Quantitative, Dynamic Functional 1H MRS of Human Brain

体内核磁共振波谱（MRS）是一种强大的、非侵入性的研究人脑代谢的技术。结合体内MRS和输注13c标记的底物，可以定量测量代谢通量，如脑葡萄糖利用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，在功能激活过程中的应用受到限制。在这里，将开发4T的体内MRS方法来克服这些问题，并允许对功能性代谢进行常规研究。这些方法将被应用于研究在休息和视觉刺激下人脑中葡萄糖代谢和谷氨酸能神经元活动之间的关系。通过开发先进的光谱定量和多体素定位方法，结合组织成分（灰质和白质）和功能活动的先验知识，将改进短回波时间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技术将发展成为定量动态（逆）1H-[13C]-MRS技术，用于检测具有高质子灵敏度的13C标记化合物。将在动物模型上通过比较[4-13C]-谷氨酸和谷氨酰胺在大鼠脑中的体内富集分数，与在体外提取的分数进行定量验证。然后，通过动态测量葡萄糖氧化率和谷氨酸神经递质循环率，实施逆MRS方法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。这一提议的结果将为解释功能性脑成像技术（如fMRI和PET）提供重要的神经化学联系。人脑图谱的神经化学基础可以为正常和患病脑组织之间的功能数据比较提供有价值的信息。

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.