver. The LB method resolves the hydrodynamics governed by the Navier--Stokes equations while the SL method accurately models the deformation of RBCs under numerous configurations. This method has been parallelized using Message Passing Interface (MPI) protocols for the simulation of dense suspensions of RBCs characteristic of whole blood on world-class computing resources. Simulations were performed to study rheological effects in unbounded shear using the Lees-Edwards boundary condition with good agreement with rotational viscometer results from literature. The particle-phase normal-stress tensor was analyzed and demonstrated a change in sign of the particle-phase pressure from low to high shear rates due to RBCs transitioning from a compressive state to a tensile state in the flow direction. Non-Newtonian effects such as viscosity shear thinning were observed for shear rates ranging from 14-440 inverse seconds as well as the strong dependence on hematocrit at low shear rates. An increase in membrane bending energy was shown to be an important factor for determining the average orientation of RBCs, which ultimately affects the suspension viscosity. The shear stress on platelets was observed to be higher than the average shear stress in blood, which emphasizes the importance of modeling platelets as finite particles. Hagen-Poiseuille flow simulations were performed in rigid vessels for investigating the change in cell-depleted layer thickness with shear rate, the Fåhraeus-Linqvist effect, and the process of platelet margination. The process of platelet margination was shown to be sensitive to platelet shape. Specifically, it is shown that lower aspect ratio particles migrate more rapidly than thin disks. Margination rate is shown to increase with hematocrit, due to the larger number of RBC-platelet interactions, and with the increase in suspending fluid viscosity.

Thesis (Ph. D.)--Biomedical Engineering, Georgia Institute of Technology, 2005.
Giddens, P. Don, Committee Chair ; Vito, P. Raymond, Committee Member ; Taylor, Robert, W., Committee Member ; Oshinski, John, Committee Member ; Bao, Gang, Committee Member. Includes bibliographical references.

Mechanical stresses and flow dynamics alteration in a stented artery region are known to stimulate intimal thickening and increase the risk of restenosis, the closure of a revascularized artery. Particle imaging velocimetry (PIV) is an optical flow visualization technique that can be used to characterize the local flow dynamics around different stent structures. However, the usual cylindrical stent geometries present visualization difficulties when using an optical measurement technique such as the PIV technique. Using a flat configuration of a stent model presents advantages over the usual cylindrical model. A planar stent model makes data acquisition easier in planes cutting through the model due to its flat geometry that is compatible with the PIV planar flow investigation technique. Furthermore, with the planar stent configuration model velocity measurements and their associated flow features can be done without inducing refraction of the laser light sheet occurring with the cylindrical model's curvature. The refraction of light should be avoided since measurement errors and reflections are the resulting effects of this laser light plane deviation when passing through the curvature of a cylindrical stent model.
The spatial and temporal distribution of the Wall Shear Stress (WSS), which is believed to be of primary importance in the development of restenosis should be comparable between the flat and the cylindrical stent configuration models. The velocity and shear strain rate distributions will be compared between the flat and cylindrical stent configurations using computational fluid dynamics (CFD) simulations in order to analyse the feasibility of using a flat instead of a cylindrical version of the stent model for PIV experiments. It will be shown that for a physiological pulsatile flow the flat model yields results in shear strain rate spatial and temporal distribution that is comparable to the cylindrical model. A more PIV compatible, efficient and less refractive error prone validated flat model would be advantageous when several stent designs influence on the local hemodynamics around the strut geometries have to be studied quantitatively and optimized.

Computer simulations have become a great tool to assist the medical field. The present work is a study of a non-invasive patient-specific methodology to evaluate the hemodynamic importance of coronary stenosis using computer simulations. The severity of the lesion is evaluated by the Fractional Flow Reserve, calculated by the pressure gradient before and after the lesion. The geometry models are obtained from medical images of Computed Tomography Angiography exams, and the simulations considers the pulsatile flow and the blood as a non-Newtonian fluid. The governing equations of the blood flow are solved by using Finite Element Method applied to the numerical method called Incremental Pressure Correction Scheme, and with the aid of the libraries from the open-source software FEniCS. Computer simulations of three different patients are performed and the results are compared with the invasive FFR measurements. The methodology proposed shows to be feasible in the study and analysis of stenosed coronaries.
Simulações computacionais tornaram-se uma excelente ferramenta para auxiliar a área médica. O presente trabalho é um estudo de uma metodologia não invasiva para avaliar a importância hemodinâmica de artérias coronárias com estenose através do uso de simulações computacionais. A severidade da lesão da artéria é avaliada através do Fractional Flow Reserve, calculado pelo gradiente de pressão antes e depois da lesão. Os modelos geométricos computacionais foram obtidos a partir de imagens médicas de exames de Angiografia por Tomografia Computadorizada e as simulações consideram o fluxo pulsátil e as propriedades não-Newtonianas do sangue. As equações governantes do fluxo de sangue são resolvidas utilizando o Método dos Elementos Finitos aplicado ao método numérico chamado Incremental Pressure Correction Scheme, e com o uso de bibliotecas do programa em código aberto FEniCS. Foram realizados simulações de três pacientes e os resultados foram confrontados com as medidas invasivas do FFR. A metodologia proposta mostrou-se viável para o estudo e análise de coronárias com estenose.

In the interest of furthering the understanding of hemodynamics, this study has developed a method for modeling fluid mechanics behavior in individual human carotid arteries. A computational model was constructed from magnetic resonance (MR) data of a phantom carotid bifurcation model, and relevant flow conditions were simulated. Results were verified by comparison with previous in vitro experiments. The methodology was extended to create subject-specific carotid artery models from geometry data and fluid flow boundary conditions which were determined from MR and phase contrast MR (PCMR) scans of human subjects. The influence of subject-specific boundary conditions on the flow field was investigated by comparing a model based on measured velocity boundary conditions to a model based on the assumption of idealized velocity boundary conditions. It is shown that subject-specific velocity boundary conditions in combination with a subject-specific geometry and flow waveform influence fluid flow phenomena associated with plaque development. Comparing a model with idealized Womersley flow boundary conditions to a model with subject-specific velocity boundary conditions demonstrated the importance of employing inlet and flow division data obtained from individual subjects in order to predict accurate, clinically relevant, fluid flow phenomena such as low wall shear stress areas and negative axial velocity regions. This study also illustrates the influence of the bifurcation geometry, especially the flow divider position, with respect to the velocity distribution of the common carotid artery on the development of flow characteristics. Overall it is concluded that accurate geometry and velocity measurements are essential for modeling fluid mechanics in individual human carotid arteries for the purpose of understanding atherosclerosis in the carotid artery bifurcation.

Understanding cardiac pumping function is crucial to guiding diagnosis, predicting outcomes of interventions, and designing medical devices that interact with the cardiovascular system.  Computer simulations of hemodynamics can show how the complex cardiovascular system is influenced by changes in single or multiple parameters and can be used to test clinical hypotheses. In addition, methods for the quantification of important markers such as elevated arterial stiffness would help reduce the morbidity and mortality related to cardiovascular disease. The general aim of this thesis work was to improve understanding of cardiovascular physiology and develop new methods for assisting clinicians during diagnosis and follow-up of treatment in cardiovascular disease. Both computer simulations and medical imaging were used to reach this goal. In the first study, a cardiac model based on piston-like motions of the atrioventricular plane was developed. In the second study, the presence of the anatomical basis needed to generate hydraulic forces during diastole was assessed in heathy volunteers. In the third study, a previously validated lumped-parameter model was used to quantify the contribution of arterial and cardiac changes to blood pressure during aging. In the fourth study, in-house software that measures arterial stiffness by ultrasound shear wave elastography (SWE) was developed and validated against mechanical testing. The studies showed that longitudinal movements of the atrioventricular plane can well explain cardiac pumping and that the macroscopic geometry of the heart enables the generation of hydraulic forces that aid ventricular filling. Additionally, simulations showed that structural changes in both the heart and the arterial system contribute to the progression of blood pressure with age. Finally, the SWE technique was validated to accurately measure stiffness in arterial phantoms.

QC 20161115

Le modele de windkessel a ete propose pour identifier a partir de l'analyse du contour de l'onde de pression arterielle (pa), les parametres hemodynamiques du systeme arteriel comme la compliance arterielle (ca), l'inertie du volume sanguin (l), et les resistances vasculaires du systeme (r). Il s'agit d'un modele lineaire qui ne tient pas compte des variations structurales et fonctionnelles des arteres liees a la pulsatilite de la pa de ses variations entre la systole et la diastole et de la complexite de l'impedance cardiaque. L'objectif de la these est d'analyser les performances d'un modele de windkessel modifie ou les parametres ca, l et r sont ajustes de facon dynamique selon la relation non-lineaire des proprietes arterielles (compliance, diametre) en fonction de la pa. Dans un simulateur electrique reproduisant le modele les parametres suivants sont introduits : au niveau cardiaque le volume d'ejection systolique et au niveau radial les valeurs dynamiques de compliance et de diametre arteriel. Nous comparons les formes des ondes de pa lineaire ou la ca (compliance constante en fonction de la pression) et non-lineaire (compliance fonction de la pression) aux donnees experimentales. La forme de l'onde de pa obtenue par le modele non-lineaire n'est significativement pas differente de l'experimentale, tandis que dans le modele lineaire la pa systolique est sous estimee. Ce travail montre les limites de la modelisation du systeme cardio-vasculaire par le modele lineaire.

