A sonotrombólise pela combinação de ultrassom (US) e microbolhas com medicamento trombolítico tem indicado grande eficácia na quebra de coágulos in vitro, devido a efeitos de cavitação. Contudo, estudos in vivo sobre drug delivery demonstram que a cavitação de microbolhas é também capaz de abrir local e transientemente a barreira hematoencefálica (BHE) - estrutura de permeabilidade seletiva que protege o Sistema Nervoso Central. Um estudo clínico sobre sonotrombólise foi interrompido precocemente devido a evolução de casos de Acidente Vascular Cerebral isquêmicos para hemorrágicos associados a danos na BHE e formação de ondas estacionárias. Nesta tese, foram realizados estudos in vitro e in vivo sobre técnicas de US multifrequencial para trombólise. Além disso, verificou-se os limiares para a abertura da BHE e efeitos de neuromodulação ambos causados pelo ultrassom transcraniano. Foi demonstrado que o duplo feixe de US e a variação temporal de frequências (excitação codificada) são capazes de reduzir a formação de ondas estacionárias e gerar regiões focais mais confinadas do que feixes focalizados monofrequenciais. O duplo feixe foi incapaz de gerar ondas de baixa frequência para trombólise (menor ou igual a 1 Pa para feixes primários de 1,58 MPa). Exames histológicos e por imagens de ressonância magnética mostraram que a cavitação de microbolhas pode causar danos ao tecido cerebral para níveis de pressão de mesma ordem necessários para se observar efeito trombolítico. Além disso, foi observado que o US é capaz de disparar atividade neuronal causando respostas motoras e indícios de respostas associadas a modulação de atividades cognitivas. A focalização de feixes por excitação multifrequencial é um grande avanço para sonotrombólise. Contudo, a potencialização do efeito trombolítico do US por cavitação e medicamento é limitada devido a danos a BHE e critérios de exclusão do medicamento. / Sonothrombolysis by combining ultrasound (US) and microbubbles with thrombolytic drugs has been demonstrated capable of breaking blood clots in in vitro studies, due to cavitation effects. However, in vivo drug delivery studies have demonstrated that cavitation of microbubbles is also capable of opening locally and transiently the blood-brain barrier (BBB) - structure with selective permeability that protects the Central Nervous System. A sonothrombolysis clinical study was interrupted prematurely because of the occurrence of intracerebral hemorrhages after treatment associated with damages in the BBB and standing waves formation. In this dissertation, in vitro and in vivo studies evaluated techniques of multifrequency US for thrombolysis. Furthermore, the ultrasound pressure threshold to obtain the BBB opening and neuromodulation effects were explored during transcranial insonation. It has been demonstrated that the double US beam and the time variation of frequencies (coded excitation) are capable of reducing standing wave formation and generating more confined focus zones than monofrequency focused beams. The double US beam was not capable of generating low frequency waves for thrombolysis (less than or equal to 1 Pa obtained from primary beams with 1.58 MPa). Histological exams and magnetic resonance images demonstrated that microbubbles cavitation can damage the brain tissue with acoustic pressures of the same level necessary to observe thrombolytic effects. Furthermore, it was observed motor responses and other responses associated with cognitive activity triggered by US. The capability of multifrequency excitation in focusing US beams is an important advance for sonothrombolysis. However, the enhancement of fibrinolytic effect of US by microbubbles cavitation and with thrombolytic drugs is limited by associated damages to the BBB and by exclusion criteria for the use of the thrombolytic drugs.

