The overall goal of this Program project is to investigate ischemia as a secondary mechanism of tissue damage in the early period following acute brain injury. Secondary mechanisms, occurring in a delayed manner, provide the best opportunity for successful therapeutic intervention. A better understanding of the pathophysiology of secondary tissue damage following acute brain injury is important if improvements are to be made in current therapy. We will investigate two types of acute brain injury head trauma and intracerebral hemorrhage. In project 1, Drs. Michael Diringer and Robert Grubb will use positron emission tomography (PET) to investigate the occurrence and duration of focal cerebral ischemia in acute traumatic brain injury in project 2, Drs. Michael Diringer and Robert Grubb will use PET to determine the effect of hyperventilation on regional cerebral blood flow and brain oxygenation in acute traumatic brain injury. In project 3, Drs. William Powers and Michael Diringer will use PET to investigate the occurrence and duration of focal cerebral ischemia in acute intracerebral hemorrhage. In project 4, Drs. William Powers and Michael Deringer will use PET to determine th effect of pharmacologic reduction of systemic arterial pressure on regional cerebral blood flow and brain oxygenation in acute intracerebral hemorrhage. The PET Facilities Core directed by Dr Powers will coordinate those aspects of the initial acquisition, reconstruction and archiving of the PET, clinical and CT data. The PET Image Analysis Core directed by Dr. Tom Videen will implement and validate improved methods for analysis of PET images. This Program Project draws on a combination of facilities and expertise at Washington University that is unique. It combines state-of-the-artPET equipment for quantitative neuroimaging located in an intensive car unity, 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 pathophysiologic information about the role of ischemia in producing secondary tissue damage in patients with acute brain injury due to head trauma and intracerebral hemorrhage. This information is will provide new understanding of the pathophysiology of these conditions which will be important in guiding future research toward the most fruitful approaches for ameliorating the devastating impact of acute brain injury. The results of these studies will have immediate and direct applicability to the thousands of patients each year who suffer from these diseases.