Infant Atlas of Brain Perfusion

摘要 人类婴儿期的特点是大脑功能和结构的异常成熟， 一生中最高的变化率。这些动态的大脑过程得到了显著的支持 增加局部脑血流量(RCBF)以满足脑部快速生长的代谢需求 婴儿期。破坏性的大脑疾病，如脑缺血和中风，也会在婴儿期和他们的短期内发生。 长期的后果表现为脑损伤部位的rCBF和功能的变化。 以及相互连接的区域。标准化的全脑群体平均三维(3D)发育 脑血流灌注图谱不仅对了解正常的婴儿脑发育有广泛的影响 但也有脑部疾病。如果没有正常的参考值，就不可能检测到改变rCBF的疾病。 尽管影响很大，但到目前为止，还没有婴儿的rCBF图谱和脑轨迹。我们的目标是 建立首个特定年龄、全脑人群平均的3D婴儿血流灌注图谱和轨迹 通过rCBF测量进行量化，并描述它们的功能和行为相关性。适应，适应 相对较小的婴儿大脑，高分辨率(2.5x2.5x2.5mm3)的rCBF将使用 新的动脉自旋标记(ASL)灌注MRI技术(AIM 1-2)，提供对 脑生理学的基本属性。我们还将系统地描绘机制关系 婴儿局部脑血流动力学与相应的脑功能和行为成熟之间的关系(目标3)。 这些图谱将作为诊断筛查工具，通过提供正常的rCBF分布和变异性 (例如，z-sore图)在多个关键的婴儿发育阶段，以及填补神经科学知识 缺乏基本的脑生理特性的差距。ASL灌注核磁共振使用磁性标记 动脉血水质子作为内源性示踪剂。最近开发的一种3D螺旋ASL MRI方法使用 具有背景抑制、三维螺旋堆叠读出和并行的伪连续标记(PCASL) 成像，使建立高质量的婴儿rCBF图谱成为可能，分辨率为2.5x2.5x2.5mm3或 再高一点。本研究将利用两个资助项目(R01HD093776和R01MH092535)，这两个项目将提供 儿童医院相对较大婴儿队列的招募资源和行为评估 来自费城。在优化了婴儿3D螺旋pCASL灌注MRI序列后，我们将使用 从0.5个月、3个月、6个月、9个月、12个月、18个月和24个月的健康婴儿(最初n=232)获取数据的优化序列 时间点)，用于制作特定年龄的人口平均地图集。由此产生的高质量和高分辨率 不同年龄的全脑血流灌注图谱、rCBF的纵向成熟曲线以及个体 数据集将是第一个面向婴儿的数据集，将是宝贵的共享资源。大脑感兴趣区 RCBF变化与功能或行为成熟高度相关也可作为预后指标 预测脑部疾病婴儿功能和行为改变的生物标志物。

Abstract Human infancy is characterized by extraordinary maturation of brain function and structure with the highest change rate across the life span. These dynamic brain processes are supported by significant increases in regional cerebral blood flow (rCBF) to meet the metabolic demands of rapid brain growth during infancy. Devastating brain disorders such as cerebral ischemia and stroke also occur in infancy and their short- and long-term consequences are manifested by changes in rCBF and function around the injured brain site and connected areas. A standardized whole-brain population-averaged three-dimensional (3D) developmental perfusion atlas of rCBF would have a broad impact on understanding not only normal infant brain development but also brain disorders. Without a normal reference, it is not possible to detect disorders that alter rCBF. Despite its significant impact, to date, the rCBF atlas and trajectory of infant brain are not available. The goal is to establish the first age-specific whole-brain population-averaged 3D infant perfusion atlases and trajectories quantified by rCBF measures, as well as to delineate their functional and behavioral correlations. To adapt to relatively small infant brain, high-resolution (2.5x2.5x2.5mm3) rCBF will be obtained noninvasively using a novel arterial spin labeled (ASL) perfusion MRI technique (Aim 1-2), providing absolute quantification of a fundamental property of brain physiology. We will also systematically delineate the mechanistic relationship between infant rCBF dynamics and the maturation of corresponding brain function and behavior (Aim 3). These atlases will serve as a diagnostic screening tool by providing normal rCBF distribution and variability (e.g. z-sore maps) at multiple critical infant developmental stages as well as fill the neuroscientific knowledge gap of lacking fundamental brain physiological properties. ASL perfusion MRI uses magnetically labeled arterial blood water protons as an endogenous tracer. A recently developed 3D spiral ASL MRI method uses pseudo-continuous labeling (pCASL) with background suppression, a 3D stack-of-spiral readout and parallel imaging, making it possible to establish the high-quality infant rCBF atlas at resolution of 2.5x2.5x2.5mm3 or higher. This study will leverage two funded projects (R01HD093776 and R01MH092535) that will provide resources of recruitment and behavioral assessment of a relatively large infant cohort at the Children’s Hospital of Philadelphia. After optimizing the 3D spiral pCASL perfusion MRI sequence for infants, we will use the optimized sequence to acquire data from healthy infants at 0.5, 3, 6, 9, 12, 18 and 24 months (n=232 at initial time point) for making age-specific population-averaged atlases. The resulting high-quality and high-resolution age-specific whole brain perfusion atlases, the longitudinal maturational curves of rCBF, as well as individual dataset will be the first for infants, and will be valuable shared resources. The brain regions-of-interests where rCBF change is highly correlated with functional or behavioral maturation may also be used as prognostic biomarkers for predicting altered function and behavior in infants with brain disorders.