Technology development and neuroimaging for 5 year old children with HIV infectio

5 岁 HIV 感染儿童的技术开发和神经影像学

• 批准号: 8133656
• 负责人: Barbara Laughton
• 金额: $ 16.24万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-15 至 2013-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8133656
• 关键词: 5 year old; AIDS/HIV problem; Accounting; Acquired Immunodeficiency Syndrome; Addendum; Africa; Africa South of the Sahara; Age; Allegra; Anesthesia procedures; Anisotropy; Anti-Retroviral Agents; Aventyl; Basal Ganglia; Birth; Boston; Brain; Brain imaging; CD4 Lymphocyte Count; Cessation of life; Characteristics; Child; Choline; Chronic; Clinical; Clinical Research; Cognitive; Cognitive deficits; Collaborations; Communicable Diseases; Creatine; Data; Developing Countries; Development; Diffusion; Diffusion Magnetic Resonance Imaging; Diffusion weighted imaging; Disease; Enrollment; Environment; Funding; General Hospitals; HIV; HIV Infections; HIV diagnosis; Home environment; Housing; Image; Image Analysis; Imaging Techniques; Imaging technology; Improve Access; Infant Mortality; Inositol; International; Intervention; Life; Magnetic Resonance; Magnetic Resonance Imaging; Maps; Massachusetts; Measures; Methods; Metric; Motion; N-acetylaspartate; National Institute of Allergy and Infectious Disease; Neuraxis; Neurocognitive; Participant; Penetration; Perinatal; Physiologic pulse; Plasma; Population; Prevention therapy; Protocols documentation; Recruitment Activity; Research; Research Infrastructure; Research Personnel; Resolution; Resources; Risk; School-Age Population; Sedation procedure; Site; Slice; South Africa; Spectrum Analysis; Structure; Students; System; Techniques; Technology; Testing; Thick; Time; Tissues; Training; Universities; Vaccines; Viral Load result; Virus; Visit; Walking; Work; antiretroviral therapy; arm; bioimaging; brain metabolism; clinical practice; cohort; experience; fetal; gray matter; improved; meetings; mental development; morphometry; neurodevelopment; neuroimaging; neuropsychological; programs; prospective; relating to nervous system; sound; spectroscopic imaging; technology development; transmission process; visual-motor integration; white matter

DESCRIPTION (provided by applicant): While sub-Saharan Africa is home to 10% of the world's population, 90% of the world's HIV-infected children live in the region. The majority of these (16% or 280,000) live in South Africa, where HIV/AIDS accounts for 57% of deaths in children below 5 years of age. With improving access to antiretroviral treatment (ART), the disease is changing from fatal to chronic. However, central nervous system penetration by ART is limited and the brain is a reservoir for the virus, with dramatic consequences to the developing fetal/child brain. The "Children with HIV early antiretroviral therapy" (CHER) project is a project supported by the Comprehensive International Program for Research on AIDS in South Africa (CIPRA-SA), that has been following a cohort of children born with HIV. Controls were recruited by an interlinking vaccine trial also supported by CIPRA-SA. This is a unique and extremely well characterized cohort of children in three treatment arms in which (1) ART was delayed until immunological/clinical criteria were met, (2) ART commenced before 12 weeks and was interrupted after 40 weeks and (3) ART commenced before 12 weeks and was interrupted after 96 weeks. After two years, results showed that early HIV diagnosis and ART reduced early infant mortality by 76% and HIV progression by 75%. As an addendum to the CHER study, Dr. Barbara Laughton is performing comprehensive neurodevelopmental testing on the participants at the Cape Town Site. The children in the study will be turning 5 years old and returning for their last visit starting June 2010, and this is a unique opportunity to perform magnetic resonance neuroimaging in the children already enrolled to better understand the neural correlates of HIV/AIDS and effects of ART on the developing brain. Neurodevelopment studies in children with HIV in developing countries are rare and brain imaging studies of young children with HIV are rare anywhere. The Cape Town subset of the CHER cohort and controls (210 children) is being studied just a few minutes' walk from the Cape Universities Brain Imaging Center (CUBIC). This facility houses a state-of-the-art Siemens 3 T Allegra MRI research scanner optimized for brain imaging and is unique in Africa. We propose a comprehensive brain imaging study that includes morphometry, spectroscopy and diffusion tensor imaging. We aim to correlate cognitive and clinical metrics with quantitative imaging results, and hope to identify non-imaging metrics providing the best assessment of impaired brain development to guide intervention in resource-poor environments where imaging may be unavailable. This project represents a new collaboration between Dr. Barbara Laughton (Stellenbosch University), Dr. Ernesta Meintjes (University of Cape Town) and Dr. Andri van der Kouwe (Massachusetts General Hospital) and builds on an existing collaboration between the latter two investigators who are developing motion correction technology. The project will build capacity for advanced image acquisition and brain analysis methods in young children without the risk of sedation or anesthesia. PUBLIC HEALTH RELEVANCE: Most of the world's children born with HIV live in sub-Saharan Africa. With increased access to antiretroviral treatment (ART), these children are surviving longer with chronic HIV infection. There is a concomitant increase in cognitive deficits and impaired brain development by the time the children reach school age. In this project we will establish collaboration between the Universities of Stellenbosch and Cape Town and the Massachusetts General Hospital, to build infrastructure for motion-corrected MRI to study the brains of an existing cohort of 5-year old children started early on ART (CIPRA-SA/CHER). We will correlate clinical and neurocognitive measures with structural, diffusion and spectroscopic data to better understand HIV-infected brain development and identify the best methods to assess impaired brain development in resource-limited settings where MRI is not available.

