Modeling and Characterization of Microbubble Contrast Agents for Medical Imaging and Drug Delivery

用于医学成像和药物输送的微泡造影剂的建模和表征

• 批准号: 0651912
• 负责人: Anette Karlsson
• 金额: $ 24万
• 依托单位: University of Delaware
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-04-01 至 2012-03-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0651912&HistoricalAwards=false
• 关键词: Modeling; Characterization; Microbubble; Contrast; Agents

National Science Foundation - Division of Chemical &Transport Systems Particulate & Multiphase Processes Program (1415)Proposal Number: 0651912Principal Investigators: Sarkar, KausikAffiliation: University of DelawareProposal Title: Modeling and Characterization of Microbubble Contrast Agents for Medical Imaging and Drug DeliveryIntellectual MeritMicrobubbles are injected into a patient's body to enhance the contrast of an ultrasound image. They are also designed to deliver drugs to target tissues. The goal of this proposal is to use experiments and analysis to develop mathematical models, and to characterize these microbubble contrast agents with a view to improving their design. The focus of the effort is on modeling the protective encapsulation of a contrast microbubble made of proteins and lipids, and microbubble breakup under acoustic excitation. New interface models will be developed for the encapsulation with intrinsic surface rheological properties, and these properties will be determined for several contrast microbubbles by in vitro acoustic (attenuation and scattering) experiments. A computational code to simulate large oscillation of a microbubble under ultrasonic excitation will also be developed.Despite previous attempts, currently there is no reliable model of encapsulated contrast microbubbles which has been systematically validated against experimental observations. A novel acoustic method will be used to determine the interfacial rheology. The same acoustic setup will also be used to investigate the microbubbles' response to ultrasound excitation. The rheological properties of a microbubble will be determined using the attenuation of an ultrasound pulse passing through a microbubble emulsion. The validity of the rheological model, and whether it extends beyond the attenuation data, will be determined by comparing model predictions with the microbubbles' scattered response. The specific aims of this proposal are:1. Develop dynamical models of contrast agents. Model a bubble encapsulation as an interface with characteristic surface rheological parameters. Obtain nonlinear bubble dynamics equations. Use them to predict attenuation and scattering of ultrasound in an emulsion of contrast agent.2. Measure rheological properties of contrast microbubbles and investigate model behaviors. Experimentally determine attenuation and scattering of ultrasound through an emulsion of contrast microbubbles. Use results to validate models. Compare performance with existing models. Modify and implement additional features to improve models. Perform experiments and simulations for varying concentration and excitation parameters (amplitude, frequency and pulse-repetition frequency).3. Investigate bubble oscillation, stability and destruction. Develop a Boundary Element Method (BEM) based computational code to investigate large deformation of contrast microbubbles. Develop an analytical model of bubble growth and shrinkage due to gas permeation through encapsulation. Broader ImpactAlthough the ultrasound remains the safest and the most popular (one in every three imaging in the world) means of imaging, its utility is limited due to poor contrast - 20% of the 17 million echocardiographies performed in the United States in 2000 were suboptimal. A good contrast agent will enable reliable imaging of abnormal blood flows leading to early diagnosis of disease. Current methods of contrast agent design and use are empirical. Our research will help develop a rigorous methodology to customize contrast agent design for specific tasks and applications. The proposal will help train ME undergraduate and graduate students in the non-traditional cross-disciplinary interface of biology and mechanics. The PI has established a link with a collaborator in Morgan State University (an HBCU) to identify talented undergraduate research internships and to groom them for graduate study at UD.

国家科学基金会 - 化学与运输系统部颗粒与多相过程计划 (1415) 提案编号：0651912 主要研究者：Sarkar, Kausik 所属机构：特拉华大学提案标题：用于医学成像和药物输送的微泡造影剂的建模和表征智力优点将微泡注入患者体内以增强超声对比度 图像。它们还被设计用于将药物输送到目标组织。该提案的目标是利用实验和分析来开发数学模型，并表征这些微泡造影剂，以改进其设计。这项工作的重点是模拟由蛋白质和脂质制成的对比微泡的保护性封装，以及声学激励下微泡的破裂。将为具有内在表面流变特性的封装开发新的界面模型，并且将通过体外声学（衰减和散射）实验确定几种对比微泡的这些特性。还将开发一种计算代码来模拟超声波激励下微泡的大振荡。尽管之前进行了尝试，但目前还没有经过实验观察系统验证的可靠的封装对比微泡模型。将使用一种新颖的声学方法来确定界面流变性。相同的声学装置也将用于研究微泡对超声激励的响应。微泡的流变特性将利用穿过微泡乳液的超声波脉冲的衰减来确定。流变模型的有效性以及它是否超出衰减数据，将通过将模型预测与微泡的分散响应进行比较来确定。本提案的具体目标是： 1．开发造影剂的动力学模型。将气泡封装建模为具有特征表面流变参数的界面。获得非线性气泡动力学方程。用它们来预测超声在造影剂乳液中的衰减和散射。2．测量对比微泡的流变特性并研究模型行为。通过实验确定超声通过对比微泡乳液的衰减和散射。使用结果来验证模型。与现有模型进行性能比较。修改并实现附加功能以改进模型。对不同的浓度和激励参数（振幅、频率和脉冲重复频率）进行实验和模拟。3．研究气泡振荡、稳定性和破坏。开发基于边界元法 (BEM) 的计算代码来研究对比微泡的大变形。开发封装气体渗透导致的气泡生长和收缩的分析模型。更广泛的影响 尽管超声仍然是最安全和最流行（世界上三分之一的成像）的成像手段，但由于对比度差，其实用性受到限制 - 2000 年在美国进行的 1700 万例超声心动图检查中，有 20% 的效果不理想。良好的造影剂能够对异常血流进行可靠成像，从而实现疾病的早期诊断。当前造影剂设计和使用的方法是经验性的。我们的研究将有助于开发严格的方法，为特定任务和应用定制造影剂设计。该提案将有助于在生物学和力学的非传统跨学科交叉领域培养工程硕士本科生和研究生。 PI 与摩根州立大学 (HBCU) 的合作者建立了联系，以寻找有才华的本科生研究实习机会，并培养他们在 UD 进行研究生学习。