The overall goal of this Program Project is to investigate the pathophysiological changes that occur during injury and treatment in human subjects with acute brain damage. We will investigate three types of acute brain injury: intracerebral hemorrhage, ischemic stroke and head trauma. In Project 1, Dr. Allyson Zazutia will investigate the mechanism, extent and clinical importance of edema following intracerebral hemorrhage. In Project 2, Drs. William Powers and Venkatesh Aiyagari will use PET to determine the effect of pharmacologic reduction of systemic arterial pressure on regional cerebral blood flow in acute ischemic stroke. In Project 3, Drs. Michael Diringer and Robert Grubb will investigate the pathophysiological effects of mannitol and hypertonic saline on brain edema due to ischemic stroke and head trauma. The Imaging Core will perform acquisition, reconstruction, processing and archiving of the PET, MR and CT data for Projects 1,2 and 3 as well as validate recently developed MR methods of CBF and OEF estimation against gold-standard techniques. The Radiochemistry Core will provide radiopharmaceuticals for Projects 1,2 and 3 as well as construct a steady state oxygen-15 gas inhalation system to permit PET studies in subjects who are not endotracheally intubated or who cannot actively inhale. This Program Project draws on a combination of facilities and expertise at Washington University that is unique. It combines state-of-the art quantitative neuroimaging, expertise in the care of critically ill neurological patients and many years experience in studying cerebral blood flow and metabolism. This research will provide fundamentally important pathophysiological information to guide future research toward the most fruitful approaches for ameliorating the devastating impact of acute brain injury.