Image-guided sonothrombolysis was prototyped on a modified ultrasound imaging system iE33 and further evaluated using a porcine acute ischemic stroke model. After 20 to 40 minute sonothrombolysis treatment with systemic infusion of Definity microbubbles, contrast reperfusion and arterial recanalization were observed on low MI ultrasound contrast imaging and X-ray based angiography, respectively. The study indicates that a modified diagnostic imaging system can be utilized with systemic microbubble infusion to rapidly restore cerebral blood flow in acute ischemic stroke.