Quantitative, Dynamic Functional 1H MRS of Human Brain

体内核磁共振波谱(MRS)是研究(人类)脑代谢的一种强大的、非侵入性的技术。体内MRS和13C标记底物的输注相结合，可以定量测量代谢通量，如大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一直受到限制。在这里，4T的体内MRS方法将被开发出来，以克服这些问题，并允许进行常规的功能代谢研究。然后，这些方法将被用于研究休息和视觉刺激时人类大脑中葡萄糖代谢和谷氨酸能神经元活动之间的关系。短回声时间MRS将通过开发先进的光谱量化和多体素定位方法来改进，该方法结合了组织成分(灰质和白质)和功能活动的先验知识。接下来，这项技术将应用于人脑，以建立不同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的~1H-[~(13)C]-MRS技术，用于检测具有高质子灵敏度的~(13)C标记化合物。通过比较大鼠脑内[4-13C]-谷氨酸和谷氨酰胺在体内的部分富集量，以及体外提取液中的富集量，将在动物模型上验证定量性质。然后将实施反向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解释功能性脑成像技术提供必要的神经化学联系，如功能磁共振成像和正电子发射计算机断层扫描。人脑成像的神经化学基础可以提供关于正常和病变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.