Thérapies ultrasonores cardiaques guidées par élastographie et échographie ultrarapides

Atrial fibrillation (AF) affects 2-3% of the European and North-American population, whereas ventricular tachyarrhythmia (VT) is related to an important risk of sudden death. AF and VT originate from dysfunctional electrical activity in cardiac tissues. Minimally-invasive approaches such as Radio-Frequency Catheter Ablation (RFCA) have revolutionized the treatment of these diseases; however the success rate of RFCA is currently limited by the lack of monitoring techniques to precisely control the extent of thermally ablated tissue.The aim of this thesis is to propose novel ultrasound-based approaches for minimally invasive cardiac ablation under guidance of ultrasound imaging. For this, first, we validated the accuracy and clinical viability of Shear-Wave Elastography (SWE) as a real-time quantitative imaging modality for thermal ablation monitoring in vivo. Second we implemented SWE on an intracardiac transducer and validated the feasibility of evaluating thermal ablation in vitro and in vivo on beating hearts of a large animal model. Third, a dual-mode intracardiac transducer was developed to perform both ultrasound therapy and imaging with the same elements, on the same device. SWE-controlled High-Intensity-Focused-Ultrasound thermal lesions were successfully performed in vivo in the atria and the ventricles of a large animal model. At last, SWE was implemented on a transesophageal ultrasound imaging and therapy device and the feasibility of transesophageal approach was demonstrated in vitro and in vivo. These novel approaches may lead to new clinical devices for a safer and controlled treatment of a wide variety of cardiac arrhythmias and diseases.La fibrillation atriale affecte 2-3% des européens et nord-américains, les tachycardies ventriculaires sont liées à un risque important de mort subite. Les approches minimalement invasives comme l’Ablation par Cathéter Radiofréquence (RFCA) ont révolutionné le traitement de ces maladies, mais le taux de réussite de la RFCA est limité par le manque de techniques d’imagerie pour contrôler cette ablation thermique.Le but de cette thèse est de proposer de nouvelles approches ultrasonores pour des traitements cardiaques minimalement invasifs guidés par échographie.Pour cela nous avons d’abord validé la précision et la viabilité clinique de l’Élastographie par Ondes de Cisaillement (SWE) en tant que modalité d’imagerie quantitative et temps réel pour l’ablation thermique in vivo. Ensuite nous avons implémenté la SWE sur un transducteur intracardiaque et validé la faisabilité d’évaluer l’ablation thermique in vitro et in vivo sur cœur battant de gros animal. Puis nous avons développé un transducteur intracardiaque dual-mode pour effectuer l’ablation et l’imagerie ultrasonores avec les mêmes éléments, sur le même dispositif. Les lésions thermiques induites par Ultrasons Focalisés de Haute Intensité (HIFU) et contrôlées par la SWE ont été réalisées avec succès in vivo dans les oreillettes et les ventricules chez le gros animal. Finalement la SWE a été implémentée sur un dispositif d’imagerie et thérapie ultrasonores transœsophagien et la faisabilité de cette approche a été démontrée in vitro et in vivo. Ces approches originales pourraient conduire à de nouveaux dispositifs cliniques pour des traitements plus sûrs et contrôlés d’un large éventail d’arythmies et maladies cardiaques

0059 : Non invasive ultrasonic chordal cutting

ObjectiveChordal cutting targeting leaflet tethering has been described to improve the efficiency of annuloplasty during ischemic mitral regurgitation surgery. Histotripsy is an ultrasound based technique for tissue fragmentation through the cavitation generated by a very intense ultrasonic pulse. In this study we investigate the feasibility of using histotripsy for chordal cutting to avoid cardiopulmonary bypass and invasive surgery in infarcted heart.MethodsExperiments were performed in vitro in explanted sheep heart (N=10) and in vivo in sheep beating heart (N=5, 40+/-4kg). In vitro, the mitral valve basal chordae was removed, fixed on a holder in a water tank. The ultrasound pulses were emitted from the therapeutic device (1- MHz focused transducer, pulses of 8μs duration, peak negative pressure of 17 MPa, repetition frequency of 100Hz) placed at a distance of 64mm. In vivo, we performed sternotomy and the device was applied on the thorax cavity which was filled out with water. We analysed MV coaptation and chordae by real time 3D echocardiography. The animals were sacrificed at the end of the procedure, for postmortem anatomical exploration of the heart.ResultsIn vitro, all the basal chordae were completely cut. The mean procedure time was 5.5 (+/-1.7) minutes. The diameter of the chordae was the main criteria affecting the duration of procedure. In the sheep, central basal chordae of anterior leaflet were completely cut. The mean procedure time was 22 (+/-9) minutes. By echography, the sectioned chordae was visible and no mitral valve prolapse was found. All the postmortem anatomical exploration of hearts confirmed the section of the basal chordea. No additional lesions were objectified.ConclusionsNoninvasive ultrasound histotripsy succeed to cut mitral valve basal chordae in vitro and in vivo in beating heart. If positive, this will open the door of completely noninvasive technique for MV repair especially in case of ischemic or functional MR