L'aorte conduit le sang oxygéné aux organes et amortit l'onde pulsatile cardiaque. Au cours du vieillissement, elle est exposée à des altérations hémodynamiques et à une rigidité augmentée, elle-même associée à la mortalité.L'objectif de ma thèse est de proposer, à partir de l'IRM et des simulations, des indices non-invasifs de l'hémodynamique aortique locale, qui soient simples, rapides et complémentaires aux indices IRM de géométrie et de fonction aortiques établis.Un premier volet est consacré au développement et la personnalisation d'un modèle 1D de l'aorte descendante, validé qualitativement et quantitativement avec des données IRM sur 7 sujets, afin d'extraire des paramètres de pression, vitesse et surface.Un second volet, dédié aux données IRM, est centré sur :la comparaison de 7 méthodes d'évaluation de la pulsatilité aortique et leur validation avec la référence sur 70 sujets sainsla quantification du flux réverse aortique et l'étude de sa variation avec l'âge, ainsi que l'identification de ses déterminants sur 96 sujets sainsl'estimation automatique d'indices hémodynamiques de la sténose valvulaire aortique (SVA) et leur comparaison à l'échocardiographie Doppler sur 53 patients avec une SVA et 21 contrôles.Ainsi, le modèle aortique pourrait aider à identifier les déterminants des altérations aortiques et à consolider les observations in vivo. Par ailleurs, les outils mis au point pour l'analyse reproductible des données d'IRM fournissent des indices caractéristiques du vieillissement, qui pourraient être étudiés vis-à-vis des organes cibles (coeur, cerveau, rein, etc.) dans les pathologies cardiovasculaires (hypertension artérielle, drépanocytose).

L'hémodynamique (la manière dont le sang coule) est aujourd'hui considérée par la communauté médicale comme un marqueur prépondérant dans l'apparition et dans l'évolution de certaines pathologies cardiovasculaires (formation d’un caillot sanguin, anévrisme, sténose...). Les récents progrès technologiques ont permis d'adapter l'Imagerie par Résonance Magnétique (IRM) à l'exploration vélocimétrique 3D du système cardiovasculaire grâce à l'IRM de flux 4D. En plus d'être non invasive et non ionisante, cette technique ouvre l'accès à l'évaluation de quantités dérivées du champ de vitesse telles que la pression ou le frottement pariétal, pertinentes lors des diagnostics médicaux, mais difficilement accessibles par imagerie. Néanmoins, les contraintes technologiques (temps d'acquisition, résolution spatiale, dépendance aux vitesses d'encodages) limitent la précision des mesures. De plus, les complexités intrinsèques au processus d’acquisition en IRM rendent difficilement identifiables les sources d'erreurs de mesures.Cette thèse à pour but de développer une méthodologie standardisée permettant l'évaluation systématique des mesures par IRM de flux 4D dans un régime d'écoulement complexe. Dans ce but, un fantôme IRM compatible capable de générer un écoulement typique de ceux observés dans la circulation thoracique (crosse aortique, bifurcation, anévrisme) est conçu et intégré à un banc d'essai expérimental. L'écoulement est prédit par simulation numérique (Mécanique des fluides Numérique) et simultanément mesuré par IRM de flux 4D.Grâce à une évaluation rigoureuse des différences entre ces deux modalités, on montre d’abord que la simulation numérique peut être considérée comme une représentation fidèle du champ de vitesse réel.Une évaluation rigoureuse des différences entre ces deux modalités permet de considérer la simulation numérique comme l’écoulement de référence représentant le champ de vitesse réel. L'analyse met aussi en lumière d'une part des erreurs typiques de mesures du champ de vitesse par IRM de flux 4D, ainsi que des erreurs relatives au calcul de quantités dérivées (pression et le frottement pariétal).Enfin, une méthodologie de simulation du processus d'acquisition en IRM est développée. Couplée avec la MFN, celle-ci permet de reconstruire des images IRM synthétiques correspondant à l'écoulement de référence mesuré par un protocole d'acquisition donné, mais exemptes de toutes erreurs expérimentales. La capacité à produire des images in silico permet notamment d’identifier les sources d’erreurs (matériel, logiciel, séquence) en IRM de flux 4D
Hemodynamics (blood flow dynamics) is now recognized as a key marker in the onset and evolution of many cardiovascular disorders such as aneurysms, stenoses, or blood clot formation. As it provides a comprehensive access to blood flows in-vivo, time-resolved 3D phase-contrast magnetic resonance imaging (or 4D Flow MRI) has gained an increasing interest over the last years and stands out as a highly relevant tool for diagnosis, patient follow-up and research in cardiovascular diseases. On top of providing a non-invasive access to the 3D velocity field in-vivo, this technique allows retrospective quantification of velocity-derived hemodynamic biomarkers such as relative pressure or shear stress, which are pertinent for medical diagnosis but difficult to measure in practice. However, several acquisition parameters (spatio-temporal resolution, encoding velocity, imaging artifacts) might limit the expected accuracy of the measurements and potentially lead to erroneous diagnosis. Moreover, the intrinsic complexities of the MRI acquisition process make it generally difficult to localize the sources of measurement errors.This thesis aims at developing a methodology for the assessment of 4D Flow MRI measurements in complex flow configuration. A well-controlled experiment gathering an idealized in-vitro flow phantom generating flow structures typical of that observed in the cardiovascular system is designed. The flow is simultaneously predicted by means of a high-order Computational Fluid Dynamics (CFD) solver and measured with 4D flow MRI. By evaluating the differences between the two modalities, it is first shown that the numerical solution can be considered very close to the ground truth velocity field. The analysis also reveals the typical errors present in 4D flow MRI images, whether relevant to the velocity field itself or to classical derived quantities (relative pressure, wall shear stress). Finally, a 4D Flow MRI simulation framework is developed and coupled with CFD to reconstruct the synthetic MR images of the reference flow that correspond to the acquisition protocol, but exempted from experimental measurement errors. Thanks to this new capability, the sources of the potential errors in 4D Flow MRI (hardware, software, sequence) can be identified

Thesis (MScEng)--Stellenbosch University, 2012.
ENGLISH ABSTRACT: Bioprosthetic heart valves (BHVs) for transcatheter aortic valve implantation (TAVI) have been rapidly developing over the last decade since the first valve replacement using the TAVI technique. TAVI is a minimally invasive valve replacement procedure offering lifesaving treatment to patients who are denied open heart surgery. The biomedical engineering research group at Stellenbosch University designed a 19 mm balloon expandable BHV for TAVI in 2007/8 for testing in animal trials. In the current study the valve was enlarged to 23 mm and 26 mm diameters. A finite element analysis was performed to aid in the design of the stents. New stencils were designed and manufactured for the leaflets using Thubrikar‟s equations as a guide. The 23 mm valve was manufactured and successfully implanted into two sheep. Fluid structure interaction (FSI) simulations constitute a large portion of this thesis and are being recognized as an important tool in the design of BHVs. Furthermore, they provide insight into the interaction of the blood with the valve, the leaflet dynamics and valve hemodynamic performance. The complex material properties, pulsating flow, large deformations and coupling of the fluid and the physical structure make this one of the most complicated and difficult research areas within the body. The FSI simulations, of the current valve design, were performed using a commercial programme called MSC.Dytran. A validation study was performed using data collected from a cardiac pulse duplicator. The FSI model was validated using leaflet dynamics visualisation and transvalvular pressure gradient comparison. Further comparison studies were performed to determine the material model to be used and the effect of leaflet free edge length and valve diameter on valve performance. The results from the validation study correlated well, considering the limitations that were experienced. However, further research is required to achieve a thorough validation. The comparative studies indicated that the linear isotropic material model was the most stable material model which could be used to simulate the leaflet behaviour. The free edge length of the leaflet affects the leaflet dynamics but does not greatly hinder its performance. The hemodynamic performance of the valve improves with an increase in diameter and the leaflet dynamics perform well considering the increased surface area and length. Many limitations in the software prevented more accurate material models and flow initiation to be implemented. These limitations significantly restricted the research and confidence in the results. Further investigation regarding the implementation of FSI simulations of a heart valve using the commercial software is recommended.
AFRIKAANSE OPSOMMING: Bio-prostetiese hartkleppe (Bioprosthetic Heart Valves - BHVs) wat gebruik word vir transkateter aortaklep-inplantings (Transcatheter Aortic Valve Implantation - TAVI) het geweldig vinnige ontwikkeling getoon in die afgelope tien jaar sedert die eerste klepvervanging wat van die TAVI prosedure gebruik gemaak het. TAVI is ʼn minimaal indringende klepvervangingsprosedure wat lewensreddende behandeling bied aan pasiënte wat ope-hart sjirurgie geweier word. Die Biomediese Ingenieurswese Navorsingsgroep (BERG) by Stellenbosch Universiteit het in 2007/8 ʼn 19 mm ballon-uitsetbare BHV vir TAVI ontwerp vir eksperimente met diere, en hierdie tesis volg op die vorige projekte. In die huidige studie is die klep vergroot na 23 mm en 26 mm in deursnee. ʼn Eindige element analise is gedoen om by te dra tot die ontwerp van die rekspalke vir die klep. Nuwe stensils is ontwerp en vervaardig vir die klepsuile, deur gebruik te maak van Thubrikar se vergelykings. Die 23 mm klep is vervaardig en suksesvol in twee skape ingeplant. Vloeistruktuur interaksie (Fluid Structure Interaction (FSI)) simulasies vorm ‟n groot deel van die tesis en word gesien as ʼn noodsaaklike hulpmiddel in die ontwerp van BHVs. Die simulasies verskaf ook insig in die interaksie van die bloed met die klep, die klepsuil-dinamika en die klep se hemodinamiese werkverrigting. Die komplekse materiaal eienskappe, polsende vloei, grootskaalse vervorming, die verbinding van die vloeistof en die fisiese struktuur maak van hierdie een van die mees gekompliseerde voorwerpe om te simuleer. Die FSI simulasies van die huidige ontwerp, is uitgevoer deur van kommersiële sagteware, MSC.Dytran, gebruik te maak. ʼn Geldigheidstudie wat data gebruik het vanaf die hartklop-nabootser, is uitgevoer. Die FSI model word geverifieer deur klepsuil dinamika visualisering en ʼn vergelyking van die drukgradiënt gebruik te maak. Verdere vergelykende studies is uitgevoer om te bepaal watter materiaal model om te gebruik, asook die uitwerking van die klepsuil-vrye rand en klepdeursnee op die klep se werkverrigting. Die resultate van die studie korreleer goed, in ag genome die beperkings wat ervaar is. Verdere navorsing is egter nodig vir ʼn volledige geldigheidstudie. Vergelykende studies het getoon dat die liniêre isotropiese materiaalmodel die meer stabiele materiaalmodel is wat kan gebruik word om klepsuilgedrag te simuleer. Die vrye-rand lengte van die klepsuil affekteer die dinamika van die klepsuil, maar belemmer nie die werkverrigting grootliks nie. Die hemodinamiese werkverrigting van die klep verbeter met die toename in deursnee en die klepsuil-dinamika vertoon goed in ag genome die verhoogde oppervlak area en lengte. Die vele beperkings in die sagteware het die implementering van meer akkurate materiaalmodelle verhoed. Hierdie beperkings het ʼn verminderde vertroue in die resultate tot gevolg gehad. Verdere ondersoek rakende die implementering van die FSI simulasies van ʼn hartklep deur kommersieel beskikbare sagteware te gebruik, word aanbevel.

