Atherothrombosis can induce acute myocardial infarction and stroke by progressive stenosis of a blood vessel lumen to full occlusion. The goal of this research is to determine what shear rates are pertinent to an occluding blood vessel, the rate of thrombus growth relative to wall shear rates, and to develop a predictive model for estimating length of time to thrombus occlusion for a given atherosclerotic lesion. Computational studies of severely stenotic idealized vessels were performed to investigate the wall shear rates that may exist. The study shows that maximum shear rates in severe short stenoses were found to exceed 250,000 1/s (9,500 dynes/cm2). We utilize an in vitro experiment consisting of blood flow through a collagen coated stenosis to study the rate of thrombus growth. Growth is monitored through light microscopy and a camera. Computational fluid dynamics are used to determine shear rates along the thrombus surface as it grows. We found a strong positive correlation between thrombus growth rates and shear rates up to 6,000 1/s after a log-log transformation (r=0.85, p<0.0001). Growth rates at pathologic shear rates were typically 2-4 times greater than for physiologic shear rates below 400 s-1. To determine whether transport or kinetic binding limits the rate of thrombus growth, a computational model of platelet transport was developed. The model allows for thrombus growth by occluding computational cells. We show that thrombus is transport rate-limited for shear rates below 6,000 1/s, while it is more likely to be kinetic rate-limited for higher shear rates. Predictions of occlusion times based on the model demonstrate that increases in stenosis severity results in decreased time to occlusion.

A computational model of thrombus initiation and aggrandizement was proposed. The model separated the thrombotic process into three mechanisms, including shear enhanced diffusivity, platelet margination, and platelet adhesion. The model indicates that transport mechanisms may be the rate limiting condition of thrombus formation at physiological shear rates and that at higher shear rates; platelet binding becomes the rate limiting condition. Additionally a wall shear rate of 20000 s-1 and above should be considered as a new criterion for prophylactic treatment of an atherosclerotic lesion.

Ventricle Assist Devices (VADs), which are typically either axial or centrifugal flow pumps implanted on the aortic arch, have been used to support patients who are awaiting cardiac transplantation. Success of the apparatus in the short term has led to long term use. Despite anticoagulation measures, blood clots (thrombi) have been known to form in the device itself or inside of the heart. The Ventricle Assist Devices supply blood flow via a conduit (cannula) implanted on the ascending aorta. Currently, the implantation angle of the VAD cannula is not taken into consideration. Since the VADs supply a significant amount of blood flow to the aorta, the implantation angle can greatly affect the trajectory of the formed thrombi as well as the cardiac flow field inside of the aortic arch. This study aims to vary the implantation angle of a pediatric Left Ventricle Assist Device (LVAD) through a series of computational fluid dynamics (CFD) software simulations focusing on the aortic arch and its branching arteries of a 20 kg pediatric patient in order to reduce the occurrence of stroke.

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L'objectif de ce travail est de contribuer à une meilleure prédiction de la rupture des Anévrismes de l'Aorte Abdominale. Pour ce faire, des simulations par éléments finis ont été mises en oeuvre sur des anévrismes modèles dans des conditions proches de la réalité physiopathologique, i.e. en tenant compte de l'anisotropie de la paroi anévrismale, du caractère poreux du thrombus et des Interactions Fluide-Structure. Dans la première partie, une étude statique en l'absence du thrombus a permis de mettre en évidence l'influence de la géométrie de l'anévrisme et du comportement mécanique (isotrope ou anisotrope) de la paroi sur la distribution des contraintes, i.e. la rupture potentielle de l'anévrisme, ainsi que sur l'évolution du module de Peterson. Dans la seconde partie, une modélisation poro-hyperélastique du thrombus est proposée, en s'appuyant sur des données expérimentales de la littérature. La prise en compte de ce comportement et des Interactions Fluide-Structure montre que la pression intra-thrombus demeure du même ordre de grandeur que la pression intra-luminale, conformément à des mesures in vivo réalisées par ailleurs. Enfin, nous montrons que ceci n'est pas en contradiction avec une réduction du risque de rupture potentielle de l'anévrisme.

