Abstract 10694: Optimal Frequency and Acoustic Pressure for Sonothrombolysis with Microbubbles in a Flow System: Clinical Implications

Abstract

BACKGROUND: Ultrasound exposure of microbubble (MB) contrast agents has been shown to lyse thrombus, yet characterization of the effect of acoustic pressure (AP) and frequency is incomplete. Our aim was to quantify the determinants of sonothrombolysis with MBs.

METHODS: Cylindrical porcine clots (1.3 cm diameter) from whole blood were created with a central lumen (2 mm) for infusion of lipid-shelled perfluorocarbon MB (1x10⁷ mL^-1). The central portion of the clot was positioned at the focus of a therapeutic transducer (frequency 0.04, 0.25 or 1.01 MHz) at a wide range of peak negative AP (PNAP). Clots were treated for 20 minutes with pulsed ultrasound at 0.3% duty cycle with grouped in on-off cycles to allow complete replenishment of MBs. A linear-array imaging transducer (7 MHz) was used to measure the location and dimension of clot invagination produced by sonothrombolysis. A broadband passive cavitation detector was used to monitor acoustic activity.

RESULTS: Clot lysis did not occur at 0.04 MHz despite the presence of inertial cavitation. At 0.25 and 1.05 MHz, there was incremental clot lysis which was related to AP and, for any given AP, was greater for 1.05 MHz. Clot lysis was seen at PNAP ≥0.5 MPa. At 0.25 MHz there was both stable and inertial cavitation and clot lysis was located in the far wall which visually was due to primary radiation forces on the MBs. At 1.05 MHz, inertial cavitation was dominant and there was a transition of clot lysis from near to far wall as AP was increased.

CONCLUSION: At the frequencies tested, sonothrombolysis with MBs was most efficient at 1.05 MHz rather than at lower frequencies. The spatial location of sonthrombolysis varies with power and frequency which likely is determined by the degree of inertial cavitation (microbubble destruction) and radiation forces. These data provide important guidance for optimizing clinical devices to be used for sonothrombolysis in patients.