Noninvasive Metabolic Signatures to Improve Management of Molecular Subtypes of Glioma

无创代谢特征可改善神经胶质瘤分子亚型的管理

• 批准号: 9790509
• 负责人: Susan M Chang
• 金额: $ 215.77万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-07-01 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9790509
• 关键词: Behavior; Biological; Biological Assay; Biological Markers; Brain; Cells; Characteristics; Clinic; Clinical; Clinical Services; Data; Data Analyses; Data Set; Development; Diagnosis; Diffusion; Disease; Evaluation; Foundations; Functional Imaging; Genes; Genomics; Geography; Glioblastoma; Glioma; Goals; Grant; Heterogeneity; Image; Imaging Techniques; Infrastructure; Lesion; Magnetic Resonance Imaging; Malignant - descriptor; Maps; Metabolic; Metabolic Marker; Metabolism; Molecular; Monitor; Multimodal Imaging; Mutation; Outcome; Patients; Perfusion; Physiological; Positioning Attribute; Pre-Clinical Model; Predictive Value; Program Research Project Grants; Property; Protocols documentation; Recurrence; Regulation; Research; Residual Tumors; Resources; Role; Sampling; Scanning; Signal Transduction; Spectrum Analysis; Subgroup; Techniques; Telomerase; Therapeutic; Tissue Sample; Translating; Tumor Biology; Tumor Burden; Tumor Markers; World Health Organization; clinical translation; clinically relevant; data acquisition; image guided; imaging biomarker; imaging modality; imaging scientist; improved; in vivo; individual patient; innovation; insight; metabolic imaging; molecular subtypes; multimodality; mutant; mutational status; neoplastic cell; neuro-oncology; neuroimaging; novel; novel imaging technology; novel therapeutics; oligodendroglioma; outcome forecast; pre-clinical; prediction algorithm; prognostic value; promoter; recruit; tool; treatment response; treatment strategy; tumor; tumor behavior

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.

本P01提案的总体目标是改善不同分子的患者的管理