Microbubbles have shown great promise as ultrasound contrast agents and have been used in a range of clinical applications including cardiovascular diseases and cancer. They are extremely sensitive as contrast agents – under the right ultrasound frequency a single micron-sized bubble can be detected, as they can resonant under ultrasound and oscillate in a highly nonlinear way.
We are interested in studying the physical behaviour of these microbubbles and their effects on micro-vascular imaging and quantification , particularly their interaction with ultrasound [2-4] and in vivo environment (e.g. surrounded or attached to a vascular wall [5,6]).
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We are also interested in studying nano-sized phase-change droplets which can be vaporised into bubbles by ultrasound and/or light . While microbubbles are confined within vessels, such nano-sized droplets could leak out of the vessel and extend the ultrasound contrast to extravascular space.
Finally we also link the physics of contrast agent bubbles to that of other instances of gas bubbles in the bloodstream such as the decompression bubbles seen in astronauts and divers, and what determines their clinical presentation [8,9,10].
Some example projects:
Bubbles responses in different size vessels
When used in vivo, microbubble ultrasound contrast agents (UCAs) are distributed in vessels of different sizes. However the current understanding of the response of UCAs in vessels of various diameters is still limited. Such knowledge is important for quantitative contrast enhanced ultrasound imaging and therapy. In particular, the contribution of UCAs in different sized vessels to the overall received signal from a perfused region in vivo is not clear and better understanding of the scaling of UCA response with vessel size would be a first step in this direction. Small blood vessels play a significant role in disease progression in the form of neovascularisation supplying cancer tumor or atherosclerotic lesions, thus quantifying UCA signal in these would inform staging during diagnosis on the imaging side and help for UCA-mediated drug delivery on the therapy side. We are working on both experimental and modelling approaches to study these phenomena [11-13].
Phase-change contrast agents
One challenge of the microbubble mediated ultrasound techniques is that microbubbles are limited to intravascular applications due to their relatively large size compared to the particle extravasation size limit (e.g. 100-750 nm for tumour vessels). However phase-change contrast agents (PCCA), in the form of nano-scale droplets (peak size: 200–300 nm), provide a safe approach extending the ultrasound contrast beyond the vasculature. We are developing such contrast agents and methodologies for characterising them acoustically and optically (See Figure below), and exploring their potential application in both ultrasound and photo acoustic imaging . This is a collaboration with Prof. Terry Matsunaga from University of Arizona.
- Tang, M.X., et al., Quantitative contrast-enhanced ultrasound imaging: a review of sources of variability. Interface Focus, 2011. 1(4): p. 520-539.
- Tang, M.X. and R.J. Eckersley, Nonlinear propagation of ultrasound through microbubble contrast agents and implications for imaging. IEEE Trans Ultrason Ferroelectr Freq Control, 2006. 53(12): p. 2406-15.
- Tang, M.X. and R.J. Eckersley, Frequency and pressure dependent attenuation and scattering by microbubbles. Ultrasound Med Biol, 2007. 33(1): p. 164-8.
- Tang, M.X., et al., Attenuation correction in ultrasound contrast agent imaging: elementary theory and preliminary experimental evaluation. Ultrasound Med Biol, 2008. 34(12): p. 1998-2008.
- Loughran, J., et al., Effect of ultrasound on adherent microbubble contrast agents. Phys Med Biol, 2012. 57(21): p. 6999-7014.
- Casey, J., et al., Single bubble acoustic characterization and stability measurement of adherent microbubbles. Ultrasound Med Biol, 2013. 39(5): p. 903-14.
- Li, S., et al., Quantifying activation of perfluorocarbon-based phase-change contrast agents using simultaneous acoustic and optical observation. Ultrasound Med Biol, 2015. 41(5): p. 1422-31.
- Papadopoulou V, Eckersley RJ, Balestra C, Karapantsios TD, Tang M-X. A critical review of physiological bubble formation in hyperbaric decompression. Advances in colloid and interface science. 2013;191–192(0):22-30.
- Papadopoulou V, Tang M-X, Balestra C, Eckersley RJ, Karapantsios TD. Circulatory Bubble Dynamics: From Physical to Biological Aspects. Advances in colloid and interface science. 2014; 206:239-249.
- Papadopoulou V, Evgenidis S, Eckersley RJ, Mesimeris T, Balestra C, Kostoglou M, Tang MX, Karapantsios TD. Decompression induced bubble dynamics on ex-vivo fat and muscle tissue surfaces with a new experimental set up. Colloids and Surfaces B: Biointerfaces. 2015; 129:121-129.
- Ward M, Yildiz Y, Papadopoulou V, Eckersley RJ, Tang M-X. Modelling of ultrasound contrast agent oscillations in vessels based on an infinite mirror image method. 2015 IEEE International Ultrasonics Symposium, Taipei, Taiwan, 21-24 Oct 2015.
- Jamalian S, Lin S, Feldman C, Yildiz Y, Papadopoulou V, Ward M, Eckersley RJ, Tang M-X, Moore J. Development of a branched micro-fluidic platform for acoustic quantification of microbubble populations (Invited). The 21st European Symposium on Ultrasound Contrast Imaging, Rotterdam, 21-22 Jan 2016.
- Lin S, Feldman C, Jamalian S, Yildiz Y, Papadopoulou V, Ward M, Eckersley RJ, Moore J, Tang M-X. Acoustic quantificantion of micro bubble populations in a branched microvasculature phantom. The 21st European Symposium on Ultrasound Contrast Imaging, Rotterdam, 21-22 Jan 2016.
- Li, S., Lin, S., Cheng, Y., Matsunaga, T. O., Eckersley, R. J., & Tang, M. X. (2015). Quantifying activation of perfluorocarbon-based phase-change contrast agents using simultaneous acoustic and optical observation. Ultrasound in medicine & biology, 41(5), 1422-1431.