Guided longer pulses from a diagnostic ultrasound and intraclot microbubble enhanced catheter-directed thrombolysis in vivo

The mechanism of ultrasound thrombolysis (UT) is generally attributed to cavitation. The insufficiency of microbubbles (MB) to serve as cavitation nuclei in the vessel-obstructing thrombi significantly reduces the effectiveness of UT. Taking advantage of the widely performed catheter-directed therapy (CDT), in a thrombo-embolized rabbit IVC model with a simultaneous catheter directed rt-PA thrombolysis procedure, guided moderate mechanical index longer pulses from a modified diagnostic ultrasound transducer, combined with an intraclot infusion of MB, significantly accelerated the thrombolysis process. The higher thrombolysis efficacy score and consistent elevated post-treatment plasma concentration level of D-Dimer, a product of fibrinolysis, both indicated the superiority of CDT + UT over CDT/UT alone. Pathologic examination of the treated occluded IVC segments revealed an almost complete dissolution of the thrombi treated with CDT + UT. There was no evidences of thrombo-embolism or local thrombus formation in the cardiac-pulmonary vessels. Combined with intraclot infusion of MB, guided longer pulse ultrasound from a diagnostic transducer is able to safely and significantly improve a catheter-directed thrombolysis procedure. It thus has the potential to achieve earlier clot removal, administration of a lower dosage of thrombolytic agent and, consequently, a lower incidence of thrombolysis-related side effects.