Ultrasound-induced blood clot dissolution without a thrombolytic drug is more effective with lower frequencies

Therapeutic ultrasound as stand-alone therapy or in combination with rt-PA has proven to be an effective measure for recanalisation of acute vessel occlusion in different in vitro and in vivo studies. Uncertainty still exists concerning the optimal frequency and intensity with regard to the thrombolytic efficacy of ultrasound. The purpose of this study was a direct comparison of different ultrasound frequencies, when otherwise using identical measurement settings and parameters.

Ultrasound-induced dissolution of fresh human blood clots was studied in a flow system using low-frequency continuous wave ultrasound of 20, 40 and 60 kHz. After calibration of each ultrasound probe, blood clots were exposed to local time average intensities of either 0.12 or 0.2 W/cm2. Exposure time of the clots to ultrasound was 10 min, the number of treated clots in each experimental group was 12.

As tested with 0.2 W/cm2, we found the most pronounced thrombolytic effect with the 20-kHz probe (weight loss of blood clots: 52.4%) and the 40-kHz probe (49.4%), as compared to the 60-kHz probe (21.4%) and the control group (18.5%). The difference between the 20- and 60-kHz probes was statistically significant (p < 0.001). The treatment effect was clearly intensity dependent with a less pronounced, but still significant treatment effect at 0.12 W/cm2 (24.5% at 20 kHz; p < 0.001 compared to 0.2 W/cm2; p = 0.045 compared to controls).

These data show that therapeutic efficacy of ultrasound, in absence of a thrombolytic drug, is frequency and intensity dependent with best results at low frequencies. With continuous wave transmission, the benefit may be limited to the very low frequency range. The results are a basis for further evaluation in animal models.