MICRO-PET/MICRO-CT STUDIES FOR PERMEABILITY MEASUREMENT

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目及 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 该提案的主要目标是通过使用新型CT造影剂碘化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观球形囊泡，可以封装碘化造影剂。 具体的特征，如囊泡大小，化学亲和性和热（或pH）敏感性可以工程化。 我们将使用的药物是聚乙二醇（PEG）包被的脂质体，其血管内循环半衰期约为6-8小时。 这些特征允许在简单的IV注射后几个小时的血池成像，并且还应该降低药剂外渗到肿瘤结节中的速率。 脑血容量（CBV）和脑血渗透性（PS）的无创性评价是一种肿瘤分级和疗效评价的方法。 基于正电子发射断层扫描（PET）的CBV和PS方法由于以下原因而具有显著的缺点：（1）示踪剂从血管内空间泄漏到肿瘤床中，以及（2）相对低的空间分辨率。 计算机断层扫描（CT）方法的优点是高空间分辨率，信号强度和造影剂浓度之间的直接线性关系，以及缺乏对血液制品伪影的脆弱性。 对于CT和PET（以及MR），渗漏的血脑屏障会产生错误，需要使用去卷积算法来推导CBV和PS。

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.