L'étude de l'hémodynamique, c'est-à-dire de la dynamique du sang, est considérée par la communauté médicale comme un biomarqueur essentiel pour caractériser l'apparition et le développement des pathologies cardiovasculaires. Historiquement, l'imagerie à résonance magnétique (IRM), technique non-invasive et non-ionisante, permet de reconstruire des images morphologiques des tissus biologiques. Des progrès récents lui donnent aussi accès à l'évolution temporelle du champ de vitesse du sang dans les trois directions de l'espace. Cette technique, connu sous le nom d'IRM de flux 4D, est encore peu utilisée dans la pratique clinique étant donné sa faible résolution spatio-temporelle et sa longue durée d'acquisition.Cette thèse a pour but d'étudier les performances de la séquence de flux 4D. Dans un premier temps, l'impact de séquences accélérées (GRAPPA, compressed sensing) sur la reconstruction des champs de vitesse est étudié dans un cadre combinant mesures expérimentales sur un fantôme imageur de flux et simulations de mécanique des fluides numérique (MFN). On montre que l'acquisition hautement accélérée avec compressed sensing est en bon accord avec la simulation numérique si les corrections appropriées sont appliquées, notamment par rapport aux courants de Foucault. Dans un second temps, l'impact d'un paramètre de séquence, l'écho partiel, est examiné. L'étude est conduite avec une méthodologie couplant la simulation du processus d'acquisition IRM avec la MFN et permettant de reconstruire des images synthétiques d'IRM. Cette configuration permet de s'affranchir des erreurs expérimentales pour s'intéresser uniquement aux erreurs intrinsèques au processus IRM. Deux séquences constructeur réalistes, sans et avec écho partiel, sont simulées sur deux types d'écoulement dans un fantôme de flux numérique. Pour les deux écoulements, la séquence avec écho partiel donne globalement de meilleurs résultats. Il est ainsi suggéré que l'effet d'atténuation des artéfacts de déplacement permise par l'écho partiel est plus important que celui de réduction du signal IRM acquis que ce paramètre engendre. De plus, la simulation couplée IRM-MFN apparaît comme un outil d'intérêt dans le contexte de la conception et de l'optimisation de séquences IRM et pourrait être étendu à d'autres types de séquences
The study of hemodynamics, i.e. the dynamics of blood flow, is considered by the medical community as an essential biomarker to characterize the onset and the development of cardiovascular pathologies. Historically, magnetic resonance imaging (MRI), a non-invasive and non-ionizing technique, allows to reconstruct morphological images of the biological tissues. Recent progresses have made it possible to access the temporal evolution of the blood velocity field in the three spatial directions. This technique, known as 4D flow MRI, is still little used in the clinical practice due to its low spatiotemporal resolution and its long scan time.This thesis aims at studying how the 4D flow MRI sequence performs. To begin with, the impact of accelerated sequences (GRAPPA, compressed sensing) on reconstructed velocity fields is studied in a framework combining experimental measurements in a flow phantom and computational fluid dynamics (CFD) simulations. It is shown that the highly accelerated sequence with compressed sensing is in good agreement with numerical simulation as long as appropriate corrections are applied, namely with respect to the eddy currents. Then, the impact of a sequence parameter, namely partial echo, is investigated. The study is conducted thanks to a methodology coupling the simulation of the MR acquisition process with CFD and allowing to reconstruct synthetic MR images (SMRI). This configuration is freed from experimental errors and allows to only focus on the errors intrinsic to the MRI process. Two realistic constructor sequences, without and with partial echo, are simulated for two types of flow in a numerical flow fantom. For both flows, the sequence with partial echo results in overall better results. It suggests that the mitigation of the displacement artifacts made possible by the partial echo has a greater impact than the reduced MR signal acquired that it induces. Furthermore, the coupled MRI-CFD simulation appears as a tool of interest in the context of sequence design and optimization. It could be expanded to other types of MR sequences

Cette thèse, réalisée dans le cadre du projet Mivana, est consacrée à la modélisation et à la simulation numérique de dispositifs cardiaques implantables. Ce projet est mené par les start-up Kephalios et Epygon, concepteurs de solutions chirurgicales non invasives pour le traitement de la régurgitation mitrale. La conception et la simulation de tels dispositifs nécessitent des méthodes numériques efficaces et précises capables de calculer correctement l’hémodynamique cardiaque. C’est le but principal de cette thèse. Dans la première partie, nous décrivons le système cardiovasculaire et les valves cardiaques avant de présenter quelques éléments de théorie concernant la modélisation mathématique de l’hémodynamique cardiaque. En fonction du degré de complexité adopté pour la modélisation des feuillets de la valve, deux approches sont identifiées : le modèle de surfaces résistives immergées et le modèle complet d’interaction fluide-structure. Dans la deuxième partie, nous étudions la première approche qui consiste à combiner une modélisation réduite de la dynamique des valves avec un découplage cinématique de l’hémodynamique cardiaque et de l’électromécanique. Nous l’enrichissons de données physiologiques externes pour la simulation correcte des phases isovolumétriques, pierres angulaires du battement cardiaque, permettant d’obtenir un modèle relativement précis qui évite la complexité des problèmes entièrement couplés. Ensuite, une série d’essais numériques sur des géométries 3D physiologiques, impliquant la régurgitation mitrale et plusieurs configurations de valves immergées, illustre la performance du modèle proposé. Dans la troisième et dernière partie, des modèles complets d’interaction fluide-structure sont considérés. Ce type de modélisation est nécessaire pour étudier des problèmes plus complexes où la précédente approche n’est plus satisfaisante, comme par exemple le prolapsus de la valve mitrale ou la fermeture d’une valve mécanique. D’un point de vue numérique, le développement de méthodes précises et efficaces est indispensable pour pouvoir simuler de tels cas physiologiques. Nous considérons alors une étude numérique complète dans laquelle plusieurs méthodes de maillages non compatibles sont comparées. Puis, nous présentons un nouveau schéma de couplage explicite dans le cadre d’une méthode de type domaine fictif pour lequel la stabilité inconditionnelle au sens de la norme en énergie est démontrée. Plusieurs exemples numériques en 2D sont proposés afin d’illustrer les propriétés et les performances de ce schéma. Enfin, cette méthode est finalement utilisée pour la simulation numérique 2D et 3D de dispositifs cardiovasculaires implantables dans un modèle complet d’interaction fluide-structure
This thesis, taking place in the context of the Mivana project, is devoted to the modeling and to the numerical simulation of implantable cardiovascular devices. This project is led by the start-up companies Kephalios and Epygon, conceptors of minimally invasive surgical solutions for the treatment of mitral regurgitation. The design and the simulation of such devices call for efficient and accurate numerical methods able to correctly compute cardiac hemodynamics. This is the main purpose of this thesis. In the first part, we describe the cardiovascular system and the cardiac valves before presenting some standard material for the mathematical modeling of cardiac hemodynamics. Based on the degree of complexity adopted for the modeling of the valve leaflets, two approaches are identified: the resistive immersed surfaces model and the complete fluidstructure interaction model. In the second part, we investigate the first approach which consists in combining a reduced modeling of the valves dynamics with a kinematic uncoupling of cardiac hemodynamics and electromechanics. We enhance it with external physiological data for the correct simulation of isovolumetric phases, cornerstones of the heartbeat, resulting in a relatively accurate model which avoids the complexity of fully coupled problems. Then, a series of numerical tests on 3D physiological geometries, involving mitral regurgitation and several configurations of immersed valves, illustrates the performance of the proposed model. In the third and final part, complete fluid-structure interaction models are considered. This type of modeling is necessary when investigating more complex problems where the previous approach is no longer satisfactory, such as mitral valve prolapse or the closing of a mechanical valve. From the numerical point of view, the development of accurate and efficient methods is mandatory to be able to compute such physiological cases. We then consider a complete numerical study in which several unfitted meshes methods are compared. Next, we present a new explicit coupling scheme in the context of the fictitious domain method for which the unconditional stability in the energy norm is proved. Several 2D numerical examples are provided to illustrate the properties and the performance of this scheme. Last, this method is finally used for 2D and 3D numerical simulation of implantable cardiovascular devices in a complete fluid-structure interaction framework

