The enhancement of ultrasound-induced cell destruction, lysis, and sonoporation in low cell concentration suspensions (2×105/mL) by the presence of contrast agents (gas bubble to cell ratio=230) was demonstrated using cervical cancer cells (HeLa S3) suspensions containing micron-size denatured albumin microspheres filled with air (Albunex®) or octafluoropropane (Optison™). The suspensions were insonificated by 2-MHz continuous or tone burst ultrasound in near field. The spatial peak-pressure amplitude was 0.2 MPa. The enhancement of cell destruction due to Optison™ was shown to be much higher than that due to Albunex® for similar bubble concentration and ultrasound conditions. For tone burst exposures, significant lysis and sonoporation only occurred in the presence of a contrast agent. The majority of the bioeffects observed occured in the first 5 min of exposure. The relationship between the enhancement of bioeffects and duty cycle of tone burst ultrasound appears to indicate that both stable gas spheres of contrast agents and cavitation nuclei created by the disruption of the gas spheres play a significant role in causing the bioeffects.

1.
Apfel
,
R. E.
(
1997
). “
Sonic effervescence: A tutorial on acoustic cavitation
,”
J. Acoust. Soc. Am.
101
,
1227
1237
.
2.
Beissner, K. (1992). “Radiation force and force balances,” in Ultrasonic Exposimetry, edited by M. Ziskin and P. Lewin (CRC Press, Boca Raton, FL).
3.
Bao
,
S.
,
Thrall
,
B. D.
, and
Miller
,
D. L.
(
1997
). “
Transfection of a reporter plasmid into cultured cells by sonoporation in vitro
,”
Ultrasound Med. Biol.
23
,
953
959
.
4.
Brayman
,
A. A.
,
Strickler
,
P. L.
,
Luan
,
H.
,
Barned
,
S. L.
,
Raeman
,
C. H.
,
Cox
,
C.
, and
Miller
,
M. W.
(
1997
). “
Hemolysis of 40% hematocrit Albunex®-supplemented human erythrocytes by pulsed ultrasound frequency, acoustic pressure and pulse length dependence
,”
Ultrasound Med. Biol.
23
,
1237
1250
.
5.
Brown
,
J.
,
Alderman
,
J.
,
Quedens-Case
,
C.
, and
Taylor
,
K. J. W.
(
1996
). “
Enhancement demonstration of neovascularity in a VX2 carcinoma by ultrasound contrast (FS069, MBI Inc.)
,”
J. Ultrasound Med.
15
,
S18
.
6.
Dittrich
,
H. C.
,
Bales
,
G. L.
,
Hunt
,
R. M.
,
McFerran
,
B. A.
,
Leopold
,
G. R.
, and
Greener
,
Y.
(
1994
). “
Multiple organ tissue perfusion by intravenously (IV) administered novel ultrasound contrast agents in dogs
,”
J. Ultrasound Med.
12
,
S9
.
7.
Dittrich
,
H. C.
,
Kuvelas
,
T.
,
Dadd
,
K.
,
Burns
,
D.
,
Compton
,
H.
,
Mizoguchi
,
A.
, and
Widder
,
K.
(
1995
). “
Safety and efficacy of the ultrasound contrast agent FS069 in normal human: results of a phase one trial
,”
Circulation
92
,
I464
.
8.
Goldberg, B. B. (1993). “Ultrasound contrast agents,” in Advances in Ultrasound Techniques and Instrumentation, edited by P. N. T. Wells (Churchill Livingstone, New York), pp. 35–45.
9.
Gormley
,
G.
, and
Wu
,
J.
(
1998
). “
Acoustic streaming near Albunex® spheres
,”
J. Acoust. Soc. Am.
104
,
3115
3118
.
10.
Greenleaf, J. F, Greenleaf, W. J., Kinnick, R., Sarkar, G., and Bolander, M. A. (pp. 1998). Enhancement of Ultrasound Mediated Transfection with Cavitation Micronuclei, Proceedings, 16th International Congress on Acoustics and 135th Meeting Acoustical Society of America, Seattle, 1447–1448.
11.
Killam
,
A. L.
,
Greener
,
Y.
,
McFerran
,
B. A.
,
Maniquis
,
J.
,
Bloom
,
A.
,
Widder
,
K.
, and
Dittrich
,
H. C.
(
1998
). “
Lack of bioeffects of ultrasound energy after intravenous administration of FS069 in the anesthetized rabbit
,”
J. Ultrasound Med.
17
,
349
356
.
12.
Marsh
,
J. N.
,
Hall
,
C. S.
,
Hughes
,
M. S.
,
Mobley
,
J.
,
Miller
,
J. G.
, and
Branenburger
,
G. H.
(
1997
). “
Broadband through-transmission signal loss measurements of Albunex® suspensions at concentrations approaching in vivo doses
,”
J. Acoust. Soc. Am.
101
,
1155
1161
.
13.
Miller
,
D. L.
, and
Thomas
,
R. M.
(
1996
). “
Contrast-agent gas bodies enhance hemolysis induced by lithotripter shock waves and high-intensity focused ultrasound in whole blood
,”
Ultrasound Med. Biol.
22
,
1089
1095
.
14.
Miller
,
D. L.
,
Gies
,
R. A.
, and
Chrisler
,
W. B.
(
1997
). “
Ultrasonically induced hemolysis at high cell and gas body concentrations in a thin-disc exposure chamber
,”
Ultrasound Med. Biol.
23
,
625
633
.
15.
Miller
,
D. L.
, and
Gies
,
R. A.
(
1998
). “
Enhancement of ultrasonically-induced hemolysis by perfluorocarbon-based compared to air-based echo-contrast agents
,”
Ultrasound Med. Biol.
24
,
285
292
.
16.
Miller
,
M. W.
,
Miller
,
D. L.
, and
Brayman
,
A. A.
(
1996
). “
A review of in vitro bioeffects of inertial ultrasonic cavitation from a mechanistic perspective
,”
Ultrasound Med. Biol.
22
,
1131
1154
.
17.
Nyborg, W. L. (1996). “Basic physics of low frequency therapeutic ultrasound,” in Ultrasound Argioplasty, edited by R. J. Siegel (Kluwer Academic, Boston).
18.
Worthington
,
A. E.
,
Thompson
,
J
,
Rauth
,
A. M.
, and
Hunt
,
J. W.
(
1997
). “
Mechanism of ultrasound enhanced porphyrin cytotoxicity. Part I. A search for free radical effects
,”
Ultrasound Med. Biol.
23
,
1095
1105
.
19.
Wu
,
J.
, and
Tong
,
J.
(
1998
). “
Experimental study of stability of contrast agents in an ultrasound field
,”
Ultrasound Med. Biol.
24
,
257
265
.
This content is only available via PDF.
You do not currently have access to this content.