Coated microbubbles, unlike tissue are able to scatter sound subharmonically. Therefore, the subharmonic behavior of coated microbubbles can be used to enhance the contrast in ultrasound contrast imaging. Theoretically, a threshold amplitude of the driving pressure can be calculated above which subharmonic oscillations of microbubbles are initiated. Interestingly, earlier experimental studies on coated microbubbles demonstrated that the threshold for these bubbles is much lower than predicted by the traditional linear viscoelastic shell models. This paper presents an experimental study on the subharmonic behavior of differently sized individual phospholipid coated microbubbles. The radial subharmonic response of the microbubbles was recorded with the Brandaris ultra high-speed camera as a function of both the amplitude and the frequency of the driving pulse. Threshold pressures for subharmonic generation as low as 5 kPa were found near a driving frequency equal to twice the resonance frequency of the bubble. An explanation for this low threshold pressure is provided by the shell buckling model proposed by Marmottant et al [J. Acoust. Soc. Am. 118, 3499–3505 (2005)]. It is shown that the change in the elasticity of the bubble shell as a function of bubble radius as proposed in this model, enhances the subharmonic behavior of the microbubbles.
REFERENCES
1.
F.
Forsberg
, D. A.
Merton
, J. B.
Liu
, L.
Needleman
, and B. B.
Goldberg
, “Clinical applications of ultrasound contrast agents
,” Ultrasonics
36
, 695
–701
(1998
).2.
T.
Albrecht
and J.
Hohmann
, “Ultrasound contrast agents
,” Radiologe
43
, 793
–804
(2003
).3.
F. B.
Feinstein
, “The powerful microbubble: From bench to bedside, from intravascular indicator to therapeutic delivery system, and beyond
,” Am. J. Physiol. Heart Circ. Physiol.
287
, H450
–457
(2004
).4.
B. A.
Kaufmann
and J. R.
Lindner
, “Molecular imaging with targeted contrast ultra sound
,” Curr. Opin. Biotechnol.
18
, 11
–16
(2007
).5.
A.
Bouakaz
, S.
Frigstad
, F. J.
ten Cate
, and N.
de Jong
, “Super harmonic imaging: A new imaging technique for improved contrast detection
,” Ultrasound Med. Biol.
28
, 59
–68
(2002
).6.
V.
Mor-Avi
, E. G.
Caiani
, K. A.
Collins
, C. E.
Korcarz
, J. E.
Bednarz
, and R. M.
Lang
, “Combined assessment of myocardial perfusion and regional left ventricular function by analysis of contrast-enhanced power modulation images
,” Circulation
104
, 352
–357
(2001
).7.
D. H.
Simpson
, C. T.
Chin
, and P. N.
Burns
, “Pulse inversion Doppler: A new method for detecting nonlinear echoes from microbubble contrast agents
,” IEEE Trans. Ultrason. Ferroelectr. Freq. Control
46
, 372
–382
(1999
).8.
P. J. A.
Frinking
, A.
Bouakaz
, J.
Kirkhorn
, F. J.
ten Cate
, and N.
de Jong
, “Ultrasound contrast imaging: Current and new potential methods
,” Ultrasound Med. Biol.
26
, 965
–975
(2000
).9.
P.
Rafter
, P.
Phillips
, and M. A.
Vannan
, “Imaging technologies and techniques
,” Cardiol. Clin.
22
, 181
–197
(2004
).10.
P. M.
Shankar
, P. D.
Krishna
, and V. L.
Newhouse
, “Advantages of subharmonic over second harmonic backscatter for contrast-to-tissue echo enhancement
,” Ultrasound Med. Biol.
24
, 395
–399
(1998
).11.
D. E.
Goertz
, M. E.
Frijlink
, N.
de Jong
, and A. F. W.
van der Steen
, “High frequency nonlinear scattering from a micrometer to submicrometer sized lipid encapsulated contrast agent
,” Ultrasound Med. Biol.
32
, 569
–577
(2006
).12.
D. E.
Goertz
, M. E.
Frijlink
, D.
Tempel
, V.
Bhagwandas
, A.
Gisolf
, R.
Krams
, N.
de Jong
, and A. F. W.
van der Steen
, “Subharmonic contrast intravascular ultrasound for vasa vasorum imaging
,” Ultrasound Med. Biol.
33
, 1859
–1872
(2007
).13.
R.
Esche
, “Investigations on oscillating cavities in liquids
,” Acustica
2
, 208
–218
(1952
).14.
E. A.
Neppiras
, “Subharmonic and other low-frequency emission from bubbles in sound-irradiated liquids
,” J. Acoust. Soc. Am.
46
, 587
–601
(1969
).15.
P.
de Santis
, D.
Sette
, and F.
Wanderlingh
, “Cavitation detection: The use of the subharmonics
,” J. Acoust. Soc. Am.
42
, 514
–516
(1967
).16.
A.
Eller
and H. G.