INTRODUÇÃO: A pressão intra-abdominal tem demonstrado possuir um importante efeito sobre a homeostase, podendo ser alterada por influência de diversos fatores. A literatura atual mostra que valores de pressão intra-abdominal acima de 200 mmHg podem ser observados mesmo durante fenômenos fisiológicos como a tosse. Relatos de caso recentemente publicados descrevem o colapso total da aorta abdominal decorrente da hipertensão intra-abdominal. Neste estudo, através de simulação, aferiu-se o grau de prejuízo ao fluxo através da aorta abdominal, bem como à pressão arterial sistêmica e pressão de perfusão abdominal durante o aumento progressivo da pressão intra-abdominal. OBJETIVOS: Estimar, através de simulação, como o aumento da pressão intra-abdominal pode influenciar o status hemodinâmico, comprometendo a pressão arterial sistêmica e o fluxo através da aorta abdominal. Averiguar a validade do uso da pressão de perfusão abdominal, na forma como é calculada atualmente, como parâmetro de monitorização hemodinâmica. MÉTODOS: Um sistema circulatório artificial possibilitou a simulação dos efeitos da pressão intra-abdominal sobre o fluxo através da aorta abdominal infrarrenal (representada por um tubo de silicone) bem como sobre a pressão arterial sistêmica. Condutos prostéticos foram colocados dentro do tubo de silicone (Dacron e endoprótese) para simular uma abordagem cirúrgica sobre a aorta. Cinco cenários de experimentação simulando situações clínicas foram definidos no ponto inicial do trabalho: hipotensão grave, hipotensão leve, normotensão, hipertensão leve e hipertensão grave. RESULTADOS: Foram analisados os dados obtidos durante o incremento progressivo da pressão intra-abdominal de 10 a 230 mmHg, considerando três diferentes espécimes (tubo de silicone / tubo de silicone + Dacron / tubo de silicone + endoprótese), cinco cenários de experimentação e sete variáveis (pressões sistólica e diastólica a montante e a jusante, fluxos sistólico e diastólico e pressão de perfusão abdominal). Conforme avaliação estatística através de análise de variância, observou-se que a pressão intra-abdominal tem uma clara influência em todas as variáveis de interesse (p < 0,001), independentemente do cenário de experimentação e do espécime considerado. Utilizando-se o teste de Tukey, na comparação dos espécimes dois a dois, observou-se que a combinação tubo de silicone + endoprótese apresentou a maior resiliência aos efeitos deletérios da pressão intra-abdominal na maior parte dos cenários de experimentação (p = 0,05), para todas as variáveis, exceto para a pressão de perfusão abdominal. A pressão de perfusão abdominal, calculada através da fórmula usada na literatura atual, apresentou as maiores reduções nos experimentos envolvendo o espécime tubo de silicone + endoprótese. CONCLUSÕES: A pressão intra-abdominal tem uma clara influência sobre todas as variáveis de interesse. A fórmula que descreve o cálculo da pressão de perfusão abdominal pode não levar em consideração a relação de dependência que pode existir entre a pressão arterial média e a pressão intra-abdominal
INTRODUCTION: The intra-abdominal pressure has been shown to possess an important effect over homeostasis and might be influenced by numerous conditions. The present medical literature shows that intra-abdominal pressure values above 200 mmHg might be observed, even in physiological phenomena as coughing. Recent case reports describe the collapse of abdominal aorta due to intra-abdominal hypertension. In this study, through simulation, we measured the hazard degree to the flow through infrarenal abdominal aorta as well as to systemic arterial pressure and abdominal perfusion pressure during progressive intra-abdominal pressure increments. OBJECTIVES: To estimate, through simulation, how the intra-abdominal pressure increment would influence the hemodynamic status, compromising the systemic arterial pressure and the flow through abdominal aorta. Evaluate the validity of the abdominal perfusion pressure usage, as it is calculated today, as a reliable parameter in hemodynamic monitoring. METHODS: An artificial circulatory system enabled the simulation of the intra-abdominal pressure effects over the flow through the infrarenal abdominal aorta (represented by a silicone tube) as well as over the systemic arterial pressure. Prosthetic conduits were set inside the silicone tube (Dacron or endoprosthesis) to simulate a surgical approach over the aorta. Five experiment categories simulating clinical scenarios were defined at the study starting point: severe hypotension, slight hypotension, normotension, slight hypertension and severe hypertension. RESULTS: The data obtained along the intra-abdominal pressure increment from 10 up to 230 mmHg were analyzed considering three different specimens (silicone tube / silicone tube + Dacron / silicone tube + endoprosthesis), five experimental scenarios and seven variables of interest (upstream and downstream systolic and diastolic pressures, systolic and diastolic flow and abdominal perfusion pressure). Statistical evaluation through variance analysis showed that the intraabdominal pressure has a clear influence in all variables of interest (p < 0,001), independently of the experimental scenario or the specimen considered. The Tukey test, in the comparison of the specimens two by two, showed that the combination silicone tube + endoprosthesis had the greatest resilience to the deleterious intra-abdominal pressure effect in most part of the experimental scenarios (p = 0,05) over all the interest variables, with exception to the abdominal perfusion pressure. The abdominal perfusion pressure, calculated by the formula used in the medical literature, presented the most significant decrement along the silicone tube + endoprosthesis experiments. CONCLUSIONS: The intra-abdominal pressure has a clear influence in all variables of interest. The formula which describes the abdominal perfusion pressure calculation might not consider the dependency relationship that might exist between mean arterial pressure and the intra-abdominal pressure

Les neuropathies optiques comme le glaucome sont souvent des maladies tardives, évolutives et incurables. Malgré les progrès récents de la recherche clinique, de nombreuses questions relatives à l’étiologie de ces troubles et à leur physiopathologie restent ouvertes. De plus, les données sur les tissus postérieurs oculaires sont difficiles à estimer de façon non invasive et leur interprétation clinique demeure difficile en raison de l’interaction entre de multiples facteurs qui ne peuvent pas être facilement isolés. L’utilisation récente de modèles mathématiques pour des problèmes biomédicaux a permis de révéler des mécanismes complexes de la physiologie humaine. Dans ce contexte très enthousiasmant, notre contribution est consacrée à la conception d’un modèle mathématique et computationnel couplant l’hémodynamique et la biomécanique de l’oeil humain. Dans le cadre de cette thèse, nous avons mis au point un modèle spécifique au patient appelé simulateur virtuel de mathématiques oculaires (OMVS), capable de démêler les facteurs multi-échelles et multi-physiques dans un environnement accessible en utilisant des modèles mathématiques et des méthodes numériques avancés et innovants. De plus, le cadre proposé peut servir comme méthode complémentaire pour l’analyse et la visualisation des données pour la recherche clinique et expérimentale, et comme outil de formation pour la recherche pédagogique
Optic neuropathies such as glaucoma are often late-onset, progressive and incurable diseases. Despite the recent progress in clinical research, there are still numerous open questions regarding the etiology of these disorders and their pathophysiology. Furthermore, data on ocular posterior tissues are difficult to estimate noninvasively and their clinical interpretation remains challenging due to the interaction among multiple factors that are not easily isolated. The recent use of mathematical models applied to biomedical problems has helped unveiling complex mechanisms of the human physiology. In this very compelling context, our contribution is devoted to designing a mathematical and computational model coupling tissue perfusion and biomechanics within the human eye. In this thesis we have developed a patient-specific Ocular Mathematical Virtual Simulator (OMVS), which is able to disentangle multiscale and multiphysics factors in a accessible environment by employing advanced and innovative mathematical models and numerical methods. Moreover, the proposed framework may serve as a complementary method for data analysis and visualization for clinical and experimental research, and a training application for educational purposes

L’apport régulier en nutriment et en oxygène aux organes du corps est assuré par la contraction régulière du cœur, organe majeur du système cardiovasculaire. En conséquence de certaines pathologie, il arrive que les valves cardiaques ne fonctionnent pas correctement, pouvant entrainer un flux rétrograde de sang. Dans le cas de la valve mitrale, située entre le ventricule gauche et l'oreillette gauche, on parle de régurgitation mitrale. Il est nécessaire de quantifier au mieux la sévérité de la régurgitation mitrale pour proposer un traitement adapté. Dans la première partie de cette thèse, un modèle numérique 3D de l'hémodynamique cardiaque est présenté incluant notamment un modèle de régurgitation mitrale. On en profitera également pour proposer un modèle permettant la modélisation des phases isovolumétriques du cœur. Un modèle relativement précis de l'hémodynamique cardiaque, mais de complexité numérique raisonnable, est ainsi obtenu à l'issue de cette première partie. La seconde partie de cette thèse décrit la stratégie adoptée pour permettre la fusion de données provenant des images médicales avec des modèles numériques. Une méthode automatique permettant la personnalisation du modèle numérique développé dans la première partie du manuscrit, à partir d'images médicales, est présentée et permets dans un second temps une évaluation systématique la méthode PISA. On termine la thèse avec la présentation d'une méthode de reconstruction du flux sanguin combinant des images Doppler Couleur à des contraintes physiques liées à l'incompressibilité du sang
The regular supply of nutrients and oxygen to the organs is ensured by the regular contraction of the heart, a major organ of the cardiovascular system. As a result of certain cardiac diseases, cardiac valves may not function properly, which can lead to a retrograde flow of blood. In the case of the mitral valve, located between the left ventricle and the left atrium, it is referred to as mitral regurgitation. It is necessary to quantify the severity of mitral regurgitation in order to propose an appropriate treatment. In the first part of this document, a 3D mathematical model of cardiac hemodynamics is developed and integrates a mitral regurgitation model. We will also take the opportunity to model the isovolumetric phases of the heart. A relatively accurate model of cardiac hemodynamics, but nevertheless reasonable in term of numerical complexity, is thus obtained at the end of this first part. The second part of this document describes the strategy adopted to allow the fusion of medical images with the numerical simulations. An automatic method allowing the personalization of the mathematical model developed in the first part of the manuscript, based on medical images, is presented, allowing a systematic evaluation of the PISA method. Finally, as the methods presented are still too expensive from a numerical point of view, we conclude with the presentation of a blood flow reconstruction method combining Color Doppler images with physical constraints related to blood incompressibility

