CAREER: Dynamics of Microbubbles in the Human Circulation. Effects of Flow Pulsatility and Ultrasound Radiation.

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CBET-0748133, AlisedaThis proposal aims to understand and quantify the dynamics of microbubbles injected in the human circulation. These tiny bubbles, with sizes comparable to a red blood cell, are used toenhance ultrasound imaging and have been proposed as a vector for safe, non-intrusive drug delivery. The key physics that motivates this study is the presence of a net force on a bubble exerted by the application of ultrasound waves. This phenomenon, described by Bjerknes exactly a century ago, is being proposed as an important tool in the manipulation of microbubbles and microdroplets in many applications, specially in medicine. The coupling of this ?novel? force on the bubble with the well-known dynamics of bubbles and particles in non uniform flows must be understood before quantitative engineering design and analysis can be applied to the numerous medical diagnostic and therapeutic techniques been considered. The overarching theme of this proposal is the systematic study of the fundamental physics that control the dynamics (trajectory and volume oscillation) of bubbles in an environment dominated by a non-uniform, non-stationary velocity field, such as the one found in arteries and veins, and a high-amplitude, fast-changing pressure field, such as the one imposed by application of ultrasound. The motivation for this research is the use of microbubbles as Ultrasound Contrast Agents (UCAs) in certain areas of Diagnostic Ultrasound and the great potential that they present for new uses of Therapeutical Ultrasound, in particular in the area of targeted drug delivery. Intellectual Merit: The complex interactions of microbubbles with pulsatile flow and ultrasound waves present many open problems in the areas of multiphase flows and acoustics. The dynamics of microbubbles can be modeled by a Basset-Boussinesq-Oseen type equation, but the effect of the ultrasound-induced volume oscillations in the drag, lift and added mass terms need to be carefully studied. The coupling of the flow dynamics with the Bjerknes force exerted by the ultrasound field on the bubbles is also unknown. This proposal details a five year plan to study these problems, improve our understanding of the underlying physics and provide models that can guide applications and engineering design based on these processes. Broader Impacts: The ability to use ultrasound, a safe, non-invasive technique, to direct the motion of microbubbles towards certain regions of the circulation and to enhance their residence times in these areas will enable new therapies and diagnostic tools for a wide range of pressing medical problems such as intracraneal thrombolysis, targeted chemotherapy, myocardial perfusion and tumor vascularization assessment. The project goal will attract students from traditionally underrepresented groups into traditional fluid mechanics disciplines and help them make the link between quantitative engineering analysis and improved medical care. Age-adequate aspects of this research will be brought into the classroom for middle/high school, undergraduate and graduate students. A pulsatile flow kit will be prepared and presented to middle and high schools in the Seattle area in order to emphasize the importance of physics in medicine and biology and the increasing use of engineering quantitative tools in the design of medical procedures and devices. Undergraduates will learn, through lab session and involvement in the research, about the often confused concepts of unsteady flows, laminar vortices, flow separation and transition to turbulence, examples of which can be found in certain arteries. A specialized graduate course is been developed to introduce students to the complex fluid mechanics of the human circulation and the dynamics of microparticles (bubbles, droplets or cells) in unsteady, non uniform flows.