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: 10247777
• 负责人: Kelly N Botteron
• 金额: $ 236.03万
• 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/10247777
• 关键词: Address; Age; Age-Months; Area; Atlases; Attention; Behavior assessment; Behavioral; Biological Markers; Birth; Brain; Brain imaging; Cerebellum; Cerebrum; Characteristics; Child; Cognitive; Complex; Data; Data Set; Development; Developmental Disabilities; Diagnosis; Diffusion; Down Syndrome; Early Intervention; Evaluation; 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; 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; comorbidity; 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; support vector machine; targeted treatment; traditional therapy; visual tracking; 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.

极早期脑发育的纵向MRI特征 患有唐氏综合症的婴儿 项目总结/摘要 唐氏综合征（DS），最常见的智力残疾的遗传原因，与不同程度的 认知和行为障碍药物治疗和遗传调节剂正在出现，如果 早期与传统疗法联合使用，有望改善发育结果 儿童DS然而，对DS早期神经发育知识的严重缺乏阻碍了这些研究。 努力该提案的主要目标是开发生物标志物，作为未来特定疗法的靶点， 仔细描述早期异常神经发育模式。这项研究将是一项综合努力， WU作为协调中心和其他六个研究小组：WU，UW，CHOP，MNI，NYU和University of 明尼苏达这些小组包括ACE-IBIS（自闭症卓越中心婴儿脑成像研究） 网络，一个成熟且经验丰富的团队，在MRI领域进行了8年的富有成效的合作 自闭症高危婴儿、健康典型婴儿（TYP）的成像和行为表征，以及 患有脆性X染色体的婴儿本研究的目的是：1）明确早期脑的纵向特征 DS婴儿（3 - 24个月）与TYP婴儿和其他 使用三种不同类型的神经成像（MRI，DTI，rsfMRI）检查发育障碍（ASD和脆性X）; 2） 根据纵向结构或发育指标，建立DS婴儿发育结局的预测模型。 功能性MRI特征;以及3）表征大脑行为与协调多模式相关性 表征纵向网络成像参数之间的相互关系的婴儿期成像， 使用复杂的多变量支持向量机的认知、行为和神经发育结果 (SVM)分析战略。将对120名DS婴儿和40名TYP对照婴儿进行纵向随访，从3到 24个月MRI扫描将在自然睡眠和一系列经过充分验证的发育和 将在每次访视时完成行为评估。该项目将是第一个定义的性质， DS婴儿大脑发育改变的时间。拟议项目解决了几个关键问题， NICHD 2014-NIH唐氏综合症研究计划该研究旨在 符合基于早期脑发育成像的定量表征的建议 以及认知、行为和社会发育与DS早期异常神经发育的关系。 该项目还将提出对DS中合并ASD的调查建议， 5- 10%。IBIS网络是唯一有资格检查早期神经发育模式，利用 ASD、TYP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。很明显，量化 DS婴儿的神经发育轨迹对于确定个性化干预至关重要 策略，并评估生命早期、靶向、高度新颖和机制特异性DS的疗效 干预措施。