CT PERFUSION IMAGING USING IODINATED LIPOSOMES

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（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。所列机构为中心机构，不一定为研究者机构。该建议的主要目标是通过使用新型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观球形囊泡，可以封装碘化造影剂。囊泡大小、化学亲和力和热（或pH）敏感性可以被工程化。我们将使用聚乙二醇（PEG）包被的脂质体，其血管内循环半衰期为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。 CT研究中体素的相对增强与造影剂的体素内浓度成比例。在该实验的时间尺度上表现为真正的血池剂的试剂应保留在血管内空间内。因此，体素的相对增强应与脑血容量（CBV）成比例。这应该允许直接测量CBV，而不是需要使用去卷积方法。此外，可以在之后不久进行用标准碘化造影剂的再注射，并且可以获得更准确的渗透性表面乘积测定，因为已经准确地测量了CBV。

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.