MR Metabolic Markers for Evaluation of Patients with Recurrent Glioma

描述（由申请人提供）：本研究的目标是开发用于采集和分析复发性胶质瘤患者体内MR代谢数据的稳健工具，该工具将与最先进的MR成像方法相结合，以提供用于连续监测治疗反应的改进指标。这解决了一个重要的临床问题，这是混淆了新的治疗方法的评价，使其难以作出明智的决定，对病人的护理。对于患有高级别胶质瘤的受试者，由复发肿瘤引起的形态学变化与治疗效果（如胶质增生和水肿）之间存在不明确性。基于该R 01的当前周期的结果，用于绘制复发肿瘤的真实程度的感兴趣的代谢物是肌醇（myo-I）、N-乙酰基丁酸（NAA）、肌酸（Cr）和胆碱（Cho）。对于最初诊断为低级别胶质瘤的受试者，其病变大小正在增加，关键问题是确定他们何时经历了需要积极治疗的更恶性表型的转化。根据我们对组织样品的离体分析，在这种情况下感兴趣的其他代谢物是肌-I、谷氨酸、谷氨酰胺、甘氨酸、谷胱甘肽和2-羟基戊二酸（2 HG）。在特定目标1和2中，我们将优化并评价自动化短TE 3D MRSI的重测准确性，以及将用于检测具有复杂耦合模式和重叠共振的代谢物体内水平的单体素谱编辑和2-D COSY序列。这将对3 T和7 T扫描仪进行，以确定哪种方法和场强将为患者研究提供最确定的结果。在具体目标3中，我们将应用优化的方法检测复发性低级别胶质瘤患者的2 HG，以确定与进展时间和总生存期相关的代谢参数。在特定目标4中，我们将使用最可靠的策略对复发性高级别胶质瘤患者进行分析，以获得短TE 3D MRSI数据。这项研究的结果将为评估治疗反应和选择替代治疗提供新的指标。

DESCRIPTION (provided by applicant): The goal of this study is to develop robust tools for acquiring and analyzing in vivo MR metabolic data in patients with recurrent glioma that will be integrated with state of the art MR imaging methods to provide improved metrics for serially monitoring response to therapy. This addresses an important clinical problem, which is confounding the evaluation of novel treatments and making it difficult to make informed decisions about patient care. For subjects with high grade glioma, there is ambiguity between morphological changes that are caused by recurrent tumor and treatment effects such as gliosis and edema. Based on results from the current cycle of this R01, metabolites of interest for mapping out the true extent of recurrent tumor are myo-inositol (myo-I), N-acetylasparate (NAA), creatine (Cr) and choline (Cho). For subjects with an original diagnosis of low grade glioma who have a lesion which is increasing in size, the critical issue is to determine when they have undergone transformation to a more malignant phenotype that requires aggressive therapy. From our ex vivo analysis of tissue samples, additional metabolites of interest in this case are myo-I, glutamate, glutamine, glycine, glutathione and 2-hydroxyglutarate (2HG). In Specific Aims 1 and 2 we will optimize and then evaluate the test-retest accuracies of automated short TE 3D MRSI, as well as single voxel spectral editing and 2-D COSY sequences that will be used to detect in vivo levels of metabolites with complex coupling patterns and overlapping resonances. This will be done for both 3T and 7T scanners in order to determine which method and field strength will provide the most definitive results for patient studies. In Specific Aim 3 we will apply methods optimized for detecting 2HG to patients with recurrent low grade glioma to identify metabolic parameters associated with time to progression and overall survival. In Specific Aim 4, we will perform an analysis in patients with recurrent hig grade glioma using the most reliable strategy for obtaining short TE 3D MRSI data. The results from this study will provide new metrics for assessing response to therapy and for selecting alternative treatments.