Quantitative, Dynamic Functional 1H MRS of Human Brain

在体核磁共振波谱（MRS）是一种强大的，非侵入性的技术来研究（人类）大脑代谢. 结合体内MRS和13 C标记底物的输注，可以定量测量代谢通量，如脑葡萄糖利用率和谷氨酸神经递质循环。 然而，由于光谱和空间分辨率的限制，在功能激活期间的应用受到限制。 在这里，在体内MRS方法在4 T将开发克服这些问题，并允许功能代谢的常规研究。 这些方法将被应用于研究在休息和视觉刺激时，人脑中葡萄糖代谢和多巴胺能神经元活动之间的关系。通过开发光谱量化和多体素定位的先进方法，结合组织成分（灰色和白色物质）和功能活动的先验知识，将改善短回波时间MRS。 接下来，该技术将应用于人脑，以建立各种大脑结构中的稳态代谢物浓度。 定量1H MRS技术将发展成为一种定量和动态（逆）1H-[13 C]-MRS技术，用于检测具有质子高灵敏度的13 C标记化合物。 通过比较大鼠脑中[4- 13 C]-谷氨酸和谷氨酰胺的体内部分富集与体外提取物中获得的部分富集，在动物模型上验证定量性质。 然后将实施逆MRS方法，通过动态测量葡萄糖氧化和谷氨酸神经递质循环的速率来研究神经元能量产生与神经递质活性和循环之间的关系。 这项提议的结果将为功能性脑成像技术（如fMRI和PET）的解释提供一个重要的神经化学联系。 人脑映射的神经化学基础可以提供关于正常和患病脑组织之间的功能数据比较的有价值的信息。

In vivo NMR spectroscopy (MRS) is a powerful, non- invasive technique to study (human) brain metabolism. The combination of in vivo MRS and infusion of 13C-labeled substrates allows the quantitative measurement of metabolic fluxes, like cerebral glucose utilization and glutamate neurotransmitter cycling. However due to limitations in spectral and spatial resolution applications during functional activation have been limited. Here in vivo MRS methods at 4T will developed to overcome these problems and allow the routine study of functional metabolism. These methods will then be applied to study the relation between glucose metabolism and glutamatergic neuronal activity in the human brain during rest and visual stimulation. Short echo-time MRS will be improved through development of advanced methods for spectral quantification and multi-voxel localization incorporating prior knowledge on tissue composition (gray and white matter) and functional activity. Next, the technique will be applied to human brain in order to establish steady-state metabolite concentrations in various brain structures. The quantitative 1H MRS technique will be developed into a quantitative and dynamic (inverse) 1H-[13C]-MRS technique for the detection of 13C-labeled compounds with the high sensitivity of protons. The quantitative nature will be validated on an animal model by comparing the in vivo fractional enrichments of [4-13C]-glutamate and glutamine in rat brain, with those obtained in the extracts in vitro. The inverse MRS method will then be implemented to study the relationship between neuronal energy production and neurotransmitter activity and cycling by dynamically measuring the rates of glucose oxidation and glutamate neurotransmitter cycling. The results from this proposal will provide an essential, neurochemical link for the interpretation of functional brain mapping techniques, like fMRI and PET. A neurochemical basis of human brain mapping can provide valuable information about functional data comparisons between normal and diseased cerebral tissue.