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Acoustic Emission-Feedback Planar Ultrasound System for Localized Blood–Brain Barrier Opening Monitoring

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Abstract

Transcranial pulsed ultrasound with microbubbles has been shown to temporally open the blood–brain barrier (BBB) to allow therapeutic agents to penetrate into the CNS for improved therapeutic efficacy. Recent studies have shown the feasibility of using passive cavitation detection (PCD) for monitoring or real-time control of the BBB opening in a focused ultrasound device. Planar ultrasound has unique advantages including the capability to create larger BBB openings in a single exposure, simple operation, and reduced reliance on medical imaging for sonication guidance. This study proposes a novel planar ultrasound apparatus design that can provide real-time analysis for ultrasound BBB opening monitoring. In-vitro tube phantom experiments were conducted to characterize the dependence of the energy spectrum density (ESD) change with microbubble infusion. In-vivo experiments characterized the dependence of ESD change on BBB opening. We showed that the proposed configuration provide superior ESD detection than traditional water-immersed PCD arrangement and can well correlated with the cavitation activity either in the in vitro or in vivo measurement. The ESD response corresponds well to the occurrence of BBB-opening. In animal groups which demonstrated successful BBB-opening, the peak ESD was significantly higher (12.22 ± 7.019 and 14.763 ± 11.812 dB in 0.332 and 0.463-MPa exposure). The 5-dB ESD level was found to be a valid threshold level to discriminate between the BBB-intact and BBB-opened groups to provide both high detection sensitivity (100%) and specificity (88%). These results may facilitate the design of a planar ultrasound treatment apparatus for BBB opening and drug delivery to the brain.

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Acknowledgements

This study was supported by the Ministry of Science and Technology, Taiwan, under Grants Nos. 105-2221-E-182-022, 106-2221-E-182-002, 105-2923-B-002-001-MY3, Taiwan, French National Research Agency ANR-MOST project under Grant No. ANR-15-CE19-0003, and Chang Gung Memorial Hospital, Taiwan, under Grants Nos. CIRPD2E0051-53, CMRPD2D0111-13. We also thank the facility support from Center for Advanced Molecular Imaging and Translation, Chang Gung Memorial Hospital, Taiwan.

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Authors and Affiliations

  1. Department of Electrical Engineering, Chang Gung University, 259 Wen-Hwa 1st Road, Taoyuan, 333, Taiwan

    Chih-Hung Tsai, Yu-Xian Lin, Yu-Chien Lin & Hao-Li Liu

  2. PhD Program in Biomedical Engineering, Chang Gung University, Taoyuan, 333, Taiwan

    Ko-Ting Chen

  3. Department of Neurosurgery, Chang Gung Memorial Hospital, Taoyuan, 333, Taiwan

    Hao-Li Liu

  4. Department of Physical Medicine & Rehabilitation, National Taiwan University Hospital, Taipei, 100, Taiwan

    Wen-Shiang Chen

  5. Univ Lyon, Université Claude Bernard Lyon 1, Centre Léon Bérard, INSERM, UMR 1032, LabTAU, F-69003, Lyon, France

    Claude Inserra

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Correspondence to Hao-Li Liu.

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Tsai, CH., Chen, KT., Lin, YX. et al. Acoustic Emission-Feedback Planar Ultrasound System for Localized Blood–Brain Barrier Opening Monitoring. J. Med. Biol. Eng. 39, 277–286 (2019). https://doi.org/10.1007/s40846-018-0406-x

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