Non-invasive opening of BBB by focused ultrasound.

Authors: Hynynen K, McDannold N, Vykhodtseva N, Jolesz FA

Blood brain barrier (BBB) is a major barrier for delivering therapeutic agents in the brain. In this study we investigated the feasibility of open the BBB by using focused ultrasound. Rabbit brains were exposed to pulsed focused ultrasound while injecting ultrasound contrast agent containg microbubbles intravenously. The BBB opening was measured after the sonications by injecting MRI contrast agent i.v. and evaluating the local enhancement in the brain. Low ultrasound powers and pressure amplitudes were found to cause focal enhancement. Before sacrificing the animals trypan blue was also injected i.v.. After the sacrifice of the animals blue spots were found in the brain in the sonicated locations. This method may have potential for targeted delivery of macromolecules in the brain.

Introduction

Purpose Drug delivery with BBB opening

Study Objective To non-invasively open the blood-brain barrier using focused ultrasound.

Animal model / Human subject rabbit, New Zealand White, not reported, not reported

Disease model healthy

Targeted brain region(s) Brain

Outcomes and Safety

Summary of Outcomes MRI-guided focused ultrasound successfully and non-invasively opened the blood-brain barrier in a rabbit model

Duration of biological effect not reported

Safety-related matter The procedure was monitored via MRI, and no significant gross tissue damage was observed at therapeutic pressures.

Brain Region

Ultrasound Parameters

Ultrasound instrument single-element focused ultrasound transducer

FUS Frequency 1.5 MHz

FUS Intensity not reported

FUS Pressure 0.7 MPa

FUS Mode not reported

Pulse duration 10 ms

Duration of a single FUS session 20 s

Mechanical index 0.5715476066494083

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