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Abstract #0555

In Vivo Study of the Dynamics of Blood Brain Barrier Opening & Closure After Ultrasonic Disruption. a Quantitative Analysis

SUMMA25Benjamin Marty1, Benoit Larrat2, Mathieu Pernot2, Philippe Robert3, Marc Port3, Caroline Robic3, Denis Le Bihan1, Franck Lethimonnier1, Mickael Tanter2, Sbastien Mriaux1

1CEA/DSV/I2BM/NeuroSpin, Gif sur Yvette, France; 2Institut Langevin/ESPCI ParisTech/INSERM U979, Paris, France; 3Research Division, Guerbet, Aulnay sous Bois, France

Lately, many studies have shown the ability to disrupt locally and transiently the Blood Brain Barrier with low power ultrasound sonication of intravascular microbubbles. Here, we used contrast agents of different diameters to estimate the maximum molecule size able to penetrate cerebral tissues and T1 mapping to quantitatively study and model the closure mechanism of BBB after opening. From experimental data and BBB closure modeling, we obtained a calibration curve predicting half closure time as a function of contrast agent size. Those findings are valuable information to control precisely the amount of drug delivered across the BBB after systemic injection.

Keywords

able acoustic adjusted agent agents amount anesthesia animals around assumed background barrier blood brain bursts calibration cells cerebral characteristic chelate circulation close closure combined concentration conditions contrast control crossing dashed decade defined delimited delivered dependent derived describing detection developed deviation diameter disruption distribution division drug duration dynamics enables endothelial ensure equation equilibrium exhibiting experimental expressed findings fitted five fluid focal focused framework frequency friction function gadolinium gaps half harmonic heads highest highly hours hydrodynamic hypotheses in vivo individual induced initial injected injection inside installed intravenous invasive known larger largest limited lipid magnet mapping match mathematical mechanism model modeling molecular molecule negative numerical opened opening optimized oxides particle peak penetrate permeability pore port position power precisely predicting pressure prior procedure progressive promising properly quantification quantify quantitative radiation rats reduced release return reversible rodents safe segments sensitive shaved solution sous space square strategy strongly suggest suggesting systemic theoretical tissues transducer transient typical ultrasonic ultrasound valuable