13C SPECTROSCOPY

这是Ross修改过的Project申请。人类免疫缺陷病毒（HIV）和甲基苯丙胺（冰毒）滥用与脑损伤有关。利用质子磁共振（MR）光谱对戒断冰毒使用者和HIV阳性患者进行的研究表明，n -乙酰天冬氨酸水平降低可能表明神经元损伤或死亡。然而，损伤的机制尚不清楚。碳-13 （13C）磁共振光谱允许重要的代谢过程的体内测量，可能揭示损伤的复杂机制。为了跟踪代谢，注入isc标记的底物，13C标签掺入中间体中提供代谢信息

This is a revised application for Project by Ross. Human immunodeficiency virus (HIV) and methamphetamine (METH) abuse are associated with cerebral injury. Studies utilizing proton magnetic resonance (MR) spectroscopy in abstinent METH users and HIV+ patients have revealed reduced levels of N-acetylaspartate which may be indicative of neuronal injury or death. However, the mechanism of injury is not well understood. Carbon-13 (13C) MR spectroscopy allows for in vivo measurements of important metabolic processes that may reveal the complex mechanisms of damage. To track metabolism, a ISC-labeled substrate is infused and 13C label incorporation into intermediaries provides information on metabolic pathways. One such pathway is the neuronal tricarboxylic acid cycle (VtcaN), which is a measure of energy metabolism. In addition, glutamate-glutamine cycling (Vgln) can be quantified, providing an estimate of the glutamate neurotransmission rate. In this study, 13C MR spectroscopy will be performed during an intravenous infusion of D-glucose-1-13C to study the effects of METH+ and HIV on Vgln and VtcaN. Twenty HIV+/METH+, 20 HIV+/METH-, 20 HIV-/METH+, and 20 HIV-/METH- healthy controls will be enrolled. HIV+/METH- participants are expected to display decreased Vgln and increased VtcaN, which may be indicative of excessive glutamate neurotransmission and increased glutamate synthesis, respectively. HIV- /METH+ will show increased Vgln and decreased VtcaN reflecting a neuroadaptive response to previous heavy METH use. HIV+/METH+ are expected to have similar metabolic rate profiles as HIV+/METH- because the changes related to HIV are predicted to be of greater magnitude than those due to METH. VtcaN and Vgln will be related to measures of neurocognitive and neuromotor function. Additionally, FMRI brain response and cerebrospinal fluid markers of astrocyte and neuron function will be related to 13C spectroscopy metabolic rates.