DYNAMIC MRI AND MRS STUDIES OF FOCAL NEURAL ACTIVATION

局灶神经激活的动态 MRI 和 MRS 研究

• 批准号: 6041591
• 负责人: ROLF GRUETTER
• 金额: $ 25.29万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-04-10 至 2003-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6041591
• 关键词: Krebs' cycle; bioenergetics; bioimaging /biomedical imaging; brain circulation; brain metabolism; excitatory aminoacid; functional magnetic resonance imaging; glucose metabolism; glycogen; glycogen synthase; laboratory rat; neural transmission; neurochemistry; nuclear magnetic resonance spectroscopy; phosphorylases

DESCRIPTION (Adapted from applicant's abstract): Many functional imaging techniques are based on measuring changes in cerebral blood flow (CBF), either directly (such as radiotracer methods or perfusion MRI) or indirectly, such as blood-oxygen level dependent (BOLD) functional MRI. These changes in CBF are thought to reflect changes in cerebral metabolic activity, specifically cerebral glucose consumption, CMRglc, which in turn is thought to reflect neuronal activity. The hypotheses of this project are: A) That glutamate-glutamine cycling measured from glutamine labeling reflects neurotransmission, which is increased in focal activation (neuronal spike activity). B) That changes in neurotransmission are matched by changes in metabolic rates, such as flux through (neuronal) pyruvate dehydrogenase (CMRO2), glycolysis and malate-aspartate shuttle and that these changes are consistent with BOLD fMRI and perfusion MRI providing a coherent depiction of neurotransmission and its metabolic/hemodynamic correlates. C) Those enzymatic pathways of cerebral glycogen synthesis and breakdown are simultaneously active, such that brain glycogen concentration and cerebral activity levels modulate metabolism. With the following specific aims: 1. To simultaneously measure label incorporation into several distinct carbon positions in cerebral glutamate, glutamine and aspartate during 13C labeled glucose infusions with concomitant measurement of tissue glucose and lactate concentrations and combined with perfusion and BOLD fMRI. 2 To develop 13C NMR detection of brain glycogen concentration and metabolism. Significant phosphorylase and synthase activity as reported for brain tissue is expected to lead to label transfer from plasma glucose to brain glycogen when infusing labeled 13C glucose and thus to an observable 13C NMR signal. These aims will be achieved in rat brain using localized 1H and 13C NMR spectroscopy in conjunction with 1H fMRI of BOLD and perfusion.

描述（改编自申请人的摘要）：许多功能成像 技术基于测量脑血流量 (CBF) 的变化， 直接（例如放射性示踪剂方法或灌注 MRI）或间接，例如 血氧水平依赖 (BOLD) 功能 MRI。 CBF 的这些变化是 被认为反映了大脑代谢活动的变化，特别是 脑葡萄糖消耗，CMRglc，这反过来被认为反映了 神经元活动。 该项目的假设是： A) 谷氨酸-谷氨酰胺循环 通过谷氨酰胺标记测量的结果反映了神经传递，神经传递增加 局部激活（神经元尖峰活动）。 B) 变化在于 神经传递与代谢率的变化相匹配，例如通量 通过（神经元）丙酮酸脱氢酶 (CMRO2)、糖酵解和 苹果酸-天冬氨酸穿梭，这些变化与 BOLD fMRI 一致 和灌注 MRI 提供了神经传递及其相关的连贯描述 代谢/血流动力学相关。 C）大脑的那些酶促途径 糖原合成和分解同时活跃，这样大脑 糖原浓度和大脑活动水平调节新陈代谢。 具有以下具体目标： 1. 同时测量标签 掺入大脑谷氨酸中几个不同的碳位置， 13C 标记的葡萄糖输注过程中谷氨酰胺和天冬氨酸 测量组织葡萄糖和乳酸浓度并结合 灌注和 BOLD fMRI。 2 开发脑糖原的13C NMR检测 浓度和新陈代谢。显着的磷酸化酶和合酶活性 据报道，脑组织预计会导致血浆中的标记转移 当注入标记的 13C 葡萄糖时，葡萄糖转化为脑糖原，从而转化为 可观察到的 13C NMR 信号。这些目标将在大鼠大脑中实现 局部 1H 和 13C NMR 波谱与 BOLD 和 1H fMRI 结合 灌注。