EFSUMB EUROPEAN FEDERATION OF SOCIETIES FOR ULTRASOUND IN MEDICINE AND BIOLOGY ‘Building a European Ultrasound Community’ Young Investigator’s Award WFUMB 2011 VIENNA AUSTRIA 28 August 2011 13.50 – 15.45 10 minutes each for presentation plus 3 minutes discussion
Therapeutic Bubbles 1
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Klazina Kooiman Miranda Foppen-Harteveld , Antonius F.W. van der Steen , and Nico de Jong
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Dept. of Biomedical Engineering, Thoraxcenter, Erasmus MC, Rotterdam, the Netherlands Interuniversity Cardiology Institute of the Netherlands, Utrecht, the Netherlands 2 Dept. of Applied Physics, Physics of Fluids, University of Twente, Enschede, the Netherlands 2
ABSTRACT Purpose: Molecular imaging using ultrasound uses targeted ultrasound contrast agents that consist of encapsulated gas microbubbles. Until now, targeted microbubbles have only been used for imaging, not for therapy. In this study we investigated whether they could also be used to induce sonoporation, resulting in a transient increase in cell membrane permeability so that therapeutics can enter the cell.
Methods and materials: CD31-targeted microbubbles were made and allowed to adhere to human umbilical vein endothelial cells. Microbubble-cell behavior upon insonification at 1 MHz (10 cycle sine-wave bursts) was studied with the Brandaris 128 high-speed camera (frame rate ~ 13 MHz). Microbubble diameter (D) – time curves were extracted from the recordings and the relative vibration amplitude, D max – Dmin normalized to the resting diameter D0 sonoporation.
Results: Thirty-one cells were studied that all had one microbubble attached per cell. After insonification at 80 kPa (MI 0.08), 30% of the cells had taken up PI, while this was 20% at 120 kPa (MI 0.12), and 83% at 200 kPa (MI 0.20). Irrespective of the applied peak negative acoustic pressure, uptake of PI was observed when the relative vibration amplitude of the targeted microbubbles was larger than 0.5. No relationship was found between the position of the microbubble on the cell and induction of sonoporation.
Conclusion: This study reveals that vibrating targeted microbubbles can induce sonoporation. This feature may now be used in molecular imaging, thereby combining ultrasound imaging and therapy.