Quantitative Assessment of Angiogenesis By Perfusion MRI

描述(由申请人提供)： 广泛的长期目标：开发使用动态增强灌注磁共振成像(PMRI)评估脑肿瘤血管生成的方法。与健康相关：该项目将应用pMRI来评估接受抗血管生成和其他化疗治疗的脑肿瘤。然而，开发的方法也将有助于评估大脑外部的肿瘤性病变和脑内的非肿瘤性病变。具体目的：1)探讨脑血容量(CBV)和血管通透性的pMRI测量分别与血管和血脑屏障(BBB)破坏的组织学评估相关的假说。2)探讨pMRI对脑肿瘤分级的可行性。3)探讨pMRI可用于监测化疗疗效的假设。研究设计：1)在7T动物成像仪上对小鼠脑胶质瘤进行pMRI成像。MRI测量的CBV和血管通透性将分别与血管密度和伊文氏蓝渗出的组织学评估相关联。2)对经组织学证实的不同级别脑肿瘤患者进行CBV和血管通透性的测量，以确定这些测量结果是否能区分它们。3)将对参加新化疗药物试验的胶质瘤患者进行一系列的pMRI测量：沙利度胺联合卡铂以及烷化剂Temodar和CPT-11。MRI测量将与肿瘤大小和临床结果相关联，以确定pMRI血管生成的指征是否预测肿瘤复发。

DESCRIPTION (provided by applicant): Broad long-term objectives: To develop methods of assessing angiogenesis in brain tumors using dynamic, contrast enhanced perfusion MRI (pMRI). Health-relatedness: The project will apply pMRI to the evaluation of brain tumors undergoing antioangiogenic and other chemotherapeutic treatments. However, the developed methods will also be useful in evaluating neoplastic lesions outside the brain and non-neoplastic lesions within it. Specific aims: 1) To investigate the hypothesis that pMRI measurements of cerebral blood volume (CBV) and vascular permeability correlate with histological assessments of vascularity and blood-brain barrier (BBB) breakdown respectively. 2) To determine whether pMRI can be used to grade brain tumors. 3) To investigate the hypothesis that pMRI can be used to monitor the efficacy of chemotherapeutic treatments. Research design: 1) Murine gliomas will be imaged with pMRI on a 7T animal imager. MRI measurements of CBV and vascular permeability will be correlated with histological assessments of vascular density and Evan's blue extravasation respectively. 2) CBV and vascular permeability will be measured in patients with histologically confirmed brain tumors of different grades to determine whether these measurements differentiate between them. 3) Serial pMRI measurements will be made on glioma patients enrolled in trials of new chemotherapeutic agents: thalidomide combined with carboplatin and the alkylating agents temodar and CPT-11. MRI measurements will be correlated with tumor size and clinical outcome to determine whether pMRI indications of angiogenesis predict tumor recurrence.