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: 8333355
• 负责人: Barbara Laughton
• 金额: $ 12.46万
• 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 2014-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8333355
• 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.

描述（由申请人提供）：虽然撒哈拉以南非洲占世界人口的10%，但世界上90%的艾滋病毒感染儿童生活在该地区。其中大多数（16%或28万人）生活在南非，在那里，艾滋病毒/艾滋病占5岁以下儿童死亡人数的57%。随着获得抗逆转录病毒治疗（ART）机会的增加，该疾病正从致命转变为慢性。然而，抗逆转录病毒治疗对中枢神经系统的渗透是有限的，大脑是病毒的储存库，对发育中的胎儿/儿童大脑造成严重后果。“感染艾滋病毒的儿童早期抗逆转录病毒治疗”（CHER）项目是由南非艾滋病综合国际研究项目（CIPRA-SA）支持的一个项目，该项目一直在跟踪一群出生时携带艾滋病毒的儿童。对照是由CIPRA-SA支持的一项相互关联的疫苗试验招募的。这是一个独特且极具特征的儿童队列，分为三个治疗组，其中(1)ART延迟到满足免疫/临床标准，(2)ART在12周之前开始，并在40周后中断，(3)ART在12周之前开始，并在96周后中断。两年后，结果表明，早期艾滋病毒诊断和抗逆转录病毒治疗将早期婴儿死亡率降低了76%，将艾滋病毒进展降低了75%。作为CHER研究的补充，芭芭拉·劳顿博士正在开普敦现场对参与者进行全面的神经发育测试。参与研究的儿童将年满5岁，并于2010年6月开始进行最后一次访问，这是对已登记的儿童进行磁共振神经成像的独特机会，以更好地了解艾滋病毒/艾滋病的神经相关性以及ART对发育中的大脑的影响。在发展中国家，对艾滋病毒感染儿童的神经发育研究很少，对艾滋病毒感染儿童的脑成像研究在任何地方都很罕见。从开普敦大学脑成像中心（CUBIC）步行几分钟的路程，研究人员正在开普敦研究CHER队列的子集和对照组（210名儿童）。该设施拥有最先进的西门子3t Allegra MRI研究扫描仪，针对大脑成像进行了优化，在非洲是独一无二的。我们建议一个全面的脑成像研究，包括形态测量学，光谱学和扩散张量成像。我们的目标是将认知和临床指标与定量成像结果联系起来，并希望确定非成像指标，为大脑发育受损提供最佳评估，以指导在资源贫乏的环境中无法获得成像的干预。该项目代表了Barbara Laughton博士（Stellenbosch大学）、Ernesta Meintjes博士（开普敦大学）和Andri van der Kouwe博士（马萨诸塞州总医院）之间的新合作，并建立在后两位正在开发运动矫正技术的研究人员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情况下，为幼儿建立先进的图像采集和大脑分析方法的能力。