Two-Dimensional 3 Tesla MRS of the Brain in HIV- Infected Youth

HIV 感染青少年大脑的二维 3 Tesla MRS

• 批准号: 7494784
• 负责人: MARGARET A KELLER
• 金额: $ 17.52万
• 依托单位: LUNDQUIST INSTITUTE FOR BIOMEDICAL INNOVATION AT HARBOR-UCLA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-01 至 2010-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7494784
• 关键词: Adolescent; Adult; Affect; Age; Algorithms; Amino Acids; Aminobutyric Acid; Aminobutyric Acids; Anti-Retroviral Agents; Antioxidants; Applications Grants; Area; Attention; Basal Ganglia; Brain; Brain region; CD4 Lymphocyte Count; CD4 Positive T Lymphocytes; Cerebrum; Child; Choline; Chronic; Chronic Disease; Clinical; Cognitive; Creatine; Crowding; Cysteine; Data; Degenerative Disorder; Dementia; Detection; Development; Dimensions; Drug Metabolic Detoxication; Early treatment; Elevation; Encephalitis; Evaluation; Future; Gender; Gliosis; Glutamates; Glutamine; Glutathione; Glycine; Goals; Guidelines; HIV; HIV Infections; Health; Highly Active Antiretroviral Therapy; Impaired cognition; Individual; Inflammation; Inositol; Investigation; Left; Longitudinal Studies; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Measures; Membrane; Metabolic; Mothers; Motor; Motor Activity; N-acetylaspartate; Nervous System Trauma; Neuraxis; Neuroglia; Neurologic; Neurons; Neuropsychological Tests; Neurotransmitters; Noise; Oxidative Stress; Parkinson Disease; Pathology; Patients; Penetration; Performance; Pharmaceutical Preparations; Phosphorylcholine; Plasma; Public Health; Quality of life; Reaction; Reporting; Research Personnel; Score; Signal Transduction; Spectrum Analysis; System; Techniques; Testing; Time; Viral Load result; Youth; age related; antiretroviral therapy; base; cognitive function; cohort; computerized; critical developmental period; executive function; gamma-Aminobutyric Acid; improved; interest; motor impairment; myelination; neurocognitive test; performance tests; phosphoethanolamine; tool; transmission process; two-dimensional

DESCRIPTION (provided by applicant): HIV in adults and children has become a chronic illness and there is a critical need to develop noninvasive, reliable techniques to detect sub clinical involvement of the brain by HIV. Magnetic resonance spectroscopy (MRS) permits the study of HIV effects on cerebral metabolites, markers of neuronal and glial cell health. Most previous investigations have used 1.5 Tesla (T) scanners and one-dimensional MRS (1D-MRS) techniques. The primary goal of this study is to use an improved technique, a two-dimensional MRS technique (2D-MRS) on a 3 T scanner, to detect abnormal cerebral metabolites in HIV-infected patients, and to correlate abnormal cerebral metabolites with performance on neurocognitive tests, in order to better assess brain development and function in these individuals. A 3T scanner is expected to offer improved signal to noise ratios (SNR) and lower coefficients of variance compared to 1.5 T. The use of 2D-MRS allows the detection of many additional metabolites compared to traditional 1D-MRS by converting a crowded, overlapping 1D-MRS spectrum to a better resolved 2D spectrum through the addition of a spectral dimension. Of particular interest are GABA, an inhibitory neurotransmitter and myo-inositol (mI), a glial cell marker for which elevation suggests ongoing inflammation. Metabolite ratios to reference metabolites and metabolite concentrations will be determined. The 3 Tesla scanner combined with 2D-MRS also provides the ability to study glutathione (GSH), an important cellular antioxidant protector molecule that could assess central nervous system damage by the HIV virus. The specific aims of this study are to compare GABA, mI, choline groups, GSH and other metabolites in the right frontal brain region and right basal ganglia of 30 HIV-infected patients and 30 control subjects. Both of these areas of the brain have been documented to be involved in the central nervous system pathology of HIV. The hypotheses are that GABA and mI will be increased in HIV-infected patients while GSH will be decreased and that the changes in concentrations of these metabolites will correlate with poorer performance on neurocognitive tests of executive functioning, fine motor activity, and attention. In addition to the better assessment of brain development and function, reliable identification of perinatally HIV-infected youths with abnormal cerebral metabolites and sub clinical brain involvement by 2D-MRS (3T) may also direct earlier therapy than the current CD4 count criteria would indicate or changing existing HAART therapy to antiretroviral medications with improved CNS penetration. This study could potentially improve the quality of life of HIV-infected youths and preserve the health of the central nervous system. PUBLIC HEALTH RELEVANCE This study plans to identify metabolite markers of HIV involvement of the brain using noninvasive magnetic resonance spectroscopy in perinatally HIV-infected youths. Cerebral metabolite levels will be correlated with performance on neuropsychological tests and will identify involvement of the brain before clinical detection. Such results could dictate earlier therapy in children and youths with high CD4 cells or a change in antiretroviral medication to better treat HIV infection of the brain and improve the quality of life and neurological health of the millions of children worldwide infected with HIV from the mother.

