Aortic Valve Analysis and Area Prediction using Bayesian Modeling Miheer S. Ghotikar ABSTRACT Aortic valve stenosis affects approximately 5 out of every 10,000 people in the United States. [3] This disorder causes decrease in the aortic valve opening area increasing resistance to blood flow. Detection of early stages of valve malfunction is an important area of research to enable new treatments and develop strategies in order to delay degenerative progression. Analysis of relationship between valve properties and hemodynamic factors is critical to develop and validate these strategies. Porcine aortic valves are anatomically analogous to human aortic valves. Fixation agents modify the valves in such a manner to mimic increased leaflet stiffness due to early degeneration. In this study, porcine valves treated with glutaraldehyde, a cross-linking agent and ethanol, a dehydrating agent were used to alter leaflet material properties. The hydraulic performance of ethanol and glutaraldehyde treated valves was compared to fresh valves using a programmable pulse duplicator that could simulate physiological conditions. Hydraulic conditions in the pulse duplicator were modified by varying mean flow rate and mean arterial pressure. Pressure drops across the aortic valve, flow rate and back pressure (mean arterial pressure) values were recorded at successive instants of time. Corresponding values of pressure gradient were measured, while aortic valve opening area was obtained from photographic data. Effects of glutaradehyde cross-linking and ethanol dehydration on the aortic valve area for different hydraulic conditions that emulated hemodynamic physiological conditions were analyzed and it was observed that glutaradehyde and ethanol fixation causes changes in aortic valve opening and closing patterns. Next, relations between material properties, experimental conditions, and hydraulic measures of valve performance were studied using a Bayesian model approach. The primary hypothesis tested in this study was that a Bayesian network could be used to predict dynamic changes in the aortic valve area given the hemodynamic conditions. A Bayesian network encodes probabilistic relationships among variables of interest, also representing causal relationships between temporal antecedents and outcomes. A Learning Bayesian Network was constructed; direct acyclic graphs were drawn in GeNIe 2.0ʾ using an information theory dependency algorithm. Mutual Information was calculated between every set of parameters. Conditional probability tables and cut-sets were obtained from the data with the use of Matlabʾ. A Bayesian model was built for predicting dynamic values of opening and closing area for fresh, ethanol fixed and glutaradehyde fixed aortic valves for a set of hemodynamic conditions. Separate models were made for opening and closing cycles. The models predicted aortic valve area for fresh, ethanol fixed and glutaraldehyde fixed valves. As per the results obtained from the model, it can be concluded that the Bayesian network works successfully with the performance of porcine valves in a pulse duplicator. Further work would include building the Bayesian network with additional parameters and patient data for predicting aortic valve area of patients with progressive stenosis. The important feature would be to predict valve degenration based on valve opening or closing pattern.

Orientador: Josimeri Hebling / Resumo: Objetivo: Avaliar a estabilidade mecânica e a atividade proteolítica de interfaces produzidas pela apliação de um adesivo convencional simplificado sobre a dentina biomodificada e seca. Métodos: Superfícies planas de dentina coronária foram criadas em 64 molares hígidos. Os dentes foram divididos em 4 grupos de acordo com a solução aplicada sobre a dentina condicionada: extrato de semente de uva 5% (GSE), glutaraldeído 5% (GD), Gluma Desensitizer ou água (controle). As soluções foram aplicadas por 60s seguido de lavagem e secagem com papel absorvente. Os dentes foram então subdivididos em dois grupos, nos quais a dentina condicionada foi mantida úmida ou foi seca com ar por 60s. O adesivo Optibond foi aplicado e em seguida foi construído um cilindro de resina. Decorridas 24h, os dentes foram cortados em espécimes (0,81 mm2 ), submetidos ao ensaio de microtração imediatamente ou após 12 meses de envelhecimento. Os mesmos procedimentos adesivos foram realizados em 32 dentes adicionais. Esses dentes foram seccionados em fatias de 0,5 mm de espessura, preparadas para os ensaios de nanoinfiltração e zimografia in situ (EnzChek). Os dados de resistência de união foram submetidos aos testes de ANOVA e Tukey (p<0,05), e os ensaios de nanoinfiltração e zimografia in situ foram apresentados descritivamente. Resultados: Redução significante da resistência de união imediata (ca. 65%) e aumento da atividade proteolítica e nanoilfiltração foi observado em interfaces produzidas sobre a dent... