Collaborative Research: Engineering monodisperse lipid-coated microbubbles with distinct scattering spectra for ultrasound molecular imaging applications

合作研究：为超声分子成像应用设计具有不同散射光谱的单分散脂质涂层微泡

• 批准号: 1205322
• 负责人: Kausik Sarkar
• 金额: $ 22.5万
• 依托单位: George Washington University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-01 至 2016-12-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1205322&HistoricalAwards=false
• 关键词: Collaborative; Research; Engineering; monodisperse; lipid

1134420/1134121Porter/SarkarBubbles with diameters less than 7 µm with a narrow size distribution will be created that can help in diagnosis of several diseases through ultrasound imaging. They will be chemically engineered with a lipid shell such that they are 1) of a single size, 2) able to attach to molecules associated with a specific disease, and 3) have a unique acoustic signature based upon size and shell material properties. Targeting different bubbles to different molecules expressed by diseased cells, one can develop an accurate and cost effective ultrasound-based diagnostic system. Intellectual Merit: One of the main innovations of this effort lies in the ability to control the size of these bubbles. It will allow an accurate investigation of their acoustic properties, specifically their resonance frequencywhere they are most efficient to reflect diagnostic ultrasoundas a function of radius, acoustic pressure, and lipid shell composition. The other innovation is physics-based accurate modeling of bubble behavior. Mechanistic models that can accurately relate the molecular composition of the encapsulating lipid shell to a bubble?s acoustic signature will be developed. Experimental and theoretical methods will be utilized to evaluate the relationship between the nonlinear viscoelastic properties (i.e. the rheological relations between the stress and the deformation) of the shell and the ultrasound excitation. The distinctive feature of the model development is the dual experimental approach, where two separate sets of experiments will be used for the determination of model parameters and the independent model validation. There will be a close connection between the model development and the experiments where each effort will be constantly guided by and calibrated against the other. The results from the experimental measurements and theoretical predictions will be used to formulate a suite of lipid-coated microbubbles with distinct scattering spectra. Finally, tests will be performed to assess the ability to detect small concentrations of monodisperse lipid-coated microbubbles and distinguish echogenic signatures from distinct populations. The knowledge gained from this study will lead to the development of novel imaging schemes to specifically detect lipid-coated microbubbles targeted to multiple biomarkers. Broader Impact: The new frontier for molecular imaging is the simultaneous detection of multiple biomarkers of disease with a single diagnostic imaging modality. This is possible provided contrast agents for a specific modality targeting different biomarkers can be distinguished from each other within an image. Ultrasound may be used for this molecular imaging application provided targeted lipid-coated microbubbles with unique frequency-dependent scattering characteristics (i.e. radiated pressure signal) can be engineered. Because the scattering characteristics depend upon microbubble radius and shell material properties, tight control over the microbubble size distribution and the viscoelastic properties of the lipid shell are required to achieve this goal.Education: One graduate student in each university will be involved in this project working towards their doctoral dissertation. Both PIs are committed to spread engineering to minority students. PI-Porter serves as the faculty advisor the student-governed Minority Engineers' Society at BU, and will provide research opportunities for its members during the academic year. PI-Sarkar has already established a contact with a Professor (letter of support) in Morgan State University (HBCU) to recruit minority student intern in his lab for the summer. PI-Porter will host at least two undergraduate students each summer research student funded by the BU Undergraduate Research Opportunity Program (letter of support) to work on the production and characterization of targeted lipid-coated microbubbles. PI-Sarkar has a history of involving undergraduates in his contrast microbubble research, resulting in a publication coauthored by an undergraduate. Two undergraduate students will be working in his lab on this project. He will also connect the research lab to the very successful ?Engineering Cool Stuff? program run by the UD Engineering Outreach.

1134420/1134121Porter/sarkarbubbles的直径小于7 µm，尺寸分布窄，可以通过超声成像来帮助诊断多种疾病。它们将用脂质壳进行化学设计，使得它们是单个大小的1），2）能够附着于与特定疾病相关的分子上，并且3）具有基于尺寸和壳材料特性的独特声签名。将不同的气泡靶向由患病细胞表达的不同分子，可以开发出准确且具有成本效益的基于超声的诊断系统。知识分子优点：这项工作的主要创新之一在于能够控制这些气泡的大小。它将允许对其声学性质进行准确的投资，特别是它们的共振频率＆＃61630;在其中最有效地反映了诊断超声＆＃61630;作为半径，声压和脂质壳体组成的函数。另一个创新是基于物理的气泡行为的准确建模。可以准确地将封装脂质壳的分子组成与气泡的声学签名相关的机械模型。实验和理论方法将用于评估壳的非线性粘弹性特性（即应力与变形之间的流变关系）与超声兴奋之间的关系。模型开发的差异特征是双重实验方法，其中将使用两组单独的实验集来确定模型参数和独立的模型验证。模型开发与实验之间将有着密切的联系，在这些实验中，每项努力都将不断地指导和校准另一个努力。实验测量和理论预测的结果将用于形成具有不同散射光谱的脂质涂层微泡。最后，将进行测试以评估检测少量单分散脂质涂层微泡和不同人群中不同的回声特征的能力。从这项研究中获得的知识将导致新型成像方案的发展，以特异性检测针对多个生物标志物的脂质涂层微泡。更广泛的影响：分子成像的新边界是对具有单个诊断成像方式的多种疾病生物标志物的简单检测。可以在图像中彼此区分针对不同生物标志物的特定模态的对比度。超声可以用于这种分子成像应用，提供了具有唯一频率依赖性散射特性（即辐射压力信号）的靶向脂质涂层微泡。由于散射特性取决于微气泡半径和贝壳材料的特性，因此需要严格控制微泡大小分布和脂质壳的粘弹性才能实现此目标。这两个PI都致力于将工程学传播给少数族裔学生。 Pi-porter担任BU的教师顾问的少数族裔工程师协会，并将在学年为其成员提供研究机会。 Pi-Sarkar已经在摩根州立大学（HBCU）与教授（支持信）建立了联系，以在夏季在其实验室招募少数民族学生。 Pi-porter每年夏天至少将举办由BU本科研究机会计划（支持信）资助的每年夏季研究生，以致力于靶向脂质涂层微泡的生产和表征。 Pi-sarkar有一段历史，使大学生参与其对比微泡研究，从而导致了本科生共同撰写的出版物。两名本科生将在他的实验室从事这个项目。他还将将研究实验室连接到非常成功的？工程酷的东西吗？由UD工程外展运行的计划。