Noninvasive MR Imaging–guided Focal Opening of the Blood-Brain Barrier in Rabbits

TLDR

The study aimed to determine whether focused ultrasound can locally open the blood‑brain barrier without damaging surrounding tissue and whether MR imaging can monitor this process. Eighteen rabbits received pulsed focused ultrasound at 0.2–11.5 W in 4–6 brain sites while receiving an intravenous ultrasound contrast agent; fast or spoiled gradient‑echo MR images were acquired during sonication to monitor temperature and tissue changes, and contrast‑enhanced MR images were taken minutes and up to 48 h later, with whole‑brain histology performed. MR imaging confirmed blood‑brain‑barrier opening at targeted sites, with the lowest power levels achieving opening without neuronal damage, and contrast enhancement correlated with focal MR signal changes, demonstrating that focused ultrasound can reliably open the barrier and that MR signal changes can detect it during sonication.

Abstract

PURPOSE: To determine if focused ultrasound beams can be used to locally open the blood-brain barrier without damage to surrounding brain tissue and if magnetic resonance (MR) imaging can be used to monitor this procedure. MATERIALS AND METHODS: The brains of 18 rabbits were sonicated (pulsed sonication) in four to six locations, with temporal peak acoustic power ranging from 0.2 to 11.5 W. Prior to each sonication, a bolus of ultrasonographic (US) contrast agent was injected into the ear vein of the rabbit. A series of fast or spoiled gradient-echo MR images were obtained during the sonications to monitor the temperature elevation and potential tissue changes. Contrast material–enhanced MR images obtained minutes after sonications and repeated 1–48 hours later were used to depict blood-brain barrier opening. Whole brain histologic evaluation was performed. RESULTS: Opening of the blood-brain barrier was confirmed with detection of MR imaging contrast agent at the targeted locations. The lowest power levels used produced blood-brain barrier opening without damage to the surrounding neurons. Contrast enhancement correlated with the focal signal intensity changes in the magnitude fast spoiled gradient-echo MR images. CONCLUSION: The blood-brain barrier can be consistently opened with focused ultrasound exposures in the presence of a US contrast agent. MR imaging signal intensity changes may be useful in the detection of blood-brain barrier opening during sonication.