Quantification of Tumor Malignancy with MRI

描述（由申请人提供）：广泛的长期目的：确定哪些MR指标能够预测进展/生存时间，特别是在低级别胶质瘤中，为胶质瘤治疗分类中的组织学提供第二个参考标准。健康相关性：目前的手术和术后胶质瘤治疗是基于传统的MRI和胶质瘤的组织学特征。然而，在预测胶质瘤的真实生物学行为方面，MRI和组织学都存在局限性。MR指标，可以提供一个真正的生物侵略性的整个病变在体内的指示，将是有用的，在确定手术切除的程度，直接组织标本进一步组织学/分子分析，并分流辅助化疗和放疗后手术。具体目标：1）确定在低级别胶质瘤中从常规MRI、灌注MR和MR光谱成像获得的哪些MR指标能够预测进展/生存时间。假设1：一个或多个MR指标将能够预测肿瘤生物学行为。2)比较MR指标与其他已知预后因素（如组织学）在预测至进展/生存时间方面的作用。假设2：在预测肿瘤生物学行为方面，定量MR指标将在组织病理学评估中具有附加价值。3)确定MR指标是否可以作为化学敏感性分子特征的成像相关性。假设三：MR度量如rCBV（和其他）可以与肿瘤进展、血管生成、侵袭、增殖和化学敏感性的分子标志物如HIF-1a、FAK、VEGF/VPF、Ipl 9 q缺失相关，并且进而可以用作指导进一步分子分析、治疗和预测预后的标志物。研究设计：1）获取常规MRI、灌注（DSC MRI）和光谱（MRSI）数据集以从研究患者获得定量MR度量。2)将使用Weibull生存模型分析和Kaplan-Meier生存曲线确定哪些指标可以预测至进展时间/生存期。在预测预后方面，将与病理和其他预后因素进行比较。3)最后，MR度量将与肿瘤进展、血管生成、增殖和化学敏感性的分子标志物（诸如HIF-1 α、FAK、VEGF/VPF、Ipl 9 q缺失）相关。将使用PCR通过杂合性丢失评估分子研究。将从脑切片的石蜡卷和指甲剪中提取DNA，并使用以下引物：1. D1S1592; 2. D19S219，D19S412。

DESCRIPTION (provided by applicant): Broad long-term objectives: To determine which MR metrics are able to predict time to progression/survival, particularly in low grade gliomas, to provide a second reference standard to histology in glioma therapy triage. Health-relatedness: Current surgical and post-surgical glioma therapy is based on the conventional MRI and histologic features of a glioma. However, there are limitations with both MRI and histology in predicting the true biologic behavior of gliomas. MR metrics, which can provide an indication of the true biologic aggressiveness of an entire lesion in vivo, will be useful in determining the extent of surgical resection, direct tissue specimens for further histologic/ molecular analysis, and the triage of adjuvant chemotherapy and radiation therapy following surgery. Specific aims: 1) To determine which MR metrics obtained from conventional MRI, perfusion MR and MR spectroscopic imaging in low-grade gliomas are able to predict time to progression/survival. Hypothesis 1: One or more MR metrics will be able to predict tumor biologic behavior. 2) To compare MR metrics with other known prognostic factors (such as histology) in predicting time to progression/survival. Hypothesis 2: Quantitative MR metrics will have added value in and above histopathologic assessment in predicting tumor biologic behavior. 3) To determine if MR metrics can serve as imaging correlates for molecular signatures of chemosensitivity. Hypothesis 3: MR metrics such as rCBV (and others) can be correlated with molecular markers of tumor progression, angiogenesis, invasion, proliferation and chemosensitivity such as HIF-la, FAK, VEGF/VPF, Ipl9q deletions and in turn can be used as marker for guiding further molecular analysis, therapy and predicting prognosis. Research Design: 1) Acquire conventional MRI, perfusion (DSC MRI) and spectroscopic (MRSI) data sets to obtain quantitative MR metrics from study patients. 2) Weibull survival model analysis and Kaplan-Meier survival curves will be used to determine which metrics can predict time to progression/survival. Metrics will be compared with pathology and other prognostic factors in predicting outcome. 3) Finally MR metrics will be correlated with molecular markers of tumor progression, angiogenesis, proliferation and chemosensitivity such as HIF-la, FAK, VEGF/VPF, Ipl9q deletions. Molecular studies will be assessed by loss of heterozygosity using PCR. DNA will be extracted from paraffin curls of brain section and nail clippings and the following primers will be used: 1. D1S1592; 2. D19S219, D19S412.