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Static Magnetic Fields Dampen Focused Ultrasound-mediated Blood-Brain Barrier Opening.

Authors: Yang Y, Pacia CP, Ye D, Yue Y, Chien CY, Chen H

Background Focused ultrasound combined with microbubbles has been used in clinical studies for blood-brain barrier (BBB) opening in conjunction with MRI. However, the impact of the static magnetic field generated by an MRI scanner on the BBB opening outcome has not been evaluated. Purpose To determine the relationship of the static magnetic field of an MRI scanner on focused ultrasound combined with microbubble-induced BBB opening. Materials and Methods Thirty wild-type mice were divided into four groups. Mice from different groups were sonicated with focused ultrasound in different static magnetic fields (approximately 0, 1.5, 3.0, and 4.7 T), with all other experimental parameters kept the same. Focused ultrasound sonication was performed after intravenous injection of microbubbles. Microbubble cavitation activity, the fundamental -physical mechanism underlying focused ultrasound BBB opening, was monitored with passive cavitation detection. After sonication, contrast-enhanced T1-weighted MRI was performed to assess BBB opening outcome. Intravenously injected Evans blue was used as a model agent to evaluate trans-BBB delivery efficiency. Results The microbubble cavitation dose decreased by an average of 2.1 dB at 1.5 T (<i>P</i> = .05), 2.9 dB at 3.0 T (<i>P</i> = .01), and 3.0 dB at 4.7 T (<i>P</i> = .01) compared with that outside the magnetic field (approximately 0 T). The static magnetic field of an MRI scanner decreased BBB opening volume in mice by 3.2-fold at 1.5 T (<i>P</i> < .001), 4.5-fold at 3.0 T (<i>P</i> < .001), and 11.6-fold at 4.7 T (<i>P</i> <.001) compared with mice treated outside the magnetic field. It also decreased Evans blue trans-BBB delivery 1.4-fold at 1.5 T (<i>P</i> = .009), 1.6-fold at 3.0 T (<i>P</i> < .001), and 1.9-fold at 4.7 T (<i>P</i> < .001). Conclusion Static magnetic fields dampened microbubble cavitation activity and decreased trans-blood-brain barrier (BBB) delivery by focused ultrasound combined with microbubble-induced BBB opening. © RSNA, 2021 <i>An earlier incorrect version of this article appeared online. This article was corrected on July 8, 2021.</i>

Introduction

Purpose Drug delivery with BBB opening
Study Objective To determine how the static magnetic field strength of an MRI scanner affects focused ultrasound–microbubble–induced blood–brain barrier opening.
Animal model / Human subject mouse, C57BL/6, 8–10 weeks, male
Disease model healthy
Targeted brain region(s) Striatum

Outcomes and Safety

Summary of Outcomes Static magnetic fields (1.5-4.7 T) in MRI significantly reduced FUS-induced microbubble cavitation and BBB opening volume.
Duration of biological effect not reported
Safety-related matter Magnetic fields reduced cavitation activity, potentially offering a suppressive effect on microbubble-mediated bioeffects.

Brain Region

Ultrasound Parameters

Ultrasound instrument single-element focused ultrasound transducer
FUS Frequency 1 MHz
FUS Intensity not reported
FUS Pressure 0.3 MPa
FUS Mode not reported
Pulse duration 10 ms
Duration of a single FUS session not reported
Focal Characteristics Focal depth: none, Focal length: none, Aperture size: none
Treatment frequency Single session

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