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，并且需要开发无创，可靠的技术来检测艾滋病毒对大脑的临床临床参与。磁共振光谱（MRS）允许研究HIV对脑代谢产物，神经元和神经胶质细胞健康的影响。以前的大多数研究都使用了1.5台扫描仪和一维MRS（1D-MRS）技术。这项研究的主要目的是使用改进的技术，即3 T扫描仪上的二维MRS技术（2D-MRS），以检测HIV感染患者的脑脑代谢异常，并将脑异常代谢物与神经认知测试的表现相关，以更好地评估这些个体，以改善这些个体，以评估这些个体的大脑开发和功能。与1.5 t相比，预计3T扫描仪将提供提高信号与噪声比（SNR）和较低的差异系数。与传统的1d-MR相比，使用2D-MR可以通过将较拥挤的，重叠的，重叠的1D-MR频谱转换为通过更好地溶解的2D 2D光谱的频谱来检测许多其他代谢物。特别令人感兴趣的是GABA，GABA是一种抑制性神经递质和肌醇（MI），这是一种神经胶质细胞标记，升高表明持续的炎症。将确定代谢物与参考代谢物和代谢产物浓度的比率。 3种特斯拉扫描仪与2D-MR相结合还提供了研究谷胱甘肽（GSH）的能力，谷胱甘肽（GSH）是一种重要的细胞抗氧化剂保护剂分子，可以评估HIV病毒中枢神经系统损害。这项研究的具体目的是比较右额脑区域中的GABA，MI，GSH，GSH和其他代谢产物，以及30名HIV感染患者的右基底神经节和30名对照组。大脑的这两个区域均已证明与艾滋病毒的中枢神经系统病理有关。假设是HIV感染患者的GABA和MI将增加，而GSH将减少，并且这些代谢产物浓度的变化将与执行功能，良好运动活动和注意力的神经认知测试的性能较差相关。除了更好地评估大脑发育和功能外，对脑部HIV感染的年轻人的可靠鉴定，具有异常的脑代谢物和2D-MRS（3T）的临床脑部受累也可能与当前的CD4计数标准相比，还可能指出与现有的HAART治疗相比，与当前的CD4计数标准相比，对现有的HAART疗法对抗逆转录病毒的治疗进行了改善。这项研究可能会改善感染HIV的年轻人的生活质量，并保留中枢神经系统的健康。公共卫生相关性本研究计划使用非侵入性磁共振光谱在围产期感染HIV感染的年轻人中使用非侵入性磁共振光谱来鉴定大脑的艾滋病毒参与。脑代谢物水平将与神经心理学测试的性能相关，并在临床检测前确定大脑的参与。这样的结果可能决定了患有高CD4细胞的儿童和青少年的早期治疗，或者抗逆转录病毒药物的变化可以更好地治疗大脑的HIV感染，并改善全世界全世界感染HIV感染HIV的儿童的生活质量和神经健康健康。