Low frequency (<1 MHz) transducers for intravenous sonothrombolysis

Abstract

Venous embolism is a great challenge in the treatment of a wide range of diseases, including cardiovascular diseases and cancers. Ultrasound-mediated thrombolysis (sonothrombolysis) presents a promising treatment of venous embolism. In this paper, miniature ultrasound transducers with frequencies ranging from 250 kHz to 800 kHz were developed for microbubble/nanodroplet-mediated intravenous sonothrombolysis tests. Relative low frequency (e.g., <1 MHz) is preferred because of the findings that cavitation plays an important role in sonothrombolysis, and microbubble-associated cavitation events can be enhanced at low frequencies. Small aperture (e.g. <2 mm × 2 mm) low-frequency transducers are usually known with high electrical impedance (e.g., >1000 Ω), which is not preferred for efficient electromechanical transduction. To address this challenge, multilayer acoustic stacks were designed, fabricated, and characterized. The measured electrical impedance of these stacks is mostly closer to 50 Ω, and the peak negative pressure is higher than 1MPa. These small aperture transducers were then used in in vitro- thrombolysis tests with unretracted and retracted blood clots, showing promising lysis rates. Other techniques such as laser ultrasound transducers, vortex wave generation, and magnetic microbubbles were also investigated for thrombolysis tests.