4D Cortical Surface Analysis Tools for Study of Early Brain Development in Typical and High-risk Infants

 描述（由申请人提供）：精神分裂症是一种具有早期神经发育起源的衰弱性精神障碍。精神分裂症母亲所生的遗传高危婴儿是提高我们对精神分裂症发育起源和异常轨迹的理解的理想候选人。位于查佩尔山的北卡罗来纳州大学收集了一组独特的纵向MRI数据集，这些数据集是典型发育婴儿和头两年患有精神分裂症的高危婴儿的纵向MRI数据集，这使我们能够跟踪典型和高危婴儿在这一关键时期大脑皮层的动态发育轨迹。 阶段基于皮层表面的神经影像学数据分析在成人精神分裂症研究中发挥着越来越重要的作用，并揭示了广泛的结构和功能异常。然而，现有的皮质表面为基础的分析工具开发的成人大脑是不适合婴儿的研究，由于其显着的差异，图像对比度，皮质的sie，形状和折叠程度。此外，在纵向婴儿研究中，对每个时间点的图像的独立处理导致时间上不一致和不准确的测量。为了成为儿科神经影像学研究的独立研究者，候选人在此K01申请中建议接受发育神经生物学和神经发育障碍，高级生物统计学和婴儿MR成像技术的培训。这些培训活动将大大增加候选人在婴儿神经成像映射方面的背景，并为他成为早期大脑发育研究的领先研究者的长期目标奠定坚实的基础。在研究计划中，候选人将创建一套独特的婴儿特定的、基于4D皮质表面的神经成像分析工具，这些工具能够准确表征典型发育婴儿和精神分裂症高危婴儿的早期大脑发育。具体而言，将开发一种用于4D婴儿皮质表面的一致分割的方法（目的1）。然后，将创建一种用于4D婴儿皮层区域和局部回转发育的脑大小自适应测量的方法（目的2）。在此基础上，根据大脑皮层的动态发育轨迹，构建第一个4D婴儿大脑皮层表面图谱（目的3）。这些方法和地图集将被用来描述典型婴儿和高危婴儿的动态皮层发育轨迹（目标4）。这项研究的结果将有助于确定精神分裂症风险的早期生物标志物， 设计有针对性的先发制人的干预策略。所有创建的工具和地图集将被集成并免费向公众发布，如NITRC（www.nitrc.org）。

 DESCRIPTION (provided by applicant): Schizophrenia is a debilitating mental disorder with early neurodevelopmental origins. Genetic high-risk infants born to schizophrenic mothers are ideal candidates for improving our understanding of developmental origins and abnormal trajectories in schizophrenia. The University of North Carolina at Chapel Hill has collected a unique cohort of longitudinal MRI dataset of typically developing infants and also infants at high-risk for schizophrenia in their first two years of life, which allows us to track dynamic developmental trajectories of the cortex in both typical and high-risk infants during this critical stage. Cortical surface-based analysis of neuroimaging data is playing an increasingly critical role in adult schizophrenia studies, and has revealed widespread structural and functional abnormalities. However, existing cortical surface-based analysis tools developed for adult brains are ill-suited for infant studies, due to their dramatic differences in image contrast, cortical sie, shape, and folding degree. Moreover, independent processing of image for each time-point in the longitudinal infant studies leads to temporally inconsistent and inaccurate measurements. To become an independent investigator on pediatric neuroimaging research, the candidate proposes in this K01 application to receive training in developmental neurobiology and neurodevelopmental disorders, advanced biostatistics, and infant MR imaging techniques. These training activities will greatly augment the candidate's background in infant neuroimaging mapping and establish a solid foundation for his long-term goal of being a leading researcher on early brain development study. In the research plan, the candidate will create a unique suite of infant-specific, 4D cortical surface based neuroimaging analysis tools that enable accurate characterization of early brain development in both typically developing infants and infants at high-risk for schizophrenia. Specifically, a method for consistent parcellation of 4D infant corticl surface will be developed (Aim 1). Then, a method for brain-size-adaptive measurement of 4D infant cortical regional and local gyrification development will be created (Aim 2). After that, th first 4D infant cortical surface atlases will be constructed, based on the dynamic developmental trajectories of the cortex (Aim 3). These methods and atlases will be then used to characterize the dynamic cortex developmental trajectories in both typical infants and high-risk infants (Aim 4). Results from this research will help to identify early biomarkers of risk for schizophrenia and to design targeted preemptive intervention strategies. All created tools and atlases will be integrated and released freely to the public, such as NITRC (www.nitrc.org).