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
Abstract
Low-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.
Origin : Publication funded by an institution
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