IMAGING BRAIN FUNCTION IN CHILDREN WITH AUTISM SPECTRUM DISORDERS WITH DIFFUSE OPTICAL TOMOGRAPHY

 描述（由申请人提供）：候选人是光学放射学领域的一名坚定的科学家，他渴望成为一名独立的研究者，专注于开发新的成像策略，以阐明潜在的机制，为临床干预提供信息，并改善自闭症谱系障碍（ASD）的结果。脑功能成像的最新进展表明，神经信号可能提供有用的ASD严重程度的标志物，并可能对介入治疗敏感。然而，目前的神经成像方法（如功能性磁共振成像，fMRI）是有限的ASD由于受约束的成像环境。这位候选人一直在开发漫射光学断层扫描（DOT）方法，该方法克服了功能磁共振成像的人体工程学限制，并使用可佩戴的帽子对大脑功能进行成像。在目标1中，将在患有ASD的儿童和年龄/性别/IQ匹配的典型发育儿童（TDC）中建立基于任务的DOT方法，使用显示出对ASD诊断和社交能力敏感的生物运动处理任务。在目标2中，该提案将采用无任务DOT方法来研究与目标1相同的受试者的功能性脑组织。此外，该提案的目标3将神经影像学扩展到三个不重叠的ASD患者亚组，这些患者对fMRI研究特别具有挑战性：学龄儿童，语言能力最低，全面智商低，或社交能力评估得分严重。这些研究将具有创新性和重要性，因为DOT舒适的扫描环境将使ASD的脑成像遍及更广泛的患者，并将为ASD高危婴儿和幼儿的DOT神经成像研究奠定基础。候选人已经聚集并充分参与了一个由主要导师John Constantino博士和共同导师John Pruett博士，布拉德利Schlaggar，洛里马克森和Joseph Culver组成的优秀跨学科奖学金咨询委员会，他们是国际公认的资助科学家，在ASD研究和临床护理，儿童心理学，神经学，发展和实验心理学以及功能性脑成像。一个完善的，正式的职业发展计划建立在候选人在物理学，系统神经科学和技术开发方面的丰富经验的基础上，通过在与ASD相关的表型评估和发展与实验心理学方面的详细培训来增强他目前的技能。这个职业发展奖补充了高级认知心理学，疾病神经生物学和高级功能成像方法的世界一流课程的培训。该机构，华盛顿大学医学院，已承诺通过提供必要的实验室空间和开展拟议研究所需的财政资源来支持候选人。该培训补助金将为候选人提供自闭症研究的基础科学和临床方面，以及使用光学成像来解决ASD中的特定问题以领导自己的独立研究工作所需的关键培训期。

 DESCRIPTION (provided by applicant): The candidate is a committed scientist in optical radiology, who aspires to become an independent investigator focused on developing novel imaging strategies to elucidate underlying mechanisms, inform clinical interventions, and improve outcome of Autism Spectrum Disorder (ASD). Recent advances in functional brain imaging show promise that neural signatures may provide useful markers of ASD severity and may be sensitive to interventional therapy. However, current neuroimaging methods (e.g. functional magnetic resonance imaging, fMRI) are limited in ASD due to the constrained imaging environment. The candidate has been developing diffuse optical tomography (DOT) methods that overcome ergonomic limitations of fMRI and image brain function with a wearable cap. In Aim 1, task-based DOT methods will be established in children with ASD and age/sex/IQ- matched typically developing children (TDC) using a biological motion processing task shown to be sensitive to ASD diagnosis and social ability. In Aim 2, the proposal will employ task-free DOT methods to investigate functional brain organization of in the same subjects as Aim 1. Additionally, Aim 3 of this proposal will extend neuroimaging to three non-overlapping sub-groups of patients with ASD who have been especially challenging to study with fMRI: school-aged children that are minimally verbal, have a low full-scale IQ, or score in the severe range of social ability assessments. These studies will be innovative and significant because the comfortable scanning environment of DOT will enable brain imaging of ASD throughout an extended spectrum of patients, and will lay the groundwork for DOT neuroimaging studies on infants and toddlers at high risk for ASD. The candidate has assembled and has fully engaged a superb interdisciplinary Scholarship Advisory Committee composed of primary mentor Dr. John Constantino, and co-mentors Drs. John Pruett, Bradley Schlaggar, Lori Markson, and Joseph Culver, who are internationally-recognized funded scientists with a diverse range of expertise in ASD research and clinical care, child psychology, neurology, developmental and experimental psychology and functional brain imaging. A well-developed, formal Career Development Program builds on the candidate's extensive experience in physics, systems neuroscience, and technology development by augmenting his current skill set with detailed training in phenotypic assessment and developmental and experimental psychology as they pertain to ASD. This Career Development Award complements the training with world-class coursework in Advanced Cognitive Psychology, Neurobiology of Disease, and Advanced Functional Imaging Methods. The Institution, Washington University School of Medicine, has committed to supporting the candidate by providing the necessary laboratory space and financial resources needed to carry out the proposed research. This training grant will provide the candidate with both the basic science and clinical aspects of autism research, and the critical training period necessary to lead his own independent research effort using optical imaging to address specific questions in ASD.