Neurometabolic profile of tobacco smoking in HIV-infected Individuals

项目摘要 吸烟是一个严重的公共卫生问题，在艾滋病毒感染者中的流行率是普通人的2到3倍。 个体比一般人群更多。吸烟降低了联合抗逆转录病毒治疗和 对艾滋病毒感染者的长期生存产生重大影响。几项研究表明， 长期吸烟和艾滋病毒感染对大脑有有害的相加或协同作用， 导致更严重的精神病态、冲动和认知功能障碍。人们对此知之甚少 与艾滋病毒感染和吸烟的综合影响有关的神经化学特征。大力神是小说中的J- 差分编辑磁共振波谱(MRS)技术，可以测量多达七个低的 浓缩脑代谢物(例如，GABA)，扫描时间相对较短。然而，大力神是敏感的 对于对象运动，这既影响定位精度，也影响光谱质量。艾滋病毒感染者和 吸烟者有更大的冲动，这可能会导致更大的主体运动。因此，这样做的目的是 项目有：1)K99阶段：候选人将在指导下进行发展修正 Hercules序列，这将允许对这些神经代谢物进行强有力的研究；他还将评估 血清阴性(SN)健康对照大力神运动矫正前后的重复性；2)K99 阶段：学习使用优化的运动矫正Hercules进行试点临床研究，以评估 与SN健康对照相比，HIV感染者或吸烟者的神经代谢特征；3)R00 阶段：测量四组个体的综合神经化学特征(SN/烟草-， HIV+/烟草-，SN/烟草+，HIV+/烟草+)，使用运动校正的Hercules序列。基于 建议的临床培训和授课课程，应聘者将与经验丰富的全球公认的 MRS和临床艾滋病毒研究领域的专家，以实现五个培训目标：(1)发展专门知识 艾滋病毒感染者和吸烟者的研究设计和临床评估；(2)进行试点 研究评估艾滋病毒和吸烟对神经代谢物水平的独立影响；(3)学会 将先进的磁共振波谱技术应用于临床研究，特别是对艾滋病毒感染者和吸烟者的研究；以及 (4)学会应用先进的统计学方法分析来自患者群体的复杂临床数据。这个 候选人的长期职业目标是成为一名拥有完整技能的独立科学家 掌握MRS方法学及其临床应用技巧。经过运动校正的大力神可以应用于 也研究其他疾病的代谢过程，为这项研究计划增加范围和影响， 还响应了NIDA的使命，即从战略上支持和开展基础和临床研究 毒品使用(包括尼古丁)、其后果以及涉及的潜在神经生物学机制。

Project Summary Tobacco smoking is a serious public health concern and is 2 to 3 times more prevalent among HIV-infected individuals than the general population. Smoking reduces the efficacy of combination antiretroviral therapy and substantially impacts the long-term survival of HIV-infected individuals. Several studies have suggested that chronic tobacco (cigarette) smoking and HIV infection have harmful additive or synergistic effects on the brain, leading to greater psychopathology, impulsivity and cognitive dysfunction. Little is known about the neurochemical profile related to the combined effects of HIV infection and smoking. HERCULES is a novel J- difference-edited magnetic resonance spectroscopy (MRS) technique that can measure up to seven low- concentration brain metabolites (e.g., GABA) with relatively short scan times. However, HERCULES is sensitive to subject motion, which affects both localization accuracy and spectral quality. Both HIV-infected subjects and tobacco smokers have greater impulsivity that might lead to greater subject motion. Therefore, the aims of this project are: 1) K99 phase: the candidate will be mentored in the development of the motion-corrected HERCULES sequence, which will allow robust investigation of these neurometabolites; he will also assess the reproducibility of HERCULES with and without motion correction in seronegative (SN) healthy controls; 2) K99 phase: to learn to conduct a pilot clinical study using the optimized motion-corrected HERCULES to evaluate the neurometabolic profile of HIV-infected individuals or tobacco smokers, compared to SN healthy controls; 3) R00 phase: to measure a comprehensive neurochemical profile in four groups of individuals (SN/tobacco-, HIV+/tobacco-, SN/tobacco+, HIV+/tobacco+), using the motion-corrected HERCULES sequence. Based on the proposed clinical training and didactic courses, the candidate will work with experienced globally recognized experts in the fields of MRS and clinical HIV research to achieve five training goals: (1) develop expertise in research design and clinical assessments of HIV-infected individuals and tobacco smokers; (2) conduct a pilot study to evaluate the independent effects of HIV and tobacco smoking on neurometabolite levels; (3) learn to apply an advanced MRS technique to clinical research, especially in HIV+ individuals and tobacco smokers; and (4) learn to apply advanced statistical methods to analyze complex clinical data from patient populations. The long-term career objective of the candidate is to become an independent scientist with a complete repertoire of skills in MRS methodologies and their clinical applications. The motion-corrected HERCULES can be applied to study metabolic processes in other diseases as well, adding scope and impact to this research proposal, which is also responsive to NIDA’s mission of “strategically supporting and conducting basic and clinical research on drug use (including nicotine), its consequences, and the underlying neurobiological mechanisms involved.”