O presente trabalho reúne elementos teóricos e experimentais envolvendo os principais fenômenos hidráulicos causadores de danos em bombas hidráulicas de fluxo radial de grande porte. A preocupação do texto está centrada em proporcionar um aprofundamento técnico acerca destes fenômenos hidráulicos de cavitação, a fim de contribuir na análise e solução de problemas em sistemas de bombeamento. Além disso, este trabalho tem a pretensão de transmitir alguma experiência prática fornecida por um evento em que foi detectada a ocorrência de dois destes fenômenos hidráulicos simultâneos em um sistema de bombeamento e a partir disso, realizou-se a análise completa deste evento, incluindo as propostas de solução aos problemas encontrados, as análises técnica e econômica das alternativas de solução e a análise após a implantação da proposta escolhida. O texto apresenta também uma grande quantidade de gráficos e figuras que buscam facilitar a compreensão das definições e das análises dos fenômenos hidráulicos, além de exemplificar os danos típicos dos fenômenos pela visualização direta destes danos nas bombas. / This work presents theoretical and experimental data on the principal hydraulic phenomena responsible for damage in high loaded radial flow hydraulic pumps. The main objective is to provide a technical overview in order to contribute for the analysis and solution on these cavitation pumping systems problems. In addition this work intends to transmit practical experience through a “study of case" where two simultaneous of these hydraulic phenomena were detected. The complete analysis of technical and economical aspects of the alternatives solutions is presented including a great amount of graphs and illustrations that better explain the phenomena of cavitation in hydraulic pumps.

The effect of acoustic and hydrodynamic cavitation on the precipitation of inorganic catalytic materials was investigated. The overall objective was to understand the fundamental factors involved in synthesizing nanometer-size catalytic materials in the 1-10 nm range in a cavitating field. Materials with grain sizes in this range have been associated with enhanced catalytic activity compared to larger grain size materials. A new chemical approach was used to produce titania supported gold by coprecipitation with higher gold yields compared to other synthesis methods. Using this approach, it was determined that acoustic cavitation was unable to influence the gold mean crystallite size compared to non-sonicated catalysts. However, gold concentration on the catalysts was found to be very important for CO oxidation activity. By decreasing the gold concentration from a weight loading of 0.50% down to approximately 0.05%, the rate of reaction per mole of gold was found to increase by a factor of 19. Hydrodynamic cavitation at low pressures (6.9-48 bar) was determined to have no effect on gold crystallite size at a fixed gold content for the same precipitation technique used in the acoustic cavitation studies. By changing the chemistry of the precipitation system, however, it was found that a synergy existed between the dilution of the gold precursor solution, the orifice diameter, and the reducing agent addition rate. Individually, these factors were found to have little effect and only their interaction allowed gold grain size control in the range of 8-80 nm. Further modification of the system chemistry and the use of hydrodynamic cavitation at pressures in excess of 690 bar allowed the systematic control of gold crystallite size in the range of 2-9 nm for catalysts containing (2.27 ± 0.17)% gold. In addition, it was shown that the enhanced mixing due to cavitation led to larger gold yields compared to classical syntheses. The control of gold grain size was gained at the loss of CO activity, which was attributed to the formation of non-removable sodium titanate species. The increased mixing associated with cavitation contributed to the activity loss by partially burying the gold and incorporating more of the sodium titanate species into the catalysts. This work produced the first evidence of hydrodynamic cavitation influencing the gold crystallite size on titania supported gold catalysts and is the only study reporting the control of grain size by simple mechanical adjustment of the experimental parameters. Despite the low activity observed due to sodium titanate, the methodology of adjusting the chemistry of a precipitating system could be used to eliminate such species. The approach of modifying the chemical precipitation kinetics relative to the dynamics of cavitation offers a general scheme for future research on cavitational processing effects.

