In Vivo Determination of NAAG in Brain

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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.