DEUTERIUM NMR IMAGING OF REGIONAL TUMOR BLOOD FLOW

此应用程序的中心焦点是完成、验证和 最近在PI中开发的一种新技术的实现 重复性、非破坏性测量局部肿瘤血液实验室 在整个啮齿动物肿瘤模型中的rTBF。 吸收积分法 所使用的最小化了对动脉输入差异的敏感性 功能，并可以确定绝对TBF，而无需 对动脉输入函数进行采样。 该方法将通过以下方式进行验证： 直接比较通过NMR光谱观察测量的总TBF， 通过两种放射性标记微球测量的TBF的整个肿瘤HOD摄取 和14C-碘安替比林基本上与D20同时注射。 在完成定量绝对rTBF的方法学开发后 从静脉推注后获得的氘NMR图像， D20，将通过与rTBF进行比较来验证rTBF的此类测量 通过与D20同时注射的14C-碘安替比林测量。 的 在啮齿类动物中可以测量绝对TBF的条件 在不了解动脉输入功能的情况下， 评估在各种条件下动脉输入函数的变化， 条件和计算机模拟的影响，这种变化对 测量rTBF。 灌注急性变化的潜在影响， 使用D20注射后8至15分钟获得的图像， 为了降低摄取方法的rTBF检测限， 通过确定受影响的肿瘤的分数和 使用双荧光染料的瞬时灌注的时间尺度 肿瘤中的HOD摄取数据同时采集的技术。 将评价肿瘤大小和移植部位对rTBF的影响 以确定rTBF分布随大小的变化是否取决于 移植部位 由于肿瘤很少均匀灌注， TBF既可以影响肿瘤对治疗的反应，也可以通过以下方式改变： 治疗，这项技术应该是一个非常有价值的工具，以进一步我们的 了解TBF和治疗反应之间的关系。

The central focus of this application is the completion, validation, and implementation of a novel technique recently developed in the PI's laboratory for repeated, nondestructive measurement of regional tumor blood flow (rTBF) throughout rodent tumor models. the uptake integral approach utilized minimizes the sensitivity to differences in the arterial input function and may make it possible to determine absolute TBF without sampling the arterial input function. This approach will be validated by direct comparison of total TBF measured by NMR spectroscopic observation of whole tumor HOD uptake to TBF measured by both radiolabeled microspheres and 14C-iodoantipyrine injected at essentially the same time as the D20. After completing the development of methodology to quantitate absolute rTBF from deuterium NMR images acquired after bolus intravenous injection of D20, such measurements of rTBF will be validated by comparison to rTBF measured by 14C-iodoantipyrene injected at the same time as the D20. The conditions under which absolute TBF can be measured in rodent rumors without knowledge of the arterial input function will be assessed by evaluating the variation in the arterial input function under a variety of conditions and computer simulation of the effect of such variations on measured rTBF. The potential effect of acute changes in perfusion within tumors on the use of images acquired 8 to 15 minutes after D20 injection in order to decrease the limit of rTBF detection for the uptake method will be assessed by determining both the fraction of the tumor affected and the time scale of transient perfusion using the double fluorescent dye technique in tumors from which HOD uptake data is simultaneously acquired. The effect on rTBF of tumor size and transplantation site will be evaluated to determine if changes in the rTBF distribution with size are dependent on transplantation site. Since tumors are seldom homogeneously perfused and TBF can both affect the response of a tumor to therapy and be altered by therapy, this technique should be an extremely valuable tool to further our understanding of the relationship between TBF and therapeutic response.