In Vivo Determination of NAAG in Brain

描述（由申请人提供）：n -乙酰天冬氨酸（NAAG）是人脑中含量最多的肽。NAAG水平在精神分裂症和肌萎缩性侧索硬化症等疾病患者中被认为是异常的。直到最近，还没有无创测定脑NAAG水平的方法。传统的体内质子磁共振波谱法常用来测量NAAG和n -乙酰天冬氨酸（NAA）的联合共振，但由于NAAG和NAA的结构和光谱相似性，其单独检测NAAG和NAA的能力有限。我们最近已经证明；(a)在3特斯拉的磁场强度下，可以使用光谱编辑技术选择性地高特异性检测NAAG（和NAA）， (b)在非常高的磁场强度下（如人脑7特斯拉），并且具有足够的均匀性，可以直接使用质子磁共振光谱成像（MRSI）来分辨NAA和NAAG。在这个试点R21申请中，我们建议进一步开发和验证3 t和7T时NAAG检测和定量的方法，并将这些技术应用于3 t时精神分裂症患者的试点研究。将测量20例患者的区域NAAG水平，并与年龄和性别匹配的正常对照受试者进行比较。预计R21项目将为后续更大规模的研究提供初步数据，以充分阐明NAAG在精神分裂症中的作用。公共卫生相关性：n -乙酰天冬氨酸（NAAG）是大脑中最丰富的肽，被认为在许多大脑疾病的发病机制中起核心作用，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人脑中的NAAG。我们开发了一种利用磁共振波谱（MRS）测量NAAG的新方法。这项R21拨款的目的是扩展这项技术，并利用高场扫描仪上的磁共振光谱成像来绘制NAAG在大脑中的空间分布。开发的技术将应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对精神分裂症和治疗方法的更好理解。

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.