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Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ)
A detailed mechanical behaviour of the arterial wall is required to gain insight on the onset and progress of some cardiovascular diseases as well as to propose adequate treatments. The classical constitutive modelling approach based purely on phenomenological laws fails in representing the micromechanical phenomena which dominates important aspects of these tissues such as remodelling and rupture. In turn, the multi-scale constitutive modelling raises as a more rational alternative that allows to consider the microscopic features and interactions of the basic unit blocks of the biological tissues such as the existence of the collagen fibres,pores, etc. In this work we review the non-linear solid mechanics fundamental concepts, the linearisation of the variational principles, numerical treatment of incompressibility constraint as well the continuum damage theory. A constitutive multi-scale theory based on the existence of Representative Volume Element in the finite strain regime is presented in a variational formulation framework, where homogenization for the displacement and deformation gradient are assumed as well the energetic coupling between scales through a extended version of the Hill-Mandel principle. In this context, a number of simulations are discussed. Finally, as corollary of the continuum mechanics framework, we derive a strategy for the damage field identification which is based on the sensibility analysis of a cost functional which takes account the displacement and energies diferences.
Sabe-se que o conhecimento do comportamento mecânico da parede arterial è fundamental para a compreensão de diversas doenças cardiovasculares bem como o planejamento adequado do tratamento destas. Contudo a modelagem da resposta constitutiva deste tecido é complexa sendo que a abordagem clássica baseada puramente em leis fenomenológicas _e insuficiente para representar fenômenos micromecânicos, os quais, ademais, dominam aspectos tais como remodelagem e ruptura. A modelagem multiescala de tecidos biológicos surge então como uma alternativa mais racional para representar a resposta constitutiva destes materiais levando-se em consideração aspectos microscópicos da organização do tecido como a existência de fibras de colágeno, poros, etc. Neste trabalho revisamos os conceitos fundamentais da mecânica dos sólidos não-linear incluindo a linearização dos princípios variacionais, bem como os aspectos básicos das teoria constitutiva em grandes deformações, passando pelo tratamento da condição de incompressibilidade e a teoria do dano contínuo. Uma teoria constitutiva multiescala baseada na homogenização em um Elemento de Volume Representativo em regime de grandes deformações é apresentada em um contexto de formulações variacionais, sendo assumida a homogeneização do campo de deslocamentos e do gradiente de deformação, além da consistência energética entre escalas baseada no princípio de Hill-Mandel. Neste contexto, diversas simulações são apresentadas e discutidas. Porém, como corolário da abordagem da mecânica do contínuo, mostramos uma estratégia para a identificação do campo de dano baseado na análise de sensibilidade de um funcional custo baseado nas diferenças de campos de deslocamentos e energia de deformação.

L’implantation valvulaire aortique percutanée (TAVI) a émergé comme une alternative à la chirurgie pour les patients avec sténose sévère et haut risque chirurgical. Cette technique s’étend à une population plus large (e.g. anatomie plus complexe, risque chirurgical plus bas), ainsi qu'au traitement Valve-in-Valve (ViV) des bioprothèses (BPs) chirurgicales défaillantes. Cependant, deux complications majeures en limitent la généralisation. En TAVI « classique », la présence de fuites péripothétiques a été associée à une mortalité augmentée. Les effets du surdimensionnement de la prothèse percutanée pour assurer son étanchéité, ou de la forme de l’anneau souvent non circulaire, sur la performance hémodynamique, sont mal connus. En ViV, la présence de hauts gradients est fréquente et associée à une mortalité augmentée. Les BPs de taille nominale ≤ 21 mm et le mode de dégénérescence par sténose, facteurs mis en cause dans la sténose résiduelle et associés à une mortalité augmentée, ne sont pas assez spécifiques et il n’existe actuellement aucune recommandation pour le traitement des petites BPs. Par ailleurs, le bénéfice hémodynamique réel du ViV par rapport aux statuts avant ViV n’a pas été étudié.L’objectif général de ce travail doctoral est de comprendre les interactions entre la prothèse percutanée et l’anneau aortique ou la BP à traiter, impliquées dans la performance hémodynamique, en particulier dans des conditions d’implantation complexes, afin d’étendre les indications du TAVI. En ViV, le défi est de préciser les facteurs associés à sa performance et son utilité hémodynamique et de proposer des stratégies d’implantation afin d’optimiser le succès de la procédure
Transcatheter aortic valve implantation (TAVI) has emerged as an alternative to surgery for patients with severe aortic stenosis and high surgical risk. This technique is extending to a wider population (e.g. with more complex anatomy or lower surgical risk), as well as to patients with degenerated surgical bioprostheses (BPs). However, two major concerns remain limiting. Regarding “classical TAVI”, periprosthetic leaks have been associated with increased mortality. Oversizing is used to secure the device within the aortic annulus which is often non circular. The effects of oversizing and annulus shape on the hemodynamic performance are unknown. Regarding ViV implantations, elevated post-procedural gradients are common and have been associated with increased mortality. The principal factors associated with this residual stenosis as well as with increased risk of mortality, have been BPs label size ≤ 21 mm and mode of failure by stenosis. These factors are not specific enough and there is currently no recommendation for the treatment of small BPs. Besides, the actual hemodynamic benefit associated with ViV has not been evaluated (vs. pre ViV status).The general objective of this work is to understand the interactions between the transcatheter prosthesis and the aortic annulus or the BP to be treated, which impact the hemodynamic performance, especially in complex conditions of implantation, in order to extend the indications of TAVI. In the context of ViV, the objective is to specify the factors associated with the hemodynamic performance and utility of the treatment. The final aim is to provide strategies of implantation in order to optimize the success of the procedure

Le vieillissement est associé à des modifications morphologiques, fonctionnelles et hémodynamiques du système artériel, le plus souvent aggravées par la survenue de maladies cardiovasculaires. La compréhension de ces interactions aggravantes est importante pour réduire le risque encouru par le patient. L’imagerie médicale joue un rôle majeur dans cette perspective au travers de modalités telles que l’IRM de contraste de phase combinée à l’analyse quantitative des images obtenues ainsi qu’à la résolution numérique des équations de Navier Stokes qui régissent l’hémodynamique de l’écoulement sanguin. Cette thèse a donc pour but de mettre au point et combiner des méthodes de traitement d’images de vélocimétrie 4D acquises en IRM et de mécanique des fluides pour extraire des biomarqueurs quantitatifs tels que les cartographies de pressions intra-aortiques et leurs propagations spatio-temporelles, la contrainte de cisaillement aux parois aortiques et la vorticité intra-aortique. Nous avons ainsi montré la capacité de ces biomarqueurs à détecter les atteintes infra-cliniques liées à l’âge et à caractériser la dilatation aortique pathologique. De plus, les liens entre distributions spatio-temporelles des pressions et apparition et persistance des vortex ou encore contrainte de cisaillement ont été montrés. Dans un second travail, nous avons mis au point un modèle de simulation numérique permettant de résoudre le système d’équations de Navier-Stokes par élément finis. Une méthode de projection itérative a été appliquée à des modèles de sténose 2D et 3D ainsi qu’à des géométries aortiques 3D issues de segmentations pour valider notre implémentation. Finalement, un travail préliminaire d’application de notre modèle numérique à des géométries patients-spécifiques a été réalisé indiquant des liens encourageants entre données simulées et mesures IRM
Aging is associated with morphological, functional and hemodynamic changes in the arterial system, most often aggravated by cardiovascular disease. Understanding these aggravating interactions is important to reduce patients risk. Medical imaging plays a major role in this context through modalities such as velocity encoding MRI combined with quantitative image processing and computational resolution of Navier-Stokes equations that govern blood flow hemodynamics. The aim of this thesis is to develop and combine image processing methods dedicated to 4D flow MRI data analysis with computational fluid dynamics to extract quantitative biomarkers such as intra-aortic pressure fields and their spatio-temporal propagations, aortic wall shear stress and intra-aortic vorticity. We have demonstrated the ability of these biomarkers to detect age-related sub-clinical aortic impairment and to characterize pathological aortic dilatation. In addition, association of spatio-temporal aortic pressure distributions with vortex occurrence and duration as well as with wall shear stress were studied. In a second work, we developed a numerical simulation software to solve the Navier-Stokes system using finite element models. An iterative projection method was applied to 2D and 3D vessel stenosis models as well as to 3D geometrical aortic models resulting from segmentation to validate our implementation. Finally, a preliminary work applying our numerical model to patient-specific geometries was performed revealing encouraging associations between simulated data and MRI measures

