Stroke is one of the leading causes of death and disability world wide. Strokes are caused by narrowing or obstruction (by a clot) in an artery that supplies blood and oxygen to part of the brain. When the brain tissue does not receive adequate blood and oxygen it first ceases to function and then dies.

Currently, established treatment to limit the size of the stroke and to minimize the severity of disability is limited to a single medication, recombinant tissue plasminogen activator (tPA) a thrombolytic agent or "clot buster" that must be given in the first three hours after symptoms begin. This medication is given through the veins, and is designed to break up clots in the arteries that are the cause of many strokes. Unfortunately, most people who are having a stroke do not even reach the hospital during these first three crucial hours. Others do not improve with medication. However, there is some evidence that other types of treatment can be used, in selected patients, later in the course of stroke to limit the final size and the degree of impairment.

For instance, in some centers thrombolytic medications like tPA, are being given in the arteries up to 6 hours from the onset of stroke, when a clot that is causing the stroke is seen inside a vessel. Other patients, who are found to have severe narrowing of one or both internal carotid arteries, which supply a large part of the brain, undergo carotid endarterectomy to remove the plaque that is causing the narrowing. Finally, a few centers have reported that simply raising blood pressure with intravenous medications to improve blood flow through narrow arteries can improve function in some stroke patients. It is assumed, but not known, that all three of these treatments improve function in acute stroke by re-establishing blood flow to brain tissue that has been receiving too little blood to function, but just enough that it has not yet died.

We are now able to test this assumption with new neuroimaging techniques that differentiate areas of infarct (tissue that has already died) from regions that are receiving poor blood flow but are still salvageable. Diffusion-weighted imaging (DWI) shows areas of brain tissue that has most likely already died; whereas Magnetic Resonance Perfusion Imaging (MRPI) shows areas of brain tissue that are receiving poor or delayed blood flow, and are likely to be dysfunctional.

We will identify stroke patients in whom MRPI shows larger areas of brain tissue that are receiving poor blood flow, compared to the area of brain tissue that has already died, and offer them one of the three described treatments in the effort to improve blood flow: (1) intra-arterial thrombolysis; (2) urgent carotid endarterectomy (CEA); or (3) medically-induced blood pressure elevation. We will repeat MRPI and DWI and tests of motor function and thinking skills before and after treatment, to determine if improved blood flow to a particular region (that was at risk for stroke) corresponds to improved function. If treatment results in increased blood flow to a specific region of the brain (seen on MRPI) and results in improved performance on motor/cognitive tests at the same time, it would provide evidence that treatment works by restoring blood flow. More importantly, results of this study are expected to help physicians decide which patients would be likely to benefit from one of these treatments, on the basis of MRPI and DWI scans. Pharmacologically raising blood pressure is the least used of these treatments, and stands the most promise for treating large numbers of stroke patients, if it can be determined which patients are likely to benefit. These results would also provide the basis for conducting large, randomized clinical trials to establish the probability that each treatment will improve function in early stroke, in patients who show given MRPI and DWI profiles.

Lastly, it is expected this study will demonstrate that particular cognitive functions (e.g., distinct language or attentional skills) are impaired when a specific region of the brain is receiving poor blood flow but improve when that region shows increased blood flow with treatment. Such results would provide evidence that the part of the brain that was originally receiving inadequate blood flow is crucial for the cognitive function that improved. Thus, results from this study would help to establish the anatomical localization of specific cognitive functions.