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.

摘要： 虽然我之前的培训侧重于在神经成像方面获得坚实的技术基础 方法，随着时间的推移，我的兴趣已经从纯粹的技术重点发展到应用 神经成像用于研究儿科患者群体的脑功能障碍。K01培训和研究目标将 为我提供所需的技能和专业知识，使我在这一领域成为一名独立的临床影像研究员。 为此，我将接受先进的脑磁图(Meg)分析方面的培训。 方法对自闭症谱系障碍低功能儿童的初级感觉活动进行研究 (ASD)。尽管包括脑磁图在内的神经成像研究已经研究了ASD的感觉处理，但这些 研究主要集中在功能较高的个体，因为这些患者更能耐受 神经影像检查。这使得很大一部分自闭症患者没有得到检查和服务不足。 (大约40%的自闭症患者功能低下)。由于这种研究偏差，相对较少的是 直接了解ASD低功能个体的大脑功能，或了解ASD患者的 在功能较高的ASD中的发现推广到整个ASD人群。尽管关注的是低- 功能性ASD、K01的培训和研究具有通用性，特别适用于其他 低功能患者群体，如中度至重度智力残疾和 脑性瘫痪。对于这些服务不足、研究不足的低功能患者群体，我将 将重点放在我随后的研究上。 K01工作在几个领域取得了重大进展，这些进步推动我走向 作为一名临床影像研究人员的独立性。首先，作为我K01研究工作的一部分，我将开发技术 解决研究脑磁图功能低下人群的主要障碍的解决方案，即缺乏 来自结构核磁共振的解剖信息，以及脑磁图检查期间经常出现的相当大的受试者运动。 这项技术工作将作为一项使能技术，允许包括功能较低的 脑磁图成像研究的参与者。其次，在培训活动上花费了大量时间，这将为我提供 对神经发育中表现出的临床和行为表型有更大的了解 同时也提高了我对潜在神经生物学的理解。为此，在 在利维和米勒博士的指导下，我将参加正在进行的临床教育活动 培训心理学家和其他临床医生。我会在K01的第一年和第二年每周花一天的时间(每月两天 此后)在区域自闭症中心进行临床培训并观察临床和认知评估 中心的幼儿诊所(为6岁以下的儿童看病)和自闭症研究中心的学龄儿童 诊所。这些诊所每年接待300多名患者(~25%-50%的低功能患者)，提供了充足的机会 观察行为表型和严重程度各异的受试者。这是对 参加病例评估会议(作为临床观察的一部分)、两个月一次的临床小组会议和 定期与利维博士和米勒博士单独会面。发育障碍的神经生物学培训 以及初级感觉过程的神经生物学将通过课程和一对一的方式实现 与孔特雷拉斯医生的会面。生物学、演示和临床方面的培训、研讨会和课程 对神经发育障碍的护理将使我能够更好地预测和应对 对这些患者群体的研究，并阐明和解决这些儿科中心的生物学问题 患者群体。 这一K01的完成包含了在MEG收购和 分析。具体而言，在目标1中开发了用于基于图谱的头部建模和运动补偿的方法， 将允许在不需要核磁共振的情况下对诱发的初级感觉活动进行准确的来源定位 在大的连续运动的情况下。这些方法将使研究初级感觉过程成为可能。 低功能和不合规的患者群体。同样，实时分析系统(目标3) 在这些患者群体中代表着在获得脑磁图方面向前迈出的重要一步，承诺减少扫描 因此减少了病人的不适和疲劳。技术进步的基础将是 罗伯茨、莫舍和达默斯博士接受了高级脑磁图物理和分析方面的额外培训 通过一对一的会议和指导。这些方法的实用性和有效性将得到验证。 通过将其应用于患有自闭症的低功能儿童和青少年，以及通过增加成功 速率(可评估数据)和数据质量。对非典型感觉活动的调查，以前只报道过 在高功能ASD中，将因此在低功能ASD人群中启用，以解决 ASD感觉异常的概括性的关键且目前未被评估的问题。K01 研究将提供数据支持未来的R01，它可能会专注于对比 ASD低功能个体到非ASD神经发育障碍(例如，22q11.2缺失 综合征，脑性瘫痪)，以确定感觉处理大脑的特定路径与共同路径 神经发育障碍的异常。