A Longitudinal 3-D MRSI Study of Infants at High Risk for Autism

自闭症高危婴儿的纵向 3-D MRSI 研究

基本信息

批准号：
7844579
负责人：
STEPHEN R DAGER
金额：
$ 22.56万
依托单位：
UNIVERSITY OF WASHINGTON
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-09-30 至 2011-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7844579
关键词：
10 year old 2 year old 3-Dimensional 4 year old Address Affect Age Age-Months Autistic Disorder Behavioral Biological Biological Markers Brain Brain Chemistry Budgets Cellular Membrane Cerebrum Chemicals Child Childhood Choline Classification Clinical Cohort Studies Coupled Creatine Data Development Developmental Process Diagnosis Diagnostic Disease Early Diagnosis Family history of Fiber Follow-Up Studies Funding Gender Glutamates Goals Grant Growth Heterogeneity Image Image Analysis Imaging Techniques Individual Infant Infant Behavior Inflammation Inositol Institutes Intervention Longitudinal Studies Magnetic Resonance Imaging Measurement Measures Medial Methods Mitochondria N-acetylaspartate Neurobiology Neurologic Phenotype Procedures Process Propofol Protocols documentation Protons Recruitment Activity Relative (related person)Relaxation Research Risk Risk Marker Sampling Sampling Studies Scanning Sedation procedure Siblings Site Sleep Strategic Planning Structure Symptoms Techniques Technology Temporal Lobe Testing Time Tissues United States National Institutes of Health Variant analytical tool autism spectrum disorder base behavior test brain tissue clinical research site cohort design disorder subtype endophenotype falls follow-up gray matter high risk high risk infant improved insight magnetic resonance spectroscopic imaging mitochondrial dysfunction parent grant parent project prognostic public health relevance skills spectroscopic imaging theories

项目摘要

DESCRIPTION (provided by applicant): The aim of this proposal is to expand the scope of a funded NIH project "A longitudinal MRI Study of Infants at Risk for Autism," (RO1 HD055741- IBIS network) through adding 3-D Proton Echo Planar Spectroscopic Imaging (3D PEPSI) to allow measurements of brain chemistry in 6 month-old siblings of children diagnosed with autism (high risk) and age-matched infants without a family history of autism (low risk) who then are rescanned at 12 months and clinically assessed at 12 and 24 months. Specifically, we plan to incorporate 3D PEPSI into our ongoing MRI/DTI structural imaging protocol (29 6 month high risk infants studied to date, 71 pending for the parent project total of 100 6mo studies), and scan additional infants (20 additional scans budgeted per year during the proposed 2-year project- for a total of 90 high-risk and 40 low-risk 6 month infants) to supplement target recruitment goals of the parent grant and repeat failed studies on another night. A secondary aim of this proposal is to develop automated 3D outer volume saturation band placement techniques and QC procedures for implementation of PEPSI technology at other sites involved in our imaging consortium, UNC- Chapel Hill, U Penn/ CHOP, Wash U, and Montreal Neurological Institute (DCC), to allow multi-site 3D PEPSI follow-up studies of this longitudinal cohort. Our funded project is investigating relationships between brain structural development and autism symptom onset that typically presents between 12 and 24 months of age. The proposed supplement will add complementary brain chemical information to assess mechanisms underlying hypothesized abnormalities of brain growth (regions, tissues, structures and fiber tracts) measured by MRI/ DTI and relationships to clinical features. 3D PEPSI, recently developed and implemented on our 3T Siemens TIM Trio scanner, provides highly resolved quantifiable chemical images with improved anatomical coverage and is particularly well suited for rapid scanning of infants during normal sleep. Our research team, in addition to being highly skilled at pediatric imaging studies, is at the forefront for developing and clinically applying chemical imaging techniques and has developed analytical tools specifically designed for highly efficient, reliable, and valid processing of 3D brain chemical data. These results will provide important insights into brain development, behavioral phenotypes and the underlying neurobiology of autism. PUBLIC HEALTH RELEVANCE: Research proposed in this grant targets challenges outlined by the Interagency Autism Coordinating Committee (IACC) Strategic Plan for Autism Spectrum Disorder (ASD) Research (January 2009). Specifically, the project will address heterogeneity in 6 month-old infants at high risk for ASD due to an older affected sibling, who are imaged longitudinally at 6, 12 and 24 months, then diagnosed at 24 months that is confirmed at age 3. Brain chemical measures collected as part of this project have the potential to help identify distinct clinical subtypes of ASD having specific prognostic and treatment implications. Brain chemical measurements will provide biomarkers that may identify distinct ASD endophenotypes, for example, infants potentially having subtle mitochondrial dysfunction, and help elucidate underlying pathophysiological mechanisms responsible for brain developmental abnormalities in autism.

