PREDICTING BRAIN TUMOR CHEMOSENSITIVITY BY IN VIVO MRS

通过体内 MRS 预测脑肿瘤化疗敏感性

• 批准号: 6173846
• 负责人: RAMON GILBERTO GONZALEZ
• 金额: $ 24.12万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-09-01 至 2003-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6173846
• 关键词: astrocytoma; bioimaging /biomedical imaging; brain circulation; brain neoplasms; clinical research; functional magnetic resonance imaging; glioma; human subject; human therapy evaluation; molecular oncology; neoplasm /cancer chemotherapy; neoplasm /cancer genetics; phenotype; prognosis

The overall goal of this project is to investigate the use of MR spectroscopic and functional imaging methods to predict and assess chemotherapeutic response in brain tumors. Specifically, this work proposes to ascertain if new MR neuro-imaging techniques can discriminate between response and non-response to PCV chemotherapy in patients with anaplastic oligodendroglioma (AO) and anaplastic oligoastrocytoma (AOA). AO and AOA are unique in their chemosensitivity with approximately three-quarters of these tumors responding dramatically to the PCV regimen. Our preliminary studies show three major findings: 1) specific loss of chromosome 1p and 19q is strongly correlated with chemotherapeutic response in AO; 2) different tumor types give rise to quantifiable differences in the MRS metabolic pattern; 3) ex vivo MRS results accurately reflect in vivo MRS metabolic patterns. The discovery of the unique genetic correlates of chemosensitivity in AO and AOA presents a singular opportunity to investigate the relationship between genetics, MR detected metabolic phenotypes and chemotherapeutic response. We therefore hypothesize that metabolic and physiological MR imaging techniques can identify non-responsive tumors at an earlier time point than conventional imaging modalities. The following specific aims are designed to test this hypothesis: 1) To correlate in vivo and ex vivo MRS patterns and molecular genetics as predictors of response in untreated AO and AOA. 2) To characterize the in vivo spectroscopic patterns, rCBV maps and diffusion properties of AO and AOA prior to treatment and at specific time points during the initial cycle of chemotherapy. 3) To determine the relationship between MR metabolic, functional imaging and clinical response in patients with AO and AOA. The successful completion of this study will provide an assessment of the ability MR spectroscopic and functional imaging techniques to predict chemosensitivity prior to treatment and to monitor response throughout the therapy.

该项目的总体目标是研究使用磁共振波谱和功能成像方法来预测和评估脑肿瘤的化疗反应。 具体来说，这项工作旨在确定新的 MR 神经成像技术是否可以区分间变性少突胶质细胞瘤 (AO) 和间变性少突星形细胞瘤 (AOA) 患者对 PCV 化疗的反应和无反应。 AO 和 AOA 的化学敏感性是独一无二的，其中大约四分之三的肿瘤对 PCV 方案有显着反应。 我们的初步研究显示了三个主要发现：1）1p 和 19q 染色体的特异性丢失与 AO 的化疗反应密切相关； 2）不同的肿瘤类型导致MRS代谢模式存在可量化的差异； 3）离体MRS结果准确反映体内MRS代谢模式。 AO 和 AOA 中化学敏感性的独特遗传相关性的发现为研究遗传学、MR 检测的代谢表型和化疗反应之间的关系提供了一个独特的机会。 因此，我们假设代谢和生理 MR 成像技术可以比传统成像方式更早地识别无反应肿瘤。以下具体目标旨在检验这一假设：1) 将体内和离体 MRS 模式与分子遗传学相关联，作为未治疗 AO 和 AOA 反应的预测因子。 2) 表征治疗前和化疗初始周期特定时间点 AO 和 AOA 的体内光谱模式、rCBV 图和扩散特性。 3) 确定AO和AOA患者的MR代谢、功能成像和临床反应之间的关系。这项研究的成功完成将评估磁共振波谱和功能成像技术在治疗前预测化疗敏感性和监测整个治疗过程中反应的能力。