Noninvasive Metabolic Signatures to Improve Management of Molecular Subtypes of Glioma

本P01提案的总体目标是改善不同分子水平患者的管理。 神经胶质瘤的亚组，重点是与代谢和生理相关的新的神经影像学替代物， 每一组的变化。神经胶质瘤的组织病理学和分子亚组的划分， 通过改善诊断和预后彻底改变了神经肿瘤学领域。询问代谢和 这些亚组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的上一个周期中，我们采集了与MR匹配的图像引导组织样本的大型数据集 扩散灌注和光谱扫描我们现在寻求联合收割机， 数据分析工具，以更有效地预测肿瘤负荷和恶性行为的亚组。我们的初步 数据还表明，与IDH状态和TERT的变化相关的代谢存在差异 这些表达具有用于开发特定分子亚型的体内标记的潜力。 在这个新的建议中，我们将确定特定于每个亚型的多参数成像标记物;使用 新的基因编辑工具，以阐明影响突变型TERT启动子调控的机制， 具有不同分子和临床特征的亚组;定义TERT表达的代谢特征;和 实施新的1H和13 C代谢成像策略，用于在治疗过程中监测个体患者。 他们的疾病。这将为开发临床1H和超极化13 C代谢成像奠定基础 可以提供肿瘤复发和治疗反应的早期评估的测定。这些集成 研究将得到来自行政和临床服务核心和 生物标本和生物标志物核心。将我们的机械发现和新的成像技术转化为 临床相关的行动，我们将使用独特的基础设施，我们的小组已经建立了在以前的 循环，在细胞、临床前模型和患者中进行研究。创新研究描述了 在这项提案中，将利用由成熟的、合作的 加州大学旧金山分校的临床、生物和成像科学家。

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.