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FDA- approved uses of ultrasound contrast agents are currently limited to cardiography, so more studies are required in order to extend their use to a wider range of clinical applications. The needed studies range from basic physics experiments and mathematical modeling to experiments in animal models and clinical trials. These investigations are important to ascertain ultrasound contrast agents’ safety and their effectiveness, to detect and quantify blood flow, to image microcirculation, and to facilitate localized drug and gene delivery across the vessel wall.
The resonance frequency and the damping coefficient of a bubble in an infinite volume of liquid have been well studied. Less is known about the linear response of a bubble in a confined geometry, such a blood vessel. In such a situation the linear resonance theory needs to be modified to take into account the fact that the bubble cannot be assumed in radial motion and that the tube wall imposes boundary conditions and generates reflection. In collaboration with Dr. Hynynen, E. Sassaroli has performed numerical simulations [1, 2] to predict the resonance frequency and the damping of a gas microbubble placed on the axis of a blood vessel as a function of the radius, length, and microbubble position. It was found that the presence of the boundary represented by the blood vessel introduces a correction factor to the resonance and damping coefficient of an unconstrained microbubble. The correction factor appears to lower the free resonance frequency and damping. This knowledge can provide valuable information for the development of a strategy aimed to optimize selective acoustic energy absorption and deposition in a given vessel.
The non-linear response of bubbles in a narrow tube is however a much more difficult problem to treat theoretically and the physics related to this phenomenon needs to be further explored. Dr. Hynynen and I have investigated experimentally inertial cavitation in micrometer size silica and polyester tubes [1] and more recently in micro-tunnels embedded in gel (E. Sassaroli and K. Hynynen, Cavitation threshold of microbubbles in gel tunnels by focused ultrasound, submitted for publication). We have shown that the threshold for inertial cavitation is dependent on the tube size with an increase for smaller tubes. The evaluation of inertial cavitation in gel tunnels rather than tubes provides a novel opportunity to investigate microbubble collapse in a situation that simulates in vivo blood vessels better than tubes with solid walls do. The results of our experiments can be understood in terms of the effect on the vessel wall on the bubble inertia. The bubble inertia that greatly affects inertia cavitation, is dramatically different when the bubble is in a free field than when the bubble is in a narrow tube.
Peer Reviewed Journals
1. E. Sassaroli and K. Hynynen. Forced linear oscillations of microbubbles in blood capillaries. J. Acous. Soc. Am. 2004; 115: 3235-43.
2. E. Sassaroli and K. Hynynen. Resonance frequency of microbubbles in small blood vessels: a numerical study. Phys. Med. Biol. 2005, 50: 5293-5305.
3. E. Sassaroli and K. Hynynen, On the Impact of Vessel Size on the Threshold of Bubble Collapse. Appl. Phys. Lett. 2006; 89: 123901.
Peer Reviewed Conferences
1. E. Sassaroli and K. Hynynen, The Threshold for Bubble Collapse in Gel Embedded Microtunnels and Tubes, to be presented at the 2006 IEEE International Ultrasonics Symposium Oct 3-6 Vancouver, Canada.
2. E. Sassaroli and K. Hynynen, On the Impact of Vessel Size on the Threshold of Bubble Collapse, American Acoustical Society Meeting, Providence RI, June 2006.
3. E. Sassaroli and K. Hynynen, On the Impact of Vessel Size on the Threshold of Bubble Collapse, AIUM Annual Convention, Washington DC, March 2006.
4. E. Sassaroli and K. Hynynen, “Bubble Behavior in Narrow Vessels”, The 11th European Symposium on Ultrasound Contrast Imaging, Rotterdam, The Netherlands, January 2006.
5. E. Sassaroli and K. Hynynen. Microbubble Collapse upon focused ultrasound exposure in narrow tubes. Proceedings of the 2005 International Symposium on Therapeutic Ultrasound, Boston, MA. Oct 27-29, 2005.
6. E. Sassaroli, “Resonance frequency and damping of microbubbles in small blood vessels: a theoretical study”, 2005 Young Investigators Symposium, Concord, MA, March 2005.
7. E. Sassaroli and K. Hynynen. Resonance frequency of microbubbles in small blood vessels. Proceedings of the 2004 IEEE International Ultrasonics, Ferroelectrics and Frequency Control. Montreal, Canada. August 23-27, 2004.
8. E. Sassaroli and K. Hynynen, “Forced linear oscillations of microbubbles in blood capillaries”, ASA Meeting, Austin, Texas, November 2003.