The aim of this thesis is the problematic of abdominal aortic aneurysm wall stress in relation to a different material behavior of intraluminal thrombus, which is in most cases present in the aneurysmal volume. In this thesis, the influence of neglecting the patient-specific material properties of the intraluminal thrombus, on the aneurysmal wall stress, obtained from finite element stress-strain analysis, is investigated. In terms of solution method selection, a system approach was applied so that the solution method was selected in order to respect a system of essential variables as much as possible. The first part of this thesis is focused on a description of the problematic and the human cardiovascular system with important aspects contributing to development and growth of the abdominal aortic aneurysm. Next, this part of the thesis includes chapters devoted to the intraluminal thrombus in terms of its basic characteristics (anatomy, physiology, pathology), structure and its influence on processes within the abdominal aneurysm. The second part of this work is devoted to the accomplishment of the first and second goal of this thesis, which is analyzing the available literature to obtain mean population stiffness values of the intraluminal thrombus and conducting biaxial experimental tests of provided samples of intraluminal thrombus. The experimental testing was conducted in order to obtain the patient-specific mechanical properties, which are used as the inputs in the finite element analysis. The experimental testing confirmed the stiffness negligibility of the intraluminal thrombus’s outer layer, which is mentioned is several studies, however, the influence of this layer on resulting aneurysmal wall stress has been to this date not tested. The dominant part of this thesis is focused on the third goal of this work, which is a comparison of aneurysmal wall stress obtained from the finite element computation that included mechanical properties of intraluminal thrombus obtained either from the literature analysis of experimental testing. This part includes discerption of idealized geometry model development, which was used to analyze the sensibility of computed stresses on a number of ILT layers representing different material properties. In order to obtain this analysis, a macro was created prescribing each element of the intraluminal thrombus finite element mesh with material properties derived from its distance from the lumen. Next, this chapter contains description of patient-specific geometry models development, material models, and boundary conditions selection. In the end of this part, results of the finite element computations are presented together with their statistical analysis. Within the last part of this thesis, discussion of results and conclusions of this thesis is included. Also, an overview of important aspects entering computational modeling of abdominal aortic aneurysms is presented.

This thesis deals with stress strain analysis of an aortic abdominal aneurysm (AAA) and the influence of its contact with the spine on the extreme wall stress. The influence was tested on the idealized geometry, as well as on ten patient specific geometries obtained from computer tomography (CT-A) scans. Hyperelastic constitutive models were used for the AAA wall and intraluminal thrombus (ILT) tissue description. The prestress algorithm was used for reconstruction of the unloaded geometry to get more trustworthy results against the geometry from CT which was obtained under the blood pressure. Statistical analysis was used for the results evaluation. The maximal increase of peak wall stress was as high as 81 %.

This paper deals with the problem of abdominal aortic aneurysms (AAA), taking into account the possibility of using mechanical tests of aortic tissues for improvement of level of their constitutive models. First part of thesis deals with the introduction into the problem, description of the structure of the wall of the healthy aorta, its main components and the degenerative changes which lead to formation of AAA. This is followed by a brief excursion into constitutive modeling, which focuses closely on the description of the models used to describe the mechanical behavior of soft tissues. The theoretical part is then supplemented by a narrower selection of constitutive models used for modeling aortic wall and intraluminal thrombus, together with published results, which are reviewed and discussed at the end of this section. The main part of this thesis is devoted to tests of mechanical properties of arterial tissues. First, the methodology is presented together with the description of the customizations of the laboratory equipments together with the test rig. In addition, attention is focused on the results of mechanical tests of intraluminal thrombus, where the results of both uniaxial tensile tests and equbiaxial testing are presented. Also the influence of distance ILT from the lumen on the mechanical properties of the thrombus is examined. Another area of interest is the investigation of the effect of elastase on the chnage of mechanical properties of pig aorta. In this case, porcine aortas are experimentally tested only by biaxial testing, and the time of elastase action to alter the mechanical properties is analyzed so that the resulting tissue has a similar stress-strain response as aneurysmal tissue. Finally, the results of experimental measurements, limitations and other possible ways of research are summarized.

