A Longitudinal MRI Study Characterizing Very Early Brain Development in Infants with Down Syndrome

一项纵向 MRI 研究表征唐氏综合症婴儿早期大脑发育

• 批准号: 9789674
• 负责人: Kelly N Botteron
• 金额: $ 231.42万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-20 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9789674
• 关键词: Address; Age; Age-Months; Area; Atlases; Attention; Behavior assessment; Behavioral; Biological Markers; Birth; Brain; Brain imaging; Cerebellum; Cerebrum; Characteristics; Child; Cognitive; Comorbidity; Complex; Data; Data Set; Development; Developmental Disabilities; Diagnosis; Diffusion; Down Syndrome; Early Intervention; Evaluation; Eye; Fragile X Syndrome; Functional Magnetic Resonance Imaging; Future; Genetic; Goals; Human; Image; Impaired cognition; Impairment; Incidence; Individual; Infant; Intellectual functioning disability; Intervention; Investigation; Knowledge; Language; Life; Life Expectancy; Live Birth; MRI Scans; Machine Learning; Magnetic Resonance Imaging; Measures; Minnesota; Motor; Motor Skills; Multimodal Imaging; Myelin; National Institute of Child Health and Human Development; Nature; Neurocognitive; Neurodevelopmental Disorder; Outcome; Parietal; Pathogenicity; Pattern; Pharmacology; Pregnancy; Radiology Specialty; Recommendation; Research; Research Design; Rest; Sedation procedure; Sensory; Series; Shapes; Sleep; Social Development; Specificity; Statistical Models; Structure; Surface; Techniques; Technology; Therapeutic Intervention; Thick; Time; United States; United States National Institutes of Health; Universities; Visit; Work; autism spectrum disorder; base; behavioral impairment; brain behavior; cognitive development; congenital heart disorder; data acquisition; developmental disease; disability; experience; functional disability; gastrointestinal; high risk; imaging modality; imaging study; improved; infancy; malformation; morphometry; multimodality; neural circuit; neurodevelopment; neuroimaging; novel; personalized intervention; predictive modeling; preservation; recruit; skills; targeted treatment; traditional therapy; white matter

Longitudinal MRI Characterization of Very Early Brain Development in Infants with Down Syndrome Project Summary/Abstract Down syndrome (DS), the most common genetic cause of intellectual disability, is associated with varying degrees of cognitive and behavioral impairments. Pharmacologic therapies and genetic modulators are emerging which, if administered early in conjunction with traditional therapies, show promise for improving developmental outcomes in children with DS. However, the stark absence of early neurodevelopment knowledge in DS hampers these efforts. The main goal of this proposal is to develop biomarkers as future targets for specific therapies based on careful characterization of early aberrant neurodevelopmental patterns. This study will be a combined effort with WU as the coordinating center and six other research groups: UNC, UW, CHOP, MNI, NYU, and University of Minnesota. These groups comprise the ACE-IBIS (Autism Center of Excellence Infant Brain Imaging Study) network, a well-established and experienced group that has been productively collaborating for 8 years on MRI imaging and behavioral characterization of infants at high risk for autism, healthy typical infants (TYP), and infants with Fragile X. The aims of this proposal are: 1) Define the longitudinal characteristics of early brain development in infants (3 to 24 months) with DS in comparison to TYP infants and infants with other developmental disabilities (ASD and Fragile X) using three different types of neuroimaging (MRI, DTI, rsfMRI); 2) Develop predictive models for developmental outcomes in infants with DS based on longitudinal structural or functional MRI characteristics; and 3) Characterize brain-behavior correlates with coordinated multimodal imaging in infancy characterizing the interrelationship between longitudinal network imaging parameters and cognitive, behavioral and neurodevelopmental outcomes using sophisticated multivariate support vector machine (SVM) analytic strategies. 120 infants with DS and 40 TYP control infants will be followed longitudinally from 3 to 24 months. MRI scans will be obtained during natural sleep and a series of well-validated developmental and behavioral assessments will be completed at each visit. This project will be the first to define the nature and timing of alterations in brain development in infants with DS. The proposed project addresses several key research recommendations from the “NICHD 2014-The NIH Research Plan on Down Syndrome.” The study aims match the recommendation for the quantitative characterization based on imaging of early brain development and the relationship of cognitive, behavioral and social development to early aberrant neurodevelopment in DS. This project will also address recommendations for investigation of comorbid ASD in DS, which could be as high as 5-10%. The IBIS network is uniquely qualified to examine early neurodevelopmental patterns, utilizing the ASD, TYP and FraX infant data sets to better characterize and examine specificity of DS early developmental patterns including ASD qualities and impairments in social development. It is clear that quantification of neurodevelopmental trajectories in infants with DS will be critical to identification of personalized intervention strategies and to assess the efficacy of early life, targeted, highly novel and mechanistically specific DS interventions.

早期大脑发育的纵向MRI表征 在唐氏综合症的婴儿中 项目摘要/摘要 唐氏综合症（DS）是最常见的智障遗传原因，与不同程度有关 认知和行为障碍。药理学疗法和遗传调节剂正在出现，如果 与传统疗法结合初期管理，显示出改善发展结果的希望 在患有DS的孩子中。但是，在DS上没有早期神经发育知识的明显缺乏 努力。该提案的主要目标是开发生物标志物作为基于特定疗法的未来目标 仔细表征早期异常神经发育模式。这项研究将与 WU作为协调中心和其他六个研究小组：UNC，UW，CHOP，MNI，NYU和University of University of University 明尼苏达州。这些组包括ACE-IBI（自闭症卓越中心婴儿脑成像研究） 网络，一个建立良好且经验丰富的团队，在MRI上已经有效地合作了8年 对自闭症，健康典型婴儿（典型）和 具有脆弱X的婴儿。该提议的目的是：1）定义早期大脑的纵向特征 与其他与其他婴儿相比 使用三种不同类型的神经影像学（MRI，DTI，RSFMRI）使用发育障碍（ASD和脆弱的X）； 2） 开发基于纵向结构或DS婴儿的发育结果的预测模型 功能性MRI特性； 3）表征大脑行为与协调的多模式相关 纵向网络成像参数和 使用复杂的多元支持向量机的认知，行为和神经发育结果 （SVM）分析策略。从3到3 24个月。在自然睡眠期间将获得MRI扫描，并进行一系列经过良好验证的发育和 每次访问时将完成行为评估。该项目将是第一个定义性质和 DS婴儿大脑发育改变的时机。拟议的项目解决了几个关键 “ NICHD 2014- NIH唐氏综合症研究计划”的研究建议。该研究的目的 匹配基于早期大脑发展成像的定量表征的建议 认知，行为和社会发展与DS中异常神经发育的关系。 该项目还将解决DS合并ASD投资的建议，这可能很高 为5-10％。 IBIS网络具有独特的资格来检查早期神经发育模式，使用 ASD，典型和FRAX婴儿数据集以更好地表征和检查DS早期发育的特异性 包括ASD质量和社会发展障碍的模式。显然数量 DS婴儿的神经发育轨迹对于识别个性化干预至关重要 策略并评估有针对性的，高度新颖和机械特定的DS的早期生命的有效性 干预措施。