DYNAMIC MRI AND MRS STUDIES OF FOCAL NEURAL ACTIVATION

描述(改编自申请者摘要)：多种功能成像 这些技术基于测量脑血流量(CBF)的变化，或者 直接(如放射性示踪法或核磁共振灌注成像)或间接，如 血氧水平依赖(BOLD)功能磁共振成像。CBF的这些变化是 被认为反映大脑代谢活动的变化，具体地说 大脑葡萄糖消耗，CMRglc，这反过来被认为反映了 神经元活动。 这个项目的假设是：a)谷氨酸-谷氨酰胺循环 从谷氨酰胺标记测量的结果反映了神经传递的增加 局灶性激活(神经元棘波活动)。B)这一变化 神经传递与代谢率的变化相匹配，例如流量 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 和核磁共振灌注成像提供了神经传递的连贯描述和 代谢/血流动力学相关。C)脑内的这些酶途径 糖原合成和分解同时活跃，因此大脑 糖原浓度和大脑活动水平调节新陈代谢。 具体目标如下：1.同时测量标签 结合到大脑谷氨酸中几个不同的碳位， ~(13)C标记葡萄糖输注中的谷氨酰胺和天冬氨酸 测量组织葡萄糖和乳酸浓度，并结合 血流灌注和大胆的功能磁共振成像。2建立脑糖原~(13)C核磁共振检测方法 注意力和新陈代谢。显著的磷酸化酶和合成酶活性 据报道，脑组织有望导致从血浆中转移标记 当输注标记的13C葡萄糖时，葡萄糖到脑糖原，从而到一个 观察到的~(13)C核磁共振信号。这些目标将在大鼠大脑中实现 ~1H和~(13)C核磁共振波谱与BOLD和~1H fMRI联合应用 灌流。

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.