L’activité plaquettaire joue un rôle clé dans la physiopathologie de l’infarctus du myocarde avec sus-décalage du segment ST (IDM ST+). La réactivité plaquettaire est augmentée lors d’un IDM ST+, traité par angioplastie primaire ou par fibrinolyse avec succès. La relation entre la réactivité plaquettaire résiduelle après un pré-traitement, la charge athérothrombotique et la qualité de la reperfusion myocardique reste peu décrite dans le cadre des IDM ST+. La tomographie par cohérence optique et celle plus récente par domaine de fréquence offrent une imagerie de haute résolution permettant l’identification et la quantification précise de la charge athérothrombotique intracoronaire (CAT). La CAT résiduelle intra-stent peut aider à mieux comprendre la relation entre la réactivité plaquettaire et la reperfusion. Dans un premier temps, nous avons évalué la précision des tests VerifyNow et PFA en comparaison à l’agrégométrie optique pour la détection de l’hyperréactivité plaquettaire dans le contexte particulier des IDM ST+ traités par fibrinolyse avec succès. Nous avons aussi décrit les caractéristiques de la CAT avant et après angioplastie selon la présence d’une rupture de plaque ou d’une érosion coronaire chez des patients traités par fibrinolyse avec succès. Ensuite, nous avons étudié la relation entre la réactivité plaquettaire résiduelle (en réponse au ticagrelor et à l’aspirine) mesurée par VerifyNow et la reperfusion myocardique chez des patients traités par angioplastie primaire. En parallèle, nous avons décrit la relation entre la reperfusion myocardique et la CAT résiduelle intra-stent dans la même cohorte. / Platelet activity plays a key role in the pathophysiology of ST-segment elevation myocardial infarction (STEMI). Platelet reactivity is enhanced after STEMI treated with primary percutaneous coronary intervention (PCI) or successful thrombolysis. The relationship between residual platelet reactivity after pre-treatment, the atherothrombotic burden and the quality of reperfusion remains poorly described in STEMI. Optical coherence tomography (OCT) and optical frequency domain imaging (OFDI) provide high resolution imaging allowing identification and accurate quantification of intracoronary atherothrombotic burden (ATB). Residual in-stent ATB may help to better understand the relation between platelet reactivity and reperfusion. First, we assessed the accuracy of the point-of-care tests VerifyNow and PFA in comparison to light transmittance aggregometry to detect high on-treatment platelet reactivity (HPR) in the particular setting of STEMI successfully treated with fibrinolysis. We also described the characteristics of ATB before and after PCI according to the underlying presence of rupture or erosion in patients successfully treated with fibrinolysis. Then, we assessed the relationship between residual platelet reactivity (in response to ticagrelor and aspirin) using VerifyNow and myocardial reperfusion in primary PCI patients. In parallel, we studied the relationship between myocardial reperfusion and residual in-stent ATB in the same cohort.

Venous disease will affect 1-3% of the western world at some point in their lives, yet there are few effective treatments for the venous system [1]. One such disease is chronic venous insufficiency (CVI), a painful and debilitating illness that affects the superficial and deep vein valves of the legs. When the valves become incompetent they allow reflux and subsequent pooling of blood. Current clinical therapies are only moderately; and therefore, the need for a better solution remains. Prosthetic venous valves were constructed from a novel hydrogel biomaterial patented by Georgia Tech. The valves had flexible cusps similar to normal, anatomic venous valves. The purpose of this work was to evaluate the thrombotic potential of the GT venous valve in an in vitro study and to design a percutaneous delivery system. In vitro thrombosis model provides an appropriate intermediate step between valve development and in vivo analysis, which is necessary to determine the biocompatibility of the prosthetic device. The flow system was modified from a one-pass, flow-through thrombosis assay using whole blood [2] to mimic pulsatile physiologic conditions. Cessation of flow indicated thrombotic obstruction. Histological analysis was performed using H and E staining and Carstairs stain (specific for platelets). A group of valves were lined with Dacron to confirm the thrombotic potential of the system. All Dacron valves were occluded by thrombus connecting the polymer fibers with adherent platelets. Whole blood perfused through the GT prosthetic valves exhibited no thrombosis or platelet adherence. All GT valves were patent and competent after blood perfusion. H and E staining revealed no thrombus deposition on the GT vein valves. A percutaneous delivery system was designed after evaluating the GT valves for their compressibility and plastic deformation over time. Appropriate stents, catheters and sheaths were selected. As designed, this system will be utilized in an ovine trial of the valve. Due to the low in vitro thrombotic potential and strong history of PVA as a medical implant material, positive trial results are expected. With successful animal and human trials this valve can provide a potential intervention for the 7 million people suffering from CVI.