"Two most important events in the history of lubrication theory are attributed to Reynolds and Sommerfeld. Reynolds derived the governing equations for lubricating films in simplifying the Navier-Stokes equations considering thin-film effects. Sommerfeld obtained a closed form analytical solution to the Reynolds equation for the long bearing (one-dimensional case) with fixed constant eccentricity which results in a point symmetric pressure profile compared to an arbitrary (ambient) level. In attempting to reconcile with experimental evidence, Gumbel advanced the argument that sub-ambient pressure in a fluid film is not possible. On the basis that the fluid film would rupture, he put forth that the sub-ambient portion of the Sommerfeld solution should be discarded, a proposition that is commonly recognized as the half-Sommerfeld solution (of Gumbel). Ever since Gumbel suggested this improvement, much interest remains regarding the physical process of rupture in bearing lubricating films. In lubrication literature, cavitation is used interchangeably with rupture to indicate a condition in which an abundance of a gas phase, essentially ambient air, is present in a portion of the bearing clearance. A cogent two-phase morphology for addressing cavitation in long bearings is postulated in order to predict time-dependent fluid behavior from an initial state that is a generalization of Gumbel’s half-Sommerfeld solution. The ultimate steady-state is presumed to satisfy the hypothesis of Swift and Stieber that an ambient condition is reached by the rupture point at an unspecified location simultaneously with a vanishing pressure gradient. A trans-rupture continuity equation, as proposed by Olsson, determines a formula for the speed of a moving rupture point requiring a specific model of the two-phase flow in the rupture region. Employing an adhered film model, sequential application of Olsson’s equation to the rupture points of the intermediate states between the half-Sommerfeld and Swift-Stieber states renders an interpretation of a time-dependent progression towards a steady-state solution. Closed form analytical formulas, which readily combine to provide an exact solution to the Reynolds equation are derived with the start (formation point) of the full-film other than the customary bearing maximum gap and with the rupture point at any assigned intermediate location. Each valid solution for an intermediate state yields an invariant flux that must satisfy a window of constraints to exclude the possibility of sub-ambient pressures. A complete set of such valid solutions exists for each fixed eccentricity and can be depicted as a contour plot of the invariant flux with formation and rupture points as coordinates. The method can readily be extended to two-dimensions, offering a promising alternative to the Elrod cavitation algorithm, which is commonly used in more comprehensive bearing analyses."

Thesis. 1979. Ph.D.--Massachusetts Institute of Technology. Dept. of Ocean Engineering. / MICROFICHE COPY AVAILABLE IN ARCHIVES AND ENGINEERING. / Bibliography: leaves 154-158. / Ph.D.

Ultrasound, applied in combination with microbubbles, has potential as a means to enhance the uptake of therapeutic agents, which could include drugs and nucleic acids, into biological cells. This process is commonly referred to as 'sonoporation', and the enhanced uptake can be caused through the incident ultrasonic pressure fi eld causing radial oscillations (cavitation) in the microbubbles, amongst other possibilities. However, the mechanisms responsible for any resultant increase in cell membrane permeability are not yet fully understood. This project focussed on achieving a more fundamental understanding of these salient processes by building on a platform of previous work within the group. One strand of the project involved a complete characterisation of the performance of a rotating mirror high speed camera (Cordin 550-62) that was previously used by our group [and others] to investigate microbubble cavitation phenomena and interactions with proximal cell membranes. Speci cally, I present herein an investigation into the image formation process with this type of camera, the essence of which stymied previous data interpretations. I demonstrate that an inherent asynchrony in the exposure of pixels within individual image frames leads to a temporal anomaly. This was achieved using low cost, flashing LED lights and resulted in the extraction of an algorithm to correct for the temporal anomaly. In a slightly diff erent context, the delivery of suitable ultrasonic fields is necessary to achieve a uniform treatment across a therapeutic target. This thesis also reports on a study on the design of ultrasonic lenses to alter the focal region of a focussed ultrasound transducer with the aim of producing focal regions that can enable sonoporation of tumours of varying sizes. We show that the use of lenses can be an inexpensive alternative to more complex systems such as phased array transducers. Design modelling and experimental testing of lens prototypes are presented along with preliminary results with tissue mimicking polyacrylamide gel phantoms. The target environment in which the process of sonoporation will be clinically useful (i.e. in the physiological circulation) can be simpli ed as a microfluidic system. One strategy for bubble mediated therapy involves the use of a pro-drug approach, that is, when two otherwise benign ingredients are loaded onto separate microbubble populations, but can become mixed at the anatomical target site by the action of focussed ultrasound whereupon a potent drug is produced. The required mixing can be achieved by the violent coalescence of nearby cavitating bubbles, their reaction product then being released and di ffused into the interiour of nearby cells through sonoporation. A study related to this field is presented here where laser induced thermocapillary flows are shown to cause mixing of the content of a drop in a microfluidic channel in a bid to understand the mixing process at a level that may assist future microbubble engineering strategy. To summarise then, the work presented in this thesis has consolidated earlier unpublished data sets achieved by the group, providing new and exacting experimental evidence and an accurate algorithm that will facilitate post-processing of that earlier data (Chapters 2-3). Moreover, group aspirations to translate earlier in-vitro work on sonoporation towards next phase medical-phantom exposures have been boosted through the provision of a new direction involving acoustic lensing, the experimental data from which was used to completely validate existing models for our own design scenarios (Chapter 4). Finally, previous unpublished observations on microbubble coalescence undertaken by the group suggested a means to implement pro-drug delivery with direct in-situ mixing. Such suggestions were explored within microfluidic contexts using lasers to control and visualise the mixing processes that might arise in such situations (Chapter 5). All of these new insights have served to consolidate the group's previous and as yet unpublished data, opening the way for dissemination with confidence in the integrity of that data, and have also extended group capability and expertise in the areas of MHz-rate high speed framing cameras, the fabrication of acoustic lenses, and with microfluidic mixing.

