BLOOD VESSELS IN COLORECTAL TUMOR MODEL--RESPONSE TO ANGIOGENIC THERAPIES

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 本项目的目的是研究结直肠肿瘤模型中血管的发育以及对抗血管生成治疗的反应。来自人类细胞系的肿瘤将被植入小鼠的侧腹，并将用两种不同的方式进行成像：X射线和MRI。基于X线的技术将是数字减影血管造影术（DSA），而基于MR的技术将是动态对比增强（DCE）MRI和血管造影术。安维汀和伊立替康是将在该项目中使用的潜在药物。将研究密度、血管数量和迂曲度作为肿瘤大小和药物剂量的函数。 1)体内MRI（141 B Bryan）。高分辨率MR血管造影将用于研究肿瘤中血管的解剖分布。DCE-MRI将通过量化造影剂从血管内到血管外空间的转移率（血管泄漏的测量），用功能信息补充解剖测量。将使用定制表面线圈进行信号接收。在这些扫描中使用的造影剂将是Magnevist和血池脂质体钆。MR扫描的成像时间约为45分钟。 2)体内X射线（131 Bryan）。DSA成像提供了MR不易实现的快速采集选项，能够以心跳分辨率研究造影剂摄取和/或清除。通过时间密度曲线（TDC）的分析，可以区分动脉和静脉通路。TDC还用于测量感兴趣区域中的平均通过时间、血流量和血容量。将在尾静脉和/或股动脉（或颈动脉，如果肿瘤植入颈部）中注射Isovue 250。DSA扫描的成像时间约为20分钟。 3)成像研究完成时，通过麻醉剂过量处死动物，切除肿瘤并固定在福尔马林或布因中进行常规组织学检查。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The purpose of this project is to study the development of blood vessels in a colorectal tumor model and the response to anti-angiogenic therapies. Tumors from a human cell line will be implanted on the flank of mice and will be imaged with two different modalities: x-ray and MRI. The x-ray based technique will be digital subtraction angiography (DSA) while the MR-based techniques will be dynamic contrast enhanced (DCE) MRI and angiography. Avastin and Irinitecan are potential drugs that will be utilized in this project. The density, number of vessels, and tortuosity will be studied as a function of tumor size and drug dose. 1) In-vivo MRI (141B Bryan). High resolution MR angiography will be used to study the anatomical distribution of blood vessels in the tumor. DCE-MRI will complement the anatomical measurements with functional information by quantifying the transfer rate of contrast from intravascular to extravascular space which is a measure of vessel leakiness. A custom build surface coil will be used for signal reception. The contrast agents employed in these scans will be Magnevist and blood-pool liposomal gadolinium. Imaging time for MR scans will be approximately 45 minutes. 2) In-vivo X-ray (131 Bryan). DSA imaging provides fast acquisition options not easily achieved with MR that enables the study of contrast uptake and/or clearance at heartbeat resolution. Arterial supply can be distinguished from venous pathways through the analysis of time density curves (TDC). TDCs are also used to measure the mean transit time, blood flow, and blood volume in a region of interest. Isovue250 will be injected in the tail vein and/or femoral artery (or carotid artery if the tumors are implanted in the neck). Imaging time for DSA scans will be approximately 20 minutes. 3) At the completion of the imaging studies, animals will be sacrificed by anesthetic overdose and tumors will be excised and fixed in formalin or Bouin's for conventional histology.