Application of low-frequency ultrasound for clot disruption has been suggested as a potential therapy to enhance thrombus dissolution, but the optimal mode for delivery of ultrasound with clot-disruptive properties has not yet been extensively explored. Target-specific effects are desirable and may be accomplished by focusing the ultrasound. Adequate focusing, however, requires a short wavelength. The aim of this study was to compare the clot-disruptive effects of different modalities of focused acoustic energy. An in vitro model (10 blood clots for each modality) was used to test the clot-disruptive capacity of (i) shock waves generated in an electrohydraulic lithotriptor; (ii) focused continuous ultrasound of frequency 1.1 MHz, delivered from a specially constructed piezoelectric transducer; and (iii) focused pulse-modulated ultrasound of frequency 1.1 MHz delivered from the same transducer. Exposure to 30 s of focused pulse-modulated ultrasound caused a marked reduction (99±2%) in clot weight compared with 30 shock waves (11±5%) or 30 s exposure to focused continuous wave ultrasound (11±6%) (P< 0.0001). The observed marked and rapid disruptive effect on blood clots of focused high-frequency ultrasound indicates an alternative approach for external ultrasound-mediated thrombus destruction in vivo. The focused pulse-modulated technique has potential to exhibit the desired effect in a well-defined target volume and provides the means for control of the average power.

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