Development and validation of a motorized focused ultrasound system for the controlled delivery of large molecules to the rodent brain under 7T MRI guidance

Congrès sous l’égide de la Société Française de Génie Biologique et Médical (SFGBM)National audienceThe use of focused ultrasound combined with microbubbles has shown the capability to increase the permeability of the Blood Brain Barrier (BBB) locally, transiently and non-invasively, allowing the delivery of large molecules to the brain. Magnetic Resonance Imaging is of great interest to precisely monitor the disruption. In this study, we have shown the possibility to use our motorized system to open the BBB along arbitrary trajectories under 7T MRI guidance and to test different acoustic conditions on a single animal

A new 3MW ECRH system at 105 GHz for WEST

The aim of the WEST experiments is to master long plasma pulses (1000s) and expose ITER-like tungsten wall to deposited heat fluxes up to 10 MW/m$^2$. To increase the margin to reach the H-Mode and to control W-impurities in the plasma, the installation of an upgraded ECRH heating system, with a gyrotron performance of 1MW/1000s per unit, is planned in 2023. With the modifications of Tore Supra to WEST, simulations at a magnetic field B$_0$∼3.7T and a central density n$_{e0}$∼6 × 10$^{19}$ m$^{−3}$ show that the optimal frequency for central absorption is 105 GHz. For this purpose, a 105 GHz/1MW gyrotron (TH1511) has been designed at KIT in 2021, based on the technological design of the 140 GHz/1.5 MW (TH1507U) gyrotron for W7-X. Currently, three units are under fabrication at THALES. In the first phase of the project, some of the previous Tore Supra Electron Cyclotron (EC) system components will be re-installed and re-used whenever possible. This paper describes the studies performed to adapt the new ECRH system to 105 GHz and the status of the modifications necessary to re-start the system with a challenging schedule

Comparative developmental profile of the neuropeptide Y Y1 receptor gene and protein in the rat brain

NRC publication: Ye

Magnetic resonance-guided motorized transcranial ultrasound system for blood-brain barrier permeabilization along arbitrary trajectories in rodents

International audienceBackground: Focused ultrasound combined with microbubble injection is capable of locally and transiently enhancing the permeability of the blood-brain barrier (BBB). Magnetic resonance imaging (MRI) guidance enables to plan, monitor, and characterize the BBB disruption. Being able to precisely and remotely control the permeabilization location is of great interest to perform reproducible drug delivery protocols. Methods: In this study, we developed an MR-guided motorized focused ultrasound (FUS) system allowing the transducer displacement within preclinical MRI scanners, coupled with real-time transfer and reconstruction of MRI images, to help ultrasound guidance. Capabilities of this new device to deliver large molecules to the brain on either single locations or along arbitrary trajectories were characterized in vivo on healthy rats and mice using 1.5 MHz ultrasound sonications combined with microbubble injection. The efficacy of BBB permeabilization was assessed by injecting a gadolinium-based MR contrast agent that does not cross the intact BBB. Results: The compact motorized FUS system developed in this work fits into the 9-cm inner diameter of the gradient insert installed on our 7-T preclinical MRI scanners. MR images acquired after contrast agent injection confirmed that this device can be used to enhance BBB permeability along remotely controlled spatial trajectories of the FUS beam in both rats and mice. The two-axis motor stage enables reaching any region of interest in the rodent brain. The positioning error when targeting the same anatomical location on different animals was estimated to be smaller than 0.5 mm. Finally, this device was demonstrated to be useful for testing BBB opening at various acoustic pressures (0.2, 0.4, 0.7, and 0.9 MPa) in the same animal and during one single ultrasound session

Empirical and Theoretical Characterization of the Diffusion Process of Different Gadolinium-Based Nanoparticles within the Brain Tissue after Ultrasound-Induced Permeabilization of the Blood-Brain Barrier

International audienceLow-intensity focused ultrasound (FUS), combined with microbubbles, is able to locally, and noninvasively, open the blood-brain barrier (BBB), allowing nanoparticles to enter the brain. We present here a study on the di usion process of gadolinium-based MRI contrast agents within the brain extracellular space after ultrasound-induced BBB permeabilization. ree compounds were tested (MultiHance, Gadovist, and Dotarem). We characterized their di usion through in vivo experimental tests supported by theoretical models. Speci cally, by estimation of the free di usion coe cients from in vitro studies and of apparent di usion coe cients from in vivo experiments, we have assessed tortuosity in the right striatum of 9 Sprague Dawley rats through a model correctly describing both vascular permeability as a function of time and di usion processes occurring in the brain tissue. is model takes into account acoustic pressure, particle size, blood pharmacokinetics, and di usion rates. Our model is able to fully predict the result of a FUS-induced BBB opening experiment at long space and time scales. Recovered values of tortuosity are in agreement with the literature and demonstrate that our improved model allows us to assess that the chosen permeabilization protocol preserves the integrity of the brain tissue

Characterization of the diffusion process of different Gadolinium-based nanoparticles within the brain tissue after ultrasound induced Blood-Brain Barrier permeabilization

International audienceWe present here a new method to study the diffusion process of Gadolinium-based MRI Contrast Agents within the brain extracellular space after ultrasound-induced Blood-Brain Barrier permeabilization. Four compounds were tested (MultiHance, Gadovist, Dotarem and AGuIX). By estimating the Free Diffusion Coefficients from in vitro studies, and the Apparent Diffusion Coefficients from in vivo experiments, an evaluation of the tortuosity (λ) in the right striatum of 11 Sprague-Dawley rats has been performed. The values of λ are in agreement with literature and demonstrate that the chosen permeabilization protocol maintains the integrity of brain tissue