PROTON MRS STUDIES OF CEREBRAL INJURY IN HIV INFECTION

HIV 感染引起的脑损伤的质子 MRS 研究

• 批准号: 6393542
• 负责人: BRADFORD NAVIA
• 金额: $ 92.38万
• 依托单位: TUFTS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-04-01 至 2005-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6393542
• 关键词: AIDS dementia complex; AIDS therapy; HIV infections; antiAIDS agent; basal ganglia; bioimaging /biomedical imaging; brain injury; chemokine; clinical research; frontal lobe /cortex; human subject; human therapy evaluation; longitudinal human study; mathematical model; neuropsychological tests; nuclear magnetic resonance spectroscopy

The recent introduction of highly active antiretroviral therapy (HAART) has dramatically altered the natural history of the AIDS epidemic. Nonetheless, the spectrum and extent of neurological injury in this setting, its relationship to neurocognitive function and responsiveness to changes in antiretroviral therapy remain important and unresolved issues. This application to renew support for the HIV MRS consortium proposes a five year cross sectional and longitudinal study to examine the pattern and dynamics of regional injury in the HIV infected brain in the setting of HAART. During the first two years of the current grant cycle, the MRS consortium identified significant relation- ships between metabolic abnormalities in the subcortical regions and cognitive function. Specifically, lower levels of NAA in the frontal white matter distinguished ADC from NA subjects; significant increases in Cho and MI were found in the neuroasymptomatic (NA) group compared to controls and neuropsychological performance was significantly correlated with metabolite levels in the subcortical regions, particularly the basal ganglia. MRS thus provides a valuable, noninvasive in vivo method to study and monitor changes in the cerebral microenvironment. Recent data support the hypothesis that cognitive impairment and its response to treatment correlates strongly with virological and immunologic activity in the CSF. Yet little is known about the relationships of these events to varying patterns of brain injury in the setting of HAART. The MRS consortium will undertake the following specific aims: 1) Examine the response of the cerebral microenvironment to varying levels of HIV RNA and chemokines in the CSF and peripheral compartments of 80 ADC and 80 NA subjects in relationship to changes in antiretroviral therapies and neurocognitive performance; 2) Determine the extent and significance of CNS injury in NA subjects with advanced disease in relationship to the development of neurocognitive impairment; and 3) Assess the evolution of brain injury patterns in ADC and NA subjects and the impact of host and viral factors using longitudinal statistical models. MRS studies of the basal ganglia, frontal white matter and cortex will be combined with measurements of cognitive function and assays of HIV RNA and markers of immune activation, including chemokines in the CSF and peripheral compartments of 100 subjects with HIV RNA greater than 2000 copies/ml undergoing changes in antiretroviral therapy and 60 subjects on stable therapy with undetectable plasma HIV RNA. Longitudinal and cross sectional analysis will be done incorporating various univariate, multivariate, and regression models that will allow us 1) to compare and correlate the magnitude and duration of the metabolic and neurocognitive response in relation to levels of HIV RNA and immune activation in the CSF and peripheral compartments and 2) to assess the relative contributions and interactions of these host and viral factors to brain injury and cognitive performance.

最近采用的高效抗逆转录病毒疗法（HAART）大大改变了艾滋病流行的自然历史。 尽管如此，在这种情况下神经损伤的范围和程度，其与神经认知功能的关系以及对抗逆转录病毒治疗变化的反应性仍然是重要且尚未解决的问题。 该申请重新支持HIV MRS联盟，提出了一项为期五年的横断面和纵向研究，以检查HAART背景下HIV感染脑区域损伤的模式和动力学。 在当前资助周期的前两年，MRS联盟确定了皮质下区域代谢异常与认知功能之间的重要关系。 具体而言，较低水平的NAA在额叶白色的问题区分ADC从NA科目;显着增加Cho和MI被发现在神经无症状（NA）组相比，对照组和神经心理学性能显着相关的代谢物水平在皮质下区域，特别是基底神经节。 因此，MRS提供了一种有价值的，非侵入性的体内方法来研究和监测大脑微环境的变化。 最近的数据支持这一假设，即认知障碍及其对治疗的反应与CSF中的病毒学和免疫学活性密切相关。然而，在HAART的背景下，这些事件与不同模式的脑损伤之间的关系知之甚少。MRS联盟将承担以下具体目标：1）检查大脑微环境对80名ADC和80名NA受试者的CSF和外周室中不同水平的HIV RNA和趋化因子的反应，以及与抗逆转录病毒治疗和神经认知性能变化的关系; 2）确定患有晚期疾病的NA受试者中CNS损伤的程度和意义与神经认知障碍的发展的关系;和3）使用纵向统计模型评估ADC和NA受试者中脑损伤模式的演变以及宿主和病毒因素的影响。 基底神经节、额叶白色物质和皮质的MRS研究将与认知功能测量和HIV RNA和免疫活化标志物测定相结合，包括100例接受抗逆转录病毒治疗的HIV RNA大于2000拷贝/ml的受试者和60例接受稳定治疗且血浆HIV RNA检测不到的受试者的CSF和外周隔室中的趋化因子。 纵向和横断面分析将结合各种单变量，多变量，和回归模型，使我们能够1）比较和关联代谢和神经认知反应的幅度和持续时间与CSF和外周隔室中HIV RNA水平和免疫激活的关系，以及2）评估这些宿主和病毒因素对脑损伤和认知能力的相对贡献和相互作用。