描述（由申请人提供）：虽然撒哈拉以南非洲是世界人口10％的家园，但世界上90％的艾滋病毒感染儿童居住在该地区。其中大多数（16％或280,000）生活在南非，艾滋病毒/艾滋病占57％以下儿童死亡的57％。随着改善抗逆转录病毒治疗（ART）的机会，该疾病正在从致命变为慢性。然而，中枢神经系统通过艺术渗透是有限的，大脑是病毒的储层，对发展中的胎儿/儿童大脑产生巨大后果。 “艾滋病毒早期抗逆转录病毒疗法的儿童”（CHER）项目是一个项目，该项目得到了南非艾滋病研究综合国际艾滋病研究计划（CIPRA-SA）的支持，该计划一直在追随一群患有艾滋病毒的孩子。通过CIPRA-SA支持的一项相互联系的疫苗试验招募了对照。这是一个独特且极其特征的儿童在三个治疗臂中的队列，其中（1）ART延迟到满足免疫学/临床标准，（2）ART在12周之前开始，在40周之前开始中断，（3）ART在12周之前开始，并在96周后被中断。两年后，结果表明，早期的HIV诊断和ART将婴儿早期死亡率降低了76％，HIV的进展降低了75％。作为雪儿研究的附录，芭芭拉·劳顿（Barbara Laughton）博士正在开普敦遗址的参与者进行全面的神经发育测试。研究中的孩子将满足5岁的年龄，并从2010年6月开始返回上次访问，这是对已经入学的儿童进行磁共振神经影像学的独特机会，以更好地了解艾滋病毒/艾滋病的神经相关性以及艺术对发展中大脑的影响。 发展中国家艾滋病毒儿童的神经发育研究很少见，对艾滋病毒幼儿的脑成像研究在任何地方都很少见。 Cher Cohort和Controls的开普敦子集（210名儿童）距离开普大学脑成像中心（Cubic）仅几分钟。该设施容纳了最先进的西门子3 t Allegra MRI研究扫描仪，可针对大脑成像进行优化，在非洲是独一无二的。我们提出了一项全面的大脑成像研究，其中包括形态计量学，光谱和扩散张量成像。我们旨在将认知和临床指标与定量成像结果相关联，并希望确定对大脑发育受损的最佳评估的非成像指标，以指导在可能无法进行成像的资源贫乏环境中进行干预。 该项目代表了Barbara Laughton博士（Stellenbosch University），Ernesta Meintjes（开普敦大学）和Andri Van der Kouwe博士（马萨诸塞州综合医院）之间的新合作，并建立在后者两位正在开发运动校正技术的后者之间的现有合作基础上。该项目将在没有镇静或麻醉风险的幼儿中建立高级图像获取和大脑分析方法的能力。 公共卫生相关性：世界上大多数患有艾滋病毒的儿童生活在撒哈拉以南非洲。随着抗逆转录病毒治疗（ART）的增加，这些儿童在慢性HIV感染中的存活时间更长。到儿童达到学龄之时，认知缺陷和大脑发育障碍也随之增加。在这个项目中，我们将建立斯泰伦博斯大学和开普敦大学和马萨诸塞州综合医院之间的合作，以建立运动校正的MRI基础设施，以研究现有的5岁儿童队列的大脑早期开始艺术（Cipra-Sa/Cher）。我们将将临床和神经认知度量与结构，扩散和光谱数据相关联，以更好地了解感染HIV的大脑发育，并确定在没有MRI的资源有限设置中评估脑发育受损的最佳方法。