A Longitudinal MRI Study of Infants at Risk for Autism

描述(由申请人提供)：本自闭症卓越中心(ACE)网络的申请是由四个临床地点的研究人员共同努力完成的：北卡罗来纳大学(UNC)、华盛顿大学(UW)、华盛顿大学(Wu)和耶鲁大学；以及蒙特利尔神经研究所(MNI)的一个数据协调中心(DCC)，以对6、12和24个月大的自闭症高危婴儿(即自闭症患者的兄弟姐妹)进行纵向MRI/DTI和行为研究。多条综合证据(来自核磁共振、尸检和头围研究)证明了自闭症患者的大脑增大。核磁共振研究显示，早在两岁时，大脑皮质灰质和白质就普遍增大，并选择了皮质下结构。纵向头围研究表明，大脑过度生长开始于生命第一年的后期。来自自闭症患者婴儿兄弟姐妹(因此患自闭症谱系障碍或ASD的风险很高的婴儿兄弟姐妹)的行为研究数据表明，这种疾病的一些决定性特征在6个月大时不存在(例如，社会缺陷)，并在12个月大时首次出现。现在有了新的成像方法，这些方法提供了非常详细的MRI数据，非常适合对非常年幼的儿童进行快速扫描。研究人员的MRI研究团队开发了专门设计的图像处理工具，用于高效、可靠和有效地处理从出生到两岁的MRI数据。研究人员最近就这一应用开发了新的行为评估工具(AOSI和FYI)，现在可以对12个月大的婴儿进行有效的筛查和检测，这些婴儿可能在两岁时符合自闭症标准。在这项申请中，他们建议使用这些新方法对自闭症患者6个月大的婴儿兄弟姐妹进行纵向MRI/DTI研究，并在12个月和24个月大时进行随访。这项研究将为MRI和DTI测量的早期脑过度生长(区域、组织、结构和纤维束)的轨迹及其与临床特征的潜在关系提供重要的新信息。它有可能提供对发育的大脑和行为表型以及神经生物学机制的洞察，这将为其他层面的分析(例如，这一时期的分子生物学研究)提供信息，在似乎是自闭症发病机制发展的关键时期。

DESCRIPTION (provided by applicant): This application for an Autism Centers of Excellence (ACE) Network is a collaborative effort by investigators at four clinical sites: University of North Carolina (UNC), University of Washington (UW), Washington University (WU), and Yale University; and one data coordinating center (DCC) at the Montreal Neurological Institute (MNI) to conduct a longitudinal MRI/DTI and behavioral study of infants at high risk for autism (i.e., siblings of autistic individuals) at 6, 12, and 24 months of age. Multiple lines of converging evidence (from MRI, post-mortem, and head circumference studies) document brain enlargement in autism. MRI studies have revealed generalized enlargement in cerebral cortical gray and white matter, and selected subcortical structures as early as two years of age. Longitudinal head circumference studies suggest the onset of brain overgrowth beginning in the latter part of the first year of life. Data from behavioral studies of infant siblings of autistic individuals (infant siblings who are therefore at high risk for developing an autism spectrum disorder, or ASD) suggest that some of the defining features of this condition are not present at six months of age (e.g., social deficits) and have their first appearance by 12 months. New imaging methods are available that now provide highly detailed MRI data and are well suited for rapid scanning of very young children. The investigators' MRI research team has developed image processing tools specifically designed for highly efficient, reliable, and valid processing of MRI data from birth to two years of age. New behavioral assessment tools (the AOSI and FYI), recently developed by investigators on this application, now enable the efficient screening and detection, at 12 months, of infants who are likely to meet criteria for autism at age two. In this application they propose to employ these new methods to conduct a longitudinal MRI/DTI study of six months old infant sibs of autistic individuals, with follow-up at 12 and 24 months of age. This study will provide important, new information about the trajectory of early postnatal brain overgrowth (regions, tissues, structures, and fiber tracts), as measured on MRI and DTI, and its potential relationship to clinical features. It has the potential to provide insights into developmental brain and behavioral phenotypes, as well as neurobiological mechanisms, that will inform other levels of analysis (e.g., molecular biological studies of this period), during what appears to be a critical period of development in the pathogenesis of autism.