La placentation humaine est de type hémomonochoriale, le sang maternel est directement en contact avec le syncytiotrophoblaste. Les flux sanguins maternels, dans la chambre intervilleuse, exercent des forces mécaniques de cisaillement (shear stress) sur la surface microvillositaire du syncytiotrophoblaste. Les effets physiologiques du shear stress exercé par les flux sanguins sur l’endothélium vasculaire artériel et veineux ont fait l’objet de nombreux travaux scientifiques. En revanche, les effets biologiques du shear stress sur le syncytiotrophoblaste humain n’ont jamais été explorés. L’objectif de ce travail était premièrement d’évaluer les valeurs du shear stress exercé in vivo sur le syncytiotrophoblaste humain au cours des grossesses normales, puis de mettre au point un modèle de culture primaire dynamique afin de reproduire les conditions physiologique et d’étudier in vitro la réponse biologique du syncytiotrophoblaste au shear stress. En dépit d’un débit sanguin maternel intraplacentaire important, estimé entre 400 et 600 mL.min-1, le shear stress moyen exercée par le syncytiotrophoblaste est estimée entre 0.5±0.2 et 2.3±1.1 dyn.cm-2. Nos résultats montrent cependant que l’intensité du shear stress est très hétérogène tant à l’échelle de la chambre intervilleuse que de la villosité terminale. Nous avons développé un modèle de culture cellulaire dynamique en condition de flux adapté au syncytiotrophoblaste humain. Ce modèle permet d’appliquer un shear stress égal et constant sur toutes les cellules cultivées et reproductible à chaque culture primaire. Aux gammes de shear stress étudiées (1 dyn.cm-2), nous n’avons pas mis en évidence de diminution de la viabilité cellulaire ni de déclenchement des processus précoces d’apoptose en conditions dynamiques comparativement aux conditions statiques. Deux types de chambre de perfusion permettent d’étudier des réponses cellulaires au shear stress à court et long terme selon des temps d’exposition allant de 5 minutes à 24 heures. Ce modèle expérimental a permis de montrer que le syncytiotrophoblaste humain en culture primaire est mécanosensible. La réponse cellulaire à des niveaux de shear stress de 1 dyn.cm-2 est multiple selon les temps d’exposition et le niveau d’intégration étudié. Après 45 minutes de shear stress les taux d’AMP cyclique intracellulaires sont augmentés ce qui a pour effet d’activer la voie de signalisation intracellulaire PKA-CREB. Cette augmentation d’AMP cyclique est secondaire à la synthèse et la libération de prostaglandine E2 qui, par une boucle de régulation autocrine stimule l’adenylate cyclase. L’augmentation de la synthèse/libération de PGE2 est dépendante de l’augmentation rapide du calcium intracellulaire sous shear stress. L’exposition au shear stress de 24 heures stimule l’expression et la sécrétion du PlGF, un facteur de croissance indispensable à l’angiogenèse placentaire et pour l’adaptation maternelle à la grossesse sur le plan vasculaire. Nos travaux montrent que l’augmentation de l’AMPc intracellulaire et l’activation de la PKA contribuent à la phosphorylation de CREB, facteur de transcription régulant l’expression du PlGF
Human placentation is hemomonochorial, maternal blood circulates in direct contact with the syncytiotrophoblast. In the intervillous space, the maternal blood exerts frictional mechanical forces (shear stress) on the microvillous surface of the syncytiotrophoblast. Flowing blood constantly exerts a shear stress, on the endothelial cells lining blood vessel walls, and the endothelial cells respond to shear stress by changing their morphology, function, and gene expression. The effects of shear stress on the human syncytiotrophoblast and its biological functions have never been studied. The objectives of this study were (1) to determine in silico the physiological values of shear stress exerted on human syncytiotrophoblast during normal pregnancies, (2) to develop a model reproducing in vitro the shear stress on human syncytiotrophoblast and (3) to study in vitro the biological response of human syncytiotrophoblast to shear stress. The 2D numerical simulations showed that the shear stress applied to the syncytiotrophoblast is highly heterogeneous in the intervillous space. In spite of high intraplacental maternal blood flow rates (400-600mL.min-1), the estimated average values of shear stress are relatively low (0.5±0.2 to 2.3±1.1 dyn.cm-2). To study the shear stress-induced cellular responses during exposure times ranging from 5 minutes to 24 hours we have developed two dynamic cell culture models adapted to the human syncytiotrophoblast. We found no evidence of decreased cell viability or early processes of apoptosis in dynamic conditions (1 dyn.cm-2, 24h) compared to static conditions. Shear stress (1 dyn.cm-2) triggers intracellular calcium flux, which increases the synthesis and release of PGE2. The enhanced intracellular cAMP in FSS conditions was blocked by COX1/COX2 inhibitors, suggesting that the increase in PGE2 production could activate the cAMP/PKA pathway in an autocrine/paracrine fashion. FSS activates the cAMP/PKA pathway leading to upregulation of PlGF in human STB. Shear stress-induced phosphorylation of CREB and upregulation of PlGF were prevented by inhibition of PKA with H89 (3 μM). The syncytiotrophoblast of the human placenta is a mechanosenstive tissue

在這篇論文中，我們提出了在醫學模擬應用的血管或傷口上作相互作用的粒子血流變模型框架。通過平滑粒子流體動力學（SPH）制定的非牛頓流體，進行了血液流變學的模擬。通過建模血管壁結構虛擬粒子，流體 - 結構相互作用（FSI）是一個純粹的拉格朗日(Lagrange)顆粒模型進行建模的血管或血液的交互。我們的建議的方法基於純粹的非網格方法，可用於常見的動脈瘤和血管狹窄等病症的建立上。如需模擬開放性傷口在手術部位中發生較大的變形情況時，我們則採用質量 - 彈簧系統進行血顆粒的交互，此交互框架可應用到幾個開放性手術模擬，如骨科或胃鏡檢查為基礎的手術。無論是常見的醫療圖像：如CT血管造影（CTA）、磁共振血管造影（MRA）或基於網格的數據也可以 作為系統輸入的數據。血栓形成與溶解模型也被集成到這個流固耦合框架中。實驗結果證明採用我們建議的粒子互相作用框架在模擬血管中的凝血過程是可行的。受益於簡潔的拉格朗日粒子交互作用模擬，我們的系統可以保持在互動幀速率中。
首先，我們在這篇論文中建議把無網格流變模擬框架應用於血管手術的建模中。於非牛頓粘性流動的假設下，我們建立了血液結構的一般模型方程：以平滑粒子流體動力學實現多血粘度模型與低彈性血管壁模型。血流動力學和軟組織都可以於相同的拉格朗日粒子為基礎下模擬。在這個意義上說，通過延伸平滑粒子流體動力學的密度和動量求和不管顆粒的性質下，本論文提出了一個有效的流體 - 固體交互作用模型。該模型是特別有利於整合多種類型的介質（包括固體或液體）的。在這方面，我們進一步提出了一個與流體相關的血塊凝集溶解模型，可以適用於許多不同種類的醫學模擬：例如血栓栓塞。
其次，本論文亦提出了如何基於粒子的血液建模框架的前提下，擴展到大變形的軟組織互動。我們是以耦合雙向階段性質量 - 彈簧系統與固體顆粒，去代替無網格粒子固體的建模，用以維持真正人體組織的高保真度，此方法可以實現類似軟組織的皮膚或真皮的交互式模擬。而耦合血顆粒與平滑粒子方面，則由一個聰明的碰撞模塊處理，使得利用模擬皮膚表面之上，可以模擬出真實的表皮出血現象。該模型的動態計算進一步以物理學處理單元加速；而渲染的模型則是通過一個強大的圖形處理單元為基礎的立方體運行（marching cubes）的方法來實現。該模型已應用於全身血液管理培訓中。
In this thesis, we propose particle-based rheological modeling frameworks for blood-vessel and blood-wound interaction in medical simulation applications. The effect of blood rheology has been simulated through a smoothed particle hydrodynamics (SPH) formulation of non-Newtonian flow. By modeling the vessel wall structure as virtual particles, a pure Lagrange particle formulation for fluid-structure interaction (FSI) is proposed for modeling the blood-vessel or blood-device interaction. Our proposed framework synthesizes common vascular complication sites such as stenosis and aneurysm based on purely mesh-less approach. For larger deformation situations happened in surgical sites such as open wound, we adopt a mass-spring system to interact with the blood particles; the blood-wound interaction framework can be applied to several open surgery simulations such as orthopedics or endoscopy-based interventions. Input of the data can be obtained from either common medical modalities like computed tomographic angiography (CTA), magnetic resonance angiography (MRA) or processing mesh-based data. A thrombus (clot) formation-dissolution model is also integrated into this fluid-solid interaction framework. Results have demonstrated the feasibility of employing our proposed particle framework in simulating blood-vessel interaction in the clotting process which is essential to vascular procedure simulations. Having benefited from the elegant formulation of Lagrangian particle interaction; the simulation can be maintained at interactive frame-rates.
In this thesis, first, a meshless rheological modeling framework for medical simulation of vascular procedures is proposed. Instead of assuming a Newtonian non-viscous flow, we have built our model based on the general constitutive equation of blood. The multi-regime of viscosity in blood model with a hypoelastic model of vessel wall has been realized under a SPH formulation. The hemodynamic and the soft tissue can all be simulated under the same Lagrangian particle-based formulation. In this sense, an efficient formulation of fluid-solid interaction is proposed through extending SPH summations of density and momentum regardless the nature of particles. This model is particularly beneficial to the integration of multiple types of media (including solids or fluids). With this regards, we further propose a flow related clot aggregation-dissolution model which can be applicable to many different kinds of medical simulation e.g. thrombo-embolization.
Second, the proposed particle-based blood modeling framework has been extended to interact with large deformation of soft tissue. Instead of modeling the solid as meshless particles, a bi-phasic mass-spring system is coupled with solid particles so that an interactive simulation of skin or dermis like soft tissue can be realized with high fidelity to real human tissue. To couple with the SPH formulation of blood particles, a smart collision handling module is exploited so that a realistic bleeding simulation on top of the skin surface can be created. The dynamic computation of this model is further accelerated by the physics processing unit; while the rendering of the model is realized through a robust graphics processing unit based marching cube approach. The proposed model has been applied to provide general blood management training.
Detailed summary in vernacular field only.
Detailed summary in vernacular field only.
Detailed summary in vernacular field only.
Chui, Yim Pan.
Thesis (Ph.D.)--Chinese University of Hong Kong, 2013.
Includes bibliographical references (leaves 98-113).
Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web.
Abstracts also in Chinese.
Abstract --- p.ii
Chapter 1 --- Introduction --- p.1
Chapter 2 --- Related works on physically based fluid-structure models --- p.7
Chapter 2.1 --- Eulerian grid-based methods --- p.8
Chapter 2.2 --- Lagrangian grid-based methods --- p.9
Chapter 2.3 --- Lagrangian meshfree methods --- p.11
Chapter 2.4 --- Fluid-structure interaction (FSI) --- p.12
Chapter 2.5 --- Endovascular simulation --- p.14
Chapter 2.6 --- Overview of Our Model --- p.15
Chapter 3 --- Meshless blood-clot interaction --- p.16
Chapter 3.1 --- Basic equations of fluid dynamics --- p.17
Chapter 3.2 --- SPH basics --- p.18
Chapter 3.3 --- SPH Rheological hemodynamics of blood --- p.20
Chapter 3.4 --- SPH modeling of the hypoelastic vessel --- p.26
Chapter 3.5 --- Fluid-solid interaction model --- p.28
Chapter 3.6 --- Flow-related clot aggregation-dissolution model --- p.33
Chapter 3.7 --- Time integration --- p.36
Chapter 3.8 --- Hardware-friendly formulation --- p.37
Chapter 3.9 --- Results --- p.39
Chapter 3.9.1 --- Classical Dam-break problem --- p.41
Chapter 3.9.2 --- Poiseuille flow --- p.43
Chapter 3.9.3 --- Couette flow --- p.45
Chapter 3.9.4 --- Mechanical model with material strength --- p.47
Chapter 3.9.5 --- Hemoelastic feedback system --- p.49
Chapter 3.9.6 --- Clotting in a stenosed vessel --- p.52
Chapter 3.9.7 --- Timing results --- p.53
Chapter 4 --- Meshless modeling of thrombo-embolization --- p.55
Chapter 4.1 --- Modeling framework for thrombus formation within blood vessel . --- p.60
Chapter 4.2 --- Geometric Modeling and Flow Simulation --- p.61
Chapter 4.2.1 --- Data processing on vascular data --- p.61
Chapter 4.2.2 --- Blood-Vessel particle distribution --- p.62
Chapter 4.2.3 --- Blood-structure Interaction --- p.65
Chapter 4.3 --- Visualization and Thrombosis Simulation --- p.66
Chapter 4.3.1 --- Flow Visualization --- p.66
Chapter 4.3.2 --- Thromb-Embolization Simulation --- p.68
Chapter 4.4 --- Conclusion and discussion --- p.72
Chapter 5 --- Lagrangian modeling framework for bleeding simulation --- p.76
Chapter 5.1 --- SPH-based bleeding model --- p.78
Chapter 5.2 --- Biphasic Soft-tissue deformation --- p.79
Chapter 5.3 --- Interaction between blood and soft tissue --- p.83
Chapter 5.4 --- Integrated training for blood management --- p.87
Chapter 6 --- Discussion and Conclusion --- p.93
Bibliography --- p.98

