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In Vivo Determination of NAAG in Brain

脑中 NAAG 的体内测定

基本信息

批准号：
7743831
负责人：
PETER B BARKER
金额：
$ 20.03万
依托单位：
JOHNS HOPKINS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-12-04 至 2012-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7743831
关键词：
Age Agonist Amyotrophic Lateral Sclerosis Bipolar Disorder Brain Cerebrum Cognition Data Detection Dipeptides Disease Functional disorder Future Glutamate Carboxypeptidase II Glutamates Grant Human Human Volunteers Individual Investigation Lead Magnetic Resonance Spectroscopy Maps Measurement Measures Mental disorders Methods N-Methyl-D-Aspartate Receptors N-acetylaspartate N-acetylaspartylglutamate Nerve Neuraxis Neurobehavioral Manifestations Neurologic Noise Pain Pathogenesis Patients Peptides Pharmacotherapy Pilot Projects Play Procedures Protease Inhibitor Protons Research Resolution Role Schizophrenia Sensory Receptors Signal Transduction Spatial Distribution Specificity Stroke Sum Symptoms Techniques Testing Traumatic Brain Injury Vesicle base brain volume imaging modality in vivo magnetic field metabotropic glutamate receptor 3 novel prefrontal lobe public health relevance receptor sex spectroscopic imaging

项目摘要

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.

描述（由申请人提供）：N-乙酰基谷氨酸盐（NAAG）是人脑中含量最丰富的肽。NAAG的水平已经被认为在患有诸如精神分裂症和肌萎缩侧索硬化症等疾病的患者中是异常的。直到最近，还没有可用于非侵入性测定脑NAAG水平的方法。传统的在体质子磁共振波谱已被频繁地用于测量NAAG和N-乙酰天冬氨酸（NAA）的组合共振，但它只有有限的能力，分别检测的单个组件，NAAG和NAA，因为它们的结构和光谱的相似性。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，人脑为7特斯拉）和足够的均匀性下，可以使用质子MR光谱成像（MRSI）直接解析NAA和NAAG。在这个试点R21的应用程序中，我们建议进一步开发和验证NAAG检测和定量的方法在3和7 T，并将这些技术应用到一个试点研究的精神分裂症患者在3 T。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-乙酰基谷氨酸（NAAG）是脑中最丰富的肽，并且被认为在许多脑疾病的发病机制中起中心作用，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。我们已经开发了一种新的方法来测量NAAG使用磁共振波谱（MRS）。这项R21资助的目的是扩展这项技术，并使用高场扫描仪上的MR光谱成像绘制NAAG在大脑中的空间分布。所开发的技术将应用于精神分裂症患者NAAG水平的试点研究。从长远来看，这项研究可能会导致更好地了解精神分裂症和治疗方法。