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地区人口占世界人口的 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 280,000 人）生活在南非，该国 5 岁以下儿童死亡人数中 57% 是由艾滋病毒/艾滋病造成的。随着抗逆转录病毒治疗（ART）的普及，这种疾病正在从致命转变为慢性。然而，抗逆转录病毒疗法对中枢神经系统的渗透有限，而且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）项目是南非艾滋病综合国际研究计划（CIPRA-SA）支持的一个项目，该项目一直在跟踪一群出生时感染艾滋病毒的儿童。对照是通过一项也得到 CIPRA-SA 支持的互连疫苗试验招募的。这是一个独特且特征极其明确的儿童队列，分为三个治疗组，其中 (1) ART 被推迟直至满足免疫学/临床标准，(2) ART 在 12 周前开始，并在 40 周后中断，(3) ART 12周前开始，96周后中断。两年后，结果显示，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%，艾滋病毒进展降低了 75%。作为 CHER 研究的补充，Barbara Laughton 博士正在开普敦基地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，并从 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艾滋病毒/艾滋病的影响艺术对大脑发育的影响。 在发展中国家，对感染艾滋病毒的儿童进行的神经发育研究很少，而在任何地方，对感染艾滋病毒的幼儿进行的脑成像研究都很罕见。 CHER 队列和对照组（210 名儿童）的开普敦子集正在距离开普大学脑成像中心 (CUBIC) 仅几分钟步行路程处进行研究。该设施拥有最先进的西门子 3 T Allegra MRI 研究扫描仪，针对脑成像进行了优化，在非洲是独一无二的。我们提出了一项全面的脑成像研究，包括形态测量、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相关联，并希望确定非成像指标，为受损的大脑发育提供最佳评估，以指导对可能无法获得成像的资源匮乏环境进行干预。 该项目代表了 Barbara Laughton 博士（斯泰伦博斯大学）、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，并建立在后两位研究人员之间的现有合作基础上。正在开发运动校正技术。该项目将培养幼儿先进图像采集和大脑分析方法的能力，而无需使用镇静或麻醉的风险。

项目成果

Cine magnetic resonance imaging with simultaneous audio to evaluate pediatric velopharyngeal insufficiency.

具有同步音频的电影磁共振成像可评估小儿腭咽闭合不全。

• 发表时间: 2011-03
• 作者: Silver, Amanda L;Nimkin, Katherine;Ashland, Jean E;Ghosh, Satrajit S;van der Kouwe, Andre J W;Brigger, Matthew T;Hartnick, Christopher J
• 通讯作者: Hartnick, Christopher J