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， 个人比一般人。吸烟会降低抗逆转录病毒联合治疗的疗效， 对艾滋病毒感染者的长期生存产生重大影响。一些研究表明， 长期吸烟和艾滋病毒感染对大脑有有害的叠加或协同作用， 导致更严重的精神病理学冲动和认知功能障碍很少有人知道的 与艾滋病毒感染和吸烟的综合影响有关的神经化学概况。赫耳墨斯是一个新的J- 差分编辑磁共振波谱（MRS）技术，可以测量多达7个低- 浓度脑代谢物（例如，GABA），扫描时间相对较短。然而，赫拉克勒斯是敏感的， 受试者运动，这影响定位精度和频谱质量。HIV感染者和 吸烟者具有更大的冲动性，这可能导致更大的主体运动。因此，这一目标 项目是：1）K99阶段：候选人将在运动校正的发展指导 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 在血清阴性（SN）健康对照组中进行和不进行运动校正的HERCULES的重现性; 2）K99 阶段：学习使用优化的运动校正HERCULES进行试点临床研究，以评估 与SN健康对照相比，HIV感染个体或吸烟者的神经代谢特征; 3）R 00 阶段：测量四组个体（SN/烟草-， HIV+/烟草-、SN/烟草+、HIV+/烟草+），使用运动校正的HERCULES序列。基于 建议临床培训和教学课程，候选人将与经验丰富的全球公认的 MRS和临床HIV研究领域的专家，以实现五个培训目标：（1）发展专业知识， 对艾滋病毒感染者和吸烟者进行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MRS技术应用于临床研究，特别是在HIV+个体和吸烟者中;以及 (4)学习应用先进的统计方法来分析患者群体的复杂临床数据。的 候选人的长期职业目标是成为一名独立的科学家， MRS方法学及其临床应用的技能。运动校正的HERCULES可以应用于 研究其他疾病的代谢过程，增加了这项研究提案的范围和影响， 也是响应NIDA的使命“战略支持和进行基础和临床研究， 药物使用（包括尼古丁），其后果以及相关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.”