Abstract
Ultrasound contrast agents (UCAs) are widely used in Doppler studies, either for simple echo enhancement purposes, or to increase the low signal-to-clutter ratio typical of microcirculation investigations. Common to all Doppler techniques, which are briefly reviewed in this paper, is the basic assumption that possible phase and amplitude changes in received echoes are only associated with UCA microbubble movements due to the drag force of blood. Actually, when UCAs are insonified, phenomena such as rupture, displacement due to radiation force, and acoustically driven deflation might influence the results of Doppler investigations. In this paper, we investigate the possible Doppler effects of such phenomena by means of a numerical simulation model and a special acousto-optical set-up which allows analysis of the behavior of individual microbubbles over relatively long time intervals. It is thus found that all phenomena produce evident Doppler effects in vitro, but that bubble displacement and deflation in particular, are not expected to significantly interfere with clinical measurements in standard conditions.








Similar content being viewed by others
References
Auton TR, Hunt JCR, Prud’homme M (1988) The force exerted on a body in inviscid unsteady non-uniform rotational flow. J Fluid Mech 197:241–257. doi:10.1017/S0022112088003246
Becher H, Schlief R (1989) Improved sensitivity of color Doppler by SH U 454. Am J Cardiol 64:374–377. doi:10.1016/0002-9149(89)90538-9
Bevan PD, Karshafian R, Tickkner EG, Burns PN (2007) Quantitative measurement of ultrasound disruption of polymer-shelled microbubbles. Ultrasound Med Biol 33(11):1777–1786. doi:10.1016/j.ultrasmedbio.2007.05.013
Bjerknes V (1906) Fields of force. Columbia University Press, New York
Bleeker H, Shung K, Barnhart J (1990) On the application of ultrasonic contrast agents for blood flowmetry and assessment of cardiac perfusion. J Ultrasound Med 9:461–471
Bloch SH, Wan MD, Ferrara KA (2004) Optical observation of lipid- and polymer-shelled ultrasound microbubble contrast agents. Appl Phys Lett 84(4):631–633. doi:10.1063/1.1643544
Borden MA, Longo ML (2002) Dissolution behavior of lipid monolayer-coated, air-filled microbubbles: effect of lipid hydrophobic chain length. Langmuir 18:9225–9233. doi:10.1021/la026082h
Borden MA, Kruse DE, Caskey CF, Zhao S, Dayton PA, Ferrara KW (2005) Influence of lipid shell physicochemical properties on ultrasound-induced microbubble destruction. IEEE Trans Ultrason Ferroelectr Freq Control 52(11):1992–2002. doi:10.1109/TUFFC.2005.1561668
Bouakaz A, Versluis M, de Jong N (2005) High-speed optical observations of contrast agent destruction. Ultrasound Med Biol 31(3):391–399. doi:10.1016/j.ultrasmedbio.2004.12.004
Brennen CE (1995) Cavitation and bubble dynamics. Oxford University Press, New York
Bruce MF, Averkiou MA, Skyba D, Powers JE (2000) A generalization of pulse inversion Doppler. Proc IEEE Ultrason Symp 2:1903–1906
Bruce MF, Averkiou MA, Tiemann K, Lohmaier S, Powers J, Beach K (2004) Vascular flow and perfusion imaging with ultrasound contrast agents. Ultrasound Med Biol 30(6):735–743. doi:10.1016/j.ultrasmedbio.2004.03.016
Burns PN, Powers JE, Hope Simpson D et al (1993) Harmonic contrast-enhanced Doppler as a method for the elimination of clutter: in vivo duplex and color studies. Radiology 189:285
