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

职业：人体循环中微泡的动力学。

• 批准号: 0748133
• 负责人: Alberto Aliseda
• 金额: $ 45万
• 依托单位: University of Washington
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-02-15 至 2014-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0748133&HistoricalAwards=false
• 关键词: CAREER; Dynamics; Microbubbles; Human; Circulation.

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.

CBET-0748133，Alisheda 该提案旨在了解和量化注入人体循环中的微泡的动态。这些微小气泡的大小与红细胞相当，用于增强超声成像，并被提议作为安全、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。 Bjerknes 在一个世纪前描述的这种现象被提议作为在许多应用中操纵微泡和微滴的重要工具，特别是在医学领域。这本“小说”的结合？在将定量工程设计和分析应用于考虑的众多医学诊断和治疗技术之前，必须了解非均匀流中气泡和颗粒的众所周知的动力学对气泡的作用力。 该提案的首要主题是对控制气泡动力学（轨迹和体积振荡）的基础物理进行系统研究，该环境由非均匀、非平稳速度场（例如动脉和静脉中的速度场）和高振幅、快速变化的压力场（例如应用超声波施加的压力场）主导。 这项研究的动机是在超声诊断的某些领域中使用微泡作为超声造影剂（UCA），以及它们在超声治疗新用途中的巨大潜力，特别是在靶向药物输送领域。 智力优点：微气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。微泡的动力学可以通过 Basset-Boussinesq-Oseen 型方程进行建模，但超声引起的体积振荡在阻力、升力和附加质量项中的影响需要仔细研究。流动动力学与超声波场对气泡施加的比耶克尼斯力的耦合也是未知的。该提案详细介绍了一个五年计划来研究这些问题，提高我们对基础物理的理解，并提供可以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：使用超声波这种安全、非侵入性的技术，将微泡的运动引导至循环的某些区域并延长其在这些区域的停留时间，将为解决一系列紧迫的医疗问题（例如颅内溶栓、靶向化疗、心肌灌注和肿瘤血管化评估）提供新的疗法和诊断工具。 该项目的目标将吸引传统上代表性不足的群体的学生进入传统流体力学学科，并帮助他们在定量工程分析和改善医疗保健之间建立联系。这项研究的适合年龄的方面将被带入初中/高中、本科生和研究生的课堂。将准备并向西雅图地区的初中和高中提供脉动流套件，以强调物理学在医学和生物学中的重要性以及在医疗程序和设备设计中越来越多地使用工程定量工具。本科生将通过实验室课程和参与研究，了解不稳定流、层流涡流、流动分离和湍流过渡等经常令人困惑的概念，这些概念可以在某些动脉中找到。我们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以及不稳定、不均匀流动中的微粒（气泡、液滴或细胞）的动力学。