A Dual-Frequency Intravascular Ultrasound Transducer for Amplified Nanodroplet Vaporization Effects in Cavitation-Enhanced Sonothrombolysis

Thromboembolism often leads to stroke, myocardial infarction, and other severe complications. There remains a need for new technologies for clinical thrombosis treatment. Sonothrombolysis mediated with cavitation-enhancing agents has shown promise in the treatment of thromboembolism in preclinical studies and clinical trials. Recent works have emphasized specifically efficient sonothrombolysis using phase-change nanodroplets, likely due to their generation of cavitation within the clot matrix. Yet, it has also been reported that nanodroplets might vaporize more effectively under high-frequency excitation and generate more cavitation with low-frequency excitation. Therefore, in this work, a dual-frequency (10 MHz/500 kHz) intravascular transducer intended for nanodroplet-specific sonothrombolysis was developed to improve clot mass reduction rate while retaining lower acoustic pressures than the typical nanodroplet vaporization threshold at sub-megahertz excitation (> 5 MPa). It results in a 34 % improvement of thrombolysis efficiency compared to a single low-frequency excitation.