Inertial cavitation detection during in-vitro sonothrombolysis

Background Cardiovascular diseases are the leading cause of death worldwide; a prompt intervention is needed to restore blood flow. Sonothrombolysis with or without addiction of thrombolytic drugs seems to be a promising solution, thanks to the non-invasiveness, precision and quickness of its action. Mechanical effects, rather than thermal, are employed. Even if the mechanisms involved are not completely understood, acoustic cavitation is credited to play a significant role. Materials and Methods An experimental setup to detect acoustic cavitation during in-vitro sonothrombolysis tests has been developed. A Passive Cavitation Detector (PCD), able to record pressure fluctuation of oscillating bubbles, is mounted confocally to a 1MHz focused ultrasound transducer. Confocality has been verified by a 0.2mm needle hydrophone to map the pressure fields of both devices. A LDPE tube containing the thrombus is placed at the foci thanks to a 3 axis positioning frame. A constant flow of 2ml/min is established. To detect inertial cavitation (broadband emission with an increase in white noise) , the original signal from the PCD has been filtered analogically at 5MHz in order to remove harmonic frequencies which could saturate the acquisition system. Results In-vitro sonothrombolysis tests have been carried out on human blood clots. Clots were exposed for two minutes to an acoustic field of 65W (focal length 25mm, focal diameter 3mm), with pulse length of 450μs and a duty cycle of 1:10. Acquisition of PCD signal was synchronized with the burst; two windows per second at a sampling frequency of 40MHz were acquired. Power spectral density was calculated in the 5-12MHz band, with digital notch filters at the super-harmonic frequencies, in order to quantify the cavitation dose. Figure on the left shows the results of two tests with the same acoustic parameters. Blue line refers to a test in which there was no evidence of thrombolysis. When complete thrombus disruption took place a temporal correlation between thrombolysis inception and the increment of white noise can be observed (red line). Conclusion The proposed setup demonstrated the ability to detect inertial cavitation while performing in-vitro sonothrombolysis tests; a correlation between thrombolysis inception and increment of white noise was found. Statistically significant analysis will be performed in order to verify this correlation, thus allowing the optimization of sonothrombolysis parameters and protocols in order to enhance cavitational effects.