Project Summary/Abstract Birth asphyxia, referring to oxygen deprivation due to intrapartum complications, occurs in 1 to 6 per 1000 live full-term birth. It causes hypoxic brain injuries and is one of the leading reasons of neonatal death and long-term disabilities. Non-invasive biomarkers are needed to assess the extent to which hypoxia has caused brain injury. To date, however, reliable biomarkers to predict clinical outcomes are lacking. Conventional anatomic MRI sequences (e.g. T1 and T2) can show structural lesions due to injury, but their sensitivity in detecting subtle injury and neural abnormality is limited. Therefore, the goal of this project is to develop and evaluate the clinical utility of novel biomarkers related to neonatal brain?s oxygen utilization, including cerebral metabolic rate of oxygen (CMRO2) and its key component, oxygen extraction rate (OEF). Cerebral oxygen consumption is a central piece in the pathological process underlying birth asphyxia. However, at present, there exist no practical techniques to assess cerebral oxygen metabolism in human neonates. Positron Emission Tomography (PET) methods that have been used for adult CMRO2 imaging cannot be easily used in neonatal population due to the complexity of the procedures and radiation concerns. In this project, we will develop a MR based technique to measure OEF and CMRO2 without using any exogenous contrast agent. A critical component in OEF and CMRO2 quantification is venous oxygen saturation. In this project, we will devise a novel pulse sequence, accelerated T2-Relaxation-Under-Phase- Contrast (aTRU-PC), to measure venous oxygenation in a region-specific manner, from which OEF and CMRO2 will be quantified. The project consists of three logical aims of technical development (Aim 1), validation (Aim 2), and initial demonstration of clinical utility in neonatal patients with hypoxic ischemic encephalopathy (HIE) (Aim 3). Aim 1 will focus on the development of the aTRU-PC sequence for the measurement of regional venous oxygenation in healthy neonates as well as a multi-site evaluation to examine the reproducibility and scalability of the proposed technique. Aim 2 will focus on the validation of the proposed MRI oxygenation technique in newborn piglet model. Aim 3 will focus on evaluating the clinical utility of OEF and CMRO2 as a functional biomarker in neonatal HIE. We hypothesize that OEF and CMRO2 will be associated with HIE severity and the short-term outcomes. Impact: Upon the completion of this project, we will be able to provide the neonatal neuroimaging community with a new MRI technique for quantitative assessment of brain oxygen utilization and will have demonstrated its clinical utility in HIE.