Background: The main aim was to study the effects of ultrasound (US) alone, in combination with an US contrast agent (UCA), tissue plasminogen activator (tPA), or the combination of both upon blood clots. Methods: In order to learn about sonothrombolysis with diagnostic duplex US, a simplified in vitro test model, using human whole blood clots in Petri dishes, was established. Results: A total of 286 blood clots were analyzed. Improved sonothrombolysis due to insonation with diagnostic duplex US could be achieved, whether it was used alone or in combination with tPA. Although already described, a beneficial effect of UCA microbubbles on sonothrombolysis could not be confirmed due to the study design. Conclusion: Diagnostic duplex US improves thrombolysis significantly, even when it is used without tPA. To study the effect of UCA microbubbles on sonothrombolysis appropriately, any experimental design should provide continuous replenishment of microbubbles at the target site.

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