Biomedical ultrasonics, cavitation, and sonoporation

Kotopoulis, Spiros

May 2011

Thesis or dissertation

© 2011 Spiros Kotopoulis. All rights reserved. No part of this publication may be reproduced without the written permission of the copyright holder.

This thesis treats biomedical ultrasonics, cavitation and sonoporation. Focussed ultrasound surgery can heat tissue to a temperature that causes protein denaturation and coagulative necrosis. For high-resolution focused ultrasound microsurgery, high working frequencies are necessary. We manufactured a highfrequency, high-intensity focussed ultrasound transducer, using lithium niobate as the active element. The transducer was capable of creating 2.5×3.4 (mm)2 lesions without affecting surrounding tissue.

Such disruptive effects of ultrasound also have applications outside medicine. Since cyanobacteria contain gas vesicles, we hypothesised that these can be disrupted with the aid of ultrasound. During 1-hour sonication in the clinical diagnostic range, we forced blue-green algae to sink, thus promoting natural decay.

In medical diagnostics, ultrasound contrast agents are added to the blood stream to differentiate between blood and other tissue types. We injected such lipid-shelled microbubbles into a synthetic capillary and sonicated using continuous ultrasound. The microbubbles formed clusters at a quarter wavelength apart owing to radiation forces. We observed cluster coalescence and translation towards the capillary wall.

To study acoustic cavitation, we designed and built a scientific instrument combining a pulsed laser and a high-intensity focussed ultrasound transducer, capable of nucleating at precise locations. The cavitation dynamics were recorded using highspeed cameras. At high acoustic intensities, interacting cavitation clouds were formed.

Microbubbles under sonication have been observed to create transient pores in adjacent cell membranes. This so called sonoporation has been associated with highly non-linear bubble phenomena. We observed lipid-shelled microbubbles near cancer cells under quasi-continuous low-amplitude sonication. Typically within a second of sonication, microbubbles were seen to enter the cells and dissolve. This new explanation of sonoporation was verified using high-speed photography and confocal fluorescence microscopy.

If drug and genes can be successfully coupled to acoustically active vehicles, sonoporation might revolutionise non-invasive therapy as we know it.

Department of Engineering, The University of Hull
Postema, Michiel; Walther, Thomas
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