Individual Motor Outcome Prediction in Preterm Children Using Neonatal Neuroimaging

项目摘要 仅在美国，每年就有50万婴儿早产（妊娠期<37周）， 神经发育障碍的风险增加，包括脑瘫和其他运动障碍。而 已知特定临床人群的风险增加，任何单个儿童残疾的可能性 目前不能仅根据临床风险因素准确预测，限制了我们有效地 有针对性的治疗和开发新的干预措施。先前的神经影像学研究将早产与 破坏运动系统的发育，包括运动皮层、丘脑、基底神经节， 小脑和相关的白色物质束，包括胼胝体（CC）和皮质脊髓束（CST）。 虽然这些区域之间异常的结构和功能连接与贫困有关， 运动结果，这还没有在纵向队列中以一种允许 个性化的结果预测。本研究建议使用多种先进的神经影像学方式， 统计模型如何在运动系统内的新生儿结构和功能连接的变化， 预测极早产儿（VPT; <30周妊娠）的儿童运动结局。这 调查将利用一个独特的、非常有价值的、前瞻性的纵向队列（目前正在研究 通过R 01 MH 113570），其中包括175名VPT儿童，包括41名脑瘫儿童和68名其他 运动障碍我们收集了这些儿童最先进的新生儿神经影像学数据，包括高- 分辨率解剖、功能和扩散数据。他们还接受了标准化的测试， 在2岁、5岁和9/10岁时的粗大运动功能，在各评估波中保持率>80%。 在本研究的三个目标中，将创建潜在增长曲线模型并进行比较，以确定 运动系统功能连接和CC和CST微结构的个体水平预测能力， 单独和组合，对10岁的运动轨迹的影响。这一项目将推动 我们有能力预测个别早产儿到童年中期的结果，并建立申请人的 在神经成像，纵向数据分析和科学交流的研究环境中的技能， 这些领域的专业知识。在这个过程中，她将精通必要的方法， 进一步了解早期大脑发育与高危人群残疾之间的关系， 人口。她也将准备好承担不仅强大的实验工作，而且照顾 同时有效地将她的研究与残疾 宣传。这将为申请人成为一名成功的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.