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New echocardiographic imaging modalities for guiding and monitoring of therapy by focused ultrasound of calcified aortic stenosis

Abstract : Pulsed cavitational ultrasound therapy (PCUT) is an effective non-invasive therapeutic approach in various medical indications that relies on the mechanical effects generated by inertial cavitation bubbles in a controlled focal area. It’s characterized by a short-pulse high intense focused ultrasound emission with no heating effects. This technology, developed in the 2000’s, remains however very recent and there is a need to develop new imaging modalities for the guiding and the monitoring of the procedure. In fact, the B-Mode visualization of the bubble cloud is often limited in deep organs such as the liver and the heart and remains qualitative for the operator. Moreover, inertial cavitation remains a three-dimensional phenomenon which awakens the need for a three-dimensional imaging tool development, as for safety reasons it’s essential to be able to precisely place the therapeutic focal spot on the target zone. At this date, there are no international standards for PCUT.PCUT has been proved to be an effective solution for the calcified aortic stenosis (CAS) treatment, and Cardiawave, in partnership with Physics for Medicine Paris and the European Hospital Georges Pompidou, is developing an approach which consists in repairing the aortic valve, not replacing it. No surgery is required, and it could represent an alternative and a complementary solution to current surgical interventions.The present work explores different tools for the guidance and monitoring of the PCUT treatment of CAS.First, a new modality for the cavitation cloud imaging based on a passive coherent acquisition combined with a spatiotemporal filter was developed, adapted to cardiac applications and easily transposable to commercial ultrasound devices. The modality takes advantage of the short-pulses of PCUT, and by knowing the absolute time delays it allows a “pulse-echo” coherent beamforming of the therapeutic ultrasonic field. The modality was first tested in 2D, in vitro and in vivo, then transposed to 3D.Secondly, we developed safety tools to ensure the guiding and the monitoring of the therapy. As cavitation is a three-dimensional phenomenon, following Cardiawave’s device design it was necessary to ensure the sharp positioning of the therapeutic focal spot. A new cardiac probe was designed for the project. B-Mode and bi-plane ultrafast acquisitions were developed and tested. A specific beamforming allowing a sufficient frame rate and adapted to the mechanical specifications of the probe was also set up based on theory and simulations.Simultaneously, PCUT is presented as a potential solution to treat venous thrombosis by creating a channel for blood on the thrombus, using cavitation. We proposed the design of a new therapy transducer adapted to this pathology and allowing to focus high intensity ultrasound at different depths. The design was optimized using simulations. Finally, we integrated the whole robotically assisted PCUT system for the therapy allowing cavitation monitoring and an easy positioning of the target, hopefully easily transposable to clinics.
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Daniel Suarez Escudero. New echocardiographic imaging modalities for guiding and monitoring of therapy by focused ultrasound of calcified aortic stenosis. Physics [physics]. Université Paris sciences et lettres, 2019. English. ⟨NNT : 2019PSLET015⟩. ⟨tel-02946265⟩

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