碩士
國立成功大學
航空太空工程學系
104
Hemodynamics improvement in patients with single ventricle heart defects could be accomplished by palliative surgical procedure. The purpose of the final stage surgery in total cavopulmonary connection is to reconstruct the arteriovenous shunt, as well as to separating systemic and pulmonary circulation and reduce ventricular loading. However, the increase in venous return pressure or decrease in left ventricular preload are common in these physiological circulation reconstruction, and ultimately lead to protein losing enteropathy, hepatic congestion, thromboembolism and diminished exercise capacity. It is important to optimize the TCPC flow to mitigate the abovementioned complications. Computational Fluid Dynamics has been adopted as the major analysis tool, in which both flow model and boundary condition specification are crucial. The present research proposed a hybrid circulation simulation model consisting of a continuous three-dimensional flow model and a lumped-parameter model. Three-dimensional flow field simulation uses Ansys Fluent with implicit SIMPLE algorithms in conjunction with a user-defined function to combine lumped-parameter model as the terminal boundary conditions. The lumped-parameter model is solved based on explicit fourth-order Runge-Kutta method for time stepping. A special iterative procedure connecting the Fluent solver and the lumped-parameter system is developed. The hybrid circulation model in three-dimensional hemodynamic simulation was successfully validated. The simulation results show that, for the studied cases, there is no significant difference in power loss for TCPC flow field due to velocity of venous return is too small.

碩士
國立中央大學
數學系
103
Numerical simulation of blood flow in the arteries becomes an invaluable tools to help both of the physicians to plan the surgery procedure to reduce the risk of surgery and the researchers to understand the cardiovascular diseases. To ease the numerical difficulties of blood flow simulation, blood is often assumed to be Newtonian fluid as the first approximation. However, the shear thinning effect is significant in large arteries due to the dramatic change of the shear stress during a cardiac cycle and the non-homogeneous properties of blood. Moreover, the recirculation happens frequently in the low shear rate region. To compute accurately the wall shear stress that provides more useful information to predict the formation of intimal hyperplasia, it is necessary to take the rheological effect of blood flows in to account. In this study, the non-Newtonian blood flows in different complexity of artery were numerically investigated by using 3D fully parallel incompressible fluid solver. Our fluid solver is developed based on generalized Newtonian fluid model, where the viscosity is the function of rate of strain tensor. More specifically, the more commonly-used model for blood flow simulation, the Carreau-Yasuda model, compared with Newtonian model are reported, including the investigation how the wall shear stress distribution and the streamlines and pressure distribution depend on different physiological conditions and arterial geometries.

Thesis (M. Sc.)--York University, 1999. Graduate Programme in Kinesiology and Health Science.
Typescript. Includes bibliographical references (leaves 77-83). Also available on the Internet. MODE OF ACCESS via web browser by entering the following URL: http://wwwlib.umi.com/cr/yorku/fullcit?pMQ39205.

Mestrado de dupla diplomação com o Centro Federal de Educação Tecnológica Celso Suckow da Fonseca - Cefet/RJ
Intracranial aneurysm (IA) is a cerebrovascular disease with high rates of mortality and morbidity when it ruptures. It is known that changes in the intra-aneurysmal hemodynamic load play a significant factor in the development and rupture of IA. However, these factors are not fully understood. In this sense, the main objective of this work is to study the hemodynamic behavior during the blood analogues flow inside an AI and to determine its influence on the evolution of this pathology. To this end, experimental and numerical studies were carried out, using a real AI model obtained using computerized angiography. In the experimental approach, it was necessary, in the initial phase, to develop and manufacture biomodels from medical images of real aneurysms. Two techniques were used to manufacture the biomodels: rapid prototyping and gravity casting. The materials used to obtain the biomodels were of low cost. After manufacture, the biomodels were compared to each other for their transparency and final structure and proved to be suitable for testing flow visualizations. Numerical studies were performed with the aid of the Ansys Fluent software, using computational fluid dynamics (CFD), using the finite volume method. Subsequently, flow tests were performed experimentally and numerically using flow rates calculated from the velocity curve of a patient's doppler test. The experimental and numerical tests, in steady-state, made it possible to visualize the three-dimensional behavior of the flow inside the aneurysm, identifying the vortex zones created throughout the cardiac cycle. Correlating the results obtained in the two analyzes, it was possible to identify that the areas of vortexes are characterized by low speed and with increasing the fluid flow, the vortexes are positioned closer to the wall. These characteristics are associated with the rupture of an intracranial aneurysm. There was also a good qualitative correlation between numerical and experimental results.
O aneurisma intracraniano (AI) é uma patologia cerebrovascular com altas taxas de mortalidade e morbidade quando se rompe. Sabe-se que alterações na carga hemodinâmica intra-aneurismática exerce um fator significativo no desenvolvimento e ruptura de AI, porém, esses fatores não estão totalmente compreendidos. Nesse sentido, o objetivo principal deste trabalho é o de estudar o comportamento hemodinâmico durante o escoamento de fluidos análogos do sangue no interior de um AI e determinar a sua influência na evolução da patologia. Para tal, foram realizados estudos experimentais e numéricos, utilizando um modelo de AI real obtido por meio de uma angiografia computadorizada. Na abordagem experimental foi necessário, na fase inicial, desenvolver e fabricar biomodelos a partir de imagens médicas de um aneurisma real. No fabrico dos biomodelos foram utilizadas duas técnicas: a prototipagem rápida e o vazamento por gravidade. Os materiais utilizados para a obtenção dos biomodelos foram de baixo custo. Após a fabricação, os biomodelos foram comparados entre si quanto à sua transparência e estrutura final e verificou-se serem adequados para testes de visualizações do fluxo. Os estudos numéricos foram realizados com recurso ao software Ansys Fluent, utilizando a dinâmica dos fluidos computacional (CFD), através do método dos volumes finitos. Posteriormente, foram realizados testes de escoamento experimentais e numéricos, utilizando caudais determinados a partir da curva de velocidades do ensaio doppler de um paciente. Os testes experimentais e numéricos, em regime permanente, possibilitaram a visualização do comportamento tridimensional do fluxo no interior do aneurisma, identificando as zonas de vórtices criadas ao longo do ciclo cardíaco. Correlacionando os resultados obtidos nas duas análises, foi possível identificar que as áreas de vórtices são caracterizadas por uma baixa velocidade e com o aumento do caudal os vórtices posicionam-se mais próximos da parede. Essas características apresentadas estão associadas com a ruptura de aneurisma intracraniano. Verificou-se, também, uma boa correlação qualitativa entre os resultados numéricos e experimentais.

