The mechanism of interaction between focused ultrasound and microbubbles in blood-brain barrier opening in mice

The activation of bubbles by an acoustic field has been shown to temporarily open the blood-brain barrier (BBB), but the trigger cause responsible for the physiological effects involved in the process of BBB opening remains unknown. Here, the trigger cause (i.e., physical mechanism) of the focused u...

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Bibliographic Details
Published inThe Journal of the Acoustical Society of America Vol. 130; no. 5; p. 3059
Main Authors Tung, Yao-Sheng, Vlachos, Fotios, Feshitan, Jameel A, Borden, Mark A, Konofagou, Elisa E
Format Journal Article
LanguageEnglish
Published United States 01.11.2011
Subjects
Animals
Blood-Brain Barrier - anatomy & histology
Blood-Brain Barrier - metabolism
Capillary Permeability
Contrast Media - administration & dosage
Injections, Intravenous
Magnetic Resonance Imaging
Male
Mice
Mice, Inbred C57BL
Microbubbles
Nonlinear Dynamics
Particle Size
Pressure
Sonication
Ultrasonics
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Summary:The activation of bubbles by an acoustic field has been shown to temporarily open the blood-brain barrier (BBB), but the trigger cause responsible for the physiological effects involved in the process of BBB opening remains unknown. Here, the trigger cause (i.e., physical mechanism) of the focused ultrasound-induced BBB opening with monodispersed microbubbles is identified. Sixty-seven mice were injected intravenously with bubbles of 1-2, 4-5, or 6-8 μm in diameter and the concentration of 10(7) numbers/ml. The right hippocampus of each mouse was then sonicated using focused ultrasound (1.5 MHz frequency, 100 cycles pulse length, 10 Hz pulse repetition frequency, 1 min duration). Peak-rarefactional pressures of 0.15, 0.30, 0.45, or 0.60 MPa were applied to identify the threshold of BBB opening and inertial cavitation (IC). Our results suggest that the BBB opens with nonlinear bubble oscillation when the bubble diameter is similar to the capillary diameter and with inertial cavitation when it is not. The bubble may thus have to be in contact with the capillary wall to induce BBB opening without IC. BBB opening was shown capable of being induced safely with nonlinear bubble oscillation at the pressure threshold and its volume was highly dependent on both the acoustic pressure and bubble diameter.
ISSN:1520-8524
DOI:10.1121/1.3646905