Low-frequency, low-intensity ultrasound accelerates thrombolysis through the skull

Systemic thrombolysis of acute ischemic stroke with recombinant tissue plas minogen activator (rt-PA) has been established recently. Whereas the delay to and the rate of vessel recanalization are unknown, they are likely slowe r and smaller than for local application of rt-PA, This may contribute to t he small benefits of recovery reported and stimulate further investigations to improve clot lysis, Pilot studies indicate that continuous-wave low-fre quency ultrasound (US) can accelerate rt-PA-mediated recanalization of peri pheral thrombotic vessel occlusion, For the hypothesized therapeutical purp ose in stroke treatment, we measured the attenuation of ultrasound through the skull at different frequencies and intensities (33.3 and 71.4 kHz; 0.5 and 3.4 W/cm(2)), and investigated thrombolysis in vitro (n = 125 clots). A ttenuation was lowest by transtemporal insonation of 33.3 kHz, 0.1 dB (0.9) . Thrombolysis (artificial fibrin-rich clots) was significantly increased a fter 1 h (p < 0.025) and after 3 h (p < 0.01) for US treatment in combinati on with rt-PA vs. rt-PA alone. Results suggest that US increases rt-PA-medi ated thrombolysis through the skull and may improve benefits of thrombolyti c stroke treatment in vivo. (C) 1999 World Federation for Ultrasound in Med icine & Biology.