Hansen solubility parameters obtained via molecular dynamics simulations as a route to predict siloxane surfactant adsorption

Hypothesis: The Hansen Solubility Parameters (HSP) derived from Molecular Dynamics (MD) simulations can be used as a fast approach to predict surfactants adsorption on a solid surface. Experiments and simulations: We focused on the specific case of siloxane-based surfactants adsorption on silicon oxide surface (SiO2), encountered in inkjet printing processes. A simplified atomistic model of the SiO2 surface was designed to enable the computation of its solubility parameter using MD, and to subsequently determine the interactions of the SiO2 surface with the siloxane-based surfactant and the various solvents employed. Surfactant adsorption was characterized experimentally using contact angle goniometry, ellipsometry, XPS and AFM. Findings: Comparison of the numerical results with experiments showed that the HSP theory allows to identify the range of solvents that are likely to prevent surfactant adsorption on the SiO2 surface. The proposed approach indicates that polar solvents, such as acetone and triacetin, which are strongly attracted to the silicon oxide surface might form a shield that prevents siloxane-based surfactants adsorption. This simple approach, can guide the selection of adequate solvents for surfaces and surfactants with specific chemical structures, providing opportunities for controlling interfacial adsorption

Pulsed Cavitational Ultrasound Softening: a new non-invasive therapeutic approach of calcified bioprosthetic valve stenosis 2 Brief Title: Non-invasive ultrasound therapy of calcified bioprosthesis 3 4

International audienceBackground. The majority of prosthetic heart valves currently implanted are tissue valves that can be expected to calcify with time and eventually fail. Surgical or percutaneous redux valve replacement is associated with higher rate of complications. We propose a novel non-invasive therapeutic approach based on the use of pulsed cavitational ultrasound (PCU) to improve the valvular function of degenerative calcified bioprosthesis.Objectives. Our study aims to demonstrate in vitro and in vivo on an ovine model that PCU can significantly improve the bioprosthesis opening by softening remotely the calcified stiff cusps.Methods. All the experiments were performed on calcified bioprosthetic valves explanted from human patients. PCU was performed in vitro on calcified bioprosthesis mounted on a hydraulic bench with pulsatile flow (n=8) and in vivo on an ovine model with implanted calcified bioprosthesis (n=7). We used 3D echocardiography, pressure and flow sensors, quantitative stiffness evaluation using shear wave elastography, micro-CT imaging and histology to evaluate in vitro and in vivo the effect of PCU.Results. The transvalvular gradient was found to decrease by a mean of 50% after PCU in both in vitro (from 21.1±3.9 to 9.6±1.7 mmHg, p<0.01) and in vivo setup (from 16.2±3.2 to 8.2±1.3 mmHg, p<0.01), with a decrease of valve stiffness (in vitro: from 105.8±9 to 46.6±4 kPa, p<0.01; in vivo: from 82.6±10 to 41.7±7 kPa, p<0.01) and an increase of valve area (from 1.10±0.1 to 1.58±0.1 cm2, p<0.01). Histology and micro-CT imaging showed modifications of calcification structure without loss of calcification volume or alteration of the leaflet superficial structures. Conclusions. We have demonstrated in vitro and in vivo that PCU can decrease a calcified bioprosthesis stenosis by softening the leaflets remotely. This new non-invasive approach has the potential to improve the outcome of patients with severe bioprosthesis stenosis

Pulsed Cavitational Ultrasound Softening

The authors propose a novel noninvasive therapeutic approach for degenerative calcified bioprosthetic heart valves based on pulsed cavitational ultrasound (PCU) to improve the valvular function by remotely softening calcified stiff cusps. This study aims to demonstrate both in vivo, using an ovine model with implanted human calcified bioprosthesis, and in vitro that PCU can significantly improve the bioprosthesis function. A 50% decrease of the transvalvular gradient was found, demonstrating a strong improvement of the valve opening function. This new noninvasive approach has the potential to improve the outcomes of patients with severe bioprosthesis stenosis