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Dynamic Behavior of Polymer Microbubbles During Long Ultrasound Tone-Burst Excitation and Its Application for Sonoreperfusion Therapy

  • Author Footnotes
    1 Xianghui Chen and Xucai Chen contributed equally to this article.
    Xianghui Chen
    Footnotes
    1 Xianghui Chen and Xucai Chen contributed equally to this article.
    Affiliations
    Center for Ultrasound Molecular Imaging and Therapeutics, University of Pittsburgh Medical Center, Pittsburgh, PA, USA

    Department of Cardiology, First Affiliated Hospital of Jinan University, Guangzhou, China
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  • Author Footnotes
    1 Xianghui Chen and Xucai Chen contributed equally to this article.
    Xucai Chen
    Footnotes
    1 Xianghui Chen and Xucai Chen contributed equally to this article.
    Affiliations
    Center for Ultrasound Molecular Imaging and Therapeutics, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
    Search for articles by this author
  • Jianjun Wang
    Affiliations
    Center for Ultrasound Molecular Imaging and Therapeutics, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
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  • Francois T.H. Yu
    Affiliations
    Center for Ultrasound Molecular Imaging and Therapeutics, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
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  • Flordeliza S. Villanueva
    Affiliations
    Center for Ultrasound Molecular Imaging and Therapeutics, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
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  • John J. Pacella
    Correspondence
    Corresponding author. Center for Ultrasound Molecular Imaging and Therapeutics, Heart and Vascular Institute, 200 Lothrop Street, PUH South Tower E353.8, Pittsburgh, PA 15213, USA.
    Affiliations
    Center for Ultrasound Molecular Imaging and Therapeutics, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
    Search for articles by this author
  • Author Footnotes
    1 Xianghui Chen and Xucai Chen contributed equally to this article.

      Objective

      Ultrasound (US)–targeted microbubble (MB) cavitation (UTMC)–mediated therapies have been found to restore perfusion and enhance drug/gene delivery. Because of the potentially longer circulation time and relative ease of storage and reconstitution of polymer-shelled MBs compared with lipid MBs, we investigated the dynamic behavior of polymer microbubbles and their therapeutic potential for sonoreperfusion (SRP) therapy.

      Methods

      The fate of polymer MBs during a single long tone-burst exposure (1 MHz, 5 ms) at various acoustic pressures and MB concentrations was recorded via high-speed microscopy and passive cavitation detection (PCD). SRP efficacy of the polymer MBs was investigated in an in vitro flow system and compared with that of lipid MBs.

      Discussion

      Microscopy videos indicated that polymer MBs formed gas-filled clusters that continued to oscillate, fragment and form new gas-filled clusters during the single US burst. PCD confirmed continued acoustic activity throughout the 5-ms US excitation. SRP efficacy with polymer MBs increased with pulse duration and acoustic pressure similarly to that with lipid MBs but no significant differences were found between polymer and lipid MBs.

      Conclusion

      These data suggest that persistent cavitation activity from polymer MBs during long tone-burst US excitation confers excellent reperfusion efficacy.

      Keywords

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