Microbubble potentiated ultrasound as a method of stroke therapy in a pig model: preliminary findings

Low-frequency ultrasound (LFUS) with intraarterial or intravenous microbubbles can recanalize thrombosed dialysis grafts and arteries. A similar method for declotting intracranial arteries in an animal model has been developed.

Swine underwent selective cerebral angiography, and 1 mL of 2-6 hour old clot was placed in one ascending pharyngeal artery and rete mirabile. This occluded the primary brain blood supply from the rete mirabile in the base of the skull. Human albumin octafluoropropane microbubbles were injected through the same catheter in 0.5-1.0-mL doses for a total of 4.5 mL in 21 minutes. Transcutaneous pulsed-wave 1-MHz ultrasound was administered through a temporal approach using 2.2 W/cm(2). Repeated angiography was performed through 24 minutes. Saline controls underwent an identical process on the opposite side. Declotting was graded on a scale of 0-4, and flow used the 0-3 thrombolysis in myocardial infarction (TIMI) scale. Success was defined as declotting of grade >/= 3 (>70% clearing) with flow of >/= 2.

Seven pigs received 14 declotting sequences. Average clot age was 217 minutes. Average declotting score was 3.1, and flow was 2.1 for microbubbles and 1.4 and 0.1 for saline controls, P =.016 in each. Success occurred with microbubbles in six of seven attempts and in controls in zero of seven attempts, P =.031.

LFUS with microbubble augmentation rapidly lyses intracranial clot and restores flow at ultrasound ranges similar to those required in humans. Further development of this possible acute stroke therapy is justified.