Ce travail de thèse porte sur la modélisation de la cavitation, phénomène par lequel se forment des bulles quasi vide dans un liquide en dépression. L'étude de la cavitation a donné lieu dans la littérature à plusieurs modèles. La quasi totalité de ces modèles font abstraction des interactions entre les bulles et de l'augmentation de la pression qui en résulte dans certaines phases d'évolution de la cavitation, comme l'ont observé expérimentalement Franc et al. (1995) et de Ohl (2002). Dans notre travail nous proposons un nouveau modèle d'évolution de la taille des bulles, dans lequel deux bulles non identiques sont localisées dans un volume en expansion contrôlée. La présence de deux bulles introduit une instabilité dans laquelle l'échange de vide apparaît comme un degré de liberté supplémentaire. Notre modèle inclut la possibilité pour de nombreuses petites bulles de disparaître ou non selon que leur rayon est inférieur ou pas au rayon critique. Selon ce modèle il peut y avoir de nombreux collapses de petites bulles dès l'apparition de la cavitation, ce qui est conforme à l'observation expérimentale d'un bruit dans la zone d'apparition de la cavitation Buogo et al. (2002). Le modèle révèle la pression comme une inconnue du problème pour laquelle nous avons pu mettre en évidence une équation d'évolution indépendante de celle de la masse volumique. La comparaison de la taille des bulles et de la pression en fonction du temps obtenue avec le modèle est en bon accord avec les mesures effectuées en 2002 par Ohl.

Le chargement dynamique des paliers hydrodynamiques et des amortisseurs à film fluide soumet le film lubrifiant à une action d'écrasement périodique. Cette sollicitation conditionne la portance du film lubrifiant et peut engendrer sa rupture, créant ainsi des conditions sévères de fonctionnement. L'étude approfondie, tant expérimentale que numérique du comportement du film soumis à une action d'écrasement périodique, s'avère donc indispensable pour pouvoir maîtriser les performances de ces dispositifs. <br /><br />Pour ce faire, trois codes de calcul numérique sont développés dans le cadre de cette thèse. Ces codes sont basés sur la théorie de JFO. Les équations établies sont discrétisées en différences finies et en éléments finis. Pour un film d'huile écrasé périodiquement, à faibles fréquences, entre deux surfaces conformes, les prédictions numériques de ces trois codes sont très proches. Par ailleurs, les visualisations numériques de la rupture dans les différents types de contacts ont montré l'impact de la fréquence des oscillations sur l'étendue et la durée de la rupture de film. <br /><br />L'étude expérimentale est conduite via un banc d'essai conçu puis réalisé. Deux modes de rupture de film sont identifiés : la rupture par séparation des gaz saturés et la rupture par séparation due à l'introduction de l'air ambiant. La visualisation de chaque mode est conditionnée par la fréquence des oscillations. La forme de la zone de rupture due à l'introduction de l'air ambiant dépend de la fréquence, de la hauteur du bain d'huile et de la géométrie du contact. <br /><br />Pour les surfaces non conformes, les résultats des modèles numériques sont en bon accord avec les résultats expérimentaux. Les différences constatées dans le cas des surfaces conformes sont dues aux imperfections géométriques et à la souplesse des structures qui composent le dispositif expérimental.

