Neurometabolic profile of tobacco smoking in HIV-infected Individuals

HIV 感染者吸烟的神经代谢特征

• 批准号: 10395558
• 负责人: Muhammad G Saleh
• 金额: $ 17.33万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-05-01 至 2023-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10395558
• 关键词: Affect; Age; Anaerobic Bacteria; Antioxidants; Aspartate; Basal Ganglia; Basic Science; Biochemical Process; Brain; Brain Injuries; Brain region; Cell membrane; Chemicals; Choline; Chronic; Clinical; Clinical Data; Clinical Research; Clinical assessments; Cognitive deficits; Complement; Complex; Control Groups; Development; Disease; Drug usage; Economic Burden; General Population; Glutamates; Glutathione; Goals; HIV; HIV Infections; Health; Human; Impaired cognition; Impulsivity; Individual; Investigation; Lead; Learning; Lipids; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Measurement; Measures; Mentors; Metabolic Marker; Metabolism; Methodology; Methods; Mission; Morbidity - disease rate; Morphologic artifacts; Motion; N-acetylaspartate; N-acetylaspartylglutamate; National Institute of Drug Abuse; Neurocognitive Deficit; Neuromodulator; Neuronal Injury; Neurons; Neurotransmitters; Nicotine; Noise; Oxidative Stress; Parietal; Participant; Patients; Persons; Phase; Pilot Projects; Prevalence; Protocols documentation; Protons; Psychopathology; Public Health; Reporting; Reproducibility; Research; Research Design; Research Proposals; Scanning; Scientist; Short-Term Memory; Signal Transduction; Smoker; Smoking; Socioeconomic Status; Spectrum Analysis; Standardization; Statistical Methods; System; Techniques; Technology; Time; Tobacco; Tobacco smoking behavior; Tobacco use; Training; Vendor; Viral Load result; Work; antiretroviral therapy; ascorbate; base; brain health; career; cell type; cigarette smoking; clinical application; data acquisition; executive function; experience; experimental study; gamma-Aminobutyric Acid; gray matter; improved; in vivo; interest; magnetic field; metabolic abnormality assessment; mortality; neurobiological mechanism; neurochemistry; neuroimaging; neuroinflammation; neuroregulation; neurotransmission; novel; patient population; prospective; reconstruction; sex; skills; tobacco smokers; tool; training opportunity; white matter

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.”

项目总结

项目成果

In vivo spectral editing of phosphorylethanolamine.

• DOI: 10.1002/mrm.28976
• 发表时间: 2022-01
• 期刊: Magnetic resonance in medicine
• 影响因子: 3.3
• 作者: Hui SCN;Zöllner HJ;Oeltzschner G;Edden RAE;Saleh MG
• 通讯作者: Saleh MG

Ongoing oxidative stress in individuals with post-acute sequelae of COVID-19.

• DOI: 10.1515/nipt-2022-0006
• 发表时间: 2023-06
• 期刊: NeuroImmune pharmacology and therapeutics

Influence of editing pulse flip angle on J-difference MR spectroscopy.

• DOI: 10.1002/mrm.29008
• 发表时间: 2022-03
• 期刊: Magnetic resonance in medicine
• 影响因子: 3.3
• 作者: Tapper S;Hui SCN;Saleh MG;Zöllner HJ;Oeltzschner G;Near J;Soher BJ;Edden RAE
• 通讯作者: Edden RAE

MRSCloud: A cloud-based MRS tool for basis set simulation.

• DOI: 10.1002/mrm.29370
• 发表时间: 2022-11
• 期刊: MAGNETIC RESONANCE IN MEDICINE
• 影响因子: 3.3
• 作者: Hui, Steve C. N.;Saleh, Muhammad G.;Zollner, Helge J.;Oeltzschner, Georg;Fan, Hongli;Li, Yue;Song, Yulu;Jiang, Hangyi;Near, Jamie;Lu, Hanzhang;Mori, Susumu;Edden, Richard A. E.
• 通讯作者: Edden, Richard A. E.

sLASER and PRESS Perform Similarly at Revealing Metabolite-Age Correlations.

sLASER 和 PRESS 在揭示代谢物与年龄的相关性方面表现相似。

• DOI: 10.1101/2023.01.18.524597
• 发表时间: 2023
• 期刊: bioRxiv : the preprint server for biology
• 作者: Hui,SteveCN;Gong,Tao;Zöllner,HelgeJ;Hupfeld,KathleenE;Gudmundson,AaronT;Murali-Manohar,Saipavitra;Davies-Jenkins,ChristopherW;Song,Yulu;Chen,Yufan;Oeltzschner,Georg;Wang,Guangbin;Edden,RichardAE
• 通讯作者: Edden,RichardAE