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Objective: To evaluate the mechanical stability and the proteolytic activity of bonds created by a one-step, etch-and-rinse adhesive applied to cross-linked and air-dried etched dentin. Methods: Flat coronal dentin surfaces were produced in 64 sound molars. The teeth were divided into 4 groups according to the solution applied on the etched dentin: 5% grape seed extract, 5% glutaraldehyde, Gluma Desensitizer or deionized water (control). Solutions were applied for 60s followed by rinse and blot drying. Then, the teeth were separated into two subgroups: the etched dentin was kept moist or air dried for 60s. Optibond was applied followed by a composite resin buildup. After 24h, the teeth were cut into beams (0.81 mm²) which were microtensile tested immediately or after 12mo of storage. Additional teeth (n=32) were bonded as described and cut into 0.5 mm-thick slabs. The slabs were prepared for nanoleakage and in situ zymography analyses (EnzChek). Bond strength data were submitted to ANOVA and Tukey tests (p<0.05) while nanoleakage and zymography data were descriptively reported. Results: Significant reduction in bond strength (ca. 65%) and increase of the proteolytic activity was seen when the etched dentin was air-dried without previous biomodification. Conversely, bond strengths did not differ from those produced on wet dentin when collagen was cross-linked before air-drying, irrespective of the solution. For both moist and air-dried etched dentin, collagen cross-linking res... (Complete abstract click electronic access below) / Mestre

Dans le cadre de cette thèse, les dérivés d’huiles végétales sont utilisés pour la synthèse de bioplastifiants bio-résistants pour le PVC d’une part et la plastification et la réticulation d’un élastomère d’autre part (EPDM). Les huiles ont été choisies comme matières premières renouvelables car elles ont des fonctions esters qui permettent la solubilisation du PVC et des chaines grasses compatibles avec l’EPDM. Les réactions d’ouvertures d’époxydes d’esters gras en di-esters (symétriques et dissymétriques) ont été étudiées et principalement appliquées à la plastification du PVC. L’ouverture des époxydes d’esters gras en éther-esters a aussi été étudiée, principalement pour la plastification de l’EPDM. Les conditions réactionnelles ont été optimisées par l’étude de catalyseurs, homogène (TBACl) et hétérogène (TiO2) pour l’ouverture en hydroxy-ester, et par des résines sulfoniques pour l’ouverture en éther et pour l’estérification des hydroxyles résiduels. Une large variété de réactifs choisis suivant l’application désirée a été utilisée. Le dérivé cyclohexanoate/acétate d’esters méthyliques de colza présente les meilleures propriétés plastifiantes pour le PVC mais il n’est malheureusement pas biorésistant. Les dérivés éther-ester ne sont pas stables thermiquement et ne permettent pas la plastification de l’EPDM. Un dérivé di-insaturé et peu polaire (oléate d’oléyle) a été synthétisé en vue de la plastification et la réticulation de l’EPDM. Plusieurs réactions ont été examinées pour lier l’huile et le polymère (hydrosilylation, ène-réaction et métathèse) mais la réactivité est trop faible pour permettre la réticulation / During this thesis, derivatives of vegetable oils are used to synthesize bio-resistant bio plasticizers for PVC and plasticizer / cross linker for an elastomer (EPDM). The oils possess ester functional groups which allow the solubilization of PVC and fatty chains compatible with EPDM. The reactions of epoxide ring-opening of fatty esters to di esters (symmetrical and asymmetrical) have been studied and applied mainly to the plasticization of PVC. The ring-opening of epoxides of fatty esters to ether-esters has also been studied, primarily for plasticization of EPDM. Optimization of the reaction conditions was carried: homogeneous (TBACl) and heterogeneous (TiO2) catalysts were efficient for the preparation of hydroxy-ester, and sulfonic resins in ether and the esterification of residual hydroxyls. A wide variety of reagents selected according to desired application were used. The derivative cyclohexanoate / acetate rapeseed methyl esters present the best plasticizing properties for PVC but it is unfortunately not bio-resistant. Ether-ester derivatives are not stable thermally and do not allow the plasticization of EPDM. A relatively non-polar di-unsaturated derivative (oleyl oleate) was synthesized for the plasticization and cross linking of EPDM. Several reactions are considered to link the oil and the polymer (hydrosilylation, ene- reaction and metathesis), but the reactivity is too low to allow the cross linking