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

1134420/1134121 Porter/SarkarBubbles直径小于7 µm，尺寸分布窄，可通过超声成像帮助诊断多种疾病。它们将用脂质壳进行化学工程改造，使得它们1）具有单一尺寸，2）能够附着于与特定疾病相关的分子，以及3）具有基于尺寸和壳材料特性的独特声学特征。将不同的气泡靶向病变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。 智力优势：这项工作的主要创新之一在于控制这些泡沫大小的能力。这将允许准确研究它们的声学特性，特别是它们的共振频率#61630;，其中它们最有效地反射诊断超声#61630;作为半径、声压和脂质壳成分的函数。另一个创新是基于物理的泡沫行为的精确建模。机械模型，可以准确地将分子组成的封装脂质壳的气泡？的声学签名将被开发。将利用实验和理论方法来评估壳体的非线性粘弹性性质（即应力和变形之间的流变学关系）与超声激励之间的关系。 该模型开发的显着特点是双实验方法，其中两个独立的实验集将用于确定模型参数和独立的模型验证。模型开发和实验之间将有密切的联系，每一项工作都将不断受到另一项工作的指导和校准。 从实验测量和理论预测的结果将被用来制定一套脂质涂层微泡具有不同的散射光谱。 最后，将进行试验，以评估检测小浓度单分散脂质涂层微泡的能力，并区分不同人群的回声特征。 从这项研究中获得的知识将导致开发新的成像方案，以特异性地检测针对多种生物标志物的脂质涂层微泡。更广泛的影响：分子成像的新前沿是用单一诊断成像方式同时检测疾病的多种生物标志物。 这是可能的，前提是针对不同生物标志物的特定模态的造影剂可以在图像内彼此区分。 超声波可用于该分子成像应用，前提是可设计具有独特频率依赖性散射特性（即辐射压力信号）的靶向脂质包被微泡。 由于散射特性取决于微泡的半径和外壳材料的属性，严格控制微泡的尺寸分布和脂质外壳的粘弹性属性，以实现这一目标。教育：每个大学的一名研究生将参与这个项目，并完成他们的博士论文。这两个PI都致力于向少数民族学生传播工程学。PI-波特担任BU学生管理的少数民族工程师协会的教师顾问，并将在学年期间为其成员提供研究机会。PI-Sarkar已经与摩根州立大学（HBCU）的一位教授（支持信）建立了联系，以招募少数民族学生在他的实验室实习。PI-Porter将主办至少两名本科生每个夏季研究学生由BU本科生研究机会计划（支持信）资助，致力于目标脂质涂层微泡的生产和表征。PI-Sarkar有一段让本科生参与他的对比微泡研究的历史，结果是由一名本科生合著的出版物。两名本科生将在他的实验室里从事这个项目。他还将把研究实验室与非常成功的？工程酷的东西？项目由UD Engineering Outreach运营。

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.