Optimized acoustic streaming generated at oblique incident angles to improve ultrasound thrombolysis effect

Background Combined with thrombolytic drugs and/or microbubbles, ultrasound (US) has been regarded as a useful tool for thrombolysis treatment by taking its advantages of noninvasive, non-ionization, low cost, and accurate targeting of tissues deep in body. Recently, low-intensity pulsed US, which can cause fewer complications by stable cavitation and acoustic streaming other than more violent effects, has attracted broad attention. Purpose However, the thrombolysis effect in practice might not achieve expectation because there is not an ideal parallel multilayered structure between the skin and the targeted vessel. Therefore, the current work aims to better elucidate the influence of US incident angle on the generation of acoustic streaming and thrombolysis effect. Methods Systemic numerical and experimental studies, namely, finite element modeling (FEM), particle image velocimetry (PIV), and in vitro thrombolysis measurements, were performed to estimate the acoustical/streaming field pattern, maximum flow velocity, and shear stress on the surface of thrombus, as well as the lysis rate generated at different conditions. These methods aim at verifying the hypothesis that streaming-induced vortices can further accelerate the dissolution of the thrombus and optimized thrombolysis effected can be achieved by adjusting US incident angles. Results The pool data results showed that the variation trends of the flow velocity and shear stress obtained from FEM simulation and PIV experiments are qualitatively consistent with each other. There exists an optimal incident angle that can maximize the flow velocity and shear stress on the surface of thrombus, so that superior stirring and mixing effect can be generated. Furthermore, as the flow velocity and shear stress on thrombus surface are both highly correlated with the thrombolysis effect (the correlation coefficient R1 = 0.988, R2 = 0.958, respectively), the peak value of lysis rate (increase by at least 5.02%) also occurred at 10 degrees. Conclusions The current results demonstrated that, with appropriately determined incident angle, higher thrombolysis rate could be achieved without increasing the driving pressure. It may shed the light on future US thrombolysis planning strategy that, if combined with other advanced technologies (e.g., machine-learning-based image analysis and image-guided adaptive US emission modulation), more efficient thrombolytic effect could be realized while minimizing undesired side-effects caused by excessively high pressure.