Infant Atlas of Brain Perfusion

摘要 人类婴儿期的特点是大脑功能和结构异常成熟， 整个生命周期中变化率最高。这些动态的大脑过程得到了重要的支持 增加局部脑血流量（rCBF）以满足大脑快速生长的代谢需求 婴儿期。毁灭性的脑部疾病，如脑缺血和中风，也会发生在婴儿期，而且它们的短期症状 长期后果表现为 rCBF 和受伤大脑部位周围功能的变化 和连接区域。标准化全脑群体平均三维 (3D) 发育模型 rCBF 灌注图谱不仅对理解正常婴儿大脑发育产生广泛影响 还有脑部疾病。如果没有正常参考，就不可能检测到改变 rCBF 的疾病。 尽管影响重大，但迄今为止，婴儿大脑的 rCBF 图集和轨迹尚不可用。目标是 建立第一个特定年龄的全脑群体平均 3D 婴儿灌注图谱和轨迹 通过 rCBF 测量进行量化，并描述它们的功能和行为相关性。为了适应 由于婴儿大脑相对较小，因此将使用非侵入性方法获得高分辨率 (2.5x2.5x2.5mm3) rCBF 新型动脉自旋标记 (ASL) 灌注 MRI 技术（目标 1-2），提供动脉自旋标记 (ASL) 灌注 MRI 技术的绝对量化 脑生理学的基本特性。我们还将系统地勾画出其中的机制关系 婴儿 rCBF 动态与相应大脑功能和行为的成熟之间的关系（目标 3）。 这些图谱将通过提供正常的 rCBF 分布和变异性作为诊断筛查工具 （例如 z 疼痛图）在多个关键的婴儿发育阶段以及填充神经科学知识 缺乏基本的大脑生理特性的差距。 ASL 灌注 MRI 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 3D 螺旋 ASL MRI 方法使用 具有背景抑制、3D 螺旋堆栈读出和并行的伪连续标记 (pCASL) 成像，可以建立分辨率为2.5x2.5x2.5mm3或的高质量婴儿rCBF图谱或 更高。本研究将利用两个资助项目（R01HD093776 和 R01MH092535），这将提供 儿童医院相对较大的婴儿队列的招募和行为评估资源 费城。在优化婴儿 3D 螺旋 pCASL 灌注 MRI 序列后，我们将使用 优化序列以获取 0.5、3、6、9、12、18 和 24 个月时健康婴儿的数据（初始时 n=232） 时间点）用于制作特定年龄人口平均地图集。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 纵向成熟曲线以及个体 数据集将是第一个针对婴儿的数据集，并将成为宝贵的共享资源。大脑感兴趣区域 rCBF 变化与功能或行为成熟高度相关，也可用作预后 用于预测患有脑部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.