MEG Imaging Techniques for Low-Functioning Pediatric Populations

针对低功能儿科人群的 MEG 成像技术

• 批准号: 9315934
• 负责人: Luke Bloy
• 金额: $ 17.4万
• 依托单位: CHILDREN'S HOSP OF PHILADELPHIA
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-07-15 至 2020-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9315934
• 关键词: Achievement; Acute; Address; Adolescent; Age; Algorithms; Anatomic Models; Anatomy; Area; Atlases; Auditory; Autistic Disorder; Back; Behavioral; Biological; Biology; Blinking; Brain; Cerebral Palsy; Child; Childhood; Clinic; Clinical; Clinical assessments; Data; Data Analyses; Data Quality; Data Set; Development; Disabled Persons; Disease; Educational workshop; Electrophysiology (science); Ensure; Evaluable Disease; Evaluation; Exclusion; Exhibits; Fatigue; Financial compensation; Foundations; Functional disorder; Future; Geometry; Goals; Head; Heart; Imaging Techniques; Individual; Instruction; Intellectual functioning disability; Investigation; Knowledge; Lead; Location; Magnetic Resonance Imaging; Magnetoencephalography; Measures; Methods; Modeling; Monitor; Morphologic artifacts; Motion; Multiple Sclerosis; Neurobiology; Neurodevelopmental Disorder; Neurons; Noise; Participant; Pathway interactions; Patients; Phenotype; Physics; Population; Procedures; Protocols documentation; Psychologist; Real-Time Systems; Recruitment Activity; Reporting; Research; Research Personnel; Scanning; School-Age Population; Sensory; Sensory Process; Severities; Shapes; Signal Transduction; Somatosensory Cortex; Source; Stimulus; Systems Analysis; Techniques; Technology; Time; Training; Training Activity; Validation; Visual; Work; aged; area striata; autism spectrum disorder; base; biophysical model; brain abnormalities; brain dysfunction; clinical care; clinical imaging; cognitive testing; cohort; conotruncal anomaly face syndrome; data acquisition; developmental disease; developmental neurobiology; falls; imaging study; improved; interest; meetings; neuroimaging; non-compliance; novel; patient population; pediatric patients; protocol development; relating to nervous system; response; sensor; sensory cortex; skills; somatosensory; source localization; success; tool

Abstract: Whereas my previous training has focused on acquiring a strong technical foundation in neuroimaging methods, over time, my interests have evolved from a purely technical focus towards the application of neuroimaging to study brain dysfunction in pediatric patient populations. K01 training and research goals will provide me the skills and expertise needed to excel as an independent clinical imaging researcher in this area. To this end, I will obtain training in advanced state-of-the-art magnetoencephalography (MEG) analysis methods in order to study primary sensory activity in low-functioning children with autism spectrum disorder (ASD). Although neuroimaging studies, including MEG, have investigated sensory processing in ASD, these studies have primarily focused on higher-functioning individuals, as these patients are better able to tolerate neuroimaging exams. This leaves a significant portion of the ASD population unexamined and underserved (approximately 40% of the ASD population is low-functioning). Due to this research bias, relatively little is known directly about brain function in low-functioning individuals with ASD, or about the degree to which findings in higher-functioning ASD generalize to the entire ASD population. Although focusing on low- functioning ASD, K01 training and research is generalizable, specifically applicable to the examination of other low-functioning patient populations such as individuals with moderate to severe intellectual disability and cerebral palsy. It is towards these underserved and understudied low-functioning patient populations that I will focus my subsequent research. K01 work achieves significant advancements in several areas, with advancements moving me towards independence as a clinical imaging researcher. First, as part of my K01 research work, I will develop technical solutions to address primary obstacles to studying lower-functioning populations with MEG, namely the lack of anatomical information from structural MRI and the often considerable subject motion during a MEG exam. This technical work will serve as an enabling technology, allowing the inclusion of lower-functioning participants in MEG imaging studies. Second, significant time is spent on training activities that will provide me with a greater appreciation for the clinical and behavioral phenotypes exhibited in neurodevelopmental disorders as well as improving my understanding of the underlying neurobiology. To this end, under the guidance of Drs. Levy and Miller, I will participate in ongoing educational clinical activities already in place for training psychologists and other clinicians. I will spend 1 day per week in K01 Years 1 and 2 (2 days per month thereafter) performing clinical training and observing clinical and cognitive assessments at the Regional Autism Center’s young child clinic (seeing children under 6 years) and the Center for Autism Research’s school age clinic. These clinics see over 300 patients (~25-50% low-functioning) a year, offering ample opportunity to observe subjects with a wide variety of behavioral phenotypes and severity levels. This is in addition to attending case assessment meetings (as part of clinical observation), bi-monthly clinical team meetings and regular individual meetings with Drs. Levy and Miller. Training in the neurobiology of developmental disorders as well as the neurobiology of primary sensory processes will be achieved via coursework and one-on-one meetings with Dr. Contreras. Training, workshops, and coursework in the biology, presentation and clinical care of neurodevelopmental disorders will better enable me to anticipate and address the specific challenges in the study of these patient groups and to formulate and address biological questions central to these pediatric patient populations. Completion of this K01 encompasses the achievement of significant advancements in MEG acquisition and analysis. In particular, methods for atlas-based head modeling and motion compensation, developed in Aim 1, will permit accurate source localization of evoked primary sensory activity without the requirement of an MRI and in cases of large continuous motion. These methods will enable the study of primary sensory processes in low-functioning and non-compliant patient populations. Similarly, the real-time analysis system (Aim 3) represents a significant step forward in MEG acquisition in these patient groups, promising decreased scan time and thus decreased patient discomfort and fatigue. Technical advancements will be underpinned by additional training in advanced MEG physics and analysis provided Drs. Roberts, Mosher, and Dammers through one-on-one meetings and instruction. The utility and validity of these methods will be demonstrated through their application to low-functioning children and adolescents with ASD and via increases in success rate (evaluable data) and data quality. Investigation of atypical sensory activity, previously only reported in high-functioning ASD, will thus be enabled in a low-functioning ASD population, addressing the critical and presently unevaluated question of the generalizability of sensory abnormalities in ASD. K01 research will provide data in support of a future R01 which will likely focus on contrasting the sensory activity of low-functioning individuals with ASD to non-ASD neurodevelopmental disorders (e.g., 22q11.2 deletion syndrome, cerebral palsy) to identify the specific versus common pathways of sensory processing brain abnormalities in neurodevelopmental disorders.

