MRI Based Presymptomatic Prediction of ASD

基于 MRI 的 ASD 症状前预测

• 批准号: 9981943
• 负责人: Joseph Piven
• 金额: $ 84.79万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-04-01 至 2024-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9981943
• 关键词: Affect; Age; Age-Months; Amygdaloid structure; Anisotropy; Anterior; Area; Axon; Behavior; Behavioral; Biological Markers; Brain; Brain imaging; Budgets; Cell model; Cerebrospinal Fluid; Characteristics; Clinical; Corpus Callosum; Data; Development; Diagnosis; Diagnostic; Diffuse; Diffusion; Diffusion Magnetic Resonance Imaging; Disease; Down Syndrome; Fiber; Functional Imaging; Funding; General Population; Goals; Growth; Impairment; Infant; Infant Development; Language; Life; Longitudinal Studies; MRI Scans; Magnetic Resonance Imaging; Maps; Measures; Motor; National Institute of Mental Health; Outcome; Outcome Assessment; Participant; Pattern; Predictive Value; Process; Property; Prospective cohort; Protocols documentation; Publishing; Radial; Reporting; Research; Research Personnel; Resources; Risk; Sampling; Scanning; Schedule; Siblings; Structure; Subgroup; Surface; Symptoms; Testing; Time; Work; autism spectrum disorder; base; behavior change; behavioral study; brain behavior; brain tissue; brain volume; cerebrospinal fluid flow; clinical research site; clinically actionable; cohort; density; drug development; high risk; imaging study; indexing; infancy; insight; joint attention; multimodality; nerve stem cell; outcome prediction; parent project; predictive test; prospective; rate of change; repetitive behavior; social deficits; therapeutic target; time interval; white matter

ABSTRACT This is an application for a 4 year competitive supplement to add a multimodal MRI scan, at 24 months of age, to a newly funded study that aims to replicate and extend our findings predicting autism spectrum disorder (ASD) in high familial risk (HR) infants using MRI scans in the first year of life. HR infants (who have an older affected sibling) have approximately a 12-fold increase in their risk (1/5 vs 1/59) to develop ASD. In HR infants who develop ASD, the first year of life is a period that is relatively free of the defining behavioral characteristics of the disorder, which then consolidate into full diagnosis over the second year of life and beyond. Longitudinal studies involving structural, diffusion, and functional imaging from the Infant Brain Imaging Study (IBIS) Network (https://www.ibis-network.org/) have produced new and fundamental insights into early brain and behavior changes across 6-24 months of age in infants who later meet criteria for ASD. The IBIS Network received funding in April 2019 to replicate and extend findings showing that structural and functional connectivity (fcMRI) MRI scans at 6 and 12 months of age can accurately (positive predictive values greater than 80%) predict ASD diagnosis at 24 months of age. This new study (IBIS-Early Prediction or “IBIS-EP”) seeks to advance the field toward a clinically actionable, predictive test for ASD in HR infants. The NIMH- approved budget for IBIS-EP, however, does not include support for a 24 month scan of HR infants. Without a 24 month scan, it will not be possible to replicate or extend IBIS’ critical findings about brain development [1-8], that are temporally specific and require the 24-month scan for characterization of the precise timing of brain changes. This competitive supplement would allow us to acquire, process, and analyze 24 month multimodal MRI scans for the 250 HR infants participating in the IBIS-EP study (who are already scheduled to return for 24 month diagnostic assessment). This time sensitive opportunity to leverage resources from IBIS-EP, and data from two parallel studies by IBIS co-investigators involving 80 low-risk (LR) infants, would allow us (Aim 1) to attempt to replicate our previous reports of age-specific, structural, diffusion, and functional connectivity MRI brain changes at 6-12 and 24 months; and (Aim 2) to investigate potential mechanisms underlying previously reported MRI findings in a new, prospective cohort, scanned through 24 months. Studies will examine the development of increased cerebrospinal fluid and aberrant white matter microstructure in ASD vs. HR-negative and LR groups, and test ASD outcome group-based differences in brain functional connectivity. The addition of a 24 month scan would, therefore, dramatically increase the impact of the parent project by: 1) identifying specific developmental windows (i.e., time intervals with significant group differences in change rate of brain features that correspond to later clinical outcomes); 2) identifying biomarkers of homogenous subgroups and symptom progression; and 3) identifying therapeutic targets, e.g., brain volume expansion as a marker of over- proliferation of neural progenitor cells, for study in cross-species and cellular models to aid drug development.

抽象的 这是为期4年竞争补充剂的申请，以在24个月大时添加多模式MRI扫描 一项旨在复制和扩展我们预测自闭症谱系障碍的发现的新资助的研究 （ASD）使用MRI扫描在生命的第一年使用高家族风险（HR）婴儿。人力资源部婴儿（年龄较大 受影响的兄弟姐妹的风险大约增加了12倍（1/5 vs 1/59），以发展为ASD。在人力资源婴儿中 谁发展了ASD，生命的第一年是一个相对不含定义行为特征的时期 这种疾病，然后在生命的第二年及以后整合地融合为完整的诊断。纵向 来自婴儿脑成像研究（IBIS）的结构，扩散和功能成像的研究 网络（https://www.ibis-network.org/）对早期大脑和 后来符合ASD标准的婴儿的6-24个月大的行为变化。 IBIS网络 2019年4月获得资金，以复制和扩展发现，表明结构和功能 在6和12个月大的6个月大的连接性（FCMRI）MRI扫描可以准确（正预测值更大 比80％）预测24个月大的ASD诊断。这项新研究（ibis-Early预测或“ IBIS-EP”） 试图将该领域推向人力资源婴儿中ASD的临床可行的预测测试。 nimh- 但是，IBIS-EP的批准预算不包括对24个月扫描人力资源婴儿的支持。没有一个 24个月扫描，不可能复制或扩展宜必思的有关大脑发育的关键发现[1-8]， 暂时特定的，需要进行24个月的扫描以表征大脑的精确时机 更改。这种竞争性补充剂将使我们能够获取，处理和分析24个月多模式 对参加IBIS-EP研究的250小时婴儿的MRI扫描（他们已经计划返回24 月诊断评估）。这段时间敏感的机会来利用Inibis-EP和数据的资源 从ibis共同研究者的两项平行研究中，涉及80个低风险（LR）婴儿的研究，将使我们（AIM 1）得以实现 尝试复制我们以前关于年龄特异性，结构，扩散和功能连接性MRI的报告 大脑在6-12和24个月时变化； （目标2）先前研究潜在机制 报告了在新的，前瞻性的队列中进行的MRI调查结果，该研究结果扫描到24个月。研究将检查 在ASD与HR阴性中的脑脊液和异常白质微观结构的发展开发 和LR组，并测试基于ASD结果组的大脑功能连通性差异。添加 因此 特定的发育窗口（即，大脑变化率有显着群体差异的时间间隔 与以后的临床结果相对应的功能）； 2）识别同质亚组的生物标志物和 症状进展； 3）确定治疗靶标，例如，大脑体积扩展是过度的标志 神经祖细胞的增殖，用于研究跨物种和细胞模型，以帮助药物发育。