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

这项建议旨在了解和量化注入人体循环的微泡的动态。这些微小的气泡，大小与红细胞相当，被用来增强超声成像，并已被提议作为安全、非侵入性药物输送的载体。推动这项研究的关键物理原理是超声波对气泡施加的净力。这一现象由BJernes在整整一个世纪前描述，被认为是操纵微泡和微滴的重要工具，在许多应用中，特别是在医学上。这本书的结合？小说？在将定量工程设计和分析应用于众多医学诊断和治疗技术之前，必须了解气泡和颗粒在非均匀流动中的众所周知的动力学特性对气泡的力。这一提议的主要主题是系统地研究控制气泡动力学(轨迹和体积振荡)的基本物理，在一个由非均匀、非稳定速度场(如在动脉和静脉中发现的速度场)和高幅度、快速变化的压力场(如应用超声波施加的压力场)主导的环境中。这项研究的动机是在诊断超声的某些领域使用微泡作为超声造影剂(UCAS)，以及它们为治疗性超声的新用途带来的巨大潜力，特别是在靶向药物输送领域。智能优点：微泡与脉动流和超声波的复杂相互作用在多相流和声学领域提出了许多悬而未决的问题。微气泡的动力学可以用Basset-Boussinesq-Oseen型方程来描述，但超声诱导的体积振荡在阻力、升力和附加质量项中的影响需要仔细研究。流体动力学与超声场施加在气泡上的巴耶克内斯力之间的耦合也是未知的。这项提议详细说明了一个五年计划，以研究这些问题，提高我们对基本物理的理解，并提供能够指导基于这些过程的应用和工程设计的模型。更广泛的影响：使用超声这一安全、非侵入性技术将微泡引导到循环的某些区域并延长其在这些区域的停留时间的能力，将使新的治疗方法和诊断工具能够用于各种紧迫的医疗问题，如脑内溶栓、靶向化疗、心肌灌注和肿瘤血管形成评估。该项目的目标将吸引来自传统代表性不足群体的学生进入传统的流体力学学科，并帮助他们将定量工程分析与改进的医疗保健联系起来。这项研究的适龄方面将被带入初中/高中、本科生和研究生的课堂。为了强调物理学在医学和生物学中的重要性，以及在设计医疗程序和设备时越来越多地使用工程量化工具，将准备一套脉动流动工具包，并向西雅图地区的初中和高中展示。本科生将通过实验课程和参与研究，学习经常混淆的非定常流动、层流漩涡、流动分离和过渡到湍流的概念，这些概念在某些动脉中可以找到。开发了一门专门的研究生课程，向学生介绍人体循环的复杂流体力学和微粒子(气泡、液滴或细胞)在非稳定、非均匀流动中的动力学。

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.