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

Abstract

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 • . 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. K E Y W O R D Sacoustic streaming, finite element modeling, incident angle, particle image velocimetry, ultrasound thrombolysis 5728

Enhanced thrombolytic effect induced by acoustic cavitation generated from nitrogen-doped annealed nanodiamond particles

“…Due to its potential to improve the drug efficiency and soften the surface of thrombus [15] , [44] , cavitation activity, especially the violent IC activity, is expected to become more controllable element in thrombolytic therapy to guarantee both clinical efficacy and safety. Fig.…”

“…The calcium chloride solution (Yuanye Bio-Technology Co., Ltd, China), bovine whole blood (Beibo Biology Inc., China) and bovine thrombin (MP Biomedicals Co., Ltd, USA) were used to prepare the thrombus. Urokinase (Macklin Biochemical Co., Ltd, China) was initiated by bovine plasma (Yuanye Bio-Technology Co., Ltd, China) [44] .…”

“…The blood clots were prepared following the protocols described in the previous work [44] . In brief, bovine whole blood, calcium chloride, and bovine thrombin were mixed in a thrombus container, and kept at 37 °C for 1 h. The samples were washed with PBS before used, and kept at room temperature within 3 h. These cylindrical clots were approximately 15 mm in length, with the average weight of 0.3955 ± 0.0493 g.…”

“…Each experimental group was repeated three times, resulting in a total of 18 valid clot samples used for analysis. The clot weight was measured before and after ultrasound treatment for further assessment [44] , and the lysis ratio L was calculated by: where M represents weight, subscript 1 and 2 refer to the condition that before or after treatment.…”

Enhanced Thrombolytic Effect Induced by Acoustic Cavitation Generated from Nitrogen-Doped Annealed Nanodiamond Particles

“…Each experimental group was repeated three times, resulting in a total of 18 valid clot samples used for analysis. The clot weight was measured before and after ultrasound treatment for further assessment [44], and the lysis ratio L was calculated by:…”