MICRO-PET/MICRO-CT STUDIES FOR PERMEABILITY MEASUREMENT

渗透性测量的微型 PET/微型 CT 研究

• 批准号: 7726140
• 负责人: SRINIVASAN MUKUNDAN
• 金额: $ 1.94万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-01 至 2009-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7726140
• 关键词: Affinity; Algorithms; Beds; Blood; Blood - brain barrier anatomy; Blood Circulation; Blood Volume; Cerebrum; Characteristics; Chemicals; Computer Retrieval of Information on Scientific Projects Database; Contrast Media; Disadvantaged; Encapsulated; Engineering; Evaluation; Extravasation; Funding; Goals; Grant; Half-Life; Hour; Image; Injection of therapeutic agent; Institution; Invasive; Liposomes; Measurement; Methods; Microscopic; Morphologic artifacts; Permeability; Phospholipids; Polyethylene Glycols; Positron-Emission Tomography; Rate; Research; Research Personnel; Resolution; Resources; Signal Transduction; Source; Tracer; United States National Institutes of Health; Vesicle; X-Ray Computed Tomography; base; novel; size; treatment effect; tumor

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. The primary goal of this proposal is to overcome the confounding effects of a leaky blood brain barrier by using a novel CT contrast agent, iodinated liposome. Liposomes are microscopic spherical vesicles constructed of phospholipid bilayers that can encapsulate the iodinated contrast agent. Specific features such as vesicle size, chemical affinity and thermal (or pH) sensitivities can be engineered. The agent we will use is a polyethylene glycol (PEG)-coated liposome with an intravascular circulation half-life on the order of 6-8 hours. These characteristics allow blood pool imaging for several hours after a simple IV injection, and should also decrease the rate of extravasation of the agent into the tumor interstitium. Non-invasive evaluation of cerebral blood volume (CBV) and permeability (PS) is a method for grading tumors as well as evaluating treatment effect. Positron emission tomography (PET) based CBV and PS methods suffer from significant disadvantages due to: (1) the leakage of tracer from the intravascular space into the tumor bed, and (2) the relatively low spatial resolution. Advantages of computed tomography (CT) methods are the high spatial resolution, the direct linear relationship between signal intensity and contrast agent concentration, and the lack of vulnerability to blood product artifact. With both CT and PET (and MR), a leaky blood brain barrier produces errors and requires the use of a deconvolution algorithm to derive CBV and PS.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 该提案的主要目标是通过使用新型 CT 造影剂碘脂质体来克服血脑屏障渗漏的混杂效应。脂质体是由磷脂双层构成的微小球形囊泡，可以封装碘化造影剂。 可以设计特定的特征，例如囊泡大小、化学亲和力和热（或 pH）敏感性。 我们将使用的试剂是聚乙二醇 (PEG) 包被的脂质体，其血管内循环半衰期约为 6-8 小时。 这些特性允许在简单的静脉注射后几个小时内进行血池成像，并且还应该降低药剂外渗到肿瘤间质中的速率。 无创评估脑血容量（CBV）和渗透性（PS）是肿瘤分级和评估治疗效果的一种方法。 基于正电子发射断层扫描 (PET) 的 CBV 和 PS 方法存在明显的缺点，因为：(1) 示踪剂从血管内空间泄漏到肿瘤床中，以及 (2) 空间分辨率相对较低。 计算机断层扫描 (CT) 方法的优点是空间分辨率高、信号强度和造影剂浓度之间存在直接线性关系，并且不易受到血液制品伪影的影响。 对于 CT 和 PET（以及 MR），血脑屏障渗漏会产生错误，需要使用反卷积算法来导出 CBV 和 PS。