Improved Management of GBM by Integrating Imaging and Tissue Analysis

说明)： 该项目的目标是开发和测试新的磁共振代谢成像方法，这将有助于 胶质母细胞瘤(GBM)患者复发与正常脑的鉴别及治疗效果 表征肿瘤大小和恶性潜能的时间变化对于制定 关于病人护理的基本决定。成像技术的可用性可以提供更多 可靠的肿瘤治疗反应指标，并能在早期阶段确定进展情况，对于 确定何时停止无效的治疗并选择替代策略。我们将整合 在P01的当前周期中开发和验证了多参数成像检查，并使用新的H- 1磁共振波谱成像技术和超极化C-13代谢成像新方法 开发用于评估病变的改进的MERTICS。将活体成像参数与组织学联系起来 以及项目2中正在研究的基因组特性以及项目中关于治疗效果的信息 3将为新疗法的选择和评价提供重要的新策略。 在目标1中，我们将开发和测试一种新的3D H-1 MRSI序列，它提供自动处方 并且显著改善了短回波(TE=20-35毫秒)光谱阵列的脑覆盖。这将有助于 肌醇与胆碱、肌酸和N-乙酰天冬氨酸的体内水平的估计。 在目标2中，我们将利用加州大学旧金山分校的独特经验和资源来调查 基底膜患者的超极化C-13MR代谢成像。这项令人兴奋的新技术已经成为 在临床前研究中显示，可以区分肿瘤和正常组织，并提供快速评估 对治疗的反应。 在目标3中，我们将结合图像引导组织使用目标1和目标2中开发的技术 抽样以确定以下代谢成像参数是否可以改善 复发肿瘤的特征和治疗效果：(I)胆碱与N-乙酰天冬氨酸的比值，(Ii) 肌醇/胆碱比值和超极化C-13乳酸/丙酮酸比值。 相关性(请参阅说明)： 在这个项目中，我们将把新的代谢和生理成像方法与组织研究相结合 为了确定哪些代谢成像参数在区分复发方面最有效 从治疗效果看肿瘤。这将对慢性前列腺炎患者的临床管理产生重大影响。 GBM和对新疗法的评价。

instrucfions): The goal of this project is to develop and test novel MR metabolic imaging approaches that will help to distinguish recurrent tumor from normal brain'and treatment effects in patients with glioblastoma (GBM). Characterizing temporal changes in tumor size and malignant potential is critically important for making fundamental decisions about patient care. The availability of imaging technologies that can provide more reliable metrics of tumor response to therapy and can identify progression at an early stage is critical for determining when to stop ineffective treatment and for selecting alternative strategies. We will integrate the multi-parametric imaging examination developed and validated in the current cycle of this P01 with novel H- 1 MR spectroscopic imaging techniques and new hyperpolarized C-13 metabolic imaging methods in order to develop improved mertics for evaluating the lesion. Linking in vivo imaging parameters with histological and genomic properties being studied in Project 2 and with information about therapeutic effects from Project 3 will provide important new strategies for selecting and evaluating novel therapeutics. In Aim 1 we will develop and test a novel 3D H-1 MRSI sequence that provides automated prescription and significantly improved brain coverage for short echo (TE=20-35ms) spectral arrays. This will facilitate the estimation of in vivo levels of myo-lnositol in the same acquisition as choline, creatine and N-acetylasptate. In Aim 2 we will utilize the unique experience and resources at UCSF to investigate the application of hyperpolarized C-13 MR metabolic imaging to patients with GBM. This exciting new technology has been shown in pre-clinical studies to differentiate tumor from normal tissue and provide a rapid assessment of response to therapy. In Aim 3 we will use the techniques developed in Aims 1 and 2 in conjunction with image guided tissue sampling in order to determine wheytherthe following metabolic imaging parameters can improve upon the characterization of recurrent tumor and treatment effect: (i) the choline to N-acetylaspartate index, (ii) the ratio of myo-lnositol/choline and (ill) the ratio of hyperpolarized C-13 lactate/pyruvate. RELEVANCE (See instructions): In this Project we will integrate novel metabolic and physiological imaging methods with tissue studies in order to determine which metabolic imaging parameters are the most effective in distinguishing recurrent tumor from treatment effects. This will have a major impact upon the clincial management of patients with GBM and upon the evaluation of novel therapeutics.