Noninvasive Metabolic Signatures to Improve Management of Molecular Subtypes of Glioma

这份P01提案的总体目标是改善对不同分子疾病患者的管理 神经胶质瘤亚型，关注与代谢和生理相关的新的神经成像替代物 每组的变化。胶质瘤的组织病理学和分子亚群的划分 通过改善诊断和预后，神经肿瘤学领域发生了革命性的变化。审讯新陈代谢和 这些亚群的生理特征将是神经成像领域的下一个关键进展之一。 在P01的前一个周期中，我们获取了与MR匹配的图像引导组织样本的大数据集 扩散、灌注和光谱扫描。我们现在寻求将这些技术结合起来，使用复杂的 数据分析工具可以更有效地按亚组预测肿瘤负担和恶性行为。我们的预赛 数据还表明，与IDH状态和TERT的变化相关的新陈代谢也存在差异 有可能用于开发特定分子亚型的体内签名的表达。 在这项新的提议中，我们将识别针对每个亚型的多参数成像标记；使用 新型基因编辑工具用于阐明影响突变型TERT启动子调控的机制 具有不同分子和临床特征的亚群；定义TERT表达的代谢特征；以及 实施新的1H和13C代谢成像策略，以监测患者在 他们的病。这将为开发临床1H和超极化13C代谢成像奠定基础 可以为肿瘤复发和治疗反应提供早期评估的检测方法。这些集成在一起 研究将由行政和临床服务中心和 生物标记物和生物标记物核心。将我们的机械发现和新的成像技术转化为 临床上相关的行动，我们将使用我们的团队在过去 在细胞、临床前模型和患者中进行研究的P01周期。这项创新性研究描述了 在这项提议中，将利用由久负盛名的、协作的 加州大学旧金山分校的临床、生物和成像科学家小组。

The overall goal of this P01 proposal is to improve the management of patients with different molecular subgroups of glioma, focusing on novel neuroimaging surrogates associated with metabolic and physiologic changes in each group. The delineation of histopathological and molecular subgroups of glioma has revolutionized the field of neuro-oncology by improving diagnosis and prognosis. Interrogating metabolic and physiologic signatures of these subgroups will be one of the next critical advances in the field of neuroimaging. In the previous cycle of our P01, we acquired a large dataset of image-guide tissue samples matched with MR diffusion, perfusion, and spectroscopy scans. We now seek to combine these techniques using sophisticated data analysis tools to more efficiently predict tumor burden and malignant behavior by subgroup. Our preliminary data also indicate that there are differences in metabolism associated with changes in IDH status and TERT expression that have the potential for being used in developing in vivo signatures for specific molecular subtypes. In this new proposal, we will identify multi-parametric imaging markers that are specific to each subtype; use novel gene editing tools to elucidate mechanisms that influence the regulation of mutant TERT promotor in subgroups with divergent molecular and clinical features; define metabolic signatures of TERT expression; and implement novel 1H and 13C metabolic imaging strategies for monitoring individual patients during the course of their disease. This would set the stage for developing clinical 1H and hyperpolarized 13C metabolic imaging assays that could provide early assessment of tumor recurrence and treatment response. These integrated studies will be supported by specialized resources from the Administrative and Clinical Services Core and the Biospecimen and Biomarker Core. To translate our mechanistic findings and novel imaging technologies into clinically relevant actions, we will use the unique infrastructure that our group has established over the prior cycles of this P01 to perform studies in cells, pre-clinical models, and patients. The innovative research described in this proposal will take advantage of the exceptional resources assembled by the well-established, collaborative group of clinical, biological and imaging scientists at UCSF.