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...