CT PERFUSION IMAGING USING IODINATED LIPOSOMES

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 这项建议的主要目标是通过使用一种新型的CT造影剂--碘化脂质体来克服肿瘤中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，可以包裹碘化造影剂。可以设计囊泡大小、化学亲和力和温度(或pH)敏感度。我们将使用聚乙二醇脂质体，其血管内循环半衰期为6-8小时。这些特点允许在简单的静脉注射后进行几个小时的血池成像，并且还应该减少试剂渗入肿瘤间质的速度。 体素在CT研究中的相对增强与造影剂的体素内浓度成正比。在本实验的时间尺度上表现为真正的血液池药物的药物应留在血管内空间内。因此，体素的相对增强应与脑血容量(CBV)成正比。这应该允许直接测量CBV，而不是需要使用去卷积方法。此外，标准的碘化造影剂可以很快进行再注射，而且由于已经准确地测量了CBV，因此可以获得更准确的渗透性表面乘积测定。

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 in tumors 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. Vesicle size, chemical affinity, and thermal (or pH) sensitivities can be engineered. We will use polyethylene glycol (PEG)-coated liposome with an intravascular circulation half-life 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. The relative enhancement of a voxel on a CT study is proportional to the intravoxel concentration of contrast agent. Agents that behave as true bloodpool agents on the time scale of this experiment should remain within the intravascular space. Therefore, relative enhancement of a voxel should be proportional to the cerebral blood volume (CBV). This should allow for direct measurement of CBV, rather than the need for using a deconvolution approach. Moreover, reinjection with a standard iodinated contrast agent can be performed soon afterward, and a more accurate permeability surface product determination can be obtained because CBV has been accurately measured.