Flynn
, “Generation of subharmonics of order one-half by bubbles in a sound field
,” J. Acoust. Soc. Am.
46
, 722
–727
(1969
).17.
A. I.
Eller
, “Subharmonic response of bubbles to underwater sound
,” J. Acoust. Soc. Am.
55
, 871
–873
(1974
).18.
A.
Prosperetti
, “Nonlinear oscillations of gas bubbles in liquids: Steady-state solutions
,” J. Acoust. Soc. Am.
56
, 878
–885
(1974
).19.
A.
Prosperetti
, “Nonlinear oscillations of gas bubbles in liquids. Transient solutions and the connection between subharmonic signal and cavitation
,” J. Acoust. Soc. Am.
57
, 810
–821
(1975
).20.
W.
Lauterborn
, “Numerical investigation of nonlinear oscillations of gas bubbles in liquids
,” J. Acoust. Soc. Am.
59
, 283
–293
(1976
).21.
M. S.
Plesset
and A.
Prosperetti
, “Bubble dynamics and cavitation
,” Annu. Rev. Fluid Mech.
9
, 145
–185
(1977
).22.
23.
C. E.
Brennen
, Cavitation and Bubble Dynamics
(Oxford University Press
, Oxford
, 1995
).24.
M.
Brenner
, S.
Hilgenfeldt
, and D.
Lohse
, “Single-bubble sonoluminescence
,” Rev. Mod. Phys.
74
, 425
–484
(2002
).25.
A.
Prosperetti
, “Application of the subharmonic threshold to the measurement of the damping of oscillating gas bubbles
,” J. Acoust. Soc. Am.
61
, 11
–16
(1977
).26.
N.
de Jong
and L.
Hoff
, “Ultrasound scattering properties of Albunex microspheres
,” Ultrasonics
31
, 175
–181
(1993
).27.
K.
Sarkar
, W. T.
Shi
, D.
Chatterjee
, and F.
Forsberg
, “Characterization of ultrasound contrast microbubbles using in vitro experiments and viscous and viscoelastic interface models for encapsulation
,” J. Acoust. Soc. Am.
118
, 539
–550
(2005
).28.
S.
van der Meer
, B.
Dollet
, M.
Voormolen
, C. T.
Chin
, A.
Bouakaz
, N.
de Jong
, M.
Versluis
, and D.
Lohse
, “Microbubble spectroscopy of ultrasound contrast agents
,” J. Acoust. Soc. Am.
121
, 648
–656
(2007
).29.
P. M.
Shankar
, P. D.
Krishna
, and V. L.
Newhouse
, “Subharmonic backscattering from ultrasound contrast agents
,” J. Acoust. Soc. Am.
106
, 2104
–2110
(1999
).30.
C. C.
Church
, “The effect of an elastic solid surface layer on the radial pulsations of gas bubbles
,” J. Acoust. Soc. Am.
97
, 1510
–1521
(1995
).31.
L.
Hoff
, P. C.
Sontum
, and J. M.
Hovem
, “Oscillations of polymeric microbubbles: Effect of the encapsulating shell
,” J. Acoust. Soc. Am.
107
, 2272
–2280
(2000
).32.
O.
Lotsberg
, J. M.
Hovem
, and B.
Aksum
, “Experimental observation of subharmonic oscillations in Infoson bubbles
,” J. Acoust. Soc. Am.
99
, 1366
–1369
(1996
).33.
P. D.
Krishna
, P. M.
Shankar
, and V. L.
Newhouse
, “Subharmonic generation from ultrasonic contrast agents
,” Phys. Med. Biol.
44
, 681
–694
(1999
).34.
P. H.
Chang
, K. K.
Shung
, S.
Wu
, and H. B.
Levene
, “Second harmonic imaging and harmonic Doppler measurements with Albunex
,” IEEE Trans. Ultrason. Ferroelectr. Freq. Control
42
, 1020
–1027
(1995
).35.
E.
Biagi
, L.
Breschi
, E.
Vannacci
, and L. A.
Masotti
, “Stable and transient subharmonic emissions from isolated contrast agent microbubbles
,” IEEE Trans. Ultrason. Ferroelectr. Freq. Control
54
, 480
–497
(2007
).36.
G.
Bhagavatheeshwaran
, W. T.
Shi
, F.
Forsberg
, and P. M.
Shankar
, “Subharmonic signal generation from contrast agents in simulated neovessels
,” Ultrasound Med. Biol.
30
, 199
–203
(2004
).37.
E.
Kimmel
, B.
Krasovitski
, A.
Hoogi
, D.
Razansky
, and D.
Adam
, “Subharmonic response of encapsulated microbubbles: Conditions for existence and amplification
,” Ultrasound Med. Biol.
33
, 1767
–1776
(2007
).38.
P.
Marmottant
, S.
van der Meer
, M.
Emmer
, M.
Versluis
, N.
de Jong
, S.
Hilgenfeldt
, and D.
