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

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损害。磁共振波谱（MRS）允许研究艾滋病毒对大脑代谢物、神经元和神经胶质细胞健康标志物的影响。大多数先前的研究使用1.5特斯拉(T)扫描仪和一维MRS （1D-MRS）技术。本研究的主要目标是使用一种改进的技术，即在3t扫描仪上的二维MRS技术（2D-MRS），检测hiv感染患者的异常脑代谢物，并将异常脑代谢物与神经认知测试的表现联系起来，以便更好地评估这些个体的大脑发育和功能。与1.5 t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。与传统的1D-MRS相比，2D- mrs的使用可以通过增加光谱维度将拥挤、重叠的1D-MRS光谱转换为分辨率更高的2D光谱，从而检测到许多额外的代谢物。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志物，其升高表明正在发生炎症。将确定代谢物与参考代谢物的比率和代谢物浓度。3特斯拉扫描仪结合2D-MRS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名对照者右额脑区和右基底神经节中GABA、mI、胆碱组、GSH等代谢物。大脑的这两个区域都被证明与HIV的中枢神经系统病理有关。假设在hiv感染的患者中，GABA和mI会增加，而GSH会减少，并且这些代谢物浓度的变化与执行功能、精细运动活动和注意力的神经认知测试中的较差表现相关。除了更好地评估大脑发育和功能外，通过2D-MRS （3T）可靠地识别围生期hiv感染的青少年大脑代谢物异常和亚临床脑受损伤，也可能指导比目前CD4计数标准更早的治疗，或将现有的HAART治疗改为改善中枢神经系统渗透的抗逆转录病毒药物。这项研究有可能改善感染艾滋病毒的年轻人的生活质量，并保持中枢神经系统的健康。本研究计划在围产期感染艾滋病毒的青少年中使用无创磁共振波谱识别艾滋病毒参与大脑的代谢物标记物。脑代谢物水平将与神经心理学测试的表现相关，并将在临床检测之前确定大脑的受累情况。这些结果可能要求对CD4细胞高的儿童和青少年进行早期治疗，或改变抗逆转录病毒药物，以更好地治疗大脑的艾滋病毒感染，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。

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.