In Vivo Determination of NAAG in Brain

描述(申请人提供)：N-乙酰天冬氨酸(NAAG)是人脑中含量最丰富的多肽。NAAG水平被认为在精神分裂症和肌萎缩侧索硬化症等疾病患者中是异常的。直到最近，还没有可用于非侵入性测定大脑NAAG水平的方法。传统的活体质子磁共振波谱通常被用来测量NAAG和N-乙酰天冬氨酸(NAA)的联合共振，但由于结构和光谱的相似性，它对单独检测NAAG和NAA的能力有限。我们最近已经证明：(A)在3特斯拉的场强下，有可能使用光谱编辑技术以高特异性选择性地检测NAAG(和NAA)，以及(B)在非常高的磁场强度(例如人脑的7特斯拉)和足够均匀的情况下，有可能直接使用质子磁共振光谱成像(MRSI)来解析NAA和NAAG。在R21的试点应用中，我们建议进一步开发和验证3和7T的NAAG检测和定量方法，并将这些技术应用于3T的精神分裂症患者的试点研究。将测量20名患者的局部NAAG水平，并与年龄和性别匹配的正常对照组进行比较。预计这个R21项目将为随后的更大规模的研究提供初步数据，这些研究将充分阐明NAAG在精神分裂症中的作用。公共卫生意义：N-乙酰天冬氨酸(NAAG)是大脑中含量最丰富的多肽，被认为在许多脑部疾病的发病机制中发挥核心作用，包括精神分裂症、肌萎缩侧索硬化症等。直到最近，还没有直接的方法来测量完整的人脑中的NAAG。我们发展了一种利用磁共振波谱(MRS)测量NAAG的新方法。这项R21拨款的目的是推广这项技术，并使用高场扫描仪上的磁共振光谱成像绘制NAAG在大脑中的空间分布。开发的技术将用于精神分裂症患者NAAG水平的初步研究。从长远来看，这项研究可能会导致更好地理解精神分裂症和治疗方法。

DESCRIPTION (provided by applicant): N-acetylaspartylglutamate (NAAG) is the most abundant peptide in the human brain. Levels of NAAG have been suggested to be abnormal in patients with disorders such as schizophrenia and amyotrophic lateral sclerosis, amongst others. Until recently, there were no means available for the non-invasive determination of brain NAAG levels. Conventional in vivo proton magnetic resonance spectroscopy has been frequently used to measure the combined resonance of NAAG and N-acetylaspartate (NAA), but it has only limited ability to separately detect the individual components, NAAG and NAA, because of their structural and spectral similarity. We have recently demonstrated that; (a) at field strengths of 3 Tesla, it is possible to use spectral editing techniques to selectively detect NAAG (and NAA) with high specificity, and (b) at very high magnetic field strength (e.g. 7 Tesla for human brain) and with sufficient homogeneity, it is possible to resolve NAA and NAAG directly using proton MR spectroscopic imaging (MRSI). In this pilot R21 application, we propose to further develop and validate methods for NAAG detection and quantitation at both 3 and 7T, and to apply these techniques to a pilot study of patients with schizophrenia at 3T. Regional NAAG levels in 20 patients will be measured and compared to age- and sex-matched normal control subjects. It is expected that this R21 project will provide preliminary data for subsequent, larger studies that will fully elucidate the role of NAAG in schizophrenia. PUBLIC HEALTH RELEVANCE: N-acetylaspartylglutamate (NAAG) is the most abundant peptide in the brain, and is believed to play a central role in the pathogenesis of many cerebral disorders, including schizophrenia, amyotrophic lateral sclerosis, and others. Until recently, there was no direct way of measuring NAAG in the intact human brain. We have developed a new method for measuring NAAG using magnetic resonance spectroscopy (MRS). The purpose of this R21 grant is to extend this technique and map the spatial distribution of NAAG in the brain using MR spectroscopic imaging on high field scanners. The techniques developed will be applied to a pilot study of NAAG levels in patients with schizophrenia. In the long term, this research may lead to a better understanding of schizophrenia and treatment approaches.