Paul Mondou

Authors

Paul Mondou, Sebastien Meriaux, Florent Nageotte, Jonathan Vappou, Anthony Novell, Benoit Larrat

Journal

Physics in Medicine & Biology

Date

8 September 2023

Abstract Focused ultrasound (FUS) is a non-invasive and highly promising method for targeted and reversible blood-brain barrier permeabilization. Numerous preclinical studies aim to optimize the localized delivery of drugs using this method in rodents and non-human primates. Several clinical trials have been initiated to treat various brain diseases in humans using simultaneous BBB permeabilization and drug injection. This review presents the state of the art of in vitro and in vivo cavitation control algorithms for BBB permeabilization using microbubbles (MB) and FUS. Firstly, we describe the different cavitation states, their physical significance in terms of MB behavior and their translation into the spectral composition of the backscattered signal. Next, we report the different indexes calculated and used during the ultrasonic monitoring of cavitation. Finally, the different in vitro and in vivo cavitation control strategies described in the literature are presented and compared.

Authors

Paul Mondou, Gwenael Page, Corentin Cornu, Clementine Morisset, Elias Djaballah, Audrey Fayard, Sophie Lecourtois, Marion Gay, Maxime Roustan, Julien Flament, Alexandre Vignaud, Sebastien Meriaux, Qi Zhu, Romina Aron Badin, Anthony Novell, Benoit Larrat

Journal

Physics in Medicine & Biology

Date

10 June 2025

Abstract Objective. Temporary, non-invasive, and localized permeabilization of the blood–brain barrier (BBB) can be achieved through focused ultrasound and microbubbles (MB). This technique has been extensively employed in rodent and non-human primate (NHP) studies for testing various drugs but requires precise control of ultrasonic pressure. However, controlling cavitation in NHP is challenging due to their thicker skull inducing strong ultrasonic attenuation. Furthermore, extra-cranial cavitation may occur masking the cavitation signal at the focal region (cerebral cavitation). Particularly in larger male NHP, temporal muscles are highly perfused and filled with MB. Approach. This study proposes a feedback loop control strategy to distinguish between intra- and extra-cerebral cavitation by analyzing broadband noise recorded by passive cavitation detection sensors. Main results. The frequency-dependent low-pass filtering effect by the skull allows differentiation of distinct frequency components, providing insights into cavitation origin. The present study involved 17 BBB opening experiments in NHP. Significance. Although successful BBB disruption can be achieved in NHP with thin temporal muscles (<5 mm) using a regular feedback loop algorithm, NHP having thicker muscles (>15 mm) require the use of an optimized algorithm able to specifically extract the signature of intra-cerebral cavitation.

Authors

Celestine Angla, Hamza Chouh, Paul Mondou, Gwenael Toullelan, Kevyn Perlin, Emmanuel De Schlichting, Jean-Luc Gennisson, Benoit Larrat, Sylvain Chatillon

Journal

2023 IEEE International Ultrasonics Symposium (IUS)

Date

3 September 2023

Abstract Most transcranial ultrasound simulations are based on numerical methods which have a long computation time and high memory usage. The simulation algorithm developed in this study is based on a semi-analytical field computation method. Instead of the classic ray tracing, the ultrasonic paths are computed by time of flight minimization. This method requires a smooth and homogeneous skull model, which is obtained thanks to an homogenization method developed in a previous study "unpublished" [1] and a surface modeling called "Multi-level Bspline Approximation" [2]. The simulation algorithm was numerically validated, by comparison with other solvers [3], and experimentally validated by comparison with hydrophone measured pressure fields through an ex vivo human skull.

Authors

C Angla, H Chouh, P Mondou, G Toullelan, K Perlin, V Brulon, E De Schlichting, B Larrat, J-L Gennisson, S Chatillon

Journal

Physics in Medicine & Biology

Date

24 April 2024

Abstract Objective. To optimize and ensure the safety of ultrasound brain therapy, personalized transcranial ultrasound simulations are very useful. They allow to predict the pressure field, depending on the patient skull and probe position. Most transcranial ultrasound simulations are based on numerical methods which have a long computation time and a high memory usage. The goal of this study is to develop a new semi-analytical field computation method that combines realism and computation speed. Approach. Instead of the classic ray tracing, the ultrasonic paths are computed by time of flight minimization. Then the pressure field is computed using the pencil method. This method requires a smooth and homogeneous skull model. The simulation algorithm, so-called SplineBeam, was numerically validated, by comparison with existing solvers, and experimentally validated by comparison with hydrophone measured pressure fields through an ex vivo human skull. Main results. SplineBeam simulated pressure fields were close to the experimentally measured ones, with a focus position difference of the order of the positioning error and a maximum pressure difference lower than 6.02%. In addition, for those configurations, SplineBeam computation time was lower than another simulation software, k-Wave’s, by two orders of magnitude, thanks to its capacity to compute the field only at the focal spot. Significance. These results show the potential of this new method to compute fast and realistic transcranial pressure fields. The combination of this two assets makes it a promising tool for real time transcranial pressure field prediction during ultrasound brain therapy interventions.

Authors

Ounay Ishak, Elodie Breton, Paolo Cabras, Erik Dumont, Paul Mondou, Anthony Novell, Benoit Larrat, Jonathan Vappou

Journal

Physics in Medicine & Biology

Date

21 October 2024

Abstract Objective. Focused ultrasound (FUS) is a promising non-invasive therapeutic approach that can be used to generate thermal and non-thermal bioeffects. Several non-thermal FUS therapies rely on FUS-induced oscillations of microbubbles (MBs), a phenomenon referred to as cavitation. Cavitation monitoring in real time is essential to ensure both the efficacy and the safety of FUS therapies. This study aims to introduce a new magnetic resonance (MR) method for cavitation monitoring during FUS therapies. Approach. By finely synchronizing the FUS pulse with an accelerated turbo spin-echo MR sequence, the cavitation effect could be quantitatively estimated on the acquired images at 1-Hz refresh rate. The proposed method was assessed in vitro in a water bath. A series of FUS pulses were generated on a silicone tube filled with MBs at different acoustic pressures (0.07–2.07 MPa) and pulse durations (20–2000 μs). MR images and passive cavitation detection (PCD) signals were simultaneously acquired for each FUS pulse. Main results. Inertial cavitation was found to induce a quantitatively interpretable signal loss on the MR image. The transition from stable to inertial cavitation was identified on MR cavitation maps with high repeatability. These results were found to be in good agreement with PCD measurements in terms of pressure thresholds between stable and inertial cavitation. MR cavitation imaging was shown to be sensitive to short and even ultrashort FUS pulses, from 2 ms down to 20 μs. The presented theoretical model suggests that the signal loss in MR cavitation imaging relies on susceptibility changes related to the diameter of the oscillating MBs. Significance. The proposed MR cavitation imaging method can both locate and characterize cavitation activity. It has therefore the potential to improve the efficacy and safety of FUS therapies, particularly for localized drug delivery applications.