Infant Atlas of Brain Perfusion

摘要 人类婴儿期的特征是大脑功能和结构的异常成熟， 生命周期中最高的变化率。这些动态的大脑过程是由重要的 局部脑血流量（rCBF）增加，以满足大脑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，也发生在婴儿和他们的短期- 而长期后果表现为脑损伤部位周围的rCBF和功能的变化 和连接的区域。标准化全脑群体平均三维（3D）发育 rCBF的灌注图谱不仅对理解正常婴儿的大脑发育有广泛的影响， 还有脑部疾病如果没有正常参考，则不可能检测到改变rCBF的疾病。 尽管其显著的影响，迄今为止，婴儿大脑的rCBF图谱和轨迹是不可用的。目标是 建立第一个年龄特异性全脑人群平均3D婴儿灌注图谱和轨迹 通过rCBF测量进行量化，以及描述其功能和行为相关性。适应 相对较小的婴儿大脑，高分辨率（2.5x2.5x2.5mm3）rCBF将使用非侵入性方法获得。 一种新的动脉自旋标记（ASL）灌注MRI技术（目的1-2），提供了一种绝对定量的 大脑生理学的基本特性。我们还将系统地描述机械关系 婴儿rCBF动态与相应脑功能和行为的成熟之间的关系（目的3）。 这些地图集将作为一个诊断筛选工具，提供正常的rCBF分布和变异性 (e.g. z-sore地图）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。ASL灌注MRI使用磁性标记 动脉血液水质子作为内源性示踪剂。最近开发的3D螺旋ASL MRI方法使用 具有背景抑制的伪连续标记（pCASL）、3D螺旋堆叠读出和并行 成像，使得能够以2.5x2.5x2.5mm3的分辨率建立高质量的婴儿rCBF图谱，或 高本研究将利用两个资助项目（R 01 HD 093776和R 01 MH 092535）， 在儿童医院对一个相对较大的婴儿队列进行招募和行为评估的资源 位于费城在优化婴儿3D螺旋pCASL灌注MRI序列后，我们将使用 从0.5、3、6、9、12、18和24个月的健康婴儿中采集数据的优化序列（初始时n=232 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 年龄特异性全脑灌注图谱，rCBF的纵向成熟曲线，以及个体 数据集将是婴儿的第一个数据集，将是宝贵的共享资源。大脑的兴趣区域， rCBF变化与功能或行为成熟高度相关，也可用作预后指标。 用于预测患有脑疾病的婴儿的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.