Quantification of Tumor Malignancy with MRI

描述（由申请人提供）：广泛的长期目标：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，为胶质瘤治疗分诊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常规的MRI和胶质瘤的组织学特征。然而，MRI和组织学在预测胶质瘤的真实生物学行为方面存在局限性。MR指标可以提供整个病变在体内的真实生物侵袭性的指示，将有助于确定手术切除的范围，直接组织标本进行进一步的组织学/分子分析，以及手术后辅助化疗和放疗的分类。具体目的：1)确定从低级别胶质瘤的常规MRI、灌注MR和MR光谱成像中获得的MR指标能够预测进展/生存时间。假设1：一个或多个磁共振指标将能够预测肿瘤的生物学行为。2)将MR指标与其他已知预后因素（如组织学）进行比较，以预测进展/生存时间。假设2：定量MR指标在预测肿瘤生物学行为方面将比组织病理学评估更有价值。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指标。假设3:MR指标如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-la、FAK、VEGF/VPF、Ipl9q缺失相关，反过来可以作为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，以获得研究患者的定量MR指标。2)威布尔生存模型分析和Kaplan-Meier生存曲线将用于确定哪些指标可以预测进展/生存时间。在预测预后时，将指标与病理和其他预后因素进行比较。3)最后，MR指标将与肿瘤进展、血管生成、增殖和化学敏感性等分子标志物相关，如HIF-la、FAK、VEGF/VPF、Ipl9q缺失。分子研究将通过聚合酶链反应的杂合度损失来评估。从脑切片石蜡卷和指甲剪中提取DNA，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.