Cavitation detection during ultrasound-assisted thrombolysis in porcine blood clots

Abstract

Substantial enhancement of recombinant tissue plasminogen activator (rt-PA) mediated thrombolysis can be achieved with exposure of a thrombus to pulsed ultrasound. However, the mechanism of this interaction has not yet been elucidated. In this work cavitation is investigated as a possible mechanism for enhancement in 120-kHz pulsed ultrasound-assisted thrombolysis. Porcine blood clots were immersed in plasma as control and exposed to rt-PA, ultrasound (0.35 MPa, 80% duty cycle, 1667 Hz pulse repetition frequency), or a combination of rt-PA and ultrasound. A confocally aligned active and passive cavitation detection system was employed to detect subharmonic emissions from stable cavitation and broadband superharmonic emissions from inertial cavitation. After exposure, clot mass loss was determined, and clots were subjected to immunohistochemical analysis of fibrin degradation. Spatial investigation of cavitation thresholds inside the clot, on the clot surface, and in the fluid surrounding the clot showed the threshold to be lowest on the clot surface. Stable cavitation was detected in clots exposed to ultrasound alone and a combination of rt-PA and ultrasound. Curiously, inertial cavitation was detected only in samples containing rt-PA. The presence of both stable and inertial cavitation correlated with increased clot mass loss and a distinct pattern of fibrin degradation on histologic evaluation.