The Cavitation Properties And Real-Time Control Of The Flowing Microbubbles Under Physiologically Revant Conditions

Acoustic cavitation from ultrasound-driven microbubbles can induce diverse bio-effects which are useful in clinical therapy.However,lack of insights into the cavitation dynamics of flowing microbubbles and control over the dynamics result in unwanted treatment in the treatment region,which influences the therapeutic efficacy and bio-safety.In this study,we designed the experimental platform for cavitation treatment and measurement of the flowing microbubbles and analyzed the influence of the ultrasound pulse shape(peak negative pressures,pulse length and pulse repetition frequency)and the fluid velocity on the cavitation dynamics of flowing microbubbles.Based on the experimental platform,the system of the real-time control over the acoustics intensity was developed and used to control the inertial cavitation intensity of the flowing microbubbles.An in vitro physiological-flow phantom was fabricated,in which the flowing microbubbles had a constant velocity.A 1 MHz focused transducer was used to trigger the acoustic cavitation of microbubbles.The signals were passively detected by another 7.5 MHz plane transducer.From detailed time and frequency domain analysis,we found: 1)both the peak negative pressure(PNP)and pulse length(PL)determined the pressure threshold of the stable cavitation(SC)and the inertial cavitation(IC)when the pulse repetition frequency(PRF)was smaller than the critical PRF(CPRF).2)Under the CPRF,the PL had no influence on the stable cavitation dose(SCD);however,above the CPRF,the SCD was depended on the PL.At shorter PLs,there was no relationship between the SCD and the PLs;at longer PLs,the SCD was negative related with the PRF.For the static microbubbles,the SCD was positive related with the PRF regardless of the PL.3)Under the CPRF,the inertial cavitation dose(ICD)was not related with the PRF.However,increasing the PRF above the CPRF resulted in the decreasing ICD and non-uniform spatiotemporal distribution of the IC intensity.For the static microbubbles,increasing the PRF resulted in the increasing ICD and non-uniform temporal distribution.Based on above experimental results,the system of the real-time control over the acoustics intensity was developed to resolve the non-uniform spatiotemporal distribution problems.A peristaltic pump was applied to transport microbubbles into the focal volume of the focused transducer circularly.The acoustic cavitation signals were transferred to the computer in real-time to analysis the acoustic cavitation intensity.And the control algorithm adjusted the parameters of the excited ultrasound.We proposed proportional feedback control algorithm to control the IC intensity of the flowing microbubbles.The results indicated that the control algorithm was able to adjust the IC intensity to the target IC intensity and keep it stable.We also proposed three indexes(raise time,stable ratio and integrated degree)to evaluate the performance of the control algorithm.