DYNAMIC MRI AND MRS STUDIES OF FOCAL NEURAL ACTIVATION

描述（改编自申请人摘要）：许多功能成像 技术是基于测量脑血流量（CBF）的变化， 直接地（例如放射性示踪剂方法或灌注MRI）或间接地，例如 血氧水平依赖（BOLD）功能性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 本项目的假设是：A）谷氨酸-谷氨酰胺循环 从谷氨酰胺标记测量反映了神经传递，这是增加 局部激活（神经元尖峰活动）。B）这一变化 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（CMRO 2），糖酵解和 苹果酸-天冬氨酸穿梭，这些变化与BOLD fMRI结果一致。 和灌注MRI提供了神经传递的连贯描述， 代谢/血流动力学相关性。C）那些大脑的酶途径 糖原的合成和分解是同时活跃的， 糖原浓度和大脑活动水平调节代谢。 具体目标如下：1。同时测量标签 结合到脑谷氨酸盐中的几个不同的碳位置， 谷氨酰胺和天冬氨酸在13 C标记的葡萄糖输注期间伴随 组织葡萄糖和乳酸盐浓度的测量，并结合 灌注和BOLD fMRI。2建立脑糖原的~（13）C NMR检测方法 浓度和代谢。显著的磷酸化酶和合成酶活性 如报告的脑组织，预期会导致标记从血浆转移 当输注标记的13 C葡萄糖时，葡萄糖与脑糖原结合， 可观察到的13 C NMR信号。这些目标将在大鼠脑中实现， 局部1H和13 C NMR光谱与BOLD的1H fMRI以及 灌注。

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.