Potential use of therapeutic ultrasound in ischemic stroke treatment

Systemic treatment with rtPA approved for a 3-hour window is the only estab lished causal therapy for acute stroke in the United States and Canada. Thr ombolytic therapy with rtPA demonstrated a small, although significantly re duced morbidity, in a limited number of highly selected patients. As recent ly shown, intraarterial application is favorable and opens the window of tr eatment up to 6 hours. The combination of ultrasound with thrombolytic agen ts may further enhance the potential benefit by means of enzymatic-mediated thrombolysis, which has been demonstrated in different in vitro and in viv o experiments for an accelerated recanalization of occluded peripheral and coronary vessels. Whereas no or only small attenuation of ultrasound can be expected through skin and chest, intensity will be significantly attenuate d if penetration of the skull is required. The transcranial penetration of ultrasound increases when the frequency is decreased to 20 kHz and may be t ransmitted through the skull transtemporally with tolerable attenuation up to 200 kHz. This results in. efficacy in vitro with low intensities of 0.5- 2.0 W/cm(2) systemic treatment with rtPA approved for a 3-hour window in th e nonfocused ultrasound field. Application of ultrasound insonation increas ed rtPA-mediated thrombolysis up to 20% in a static model; meanwhile, it en hanced the recanalization rate from 30%-90% in a flow model. In vitro resul ts suggest that I MHz ultrasound with 0.5 W/cm(2), established for diagnost ic purposes, may already enhance rtPA- mediated thrombolysis. Before therap eutic ultrasound can be tested clinically in acute stroke, safety of transc ranial exposure of the brain has to be confirmed. To date, animal experimen ts suggested no harm to the blood brain barrier or systemic healing with 2 W/cm(2). This combined treatment is one perspective in optimizing therapy i n acute stroke within the acute phase and may be applied easily with few li mitations.