The broad, long-term objective of this project is to improve the diagnosis and treatment of ischemic stroke patients. Ischemic stroke is the third leading cause of death and disability in the industrialized world. In the US alone, between 500,000 and 750,000 people are affected by stroke each year. In an ischemic stroke, a blood clot blocks a blood vessel feeding the brain. Acute ischemic stroke is treatable through the use of drug therapies that dissolve blood clots (thrombolysis). Thrombolysis has been shown to reduce the death and disability associated with stroke, but carries significant risk of devastating intracerebral hemorrhage (ICH), indicating the need for careful triage. Without a means to predict ICH,thrombolysis must be denied to over 90% of stroke patients. Evidence has shown that knowledge of CBF in ml/1 OOg-min can help predict ICH in acute stroke patients. A major impediment in treatment of ischemic stroke is the lack of a widely available method for quantifying CBFfor triage! This has prompted the American Heart and Stroke Association to recommend: "More research must be conducted to make these techniques, especially the MR-based methods, quantifiable". We have recently developed a novel MRI pulse sequence for quantitative CBF.We will validate this diagnostic technique in both animal models of ischemic stoke and in a patients with acute and chronic ischemia. We will show that qCBF can be used to risk stratify patients so that patients who would not normally be eligible for thrombolysis can be safely treated with this lifesaving therapy. The specific aims of this proposal are to test the following hypotheses: Specific Aim 1: MRI measurements of perfusion can accurately quantify CBF in normal canines. Specific Aim 2: MRI measurements of perfusion can accurately quantify CBF a canine model of ischemic stroke. Specific Aim 3: MRI measurements can predict CBF in chronic ischemic patients. Specific Aim 4: In acute stroke patients, quantitative CBF values can predict intracranial hemorrhage resulting from thrombolysis. Upon successful completion of this work we will have developed and validated a new MRImethod that quantifies CBFfor the triage of acute stroke patients.

R01NS049395

2006-01-01

2011-12-31