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: 6540095
• 负责人: ROLF GRUETTER
• 金额: $ 25.34万
• 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 2003-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6540095
• 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（CBF）的变化 直接（例如radiotracer方法或灌注MRI）或间接 血氧水平依赖性（BOLD）功能性MRI。 CBF中的这些变化是 被认为反映大脑代谢活性的变化，特别是 脑葡萄糖消耗，CMRGLC，这又被认为反映了 神经元活性。 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 在局灶性激活中（神经元尖峰活性）。 b）改变 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 - 天冬氨酸班车，这些变化与大胆的fMRI一致 和灌注MRI提供了对神经传递及其的连贯描述 代谢/血液动力学相关性。 c）大脑的酶促途径 糖原的合成和分解同时活跃，以使大脑 糖原浓度和脑活性水平调节代谢。 以以下特定目的：1。同时测量标签 在脑谷氨酸中掺入几个不同的碳位置， 谷氨酰胺和天冬氨酸在13C标记的葡萄糖输注和伴随的葡萄糖输注 测量组织葡萄糖和乳酸浓度，并与 灌注和大胆的fMRI。 2开发13C NMR检测脑糖原 集中和代谢。显着的磷酸化酶和合酶活性 据报道，脑组织有望导致从等离子体转移标签 当注入标记为13C葡萄糖的葡萄糖到脑糖原，从而 可观察到的13C NMR信号。这些目标将在老鼠大脑中使用 局部1H和13C NMR光谱与BOLD和1H fMRI结合 灌注。