Influence of ultrasound operating parameters on ultrasound-induced thrombolysis in vitro

The effect of operating parameters on the thrombolytic potency of ultrasound (US) is important for potential therapeutic applications, but is not fully understood. Fresh human whole-blood thrombi were exposed in vitro to focused US from a diagnostic transducer driven by an impulse generator via an amplifier to vary duration (10 to 60 min), intensity (7 to 90 W/cm(2)), frequency (2 to 4.5 MHz), pulsed wave duty cycle (1:5 to 1:100 and continuous wave mode) and pulse length (100 to 400 micros). Segments of thrombi (498 +/- 73 mg) were submersed and insonated in saline solution. Thrombolytic efficiency was expressed as percentage loss of mass compared with controls (noninsonified thrombi). Ultrasound exposure achieved a significantly higher thrombolysis than no US, 56 +/- 16 % vs. 29 +/- 11 % (n = 232, p < 10(-6)). There was an exponential saturation-type correlation with duration of insonation (r(2) = 0.64) and intensity (r(2) = 0.97), an inverse correlation with US frequency at matched intensities (r(2) = 0.76, p < 10(-5)), a logarithmic relationship with duty cycle in pulsed mode (r(2) = 0.86) and a modest direct effect of pulse length (r(2) = 0.57, p < 10(-5)). Thus, thrombolytic efficiency of US depends directly on duration, intensity, duty cycle and pulse length and inversely, on frequency.