Burns PN, Powers JE, Simpson DH, Brezina A, Kolin A, Chin CT et al (1994) Harmonic power mode Doppler using microbubble contrast agents: an improved method for small vessel flow imaging. Proc IEEE Ultrason Symp 3(1–4):1547–1550
Chomas JE, Dayton P, May D, Ferrara KW (2001) Threshold of fragmentation for ultrasonic contrast agents. J Biomed Opt 6(2):141–150. doi:10.1117/1.1352752
Chomas JE, Dayton P, Allen J, Morgan K, Ferrara KW (2001) Mechanism of contrast agent destruction. IEEE Trans Ultrason Ferroelectr Freq Control 48(1):232–248. doi:10.1109/58.896136
Church CC (1995) The effects of an elastic solid surface layer on the radial pulsations of gas bubbles. J Acoust Soc Am 97(3):1510–1521. doi:10.1121/1.412091
Dayton PA, Morgan KE, Klibanov AL, Brandenburger GH, Ferrara KW (1999) Optical and acoustical observation of the effects of ultrasound on contrast agents. IEEE Trans Ultrason Ferroelectr Freq Control 46(1):220–232. doi:10.1109/58.741536
Dayton PA, Allen JS, Ferrara KW (2002) The magnitude of radiation force on ultrasound contrast Agents. J Acoust Soc Am 112:2183–2192. doi:10.1121/1.1509428
de Jong N (1993) Acoustic properties of ultrasound contrast agents. PhD Dissertation, de Erasmus Universiteit, Rotterdam
de Jong M, Emmer C, Chin A (2007) “Compression-only” behavior of phospholipid-coated contrast bubbles. Ultrasound Med Biol 33(4):653–656. doi:10.1016/j.ultrasmedbio.2006.09.016
de Vries J, Luther S, Lohse D (2002) Induced bubble shape oscillations and their impact on the rise velocity. Eur Phys J B Cond Matt 29(3):503–509. doi:10.1140/epjb/e2002-00332-5
Di Marco P, Grassi W (2003) Experimental study on rising velocity of nitrogen bubbles in FC-72. Int J Therm Sci 42:435–446. doi:10.1016/S1290-0729(02)00044-3
Doinikov AA (1998) Acoustic radiation force on a bubble: viscous and thermal effects. J Acoust Soc Am 103(1):143–147. doi:10.1121/1.421113
Doinikov AA, Dayton PA (2007) Maxwell rheological model for lipid-shelled ultrasound microbubble contrast agents. J Acoust Soc Am 121(6):3331–3340. doi:10.1121/1.2722233
Drew DA, Lathey RT Jr (1990) Some supplemental analysis concerning the virtual mass and lift force on a sphere in a rotating and straining flow. Int J Multiph Flow 16:1127–1130. doi:10.1016/0301-9322(90)90110-5
Duck FA (1990) Physical properties of tissue. Academic press, London. Chapter 5
Eller A (1968) Force on a bubble in a standing acoustic wave. J Acoust Soc Am 43(1):170–171. doi:10.1121/1.1910755
Emmer M, van Wamel A, Goertz DE, de Jong M (2007) The onset of microbubble vibration. Ultrasound Med Biol 33(6):941–949. doi:10.1016/j.ultrasmedbio.2006.11.004
Evans DH, McDicken WN (2000) Doppler ultrasound. Physics, instrumentation, and signal processing, 2nd edn. Wiley, Chichester
Feinstein SB (2006) Contrast ultrasound imaging of the carotid artery vasa vasorum and atherosclerotic plaque neovascularization. J Am Coll Cardiol 48(2):236–243. doi:10.1016/j.jacc.2006.02.068
Fyrillas MM, Szeri A (1994) Dissolution or growth of soluble spherical oscillating bubbles. J Fluid Mech 277:381–407. doi:10.1017/S0022112094002806
Gerriets T, Seidel G, Fiss I, Modrau B, Kaps M (1999) Contrast-enhanced transcranial color-coded duplex sonography: efficiency and validity. Neurology 52(6):1133–1137
