ACT 1: PROJ 2: TARGETED HIGH-FREQUENCY ULTRASOUND-CONTRAST AGENT IMAGING

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 心血管疾病是美国主要的死亡原因，在夏威夷州尤为严重。迫切需要开发能够揭示在血管分子和细胞水平上涉及的相关生物过程的诊断成像方法。靶向超声造影剂为诊断超声增加了分子成像能力。因此，超声波在健壮性、便携性和相对低成本方面的独特优势被纳入到促进快速翻译的技术中。超声造影剂是被包裹的微泡，当受到声学激励时，它们围绕其平衡半径非线性振荡。这些试剂产生独特的散射特征，这促进了新的成像方法，使自由循环试剂的血液散射特征与周围组织的散射特征得以区分。最近的一项发展是造影剂在其外壳上附着了特定的配体，使其能够与特定的靶点结合。虽然仍处于早期开发阶段，但靶向超声造影剂为提高诊断超声的分子成像能力提供了巨大的潜力。这项研究的具体目的是：1)从高频超声的散射特征出发，从实验和理论上表征靠近血管壁和在生理流动条件下的单个和组靶剂，并开发稳健的检测方法；以及2)研究图像引导的高频白细胞功能障碍的评估方法。了解细胞层和同样的血管壁的接近程度如何改变超声合同代理的动态和散射特征，将为区分结合和非结合代理的检测方法提供基础。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Cardiovascular disease is the leading cause of death in the United States and is particularly acute in the state of Hawaii. An urgent need exists for the development of diagnostic imaging methods capable of revealing the associated biological processes involved at the molecular and cellular levels of blood vessels. Targeted ultrasound contrast agents add molecular imaging capabilities to diagnostic ultrasound. The unique advantages of ultrasound in terms of robustness, portability and relative low cost are thus incorporated into techniques to foster rapid translation. Ultrasound contrast agents are encapsulated micro-bubbles which oscillate nonlinearly about their equilibrium radius when acoustically excited. The agents produce unique scattering signatures which foster novel imaging methods that allow for the scattering signatures of blood to be distinguished from that of the surrounding tissue for freely circulating agents. A recent development has been contrast agents that have specific ligands attached on their shell allowing binding at specific targeted sites. Though still in the early stages of development, targeted ultrasound contrast agents offer great potential for improved molecular imaging capabilities for diagnostic ultrasound. The specific aims of this study are to: 1) experimentally and theoretically characterize individual and groups of targeted agents near vascular walls and under physiological flow conditions from their scattering signatures for high frequency ultrasound and develop robust detection methods; and 2) investigate methods for image-guided assessment of leukocyte dysfunction for high frequencies. An understanding of how the close proximity of cell layers and likewise vessel walls change an ultrasound contract agent's dynamics and scattering signature will provide the foundation for detection methods that can discriminate between bound and unbound agents.