抽象的： 而我以前的培训的重点是获得神经影像学的强大技术基础 随着时间的流逝，我的兴趣已经从纯粹的技术重点演变为应用 神经影像学研究小儿患者人群中的脑功能障碍。 K01培训和研究目标将 为我提供在该领域成为独立临床成像研究人员所需的技能和专业知识。 为此，我将获得先进的最新磁脑电图（MEG）分析的培训 为了研究低功能自闭症儿童的主要感觉活动的方法 （ASD）。尽管包括MEG在内的神经影像学研究已经研究了ASD的感觉处理，但 研究主要集中于更高功能的个体，因为这些患者能够更好地耐受 神经影像学检查。这使大部分ASD人口未经检查和服务不足 （大约40％的ASD人群功能低下）。由于这种研究偏见，相对几乎没有 直接知道有关ASD的低功能个体或有关大脑功能的知名度 高功能ASD的发现概括了整个ASD人群。虽然专注于低 - 功能ASD，K01培训和研究是可以推广的，特别适用于其他 低功能的患者人群，例如中度至重度智力残疾的人， 脑瘫。我将朝着这些服务不足和理解的低功能的患者人群中 集中我随后的研究。 K01工作在多个领域取得了重大进步，进步使我走向 独立作为临床成像研究人员。首先，作为我K01研究工作的一部分，我将开发技术 解决主要障碍的解决方案与MEG研究低功能的人群，即缺乏 来自结构MRI的解剖信息以及MEG考试期间经常大量的主题运动。 这项技术工作将作为一种有利的技术，允许包括低功能 MEG成像研究的参与者。其次，将大量时间用于培训活动，这将为我提供 对神经发育中暴露的临床和行为表型有了更大的认识 疾病以及改善我对潜在神经生物学的理解。为此，在 Drs的指导。 Levy and Miller，我将参加正在进行的教育临床活动 培训心理学家和其他临床医生。我将在K01年和2年（每月2天）中每周花费1天 此后）在区域自闭症中进行临床培训并观察临床和认知评估 中心的幼儿诊所（看到6岁以下的儿童）和自闭症研究中心的学龄 诊所。这些诊所每年可见300多名患者（〜25-50％的低功能），提供了充足的机会 观察具有多种行为表型和严重程度水平的受试者。这是补充 参加案件评估会议（作为临床观察的一部分），每两个月临床团队会议和 培训发育障碍的神经生物学 以及主要的感官过程的神经生物学以及一对一的课程将实现 与Contreras博士的会议。生物学，演示和临床的培训，讲习班和课程 护理神经发育障碍将使我能够预期并应对特定挑战 这些患者群体的研究并提出和解决这些小儿核心的生物学问题 患者人群。 该K01的完成涵盖了MEG获取和 分析。特别是，基于ATLA的头部建模和运动补偿的方法，在AIM 1中开发 将允许无需MRI的诱发初级感觉活动的精确来源定位 并在较大的连续运动中。这些方法将使研究中的主要感觉过程 低功能和不合规的患者人群。同样，实时分析系统（AIM 3） 在这些患者组中，MEG获取方面迈出了重要一步，承诺减少扫描 时间，从而改善了患者的不适和疲劳。技术进步将由 高级MEG物理和分析的其他培训提供了DRS。罗伯茨，莫瑟（Mosher）和索尔默（Dammers） 通过一对一的会议和指示。这些方法的效用和有效性将被证明 通过将其应用于ASD的低功能儿童和青少年，并通过增加 速率（可评估数据）和数据质量。非典型感觉活动的研究，以前仅报道 因此，在高功能的ASD中，将在低功能的ASD人群中启用 ASD中感觉异常的普遍性的关键和目前未评估的问题。 K01 研究将提供支持未来R01的数据，该数据可能会集中于对比 具有ASD至非ASD神经发育障碍的低功能个体（例如22Q11.2删除） 综合征，脑瘫），以识别感觉处理大脑的特定途径与常见途径 神经发育障碍的异常。