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.

诊断超声比其他诊断具有许多优势 技术，特别是安全性，可移植性，实时获取 图像和相对较低的成本。尽管进步很大，主要是 信号处理技术（例如灰度成像）的改进 和彩色多普勒，还有一些区域将有改进的图像对比度 有益。这些包括区分软组织 肝脏，肾脏和乳房等器官中的转移，成像 诸如血管和心脏以及组织灌注之类的腔。这 这项工作的长期目标是开发诊断超声 对比的代理人将满足医学界的需求 改善超声图像的对比度。另外，我们希望 引入对比代理针对和促进实施和 使用第二个谐波。代理的开发证明了强大 在这个新成像区域中，第二个谐波将非常有利。 具体而言，这项工作将继续以两个互补性发展， 平行方向：进一步表征和改进 双表面活性剂稳定的微泡系统，以及开发和 基于生物化聚合物聚合物聚合物poly-l-的新药物的表征 乳酸 - 糖糖苷（PLGA），是在第一个授予中开始的 时期。这两个区域都将包括体外和体内调查。 特定目标1：识别作用到的分子力 稳定表面活性剂稳定的剂并开发模型 气泡周围表面活性剂的分子排列。 实验设计将包括Langmuir-Blodgett的Instra红色分析 双表面活性剂混合物和气相色谱分析的膜 确定是否用于制造的超声步骤 代理会引起任何化学变化。这些研究的结果将 用于识别新的表面活性剂。 特定目标2：基于聚合物的代理的广泛表征。 这将包括研究制造参数对 使用微胶囊的平均尺寸，尺寸分布和壁厚 库尔特分析和扫描电子显微镜。 特定目标3：两种药物的体外声学表征 优化声学特性。测得的参数将包括背面 - 分散和衰减以及第二个谐波分析。 特定目标4：两种药物在内的体内表征包括剂量 反应，衰减后筛和多普勒增强功能以​​及对 兔子中的第二次谐波成像和狗的心脏成像。