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

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

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.