DIAGNOSITIC ULTRASOUND CONTRAST AGENTS--DEVELOPMENT AND EVALUATION

诊断性超声造影剂——开发与评估

• 批准号: 6327604
• 负责人: MARGARET A. WHEATLEY
• 金额: $ 26.78万
• 依托单位: DREXEL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-07-03 至 2001-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6327604
• 关键词: aerosols; alginates; bioimaging /biomedical imaging; clinical biomedical equipment; contrast media; dogs; drug delivery systems; drug design /synthesis /production; drug screening /evaluation; gas; gas chromatography; image enhancement; laboratory rabbit; microcapsule; noninvasive diagnosis; polymers; surfactant; ultrasonography

Diagnostic ultrasound offers many advantages over other diagnostic techniques, specifically safety, portability, acquisition of real time images, and relatively low cost. Despite great advances, primarily improvements in signal processing techniques such as gray scale imaging and color Doppler, there remain areas where improved image contrast would be of great benefit. These include differentiation of soft tissue in metastases in organs such as the liver, kidney and breast, imaging of cavities such as blood vessels and the heart, and tissue perfusion. The long term objective of this work is to develop diagnostic ultrasound contrast agents that will fulfill the needs of the medical community by improving the contrast of ultrasound images. In addition we hope to introduce contrast agent targeting and to facilitate implementation and use of the second harmonic. Development of an agent demonstrating a strong second harmonic would be highly advantageous in this new imaging area. Specifically, the work will continue to evolve in two complementary, parallel directions which are: Further characterization and improvement of a dual surfactant-stabilized micro-bubble system, and development and characterization of an new agent based on the bioerodible polymer, poly-L- lactide-co-glycolide (PLGA), which was started in the first granting period. Both areas will include in vitro and in vivo investigations. Specific aim 1: Identification of the molecular forces which are acting to stabilize the surfactant-stabilized agent and development of a model for the molecular arrangement of the surfactants around the gas bubble. Experimental design will include infra red analysis of Langmuir-Blodgett films of the dual surfactant mixtures and gas chromatographic analysis of agent to determine whether the sonication step used in the fabrication of the agent causes any chemical changes. The results from these studies will be used to identify new surfactants. Specific aim 2: Extensive characterization of the polymer-based agent. This will include studying the effects of fabrication parameters on the microcapsule mean size, size distribution, and wall thickness using Coulter analysis and scanning electron microscopy. Specific aim 3: In vitro acoustic characterization of both agents to optimize the acoustic properties. measured parameters will include back- scatter and attenuation and second harmonic analysis. Specific aim 4: In vivo characterization of both agents including dose response, attenuation back-scatter and Doppler enhancement and a study of second harmonic imaging in rabbit, and cardiac imaging in dog.

超声诊断与其他诊断相比具有许多优势 技术，特别是安全性、便携性、实时采集 图像丰富，成本相对较低。尽管取得了巨大进步，但主要是 信号处理技术的改进，例如灰度成像 和彩色多普勒，仍然存在需要改进图像对比度的区域 会有很大的好处。这些包括软组织的分化 肝、肾、乳腺等器官转移，影像学检查 血管和心脏等腔体以及组织灌注。这 这项工作的长期目标是开发诊断超声 造影剂将满足医学界的需求 提高超声图像的对比度。此外我们希望 引入造影剂靶向并促进实施和 使用二次谐波。开发具有强大实力的代理 二次谐波在这个新的成像领域将非常有利。 具体来说，这项工作将继续在两个互补的方面发展， 平行的方向是： 进一步表征和改进 双表面活性剂稳定的微泡体系的开发与研制 基于生物可蚀性聚合物聚-L-的新药剂的表征 丙交酯-乙交酯 (PLGA)，在首次授权时启动 时期。这两个领域都将包括体外和体内研究。 具体目标 1：识别作用于的分子力 稳定表面活性剂稳定剂并开发模型 气泡周围表面活性剂的分子排列。 实验设计将包括 Langmuir-Blodgett 的红外分析 双表面活性剂混合物的薄膜及其气相色谱分析 剂来确定超声处理步骤是否用于制造 该试剂会引起任何化学变化。这些研究的结果将 可用于鉴定新型表面活性剂。 具体目标 2：聚合物基试剂的广泛表征。 这将包括研究制造参数对 微胶囊的平均尺寸、尺寸分布和壁厚使用 库尔特分析和扫描电子显微镜。 具体目标 3：两种药物的体外声学表征 优化声学特性。测量的参数将包括回 散射和衰减以及二次谐波分析。 具体目标 4：两种药物的体内表征（包括剂量） 响应、衰减反向散射和多普勒增强以及研究 兔子的二次谐波成像和狗的心脏成像。