Patient description: Karen is a 72-year-old woman with hypertension and type 2 diabetes, who was hospitalized for cryptogenic stroke two weeks ago. At the time, computed tomography was negative for brain hemorrhage and she was given thrombolytic therapy with resolution of her symptoms. Transesophageal echocardiogram and magnetic resonance angiogram of brain and great vessels found no evidence of abnormalities. She presents currently with a blood pressure of 120/70 mm Hg, normal glucose, and normal sinus rhythm on a 12-lead electrocardiogram. She reports history of occasional palpitations, shortness of breath and chest pain lasting for a few minutes and then stopping on their own.

Clinical trial eligibility criteria: eligible ages (years): 18.0-85.0,  Acute Ischemic Stroke Patients must meet all of the criteria Diagnosis of acute ischemic stroke with onset less than 4.5 hours prior to the planned start of intravenous alteplase. Acute ischemic stroke is defined as a measurable neurological deficit of sudden onset, presumed secondary to focal cerebral ischemia. Stroke onset will be defined as the time the patient was last known to be without the new clinical deficit. Patients whose deficits have worsened in the last 4.5 hours are not eligible if their first symptoms started more than 4.5 hours before. If the stroke started during sleep, stroke onset will be recorded as the time the patient was last known to be at baseline Disabling neurological deficit attributable to acute ischemic stroke in the middle cerebral artery territory NIHSS less than or equal to 18 for left hemisphere strokes, NIHSS less than or equal to 16 for others Evidence of MCA occlusion (stem or branch) prior to drug administration by TCD, CTA or MRA Age 18-85 years, inclusive Able to sign informed consent For MRI Arm only Screening MRI diagnostic of focal cerebral ischemia corresponding to the clinical deficits. The MRI evaluation must involve echo planar diffusion weighted imaging, MRA, and MRI perfusion. A normal appearing MRA with an appropriate perfusion deficit is eligible. An apparent stenosis or occlusion on MRA with normal appearing perfusion distally will not be eligible. Poor quality or uninterpretable MRA will not make patient ineligible. Patients who have a normal appearing DWI are eligible Evidence on PWI MRI or a perfusion defect corresponding to the acute stroke syndrome. The PWI will be assessed by relative mean transit time (MTT) images obtained prior to the start of rt-TPA therapy  Patients will be excluded from study participation for any of the following reasons Current participation in another study with an investigational drug or device within, prior participation in the present study, or planned participation in another therapeutic trial, prior to the final (day 30) assessment in this trial Absence of acoustic window to insonate the MCA on the involved side Time interval since stroke onset of less than 3 hours is impossible to determine with high degree of confidence Symptoms suggestive of subarachnoid hemorrhage, even if CT or MRI scan is negative for hemorrhage Evidence of acute myocardial infarction defined as having at least two of the following three features: 1) Chest pain suggestive of cardiac ischemia; 2) EKG findings of ST elevation of more greater than 0.2 mV in 2 contiguous leads, new onset left bundle branch block, ST segment depression, or T-wave inversion; 3) Elevated troponin I Acute Pericarditis Women known to be pregnant, lactating or having a positive or indeterminate pregnancy test Neurological deficit that has led to stupor or coma (NIHSS level of consciousness [item I a] score greater than or equal to 2) High clinical suspicion of septic embolus