2D MR Correlational Spectroscopy Platform for Molecular and Genetic Characterizations of Glioma

用于神经胶质瘤分子和遗传特征的 2D MR 相关光谱平台

• 批准号: 9332975
• 负责人: Hui Mao
• 金额: $ 42.77万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-04-01 至 2021-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9332975
• 关键词: 19q; Address; Algorithms; Astrocytoma; Biological Markers; Brain Diseases; Brain Neoplasms; Cancer Biology; Characteristics; Classification; Clinical; Clinical Management; Collaborations; Coupled; Coupling; Data; Detection; Diagnosis; Diffuse; Disease; Early Diagnosis; Engineering; Enzymes; Genes; Glioblastoma; Glioma; Glutamates; Glutamine; Goals; Imaging Device; Imaging technology; Impairment; Individual; Infiltration; Isocitrate Dehydrogenase; Isocitrates; Lead; Link; Location; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Malignant - descriptor; Malignant Neoplasms; Measures; Metabolic; Metabolism; Methods; Molecular; Molecular Genetics; Monitor; Morphology; Motion; Mutate; Mutation; NADP; Patients; Pattern; Physiologic pulse; Procedures; Property; Protocols documentation; Research; Research Personnel; Resolution; Resources; Retreatment; Signal Transduction; Spectrum Analysis; Techniques; Technology; Testing; The Cancer Genome Atlas; Therapeutic; Tissues; Tumor Subtype; Universities; Work; academic program; alpha ketoglutarate; base; brain tissue; cancer biomarkers; clinical application; clinical practice; computerized data processing; data acquisition; imaging capabilities; improved; individualized medicine; industry partner; innovation; interest; mutant; neuro-oncology; novel; oligodendroglioma; outcome forecast; patient stratification; personalized medicine; precision medicine; programs; reconstruction; research and development; response; specific biomarkers; spectroscopic imaging; success; targeted treatment; tool; treatment response; tumor; tumor metabolism; tumor progression; two-dimensional

PROJECT SUMMARY With the growing emphases and clinical needs for molecular and genetic based diagnosis and treatment monitoring, both academic programs and scanner manufactures are making significant effort to improve and innovate magnetic resonance imaging (MRI) and spectroscopy (MRS) methods for interrogating metabolic functions and abnormalities in patients. Diffuse infiltrating low grade gliomas (LGG) are among the most lethal cancers and present great challenges in diagnosis and treatment, as they vary considerably in morphology, location, genetic alterations and response to therapy. One major challenge in the clinical management of LGG patients is the lack of accurate and non-invasive methods to stratify patients by tumor subtype to help with early diagnosis, individualized treatment and longitudinal clinical management. The discovery of heterozygous mutations in the isocitrate dehydrogenase (IDH1 and IDH2) genes in up to 70 % of LGG and secondary glioblastoma multiforme (GBM) links genetic alterations to tumor metabolism, prognosis and responses to treatment. IDH mutations lead to a neofunction of catalyzing the NADP-dependent reduction of α-ketoglutarate to oncometabolite R(-)-2-hydroxyglutarate, (2-HG). These important findings are changing the clinical paradigm of managing gliomas, if given the ability of detecting and measuring 2-HG to identify IDH mutation-bearing tumors, predict the prognosis, define subset-specific treatments and monitor therapeutic response. Our early study found the unique MR spectroscopic signature of 2-HG, which allowed us to establish 2-HG as a biomarker of IDH mutations with potential to quantify 2-HG in brain tumor patients using a spatially localized two-dimensional (2D) correlation spectroscopy (COSY) MRS method. This new strategy for detecting 2-HG can overcome the limitation of conventional 1D J-coupling editing MRS approaches in resolving 2-HG and other metabolites of interest. Investigators at Emory University in partnership with engineers from Siemens MR R&D are proposing to develop and implement a 2D COSY platform on the clinical scanner for non-invasive genetically classifying and characterizing gliomas as well as potentially monitoring retreatment responses and tumor progression in LGG patients using 2-HG as a biomarker. This project combines complementary strengths, expertise and resources of Emory and Siemens with a translational goal to integrate the latest cancer biology and biomarker research and advanced imaging technology to provide a paradigm shifting imaging tool for clinical management of brain tumors. The specific aims are: 1) to develop a sensitivity enhancing strategy with the latest 64-channel coil array and a novel coil proximity weighted parallel MR spectroscopy data acquisition and combination for 2D COSY; 2) to test, optimize and implement the developed method and to develop in-line data processing toolbox for processing and analyzing 2D COSY data on the clinical scanner; and 3) to test and validate the developed 2D COSY platform for genetically profiling gliomas using 2-HG as a marker and detecting other metabolites in patients.

项目摘要 随着对分子和遗传基础的重视和临床需求的不断增长 诊断和治疗监测，学术项目和扫描仪制造商都在进行 为改进和创新磁共振成像 (MRI) 和光谱学 (MRS) 做出巨大努力 检查患者代谢功能和异常的方法。 神经胶质瘤（LGG）是最致命的癌症之一，对诊断和治疗提出了巨大的挑战，因为 它们在形态、位置、基因改变和对治疗的反应方面差异很大。 LGG患者临床管理面临的挑战是缺乏准确和非侵入性的方法 按肿瘤亚型对患者进行分层，以帮助早期诊断、个体化治疗和纵向临床 异柠檬酸脱氢酶（IDH1 和 IDH2）杂合突变的发现。 高达 70% 的 LGG 和继发性多形性胶质母细胞瘤 (GBM) 中的基因将基因改变与肿瘤联系起来 IDH 突变导致代谢、预后和治疗反应。 NADP 依赖性 α-酮戊二酸还原为致癌代谢物 R(-)-2-羟基戊二酸 (2-HG)。 如果能够检测和治疗神经胶质瘤，重要的发现正在改变治疗神经胶质瘤的临床模式。 测量 2-HG 以识别携带 IDH 突变的肿瘤、预测预后、定义子集特异性 我们的早期研究发现了独特的 MR 光谱特征。 2-HG，这使我们能够将 2-HG 建立为 IDH 突变的生物标志物，并有可能量化 2-HG 使用空间局部二维 (2D) 相关光谱 (COSY) MRS 治疗脑肿瘤患者 这种检测 2-HG 的新策略可以克服传统 1D J 耦合的局限性。 埃默里大学的研究人员正在编辑 MRS 方法来解析 2-HG 和其他感兴趣的代谢物。 与西门子 MR R&D 的工程师合作，提议开发和实施 2D COSY 临床扫描仪上的平台，用于对神经胶质瘤进行非侵入性基因分类和表征 使用 2-HG 作为监测 LGG 患者再治疗反应和肿瘤进展的潜力 该项目结合了埃默里大学和西门子的互补优势、专业知识和资源。 其转化目标是整合最新的癌症生物学和生物标志物研究以及先进的成像技术 技术为脑肿瘤的临床管理提供范式转变的成像工具。 目标是：1）利用最新的64通道线圈阵列和新型线圈开发灵敏度增强策略 2D COSY 2) 的邻近加权并行 MR 波谱数据采集和组合进行测试； 优化并实施所开发的方法并开发在线数据处理工具箱进行处理 分析临床扫描仪上的 2D COSY 数据；3) 测试和验证开发的 2D COSY 使用 2-HG 作为标记物对神经胶质瘤进行基因分析并检测患者其他代谢物的平台。