Quantitative Cerebral Oxygen Metabolic Imaging of Acute Ischemic Stroke

The objective of this project is to develop an easily accessible MRI-based cerebral metabolic rate of oxygen consumption (CMRO2) mapping for evaluating ischemic lesion viability in acute stroke patients. Because about 90% of the brain's energy comes from oxidative phosphorylation, mapping CMRO2 holds great promise in managing various neurological diseases. In ischemia, CMRO2, equal to oxygen extraction fraction (OEF) times cerebral blood flow (CBF) scaled by arterial oxygen concentration, is the best predictor of reversible or irreversible brain tissue damage (penumbra or infarction) with the CMRO2 reduction reflecting the rate of transition to infarction, which would inform critical therapeutic decisions. While CBF is routinely mapped in MRI, CT and PET, current standard for OEF mapping is 15O PET using three radioligands (O[15O], H2[15O] and C[15O]). Extremely demanding radiochemical processes due to 15O's short 2-minute half-life make 15O PET only available at very few sites. This inability to perform OEF mapping in clinical settings has resulted in clinicians using suboptimal surrogate biomarkers of brain tissue viability such as CBF or diffusion-weighted imaging (DWI) that are known to overestimate penumbra. We propose to develop accurate MRI-based OEF using multiscale modeling approach and then CMRO2 by multiplying CBF from arterial spin labeling, validate MRI against 15O PET for CMRO2 in stroke patients with acute ischemic lesions, and compare MRI based CMRO2 vs diffusion/perfusion mismatch for prediction of final infarct volume in patients with acute ischemic stroke. Our proposal will validate MRI-based CMRO2 as a tool to assess tissue viability in acute and chronic ischemic lesions. This will allow CMRO2 mapping to be performed routinely in clinical settings and will enable vital cerebral oxygen metabolic imaging in clinical decision-making for managing patients with acute ischemic stroke and advanced atherosclerotic diseases.