描述（由申请人提供）：成人和儿童的艾滋病毒已成为一种慢性疾病，迫切需要开发无创、可靠的技术来检测艾滋病毒对大脑的亚临床影响。磁共振波谱 (MRS) 可以研究 HIV 对大脑代谢物、神经元和神经胶质细胞健康标志物的影响。之前的大多数研究都使用 1.5 Tesla (T) 扫描仪和一维 MRS (1D-MRS) 技术。本研究的主要目标是使用改进的技术，即 3 T 扫描仪上的二维 MRS 技术 (2D-MRS)，检测 HIV 感染者的异常脑代谢物，并将异常脑代谢物与表现相关联。神经认知测试，以便更好地评估这些人的大脑发育和功能。与 1.5 T 扫描仪相比，3T 扫描仪有望提供更高的信噪比 (SNR) 和更低的方差系数。与传统 1D-MRS 相比，2D-MRS 的使用可以通过转换拥挤、重叠的区域来检测许多其他代谢物。通过添加光谱维度，将 1D-MRS 光谱转化为分辨率更高的 2D 光谱。特别令人感兴趣的是 GABA（一种抑制性神经递质）和肌醇 (mI)（一种神经胶质细胞标记物），其升高表明正在进行的炎症。将确定代谢物与参考代谢物的比率和代谢物浓度。 3 Tesla 扫描仪与 2D-MRS 相结合还提供了研究谷胱甘肽 (GSH) 的能力，谷胱甘肽是一种重要的细胞抗氧化保护分子，可以评估 HIV 病毒对中枢神经系统的损害。本研究的具体目的是比较 30 名 HIV 感染者和 30 名对照受试者的右额脑区和右基底神经节的 GABA、mI、胆碱基团、GSH 和其他代谢物。大脑的这两个区域已被证明与艾滋病毒的中枢神经系统病理学有关。假设 HIV 感染者的 GABA 和 mI 会增加，而 GSH 会减少，这些代谢物浓度的变化将与执行功能、精细运动活动和注意力的神经认知测试中较差的表现相关。除了更好地评估大脑发育和功能之外，通过 2D-MRS (3T) 可靠地识别出脑代谢异常和亚临床脑受累的围产期 HIV 感染青少年，也可以指导比当前 CD4 计数标准指示的更早治疗或将现有的 HAART 疗法改为抗逆转录病毒药物，以改善中枢神经系统的渗透。这项研究可能会改善感染艾滋病毒的青少年的生活质量并保持中枢神经系统的健康。公共健康相关性 本研究计划利用无创磁共振波谱技术在围产期感染艾滋病毒的青少年中识别艾滋病毒参与大脑的代谢标志物。大脑代谢物水平将与神经心理学测试的表现相关，并在临床检测前识别大脑的参与情况。这些结果可能会要求对CD4细胞高的儿童和青少年进行早期治疗，或者改变抗逆转录病毒药物，以更好地治疗大脑中的艾滋病毒感染，并改善全世界数百万从母亲那里感染艾滋病毒的儿童的生活质量和神经系统健康。