描述（由申请人提供）：本提案的目的是通过添加 3-D 质子回波平面来扩大 NIH 资助项目“自闭症风险婴儿的纵向 MRI 研究”（RO1 HD055741-IBIS 网络）的范围光谱成像 (3D PEPSI) 可测量被诊断为自闭症（高风险）儿童的 6 个月大的兄弟姐妹和年龄匹配的婴儿的大脑化学成分无自闭症家族史（低风险），然后在 12 个月时进行重新扫描，并在 12 个月和 24 个月时进行临床评估。具体来说，我们计划将 3D PEPSI 纳入我们正在进行的 MRI/DTI 结构成像方案（迄今为止研究了 29 个 6 个月的高危婴儿，71 个待母项目总计 100 个 6 个月的研究），并扫描其他婴儿（预算中的 20 个额外扫描）在拟议的 2 年项目期间每年（总共 90 名高风险和 40 名低风险 6 个月婴儿），以补充家长补助金的目标招募目标并重复失败的研究另一个晚上。该提案的第二个目标是开发自动化 3D 外部体积饱和带放置技术和 QC 程序，以便在参与我们的成像联盟、北卡罗来纳大学教堂山分校、宾夕法尼亚大学/CHOP、华盛顿大学和蒙特利尔神经病学的其他站点实施 PEPSI 技术研究所 (DCC)，允许对该纵向队列进行多站点 3D PEPSI 后续研究。我们资助的项目正在调查大脑结构发育与自闭症症状发作之间的关系，自闭症症状通常出现在 12 至 24 个月之间。拟议的补充将添加补充性脑化学信息，以评估通过 MRI/DTI 测量的假设的脑生长异常（区域、组织、结构和纤维束）的机制以及与临床特征的关系。最近在我们的 3T 西门子 TIM Trio 扫描仪上开发和实施的 3D PEPSI 可提供高分辨率的可量化化学图像，并改善解剖覆盖范围，特别适合在正常睡眠期间对婴儿进行快速扫描。我们的研究团队除了在儿科成像研究方面拥有高超的技术外，还在化学成像技术的开发和临床应用方面处于领先地位，并开发了专门为高效、可靠和有效地处理 3D 脑化学数据而设计的分析工具。这些结果将为大脑发育、行为表型和自闭症的潜在神经生物学提供重要的见解。公共健康相关性：本次资助提出的研究针对机构间自闭症协调委员会 (IACC) 自闭症谱系障碍 (ASD) 研究战略计划（2009 年 1 月）概述的挑战。具体来说，该项目将解决由于年龄较大的受影响兄弟姐妹而导致患有 ASD 高风险的 6 个月大婴儿的异质性，这些婴儿在 6、12 和 24 个月时进行纵向成像，然后在 24 个月时进行诊断，并在 3 岁时得到确认。作为该项目的一部分收集的化学措施有可能帮助识别具有特定预后和治疗意义的 ASD 不同临床亚型。脑化学测量将提供生物标志物，可以识别不同的 ASD 内表型，例如婴儿可能存在轻微的线粒体功能障碍，并有助于阐明导致自闭症大脑发育异常的潜在病理生理机制。