MOTIVATION One of the central events in acute ischemic stroke is the decrease in delivery of oxygen to the brain, which leads to cell death and irreversible injury. To counteract this, the brain has mechanisms to increase its extraction of oxygen from the arterial blood, which can be imaged with oxygen-15 positron emission tomography (PET). Some evidence from PET exists that suggests that regions with increased oxygen extraction fraction (OEF) are particularly vulnerable in ischemic stroke. Given the sensitivity of MRI to paramagnetic deoxy- hemoglobin (the basis of the BOLD effect), it is possible to image tissue oxygen saturation (SO2). The motivation for the current study is to implement and validate two promising MR oxygenation methods, multiparametric quantitative BOLD and MR oxygenation fingerprinting for use in stroke patients. This latter technique builds on pioneering work extending the fingerprinting approach from anatomical to physiological imaging. AIMS AND METHODS Over a two-year period, we aim to perform studies to validate the performance of both of these MR oxygenation imaging protocols in normal subjects exposed to inspired gas challenges that will alter the global brain oxygenation. We will then apply the best of these two techniques to a cohort of acute ischemic stroke patients to determine the performance of the oxygenation-diffusion (O2- DWI) mismatch as a potential improved substitute for the traditional DWI-PWI mismatch. SIGNIFICANCE We believe successful attainment of these aims will markedly improve acute stroke care by validating a non-invasive MRI-based method to assess tissue oxygenation. We believe that there will be wide-reaching benefits to the development of a robust MR oxygenation method in a wide range of other neurological diseases, including carotid steno-occlusive disease, brain tumors, multiple sclerosis, and neurodegenerative disease.