Key Technology Research On Microbubble-mediated Ultrasound Thrombolysis

Thrombosis is a common pathological symptom of a variety of clinical cardiovascular and cerebrovascular diseases.The venous valve insufficiency caused by thrombosis is possible to lead to ulceration and even disability of the lower extremities,in severe cases,it can lead to sudden death related to pulmonary embolism.Removal of blood clots can effectively prevent the deterioration of this condition.However,thrombolytic drugs are limited for application due to strict time windows and few applicable targets,as well as the risk of destructive cerebral hemorrhage.Ultrasound thrombolysis technology takes the advantage of ultrasound energy to improve the permeability of thrombolytic drugs in thrombus,thus enhancing the thrombolysis effect.With the assistance of microbubbles,the microstreaming and microjets generated by acoustic cavitation effect change the fibrin structure of thrombus,leading to further thrombolysis results of medications.In response to the problems of drug thrombolysis,an interventional ultrasound thrombolysis core wire was introduced in this study,which was designed and fabricated using a series of customized miniature transducers.Microbubbles were delivered to the ultrasound irradiation area through the bypass catheter,and thrombolysis dose-effect relationship was explored based on the core wire and catheter.After obtaining suitable ranges of ultrasound excitation parameters,an excitation system was designed using Zynq 7Z020 chip based on ARM+FPGA structure and peripheral circuit.This system generated adjustable pulse-modulated signal to drive the thrombolysis ultrasound core wire.The experimental results demonstrate that microbubbles can reduce the energy required by the ultrasound core wire achieving thrombolysis.Under the condition of 1.1 MHz,60 Vpp,5%duty cycle sinusoidal pulse waves and with the assistance of 10.67 μL/mL microbubbles,ultrasound core wire achieved a higher thrombolysis rate than urokinase alone therapy.Due to the limited effective acoustic field generated by the miniature transducer itself,the higher excitation amplitude and duty cycle did not cause cavitation of the diffused microbubbles deeper inside the thrombus,so it is preliminarily believed that 60 Vpp and 5%are the optimal thrombolysis excitation parameters under the current experiment setups.Under the guidance of the experimental results of ultrasound thrombolysis dose-effect relationship,the designed thrombolysis excitation system based on Zynq 7Z020 met the requirements of excitation range.Its capability to drive ultrasound core wire has been verified on the isolated thrombus models,which is instructive for generalizing interventional ultrasound thrombolysis technology in clinical application.