Inflammation is the response of the organism to eradicate the agent of lesion or infection in order to achieve hemostasis. This response requires the migration of specific leukocyte populations from the blood circulation towards the inflamed area. Leukocyte recruitment constitutes a complex cellular process by which leukocytes are first recruited to the endothelial vascular wall of post-capillary venules across which they further extravasate into the interstitial tissue. Recruitment is mediated via cell-cell interactions between the leukocyte and the endothelium and occurs through a multi-step cascade: tethering, rolling, slow rolling, arrest, crawling, adhesion and transmigration. However, whether or not the leukocytes adhere to the endothelium depends not only on the chemical forces generated by adhesion molecules on leukocytes and endothelial cells, but also on the physical forces that act on those cells. It has been suggested that fluid shear stress resulting from blood flow also regulates leukocyte activity which makes the fluid dynamic environment of the circulation to be considered an important aspect for leukocyte recruitment and migration during the inflammatory response. Most of the studies on the inflammatory response and in particular on leukocyte recruitment are based on animal models and involve, among others, the quantification of inflammatory mediators and cellular players, and/or the analysis of the leukocyte-endothelial cell interactions by intravital microscopy. However, the contribution of hemodynamics for leukocyte recruitment has been seldom addressed in those studies. This is mostly due to the fact that the study of hemodynamics in in vivo animal models is not straightforward and moreover, that several hemodynamic parameters cannot be experimentally determined due to technical constraints. In this work, we reasoned that these limitations could be circumvented by the development and use of numerical simulations to describe leukocyte recruitment. Many of the processes, which take place in living organisms, can be expressed as mathematical equations. This applies to leukocyte recruitment, for which scarce numerical models existed before the beginning of this work. Importantly, these mathematical simulations were performed without considering simultaneously all the players in the process, namely the vessel, the blood flow and the leukocytes. Moreover, most of these studies were two dimensional, assumed blood as a Newtonian fluid with constant viscosity and did not take into account in vivo experimental data. Taken this, our major goal with this work was to understand the contribution of hemodynamics to leukocyte recruitment in inflammation. For such purpose, we aimed here at developing numerical simulations that more adequately reproduced this process. For such, we set up animal models of inflammation to obtain the experimental data required for the development of those numerical simulations. Finally, we used these models to investigate the role of hemodynamics in leukocyte recruitment in inflammation. First, we considered the simpler case of a numerical simulation that assumed leukocytes to be rigid spheres and blood, a non-Newtonian fluid. For such, we initially developed an animal model of inflammation in Wistar rats using a lipopolysaccharide (LPS) as an inflammatory agent. Blood samples were collected for determination of TNF-α levels to ensure the triggering of the inflammatory process. Importantly, the number of rolling and adherent leukocytes in post-capillary venules was monitored using an intravital microscopy approach. As expected, our results showed that there is an increase in TNF-α concentrations after 15 minutes of LPS administration and a significant increase in the number of rolling and adherent leukocytes. The recorded intravital microcopy images, along with other recorded parameters, were then used, in collaboration with a group of mathematicians, to develop a numerical model capable of describing leukocyte recruitment in the microcirculation. To evaluate the contribution of hemodynamics, the localized velocity fields and shear stresses on the surface of leukocytes and near the vessel wall contact points have been computed in two discrete situations, namely as a single leukocyte or when a cluster of them are recruited towards the vessel wall. In the first situation, our numerical results showed the presence of one region of maximum shear stress on the surface of the leuko- cyte close to the endothelial wall and of two regions of minimum shear stress on the op- posite side of the cell. The different areas of shear stress observed in the surface of the leukocyte may be important in directing it towards the endothelial wall during an inflammatory response. The identification of a region of maximum shear stress is consistent with the molecular mechanisms that govern leukocyte rolling because it may actually cor- respond to the area that supports the interaction with the endothelium. On the other hand, the relatively lower shear stress regions may correlate with leukocyte surface areas where binding to the endothelium is not occurring at the moment, thus enabling the roll- ing of the cell along the endothelium. It was also observed that the shear stress at the endothelium gets higher as a cluster of leukocytes moves in the main stream. This sug- gests that the presence of a cluster of leukocytes may potentiate leukocyte rolling, as the increase in the shear stress promoted by the recruited leukocytes may support the migra- tion and recruitment of additional cells. Despite closely simulating leukocyte recruitment, our initial numerical simulation consid- ered the simple case of leukocytes as rigid spheres. However, while circulating leukocytes maintain an approximately spherical shape, rolling leukocytes are known to deform. In order to account for the leukocyte deformability changes that occur during its recruit- ment in inflammation, we needed to assess the deformability profile of the leukocytes under flow and therefore, to “directly” observe them regardless of the other blood cells. For such, intravital microscopy was performed in the mouse cremaster of a transgenic mice strain (Lys-EGFP-ki) in which fluorescent neutrophils can be individually tracked. By using PAF as an inflammatory agent, the analysis of the leukocyte-endothelial cell interac- tions showed a continuous increase in the number of rolling and adherent neutrophils up to 4 hours after the introduction of the inflammatory stimuli, thus confirming the devel- opment of an inflammatory response. As the properties of the red blood cells modulate blood flow properties, erythrocyte deformability was also addressed in this model. A con- tinuous decrease of this parameter was observed throughout time. The decrease in the erythrocyte deformability will most probably lead to an increase in the blood viscosity and to the decrease of the blood flow velocity. These conditions should facilitate the mi- gration of leukocytes from the mainstream to the endothelial wall and promote leukocyte slow rolling and adhesion during the inflammatory response. Importantly, in the intravital microcopy images obtained with this latter model, we clearly observed the deformation of neutrophils along the endothelial wall during rolling, as well as the formation of tethers. As such, in these images, leukocyte trajectories were tracked and their velocities and diameters were measured and further applied to the numerical simulations. Using a recent validated mathematical model describing the coupled defor- mation-flow of an individual leukocyte and the respective experimental results, numerical simulations of the recruitment of an individual leukocyte and of two leukocytes under different velocities were performed, considering a constant blood viscosity. The mathe- matical models obtained showed that under conditions of increased velocity the cell movement is accelerated along the endothelial layer, favouring the dissociation of leuko- cyte-endothelium interactions at designated attraction points. These observations lead us to propose that, in order to attain an efficient inflammatory response, the blood flow ve- locity needs so as to decrease to facilitate slow rolling and subsequent adhesion. These results are corroborated by the decrease in the erythrocyte deformability observed in our animal model, which will ultimately have an impact on the blood flow velocity. Our results further showed that in the vicinity of an adherent leukocyte there is an early slight decel- eration of the rolling leukocyte when compared with the case of an individual leukocyte. As such, these observations strongly suggest that the presence of an adherent cell in the vicinity should decrease the velocity of another leukocyte that is being recruited, thus promoting its slow rolling, and contributing to its capture by the endothelial cells. Altogether, our experimental data and numerical simulations support our working hy- pothesis that the hemodynamic properties of the flow and of the cells in circulation should play an essential role in the margination and rolling of the leukocytes to the endo- thelial wall, which in turn will impact the success of the inflammatory response. In partic- ular, our results strongly suggest that changes in hemodynamic conditions, such as de- creased flow velocities and the increase of the shear stress, will contribute to target leu- kocytes to the endothelial wall. Given our results, we propose that any change in the he- modynamic properties will certainly influence the outcome of the inflammatory response. As such, the adherence of the leukocytes to the endothelium should depend not only on the relative magnitude of the chemical forces generated by the interaction of adhesion molecules between leukocytes and endothelial cells, but also on the physical forces that act on the leukocytes. In this respect, our results suggest that alterations in the blood flow, for example in the flow velocity, will occur during an inflammatory process, thus potentiating the recruitment of more leukocytes towards the inflamed area and contrib- uting to a successful inflammatory response. Overall, the numerical simulations allowed us to better understand the contribution of the hemodynamic properties of the flow to the progression of an inflammatory response and to deepen our knowledge on leukocyte recruitment in inflammation. Importantly, our work provided numerical tools that can be used for the subsequent study and modulation of the hemodynamic parameters involved in an inflammatory response. In particular, these numerical simulations will surely enable us, in the near future, to determine or es- timate a large set of parameters which are unlikely to be recoverable by in vivo experi- ments. Moreover, our methods will allow us to analyze how the parameters evolve over time. Altogether our results further reinforce the notion that the improvement and de- velopment of animal models and numerical tools will certainly provide the medical and biological community with useful tools to study leukocyte recruitment in inflammation. By closely reproducing the microcirculation and the inflammatory process, these tools will be critical for a better comprehension of the inflammatory process and of the mecha- nisms underlying a multitude of inflammatory pathological conditions.

Indiana University-Purdue University Indianapolis (IUPUI)
Atherosclerotic lesions of human beings are common diagnosed in regions of arte- rial branching and curvature. The prevalence of atherosclerosis is usually associated with hardening and ballooning of aortic wall surfaces because of narrowing of flow path by the deposition of fatty materials, platelets and influx of plasma through in- timal wall of Aorta. High Wall Shear Stress (WSS) is proved to be the main cause behind all these aortic diseases by physicians and researchers. Due to the fact that the atherosclerotic regions are associated with complex blood flow patterns, it has believed that hemodynamics and fluid-structure interaction play important roles in regulating atherogenesis. As one of the most complex flow situations found in cardio- vascular system due to the strong curvature effects, irregular geometry, tapering and branching, and twisting, theoretical prediction and in vivo quantitative experimental data regarding to the complex blood flow dynamics are substantial paucity. In recent years, computational fluid dynamics (CFD) has emerged as a popular research tool to study the characteristics of aortic flow and aim to enhance the understanding of the underlying physics behind arteriosclerosis. In this research, we study the hemo- dynamics and flow-vessel interaction in patient specific normal (healthy) and dilated (diseased) aortas using Ansys-Fluent and Ansys-Workbench. The computation con- sists of three parts: segmentation of arterial geometry for the CFD simulation from computed tomography (CT) scanning data using MIMICS; finite volume simulation of hemodynamics of steady and pulsatile flow using Ansys-Fluent; an attempt to perform the Fluid Structure Simulation of the normal aorta using Ansys-Workbench. Instead of neglecting the branching or smoothing out the wall for simplification as a lot of similar computation in literature, we use the exact aortic geometry. Segmen- tation from real time CT images from two patients, one young and another old to represent healthy and diseased aorta respectively, is on MIMICS. The MIMICS seg- mentation operation includes: first cropping the required part of aorta from CT dicom data of the whole chest, masking of the aorta from coronal, axial and saggital views of the same to extract the exact 3D geometry of the aorta. Next step was to perform surface improvement using MIMICS 3-matic module to repair for holes, noise shells and overlapping triangles to create a good quality surface of the geometry. A hexahe- dral volume mesh was created in T-Grid. Since T-grid cannot recognize the geometry format created by MIMICS 3-matic; the required step geometry file was created in Pro-Engineer. After the meshing operation is performed, the mesh is exported to Ansys Fluent to perform the required fluid simulation imposing adequate boundary conditions accordingly. Two types of study are performed for hemodynamics. First is a steady flow driven by specified parabolic velocity at inlet. We captured the flow feature such as skewness of velocity around the aortic arch regions and vortices pairs, which are in good agreement with open data in literature. Second is a pulsatile flow. Two pulsatile velocity profiles are imposed at the inlet of healthy and diseased aorta respectively. The pulsatile analysis was accomplished for peak systolic, mid systolic and diastolic phase of the entire cardiac cycle. During peak systole and mid-systole, high WSS was found at the aortic branch roots and arch regions and diastole resulted in flow reversals and low WSS values due to small aortic inflow. In brief, areas of sudden geometry change, i.e. the branch roots and irregular surfaces of the geom- etry experience more WSS. Also it was found that dilated aorta has more sporadic nature of WSS in different regions than normal aorta which displays a more uniform WSS distribution all over the aorta surface. Fluid-Structure Interaction simulation is performed on Ansys-WorkBench through the coupling of fluid dynamics and solid mechanics. Focus is on the maximum displacement and equivalent stress to find out the future failure regions for the peak velocity of the cardiac cycle.