Goertz DE, Frijlink ME, Tempel D, Bhagwandas V, Gisolf A, Krams R et al (2007) Subharmonic contrast intravascular ultrasound for vasa vasorum imaging. Ultrasound Med Biol 33(12):1859–1872. doi:10.1016/j.ultrasmedbio.2007.05.023
Goldberg BB, Liu JB, Burns PN, Merton PA, Forsberg F (1993) Galactose-based intravenous sonographic contrast agent: experimental studies. J Ultrasound Med 12(8):463–470
Goldberg BB, Raichlen JS, Forsberg F (2001) Ultrasound contrast agents: basic principles and clinical applications. 2 Sub edition. Informa Healthcare, London, pp 21–30
Guidi F, Vos H J, Tortoli P, de Jong N (2006) Simultaneous optical and acoustical observation of microbubbles behaviour. IEEE Ultrason Symp, 1358–1361
Hilgenfeldt S, Lohse D, Brenner MP (1996) Phase diagrams for luminescing bubbles. Phys Fluids 8(11):2808–2826. doi:10.1063/1.869131
Hoff L, Sontum PC, Hovem JM (2000) Oscillations of polymeric microbubbles: effect of the encapsulating shell. J Acoust Soc Am 107(4):2272–2280. doi:10.1121/1.428557
Hope Simpson D, Chin CT, Burns PN (1999) Pulse inversion Doppler: a new method for detecting nonlinear echoes from microbubble contrast agents. IEEE Trans Ultrason Ferroelectr Freq Control 46:372–382. doi:10.1109/58.753026
Johnson VE, Hsieh T (1966) The influence in trajectories of gas nuclei on cavitation inception. 6th Naval Hydrodynamics Symposium, pp 163–182
Kasai C, Namekawa K, Koyano A, Omoto R (1985) Real-time two-dimensional blood flow imaging using an autocorrelation technique. IEEE Trans Sonics Ultrason 32(3):458–464
Kaul S (1995) Myocardial contrast echocardiography in coronary artery disease: potential applications using venous injections of contrast. Am J Cardiol 75:61–68. doi:10.1016/S0002-9149(99)80529-3
Kern R, Perren F, Schoeneberger K, Gass A, Hennerici M, Meairs S (2004) Ultrasound microbubble destruction imaging in acute middle cerebral artery stroke. Stroke 35:1665–1670. doi:10.1161/01.STR.0000129332.10721.7e
Kono Y, Moriyasu F, Yamada K et al (1996) Conventional and harmonic gray scale enhancement of the liver with sonication activation of a US contrast agent. Radiology 201(P):266
Leighton TG (1994) The acoustic bubble. Academic Press, London
Leighton TG, Ramble DG, Phelps AD (1997) The detection of tethered and rising bubbles using multiple acoustic techniques. J Acoust Soc Am 101:2626–2635. doi:10.1121/1.418503
Levine RA, Teichholz LE, Goldman ME, Steinmetz MY, Baker M, Meltzer RS (1984) Microbubbles have intracardiac velocities similar to those of red blood cells. J Am Coll Cardiol 3:28–33
Magnaudet J, Legendre D (1998) The viscous drag force on a spherical bubble with a time-dependent radius. Phys Fluids 10:550–554. doi:10.1063/1.869582
Marmottant P, van der Meer SM, Emmer M, Versluis M, de Jong N, Hilgenfeldt S et al (2005) A model for large amplitude oscillations of coated bubbles accounting for buckling and rupture. J Acoust Soc Am 118(6):3499–3505. doi:10.1121/1.2109427
Matula TJ (2003) Bubble lievitation and translation under single-bubble sonoluminescence conditions. J Acoust Soc Am 114(2):775–781. doi:10.1121/1.1589753
Meyer RS, Billet ML, Holl JW (1992) Freestream nuclei and travelling bubble-cavitation. J Fluids Eng 114:672–679. doi:10.1115/1.2910084
Nanda NC, Schlief R, Goldberg BB (1997) Advances in echo imaging using contrast enhancement. Kluwer Academic Publishers, Dubai Part two: 207–479, Part Three: 491–627
