Sonothrombolysis in Ischemic Stroke

Abstract

Acute ischemic stroke remains one of the most devastating diseases when it comes to morbidity and mortality, not to mention the personal and economic burden that occurs in long-term. Intravenous thrombolysis with tissue plasminogen activator (tPA) is the only effective acute stroke therapy that improves outcome if given up to 4.5hours from symptom onset. However, recanalization rates are meager and the majority of treated patients still have residual disability after stroke, emphasizing the need for further treatment options that may facilitate or even rival the only approved therapy. Sonothrombolysis, the adjuvant continuous ultrasound sonication of an intra-arterial occlusive thrombus during thrombolysis, enhances the clot-dissolving capabilities of intravenous tPA presumably by delivering acoustic pressure to the target brain vessel. Higher recanalization rates produce a trend towards better functional outcomes that could be safely achieved with the combination of high-frequency ultrasound and intravenous tPA. However, data on ultrasound targeting of intracranial proximal occlusive lesions other than those in the middle cerebral arteries are sparse. Moreover, recent sonothrombolysis trials were exclusively conducted with operator-dependent hand-held technology hindering its further testing in clinical sonothrombolysis trials. An operator-independent 2-MHz transcranial Doppler device has been developed allowing health care professionals not formally trained in ultrasound apparatus to provide therapeutic ultrasound as needed. Currently, this operator-independent device covering 12 proximal intracranial segments that most commonly contain thrombo-embolic occlusions enters testing in a pivotal multicenter sonothrombolysis efficacy trial. If this trial demonstrates safety and efficacy, adjuvants, such as gaseous microbubbles that further potentiate the thrombolytic effect of intravenous tPA, could be tested along with this device.