Lohse
, “A model for large amplitude oscillations of coated bubbles accounting for buckling and rupture
,” J. Acoust. Soc. Am.
118
, 3499
–3505
(2005
).39.
C. T.
Chin
, C.
Lancée
, J.
Borsboom
, F.
Mastik
, M. E.
Frijlink
, N.
de Jong
, M.
Versluis
, and D.
Lohse
, “Brandaris 128: A digital 25 million frames per second camera with 128 highly sensitive frames
,” Rev. Sci. Instrum.
74
, 5026
–5034
(2003
).40.
C.
Devin
, Jr., “Survey of thermal, radiation and viscous damping of pulsating bubbles
,” J. Acoust. Soc. Am.
31
, 1654
–1667
(1959
).41.
H.
Medwin
, “Counting bubbles acoustically: A review
,” Ultrasonics
15
, 7
–13
(1977
).42.
M.
Overvelde
, V.
Garbin
, J.
Sijl
, B.
Dollet
, N.
de Jong
,, D.
Lohse
, and M.
Versluis
, “Nonlinear shell behavior of phospholipid-coated microbubbles
,” Ultrasound Med. Biol.
(2010
, in print).43.
X.
Wen
and E. I.
Franses
, “Adsorption of bovine serum albumin at the air/water interface and its effect on the formation of DPPC surface film
,” Colloids Surf., A
190
, 319
–332
(2001
).44.
C. C.
Cheng
and C. -H.
Chang
, “Retardation effect of tyloxapol on inactivation of dipalmitoyl phosphatidylcholine surface activity by albumin
,” Langmuir
16
, 437
–441
(2000
).45.
J.
Sijl
, E.
Gaud
, P. J. A.
Frinking
, M.
Arditi
, N.
de Jong
, D.
Lohse
, and M.
Versluis
, “Acoustic characterization of single ultrasound contrast agent microbubbles
,” J. Acoust. Soc. Am.
124
, 4091
–4097
(2008
).46.
V.
Garbin
, D.
Cojoc
, E.
Ferrari
, E.
Di Fabrizio
, M. L. J.
Overvelde
, S. M.
van der Meer
, N.
de Jong
, D.
Lohse
, and M.
Versluis
, “Changes in microbubble dynamics near a boundary revealed by combined optical micromanipulation and high-speed imaging
,” Appl. Phys. Lett.
90
, 114103
(2007
).47.
B.
Dollet
, S.
van der Meer
, V.
Garbin
, N.
de Jong
, D.
Lohse
, and M.
Versluis
, “Nonspherical oscillations of ultrasound contrast agent microbubbles
,” Ultrasound Med. Biol.
34
, 1465
–1473
(2008
).48.
S.
Hilgenfeldt
, D.
Lohse
, and M.
Zomack
, “Response of bubbles to diagnostic ultrasound: A unifying theoretical approach
,” Eur. Phys. J. B
4
, 247
–255
(1998
).49.
N.
de Jong
, M.
Emmer
, C. T.
Chin
, A.
Bouakaz
, F.
Mastik
, D.
Lohse
, and M.
Versluis
, “‘Compression-only’ behavior of phospholipid-coated contrast bubbles
,” Ultrasound Med. Biol.
33
, 653
–656
(2007
).50.
J.
Sijl
, M.
Overvelde
, B.
Dollet
, V.
Garbin
, N.
de Jong
, D.
Lohse
, and M.
Versluis
, “‘Compression-only’ behavior: A second order nonlinear response of ultrasound contrast agent microbubbles
,” J. Acoust. Soc. Am.
(2010
, in print).51.
M. I.
Sández
, A.
Suárez
, and A.
Gil
, “Surface pressure-area isotherms and fluorescent behavior of phospholipids containing labeled pyrene
,” J. Colloid Interface Sci.
250
, 128
–133
(2002
).52.
F.
Pétriat
, E.
Roux
, J. C.
Leroux
, and S.
Giasson
, “Study of molecular interactions between a phospholipidic layer and a pH-sensitive polymer using the Langmuir balance technique
,” Langmuir
20
, 1393
–1400
(2004
).53.
R.
Veldhuizen
, K.
Nag
, S.
Orgeig
, and F.
Possmayer
, “The role of lipids in pulmonary surfactant
,” Biochim. Biophys. Acta
1408
, 90
–108
(1998
).54.
G.
Enhorning
, “Pulsating bubble technique for evaluating pulmonary surfactant
,” J. Appl. Physiol.
43
, 198
–203
(1977
).55.
P. J. A.
Frinking
, E.
Gaud
, J.
Brochot
, and M.
Arditi
, “Subharmonic scattering of phospholipid-shell microbubbles at low acoustic pressure amplitudes
,” IEEE Trans. Ultrason. Ferroelectr. Freq. Control
57
, 1762
–1771
(2010
).© 2010 Acoustical Society of America.
2010
Acoustical Society of America
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