Dans les turbomachines et plus particulièrement dans les inducteurs, la cavitation reste un sujet de préoccupation majeure. L'évolution rapide de l'industrie dans les turbomachines combinée aux récents progrès réalisés en CFD, permettent une investigation, une analyse et un diagnostic numériques de ces machines par une meilleure connaissance des caractéristiques des écoulements dont elles sont le siège. Dans le cadre de ce travail, nous avons étudié une gamme d'inducteurs qui se différentient par certains critères géométriques en écoulements cavitants et subcavitants. Les interactions entre les divers critères géométriques étudiés, jouent sans le moindre doute un rôle important et nécessitent la prise en compte d'un couplage entre ces paramètres dans les diverses conditions de fonctionnement prévisibles (débit, NPSH, etc.). L' =un des objectifs est d'aboutir, à terme, à une amélioration du processus de conception des inducteurs. La mise en oeuvre de calculs tridimensionnels cavitants, a permis d'analyser les caractéristiques de l'écoulement dans les différentes configurations d'inducteurs pour des régimes de fonctionnement stables et instables, et de détecter les paramètres les plus importants affectant leur bon fonctionnement. Une méthodologie de modélisation des caractéristiques a pu ainsi être mise en oeuvre et appliquée sur différentes géométries avec succès. Un autre objectif poursuivi est de mieux cerner à la fois expérimentalement et numériquement le phénomène de cavitation particulièrement dans ce type de machines en écoulement stationnaire et instationnaire. Ceci a permis d'établir des méthodes précises pour la prédiction de son apparition et du développement de ses différents aspects afin de repousser les limites techniques qu'elle engendre. De manière plus générale, notre collaboration avec ANSYS-Canada et l'Université du New Brunswick au cours de ce travail, a donné lieu à la validation du modèle cavitant du code CFX5.7 sur l'un des inducteurs présentés dans ce rapport.

Lors de cette étude, nous avons développé un code d'analyse rapide de l'écoulement méridien dans les turbomachines. Ce code est basé sur la résolution des équations dynamiques moyennées qui régissent l'écoulement interne stationnaire et non visqueux dans le repère relatif. On a utilisé une combinaison linaire des équations de quantité de mouvement selon les directions axiale et radiale pour éviter au terme source des équations de devenir singulier. Le modèle ainsi développé est particulièrement adapté au cas le plus général des machines de compression ; à savoir, les machines mixtes. On a développé également les équations permettant, à l'aide de l'hypothèse d'un nombre infini d'aubages et en supposant l'écoulement axisymétrique, de calculer à la fois les forces d'aubages et la cinématique simplifiée de l'écoulement aube à aube. Celle-ci prend en compte les données géométriques fournies par les constructeurs ou les logiciels de conception globale. Cette dernière démarche assure une liaison très efficace dans le cadre de l'avant-projet des turbomachines où, dans une première approche d'optimisation, la géométrie des pales est introduite de manière très simple. Les résultats obtenus semblent très cohérents en débit nominal mais également en débit partiel comme le montrent les comparaisons qualitatives avec des résultats d'essais.