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

• 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
• 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

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（申请人提供）：这项提案的目的是扩大NIH资助的一个项目“自闭症风险婴儿的纵向MRI研究，"（RO 1 HD 055741- IBIS网络）通过添加3-D质子回波平面光谱成像（3D PEPSI），以测量被诊断患有自闭症的儿童的6个月大的兄弟姐妹的大脑化学物质这些婴儿在12个月时被重新扫描，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结构成像方案中（迄今为止，研究了29例6个月高风险婴儿，71例等待母项目，共计100例6个月研究），扫描更多的婴儿（在拟议的2年项目期间，每年预算增加20次扫描-共90名高风险和40名低风险6个月婴儿）补充父母补助金的目标招募目标，并在另一个晚上重复失败的研究。本提案的第二个目的是开发自动化3D外容积饱和带放置技术和QC程序，用于在我们的成像联盟、宾夕法尼亚大学-查佩尔山、宾夕法尼亚大学/ CHOP、华盛顿大学和蒙特利尔神经学研究所（DCC）的其他研究中心实施PEPSI技术，以允许对该纵向队列进行多中心3D PEPSI随访研究。 我们资助的项目是调查大脑结构发育和自闭症症状发作之间的关系，通常出现在12到24个月大的孩子之间。拟议的补充将增加补充脑化学信息，以评估通过MRI/ DTI测量的脑生长（区域、组织、结构和纤维束）假设异常的机制及其与临床特征的关系。最近开发的3D PEPSI在我们的3 T Siemens TIM Trio扫描仪上实现，提供了高分辨率的可量化化学图像，改善了解剖覆盖范围，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非常熟练之外，还处于开发和临床应用化学成像技术的最前沿，并开发了专门用于高效，可靠和有效处理3D脑化学数据的分析工具。这些结果将为自闭症的大脑发育，行为表型和潜在的神经生物学提供重要的见解。 公共卫生关系：这项拨款中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。具体而言，该项目将解决6个月大的婴儿由于受影响的兄弟姐妹而具有ASD高风险的异质性，这些兄弟姐妹在6个月，12个月和24个月时进行纵向成像，然后在24个月时诊断，并在3岁时确认。作为该项目的一部分，收集的脑化学测量有可能帮助识别具有特定预后和治疗意义的ASD的不同临床亚型。脑化学测量将提供生物标志物，可以识别不同的ASD内在表型，例如，婴儿可能有微妙的线粒体功能障碍，并帮助阐明潜在的病理生理机制，负责自闭症的大脑发育异常。