Ultrasound Imaging–Guided Noninvasive Ultrasound Thrombolysis

Abstract

Background —Catheter-based therapeutic ultrasound thrombolysis was recently shown to be effective and safe. The purpose of this work was to study the safety and efficacy of external high-intensity focused ultrasound thrombolysis guided by ultrasound imaging in experimental settings. Methods and Results —A therapeutic transducer was constructed from an acoustic lens and integrated with an ultrasound imaging transducer. In vitro clots were inserted into bovine arterial segments and sonicated under real-time ultrasound imaging guidance in a water tank. With pulsed-wave (PW) ultrasound, the total sonication time correlated with thrombolysis efficiency ( r 2 =0.7666). A thrombolysis efficiency of 91% was achieved with optimal PW parameters (1:25 duty cycle, 200-μs pulse length) at an intensity (I spta ) of >35±5 W/cm 2 . Ultrasound imaging during sonication showed the cavitation field as a spherical cloud of echo-dense material. Within <2 minutes, the vessel lumen evidenced neither residual clot nor damage to the arterial wall. On serial filtration, 93±1% of the lysed clot became subcapillary in size (<8 μm). In vitro safety studies, however, showed arterial damage when an I spta of 45 W/cm 2 was used for periods of ≥300 seconds. Conclusions —External high-intensity focused ultrasound thrombolysis using optimal PW parameters for periods of ≤300 seconds appears to be a safe and effective method to induce thrombolysis. The procedure can be guided by ultrasound imaging, thereby allowing the monitoring of therapy.