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(申请人提供)：成人和儿童中的艾滋病毒已成为一种慢性病，迫切需要开发非侵入性、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对大脑代谢物的影响，这些代谢物是神经元和神经胶质细胞健康的标志。以前的大多数研究都使用了1.5特斯拉(T)扫描仪和一维MRS(1D-MRS)技术。这项研究的主要目的是使用一种改进的技术，在3T扫描仪上使用二维MRS技术(2D-MRS)来检测HIV感染患者的异常脑代谢产物，并将异常脑代谢产物与神经认知测试的表现相关联，以便更好地评估这些人的脑发育和功能。与1.5T相比，3T扫描仪有望提供更好的信噪比(SNR)和更低的变异系数。与传统的1D-MRS相比，2D-MRS的使用允许检测许多额外的代谢物，方法是通过增加光谱维度将拥挤、重叠的1D-MRS频谱转换为更好的分辨率2D频谱。特别令人感兴趣的是GABA，一种抑制性神经递质和肌肌醇(MI)，一种神经胶质细胞标记物，升高表明正在发生炎症。代谢物与参考代谢物的比率和代谢物浓度将被确定。结合2D-MRS的3特斯拉扫描仪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，可以评估艾滋病毒对中枢神经系统的损害。本研究的具体目的是比较30例HIV感染者和30例对照组右侧额叶和右侧基底节的GABA、MI、胆碱基团、GSH等代谢物。大脑的这两个区域都被证明与艾滋病毒的中枢神经系统病理有关。假设艾滋病毒感染患者的GABA和mi将增加，而GSH将降低，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外，2D-MRS(3T)可靠地识别出患有围产期艾滋病毒感染、大脑代谢异常和亚临床脑部受累的青少年，也可能指导比目前的CD4计数标准所表明的更早的治疗，或者将现有的HAART治疗改为具有更好的中枢神经系统渗透性的抗逆转录病毒药物。这项研究可能会改善感染艾滋病毒的年轻人的生活质量，并保护中枢神经系统的健康。公共卫生相关性这项研究计划在围产期感染HIV的年轻人中使用非侵入性磁共振波谱来确定HIV参与大脑的代谢物标记物。大脑代谢物水平将与神经心理测试的表现相关，并将在临床检测之前确定大脑是否参与其中。这一结果可能会要求对CD4细胞水平高的儿童和青少年进行更早的治疗，或者改变抗逆转录病毒药物，以更好地治疗脑部艾滋病毒感染，并改善全球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健康。