Imaging White Matter Maturation During Healthy Brain Development

描述（由申请人提供）：大脑异常成熟被认为是导致许多心理健康和精神疾病的路径生理学和病因学，其中包括自闭症、精神分裂症、注意力缺陷和强迫症。大脑成熟的一个关键组成部分是髓鞘形成过程，即围绕白质轴突的脂肪髓鞘层的发育，它加速了大脑离散区域之间的信息传递。尽管髓鞘形成在正常脑功能中起着至关重要的作用，尽管这些有效的通讯途径的建立和维持；迄今为止，我们对髓鞘形成的时空演化还知之甚少。此外，髓磷脂成熟与认知和行为发展之间的关系，例如运动协调、语言或视觉接受的进化，仍然知之甚少。本提案旨在解决这些知识上的不足，在健康的神经发育过程中对髓鞘形成进行首次定量和纵向研究。与同步的认知和行为评估相结合，这些数据将为正常的大脑发育提供新的前景。这个规范的数据集将具有独特的定位，可以促进健康和可疑异常发育之间的具体定量比较，使研究人员能够识别和建立相关缺陷的时空模式。本研究的最终目标是定量绘制健康人群生命前5年的髓鞘形成轨迹，并研究髓鞘成熟与认知和行为发展之间的关系。为了实现这一目标，一种新的定量髓磷脂成像方法，称为mcDESPOT，将首先进一步开发和优化用于儿科参与者。利用这种优化的技术，通过在整个发育过程中获得高空间分辨率的全脑髓磷脂图谱，可以重建整个大脑的髓磷脂成熟轨迹。随访128名婴儿（3-24个月）和128名幼儿（2-5岁），分别在有效的3个月和6个月间隔进行扫描和适合年龄的心理测量测试。经过适当的调整，这些数据将产生14个年龄特异性平均髓磷脂图谱，提供体内髓磷脂成熟的第一个定量描述。这些髓磷脂测量与认知之间的关系将通过与运动协调、语言和视觉接收的认知评估进行比较来研究，为大脑如何正常发育以及每个阶段涉及哪些大脑区域提供新的见解。

DESCRIPTION (provided by applicant): Abnormal brain maturation is believed to contribute to the path physiology and etiology of a number of mental health and psychiatric disorders, amongst them autism, schizophrenia, attention deficit and obsessive-compulsive disorder. A critical component of brain maturation is the process of myelination, the development of the fatty myelin layer surrounding white matter axons, which speeds information transfer between discrete brain regions. Despite the crucial role myelination plays in normal brain function, though the establishment and maintenance of these efficient communication pathways; to date little is known quantitatively about the spatial and temporal evolution of myelination. Moreover, the relationships between myelin maturation and cognitive and behavioral development, for example the evolution of motor coordination, language or visual reception, remain poorly understood. This proposal aims to address both of these deficiencies in knowledge, performing the first quantitative and longitudinal study of myelination during healthy neurodevelopment. Paired with synchronized cognitive and behavioral assessments, this data will provide a new vista of normal brain development. This normative dataset will be uniquely positioned to facilitate specific quantitative comparisons between healthy and suspected abnormal development, allowing researchers to identify and establish the spatial and temporal patterns of relevant deficits. The ultimate goals of this research are to quantitatively map the myelination trajectory over the first 5 years of life in a healthy population, and to examine relationships between myelin maturation and cognitive and behavioral development. To achieve this aim, a new method for quantitative myelin imaging, termed mcDESPOT, will first be further develop and optimized for use in pediatric participants. Using this optimized technique, myelin maturation trajectories throughout the brain will be reconstructed by acquiring high-spatial resolution, whole-brain myelin maps at incremented time points throughout development. Following 128 infants (3-24 months of age) and 128 toddlers (2-5 years), scanning and age-appropriate psychometric testing will be performed at effective 3 and 6- month intervals, respectively. Appropriately aligned, this data will result in the creation of 14 age-specific averaged myelin maps, providing the first quantitative description of myelin maturation in vivo. Relationships between these myelin measures and cognition will be investigated through comparison with the cognitive assessments of motor coordination, language and visual reception, providing new insight into how the brain normally develops and which brain regions are involved at each stage.