DIAGNOSITIC ULTRASOUND CONTRAST AGENTS--DEVELOPMENT AND EVALUATION

与其他诊断方法相比，诊断性超声具有许多优势 技术，特别是安全性、便携性、实时获取 图像，且成本相对较低。尽管取得了巨大的进步，但主要是 改进信号处理技术，如灰度成像 和彩色多普勒，仍有一些区域可以改善图像对比度 会有很大的好处。其中包括软组织的分化。 肝脏、肾脏和乳房等器官的转移，成像 空洞，如血管和心脏，以及组织灌流。这个 这项工作的长期目标是开发诊断超声 造影剂将通过以下方式满足医学界的需求 提高超声图像的对比度。此外，我们还希望 引入造影剂靶向并促进实施和 二次谐波的使用。一种表现出强效的试剂的研制 二次谐波在这一新的成像领域将具有很大的优势。 具体地说，这项工作将继续发展为两个相辅相成、 平行的方向是：进一步表征和改进 一种双表面活性剂稳定的微泡系统，以及开发和 以生物可腐蚀性聚合物聚L为基础的新型药剂的表征 丙交酯-乙交酯共聚物(PLGA)，于第一次授予 句号。这两个领域都将包括体外和体内研究。 具体目标1：确定作用于 表面活性剂稳定剂及其稳定剂模型的研制 气泡周围表面活性剂的分子排列。 实验设计将包括朗缪尔-布洛杰特的红外分析 双表面活性剂复配物的成膜及气相色谱分析 确定超声化步骤是否用于制造 该试剂会引起任何化学变化。这些研究的结果将 用于鉴定新的表面活性剂。 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 库尔特分析和扫描电子显微镜。 具体目标3：两种制剂的体外声学特性 优化声学性能。测量的参数将包括Back- 散射和衰减以及二次谐波分析。 具体目标4：两种药物的体内特性，包括剂量 响应、衰减后向散射和多普勒增强及其研究 兔二次谐波成像和犬心脏成像。

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.