PREDICTING BRAIN TUMOR CHEMOSENSITIVITY BY IN VIVO MRS

本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，这项工作提出，以确定新的MR神经成像技术可以区分反应和非反应PCV化疗患者间变性少突胶质细胞瘤（AO）和间变性少突星形细胞瘤（AOA）。 AO和AOA在其化疗敏感性方面是独特的，大约四分之三的这些肿瘤对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）染色体1 p和19 q的特异性丢失与AO的化疗反应密切相关; 2）不同肿瘤类型引起MRS代谢模式的可量化差异; 3）离体MRS结果准确反映了体内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学治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成像技术可以在比传统成像方式更早的时间点识别无反应的肿瘤。设计以下具体目标以检验该假设：1）将体内和离体MRS模式与分子遗传学作为未治疗AO和AOA中的反应预测因子相关联。2)在治疗前和化疗初始周期的特定时间点表征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。本研究的成功完成将评估MR光谱和功能成像技术在治疗前预测化疗敏感性和在整个治疗过程中监测反应的能力。

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.