Dynamic Study of Tissue Penetration For MR Contrast Agents of Different Sizes Following Ultrasound Induced Blood Brain Barrier Disruption in Rodent Models

Benjamin Marty¹, Benoit Larrat¹, Caroline Robic², Mathieu Pernot³, Mickael Tanter³, Marc Port², Philippe Robert², Denis Le Bihan¹, Franck Lethimonnier¹, Sbastien Mriaux¹

Lately, many studies have shown the ability to disrupt transiently the Blood Brain Barrier using ultrasound sonication of intravascular microbubbles. However, BBB opening mechanism is not properly known, especially the maximum gap reachable in safe conditions. We used contrast agents of different size to study the closure mechanism of BBB and the maximum molecule size able to penetrate cerebral tissues. BBB opening was obtained in vivo for contrast agents of sizes up to 65nm and its closure exhibits a fast initial closure of largest gaps. Those findings are valuable information in the framework of high molecular weight drug delivery.