Individual Motor Outcome Prediction in Preterm Children Using Neonatal Neuroimaging

项目摘要 仅在美国，每年就有500,000名婴儿早产(怀孕37周)，使他们处于 增加神经发育障碍的风险，包括脑瘫和其他运动障碍。而当 已知特定的临床人群面临更高的风险，即任何一个儿童残疾的可能性 目前仅根据临床风险因素无法准确预测，这限制了我们有效地 以治疗为目标，开发新的干预措施。先前的神经成像研究已将早产与 运动系统发育受阻，包括运动皮质、丘脑、基底节和 小脑及相关的白质束，包括胼胝体(CC)和皮质脊髓束(CST)。 虽然这些区域的结构和功能连接异常与较差的 运动结果，这还没有在儿童时期的纵向队列中以一种允许 个性化的结果预测。这项研究建议使用多种先进的神经成像方法来 对新生儿运动系统内结构和功能连接性的变化进行统计学建模 预测早产儿(妊娠30周)的儿童期运动结果。这 调查将利用独特的、高度有价值的、预期的、纵向的队列(目前正在研究中 至R01 MH113570)，包括175名VPT儿童，其中41名脑瘫，68名其他 运动障碍。我们收集了这些孩子最先进的新生儿神经成像数据，包括 解析解剖、功能和扩散数据。他们还接受了两种罚款的标准化测试 2岁、5岁和9/10岁的粗大运动功能，在评估过程中保留率为80%。 在这项研究的三个目标中，将创建潜在增长曲线模型并进行比较，以确定 运动系统功能连通性和CC和CST微观结构的个体水平预测能力 单独的和组合的，在10岁之前的运动轨迹。这项工程将会同时推进 我们能够预测个别早产儿到童年中期的结果，并建立申请者的 具备在研究环境中进行神经成像、纵向数据分析和科学交流的技能 在这些领域有明确的专业知识。在这个过程中，她将精通必要的方法 加深对高危人群早期脑发育与残疾之间关系的理解 人口。她还将不仅准备好从事强有力的实验工作，而且还准备好照顾 神经发育障碍患者，同时有效地将她的研究与残疾相结合 倡导。这将为申请者成为一名成功的内科医生--科学家和儿童铺平道路。 神经科医生为神经发育障碍儿童创造更好的结果。

Project Summary Each year in the United States alone, 500,000 infants are born preterm (<37 weeks gestation), putting them at increased risk for neurodevelopmental disabilities, including cerebral palsy and other motor impairments. While specific clinical populations are known to be at increased risk, the likelihood of disability for any individual child cannot currently be accurately predicted based upon clinical risk factors alone, limiting our ability to effectively target therapies and develop new interventions. Prior neuroimaging studies have linked preterm birth to disrupted development of the motor system, encompassing the motor cortex, thalamus, basal ganglia, and cerebellum and associated white matter tracts including the corpus callosum (CC) and corticospinal tract (CST). While aberrant structural and functional connectivity across these regions have been associated with poorer motor outcomes, this has not been investigated across childhood in longitudinal cohorts in a way that allows for individualized outcome prediction. This study proposes to use multiple advanced neuroimaging modalities to statistically model how changes in neonatal structural and functional connectivity within the motor system can predict childhood motor outcomes in children born very preterm (VPT; <30 weeks' gestation). This investigation will leverage a unique, highly valuable, prospective, longitudinal cohort (currently being studied through R01 MH113570) that includes 175 VPT children, including 41 with cerebral palsy and 68 with other motor deficits. We collected state-of-the-art neonatal neuroimaging data for these children, including high- resolution anatomic, functional, and diffusion data. They have also undergone standardized testing of both fine and gross motor function at ages 2, 5, and 9/10 years, with retention rates >80% across assessment waves. Across the three aims of this study, latent growth curve models will be created and compared to determine the individual-level predictive ability of motor system functional connectivity and CC and CST microstructure, both individually and in combination, on motor trajectories through age 10 years. This project would both advance our ability to predict outcomes for individual preterm children into middle childhood and build the applicant's skills in neuroimaging, longitudinal data analysis, and scientific communication in a research environment with clear expertise in these areas. In the process, she would become proficient in the methods necessary for furthering our understanding of the relationships between early brain development and disability in high-risk populations. She would also become prepared to undertake not only strong experimental work, but also care for patients with neurodevelopmental disabilities while effectively integrating her research with disability advocacy. This would pave the way for the applicant to become a successful physician-scientist and child neurologist creating better outcomes for children with neurodevelopmental disabilities.