A Single High-Intensity Shock Wave Pulse With Microbubbles Opens the Blood-Brain Barrier in Rats

Focused extracorporeal shockwave (FSW), one kind of focused high-intensity pulsed ultrasound, has been shown to induce blood-brain barrier (BBB) opening in targeted brain areas in rat animal models with minimal detrimental effects below threshold intensity levels or iterations. In the current study,...

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Main Authors: Yi Kung, Hsin-Yu Huang, Wei-Hao Liao, Abel P.-H. Huang, Ming-Yen Hsiao, Chueh-Hung Wu, Hao-Li Liu, Claude Inserra, Wen-Shiang Chen
Format: Article
Language:English
Published: Frontiers Media S.A. 2020-05-01
Series:Frontiers in Bioengineering and Biotechnology
Subjects:
Online Access:https://www.frontiersin.org/article/10.3389/fbioe.2020.00402/full
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author Yi Kung
Hsin-Yu Huang
Wei-Hao Liao
Abel P.-H. Huang
Ming-Yen Hsiao
Chueh-Hung Wu
Hao-Li Liu
Claude Inserra
Wen-Shiang Chen
author_facet Yi Kung
Hsin-Yu Huang
Wei-Hao Liao
Abel P.-H. Huang
Ming-Yen Hsiao
Chueh-Hung Wu
Hao-Li Liu
Claude Inserra
Wen-Shiang Chen
author_sort Yi Kung
collection DOAJ
description Focused extracorporeal shockwave (FSW), one kind of focused high-intensity pulsed ultrasound, has been shown to induce blood-brain barrier (BBB) opening in targeted brain areas in rat animal models with minimal detrimental effects below threshold intensity levels or iterations. In the current study, we found that the thresholds could be further reduced by the addition of microbubbles (ultrasound contrast agents or UCA; SonoVue). FSW with 2 × 106 MBs/kg of UCA (20% of clinical dosage) at an intensity level of 0.1 (peak positive pressure 5.4 MPa; peak negative pressure −4.2 MPa; energy flux density 0.03 mJ/mm2) resulting in a 100% BBB opening rate without detectable hemorrhage or apoptosis in the brain. Significantly reduced free radical production was found compared with 0.5 MHz focused ultrasound at a peak negative pressure of 0.44 MPa (1% duty cycle and 4 × 107 MBs/kg of UCA). FSW devices offer advantages of commercial availability and high safety, and thus may facilitate future research and applications of focal BBB opening for oncological and pharmacological purposes.
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spelling doaj.art-36141334a0ed47f18e7763da26902f832022-12-21T22:49:31ZengFrontiers Media S.A.Frontiers in Bioengineering and Biotechnology2296-41852020-05-01810.3389/fbioe.2020.00402533590A Single High-Intensity Shock Wave Pulse With Microbubbles Opens the Blood-Brain Barrier in RatsYi Kung0Hsin-Yu Huang1Wei-Hao Liao2Abel P.-H. Huang3Ming-Yen Hsiao4Chueh-Hung Wu5Hao-Li Liu6Claude Inserra7Wen-Shiang Chen8Department of Physical Medicine and Rehabilitation, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, TaiwanDepartment of Physical Medicine and Rehabilitation, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, TaiwanDepartment of Physical Medicine and Rehabilitation, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, TaiwanDepartment of Surgery, National Taiwan University Hospital, Taipei, TaiwanDepartment of Physical Medicine and Rehabilitation, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, TaiwanDepartment of Physical Medicine and Rehabilitation, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, TaiwanDepartment of Electrical Engineering, Chang Gung University, Taoyuan, TaiwanINSERM, U1032, LabTAU, Universiteì Claude Bernard Lyon 1, Lyon, FranceDepartment of Physical Medicine and Rehabilitation, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, TaiwanFocused extracorporeal shockwave (FSW), one kind of focused high-intensity pulsed ultrasound, has been shown to induce blood-brain barrier (BBB) opening in targeted brain areas in rat animal models with minimal detrimental effects below threshold intensity levels or iterations. In the current study, we found that the thresholds could be further reduced by the addition of microbubbles (ultrasound contrast agents or UCA; SonoVue). FSW with 2 × 106 MBs/kg of UCA (20% of clinical dosage) at an intensity level of 0.1 (peak positive pressure 5.4 MPa; peak negative pressure −4.2 MPa; energy flux density 0.03 mJ/mm2) resulting in a 100% BBB opening rate without detectable hemorrhage or apoptosis in the brain. Significantly reduced free radical production was found compared with 0.5 MHz focused ultrasound at a peak negative pressure of 0.44 MPa (1% duty cycle and 4 × 107 MBs/kg of UCA). FSW devices offer advantages of commercial availability and high safety, and thus may facilitate future research and applications of focal BBB opening for oncological and pharmacological purposes.https://www.frontiersin.org/article/10.3389/fbioe.2020.00402/fullhigh-intensity pulsed ultrasoundblood-brain barriermicrobubblescavitationsafe dose
spellingShingle Yi Kung
Hsin-Yu Huang
Wei-Hao Liao
Abel P.-H. Huang
Ming-Yen Hsiao
Chueh-Hung Wu
Hao-Li Liu
Claude Inserra
Wen-Shiang Chen
A Single High-Intensity Shock Wave Pulse With Microbubbles Opens the Blood-Brain Barrier in Rats
Frontiers in Bioengineering and Biotechnology
high-intensity pulsed ultrasound
blood-brain barrier
microbubbles
cavitation
safe dose
title A Single High-Intensity Shock Wave Pulse With Microbubbles Opens the Blood-Brain Barrier in Rats
title_full A Single High-Intensity Shock Wave Pulse With Microbubbles Opens the Blood-Brain Barrier in Rats
title_fullStr A Single High-Intensity Shock Wave Pulse With Microbubbles Opens the Blood-Brain Barrier in Rats
title_full_unstemmed A Single High-Intensity Shock Wave Pulse With Microbubbles Opens the Blood-Brain Barrier in Rats
title_short A Single High-Intensity Shock Wave Pulse With Microbubbles Opens the Blood-Brain Barrier in Rats
title_sort single high intensity shock wave pulse with microbubbles opens the blood brain barrier in rats
topic high-intensity pulsed ultrasound
blood-brain barrier
microbubbles
cavitation
safe dose
url https://www.frontiersin.org/article/10.3389/fbioe.2020.00402/full
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