Extracorporeal ThromboLysis using multifrequency Ultrasound – ULysSE

The efficiency of ultrasound thrombolysis is directly related to ultrasonic cavitation, which is the violent collapse of micrometric gas bubbles generated by an ultrasonic wave of sufficient amplitude. The project aims to implement methods to stimulate the cavitation activity, while monitoring it in real-time conditions, in order to gain in terms of efficiency as well as in terms of selectivity of the method.

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Cardiovascular diseases are one of the leading causes of death worldwide. In 2008, myocardial infarction and stroke alone represented a quarter of the number of deaths worldwide.
Current methods of treatment for thrombosis, despite great progress during past two decades, still present important shortcomings: interventional techniques (thrombectomy, bypass) are invasive procedures and require specialized technical facilities and experienced staff; alternative techniques use thrombolytic agents that lead to a chemical lysis of the thrombus, but still present a high risk of severe bleeding. In all cases, quick treatment and recanalization of occluded areas is a key point for successful treatment. This is a difficult point for both types of treatment since thrombolytic agents have a slow action, while the availability of a suitable technical platform and specialized staff can cause significant delays.

The use of focused ultrasound on an occlusive thrombus could offer an interesting alternative that would allow a rapid, noninvasive and cost-effective treatment of some acute ischemic diseases. However this method, proposed since the 1990s, relies on ultrasonic cavitation which refers to the extremely violent collapse of gas bubbles generated by the presence of an ultrasonic wave of sufficient intensity. This phenomenon is particularly difficult to control, and the method is still hampered by a lack of selectivity and by the potential to generate collateral damage in surrounding healthy tissue.
The ULysSE project is based on the use of multifrequency ultrasonic excitations recently studied and that are able to stimulate the activity of cavitation locally with reduced intensities. This should lead to better preservation of healthy tissue surrounding the clot in order to develop a device for extracorporeal ultrasound thrombolysis.

For that purpose, the project lies on an interdisciplinary team consisting of specialists of ultrasonic waves and cavitation, and of medical practitioners specialized in imaging and treatment of vascular disease. The wide scientific spectrum of the team will enable to work both on fundamental aspects of the stimulation of the cavitation activity to improve the effectiveness of the technique, and on in vitro and in vivo experimentation to quickly test the therapeutic potential of the method, especially for acute ischemia of lower limbs. The fundamental approach will couple mainly numerical and experimental methods to study the mechanisms of stimulation of cavitation activity by multifrequency excitations. The objective here is to improve thrombolytic efficacy while minimizing the risk of collateral damage. The experimental in vitro stage will aim at determining the optimal parameters for treatment combining a good efficacy in thrombolysis with the absence of damage to surrounding healthy tissue. Finally, the in vivo experimentation stage should help to validate a device for extracorporeal thrombolysis for acute ischemia of lower limbs, even if the benefits of the project will involve a greater number of cardiovascular pathologies (recanalization of prosthetic bypass, venous thrombosis etc..).