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

 应聘者描述(申请人提供)：应聘者是一名致力于光学放射学的科学家，他渴望成为一名独立的研究员，专注于开发新的成像策略来阐明潜在的机制，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，神经信号可提供ASD严重程度的有用标记物，并可能对介入治疗敏感。然而，由于受限的成像环境，目前的神经成像方法(如功能磁共振成像，fMRI)在ASD中受到限制。这位候选人一直在开发漫反射光学断层扫描(DOT)方法，用可穿戴的帽子克服功能磁共振成像和脑功能成像的人体工学限制。在目标1中，将在ASD儿童和年龄/性别/智商匹配的典型发展中儿童(TDC)中建立基于任务的DOT方法，使用被证明对ASD诊断和社交能力敏感的生物运动处理任务。在目标2中，该提案将使用无任务DOT方法来研究与目标1相同的受试者的脑功能组织。此外，该提案的目标3将把神经成像扩展到三个非重叠的自闭症患者亚组，这些患者在功能磁共振成像研究中一直具有特别的挑战性：语言能力最弱、全量智商较低或在社交能力评估的严重范围内得分较高的学龄儿童。这些研究将是创新和有意义的，因为DOT舒适的扫描环境将使ASD的脑部成像能够覆盖更多的患者，并将为DOT对ASD高危婴幼儿进行的神经成像研究奠定基础。这位候选人已经组建并充分参与了一个卓越的跨学科奖学金咨询委员会，该委员会由主要导师John Constantino博士以及共同导师John Pruett、Bradley Schlaggar、Lori Markson和Joseph Culver博士组成，他们都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、神经病学、发展和实验心理学以及脑功能成像方面拥有广泛的专业知识。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，通过在与自闭症相关的表型评估和发展和实验心理学方面的详细培训来增强他目前的技能集。这一职业发展奖是对高级认知心理学、疾病神经生物学和高级功能成像方法的世界级课程的补充。该研究所，华盛顿大学医学院，承诺通过提供开展拟议研究所需的实验室空间和财政资源来支持候选人。这笔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的知识，以及领导他自己的独立研究工作所需的关键训练期，使用光学成像来解决自闭症的具体问题。

 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.