Quantification of Tumor Malignancy with MRI

MRI 定量肿瘤恶性肿瘤

• 批准号: 7221253
• 负责人: GLYN JOHNSON
• 金额: $ 29.13万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-10 至 2011-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7221253
• 关键词: Academic Medical Centers; Adjuvant; Adjuvant Chemotherapy; Age; Algorithms; Appearance; Behavior; Biological Markers; Biopsy; Biopsy Specimen; Brain; Brain Neoplasms; Cause of Death; Central Nervous System Neoplasms; Cessation of life; Choline; Chromosomes; Classification; Clip; DNA; Data Set; Diagnosis; Doctor of Medicine; Excision; Glioma; Goals; Gold; Healthcare Systems; Histologic; Histology; Histopathology; Image; Institution; Intracranial Neoplasms; Investigation; Karnofsky Performance Status; Laws; Lesion; Location; Loss of Heterozygosity; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Malignant - descriptor; Malignant Glioma; Malignant Neoplasms; Measurement; Metric; Modeling; Molecular; Molecular Analysis; Molecular Profiling; Morbidity - disease rate; Nail plate; Nature; Neoplasms; New York; Numbers; Operative Surgical Procedures; Outcome; PTK2 gene; Paraffin; Pathologist; Pathology, Other; Patients; Performance; Perfusion; Polymerase Chain Reaction; Prognostic Factor; Radiation; Radiation therapy; Radio; Range; Reference Standards; Research Design; Research Personnel; Resected; Sampling; Sampling Errors; Score; Specimen; Standards of Weights and Measures; Subgroup; Surgeon; System; Testing; Time; Tissue Sample; Tissues; Triage; Tumor Tissue; Uncertainty; Vascular Endothelial Growth Factors; Vascular Permeabilities; angiogenesis; base; chemotherapy; cost; improved; in vivo; oligodendroglioma; outcome forecast; programs; size; spectroscopic imaging; tumor; tumor progression

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.

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/存活时间，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。与健康相关：目前脑胶质瘤的手术和术后治疗是基于常规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都有局限性。MR指标可以提供体内整个病变的真实生物侵袭性的指示，将有助于确定手术切除的范围，指导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射治疗的分类。具体目的：1)确定在低级别胶质瘤中，常规MRI、MR灌注成像和MR波谱成像获得的哪些MR指标能够预测进展时间/生存时间。假设1：一个或多个MR指标将能够预测肿瘤的生物学行为。2)比较MR指标与其他已知预后因素(如组织学)在预测进展时间/生存时间方面的差异。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疗敏感性的分子标记的成像相关指标。假设3：rCBV等MR指标可与肿瘤进展、血管生成、侵袭、增殖和化疗敏感性的分子标志物如HIF-1a、FAK、VEGF/VPF、Ipl9q缺失相关，进而可作为进一步分子分析、治疗和预测预后的标志物。研究设计：1)获取常规MRI、血流灌注(DSC)和磁共振波谱(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生存曲线将被用来确定哪些指标可以预测进展/生存时间。在预测结果时，指标将与病理和其他预后因素进行比较。3)MR指标将与肿瘤进展、血管生成、增殖和化疗敏感性的分子标志物如HIF-1a、FAK、VEGF/VPF、Ipl9q缺失相关。分子研究将通过使用聚合酶链式反应的杂合性损失进行评估。从脑组织切片和指甲切片的石蜡卷曲中提取DNA，并使用以下引物：1.D1S1592；2.D19S219、D19S412。