Ophir J, Parker KJ (1989) Contrast agents in diagnostic ultrasound. Ultrasound Med Biol 15(4):319–333. doi:10.1016/0301-5629(89)90044-6
Panton R (1984) Incompressible flow. Wiley, New York
Phillips P (2001) Contrast pulse sequences (CPS): imaging nonlinear microbubbles. Proc IEEE Ultrason Symp 2:1739–1745
Postema M, Marmottant P, Lancée CT, Hilgenfeldt S, de Jong N (2004) Ultrasound-induced microbubble coalescence. Ultrasound Med Biol 30(10):1337–1344. doi:10.1016/j.ultrasmedbio.2004.08.008
Pu G, Longo ML, Borden MA (2005) Effects of microstructure on molecular oxygen permeation through condensed phospolipid monolayer. J Am Chem Soc 127:6524–6525. doi:10.1021/ja051103q
Pu G, Borden MA, Longo ML (2006) Collapse and shedding transition in binary lipid monolayer. Langmuir 22:2993–2999. doi:10.1021/la0530337
Rychak JJ, Klibanov AL, Hossak JA (2005) Acoustic radiation force enhances targeted delivery of ultrasound contrast microbubbles in vitro verification. IEEE Trans Ultrason Ferroelectr Freq Control 52(3):421–433. doi:10.1109/TUFFC.2005.1417264
Stride E, Saffari N (2003) Microbubble ultrasound contrast agents: a review. Proc Inst Mech Eng Proc Part H 217(H6):429–447. doi:10.1243/09544110360729072
Takeuchi Y (1997) Industrial use thermoplastic microballoon to mimic the contrast agents and its in-vivo behavior including released gas dynamics. Proc IEEE Ultrason Symp 2:1579–1582
Tiemann K, Lohmeier S, Kuntz S et al (1999) Real-time contrast echo assessment of myocardial perfusion at low emission power: first experimental and clinical results using power pulse inversion imaging. Echocardiography 16:799–809. doi:10.1111/j.1540-8175.1999.tb00132.x
Tienmann K, Pohl C, Schlosser T, Goenechea J, Bruce M, Veltmann C et al (2000) Stimulated acoustic emission: pseudo-Doppler shifts seen during the destruction of nonmoving microbubbles. Ultrasound Med Biol 26(7):1161–1167. doi:10.1016/S0301-5629(00)00261-1
Tortoli P, Pratesi M, Michelassi V (2000) Doppler spectra from contrast agents crossing an ultrasound field. IEEE Trans Ultrason Ferroelectr Freq Control 47:716–726. doi:10.1109/58.842061
Tortoli P, Michelassi V, Corsi M, Righi D, Takeuchi Y (2001) On the interaction between ultrasound and contrast agents during Doppler investigations. Ultrasound Med Biol 27(9):1265–1273. doi:10.1016/S0301-5629(01)00426-4
Tortoli P, Corsi M, Boni E, Arditi M, Frinking PJA (2005) Different effects of microbubble destruction and translation in Doppler measurements. IEEE Trans Ultrason Ferroelectr Freq Control 52(7):1183–1188. doi:10.1109/TUFFC.2005.1504005
Vokurka K (1986) Comparison of Rayleigh’s, Herring’s, and Gilmore’s models of a gas bubbles. Acustica 59:214
Vos HJ, Guidi F, Boni E, Tortoli P (2007) Method for microbubble characterization using primary radiation force. IEEE Trans Ultrason Ferroelectr Freq Control 54(7):1333–1345. doi:10.1109/TUFFC.2007.393
Watanabe T, Kukita Y (1993) Translational and radial motions of a bubble in an acoustic standing wave field. Phys Fluids A 5:2682–2688. doi:10.1063/1.858731
White FM (1991) Viscous fluid flow, 2nd edn. McGraw-Hill, New York
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Tortoli, P., Guidi, F., Mori, R. et al. The use of microbubbles in Doppler ultrasound studies. Med Biol Eng Comput 47, 827–838 (2009). https://doi.org/10.1007/s11517-008-0423-y
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11517-008-0423-y