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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Frontiers Media S.A.
2020-05-01
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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. |
first_indexed | 2024-12-14T19:48:20Z |
format | Article |
id | doaj.art-36141334a0ed47f18e7763da26902f83 |
institution | Directory Open Access Journal |
issn | 2296-4185 |
language | English |
last_indexed | 2024-12-14T19:48:20Z |
publishDate | 2020-05-01 |
publisher | Frontiers Media S.A. |
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series | Frontiers in Bioengineering and Biotechnology |
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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