Acoustic droplet vaporization has the potential to shorten treatment time of high-intensity focused ultrasound (HIFU) while minimizing the possible effects of microbubbles along the propagation path. Distribution of the bubbles formed from the droplets during the treatment is the major factor shaping the therapeutic region. A numerical model was proposed to simulate the bubble area evolution during this treatment. Using a linear acoustic equation to describe the ultrasound field, a threshold range was defined that determines the amount of bubbles vaporized in the treated area. Acoustic parameters, such as sound speed, acoustic attenuation coefficient, and density, were treated as a function of the bubble size distribution and the gas void fraction, which were related to the vaporized bubbles in the medium. An effective pressure factor was proposed to account for the influence of the existing bubbles on the vaporization of the nearby droplets. The factor was obtained by fitting one experimental result and was then used to calculate bubble clouds in other experimental cases. Comparing the simulation results to these other experiments validated the model. The dynamic change of the pressure and the bubble distribution after exposure to over 20 pulses of HIFU are obtained. It is found that the bubble area grows from a grainlike shape to a “tadpole,” with comparable dimensions and shape to those observed in experiments. The process was highly dynamic with the shape of the bubble area changing with successive HIFU pulses and the focal pressure. The model was further used to predict the shape of the bubble region triggered by HIFU when a bubble wall pre-exists. The results showed that the bubble wall helps prevent droplet vaporization on the distal side of the wall and forms a particularly shaped region with bubbles. This simulation model has predictive potential that could be beneficial in applications, such as cancer treatment, by parametrically studying conditions associated with these treatments and designing treatment protocols.

References

1.
Kennedy
,
J.
,
Ter Haar
,
G.
, and
Cranston
,
D.
,
2003
, “
High Intensity Focused Ultrasound: Surgery of the Future?
,”
Br. J. Radiol.
,
76
(
909
), pp.
590
599
.
2.
Kennedy
,
J.
,
Wu
,
F.
,
Ter Haar
,
G.
,
Gleeson
,
F.
,
Phillips
,
R.
,
Middleton
,
M.
, and
Cranston
,
D.
,
2004
, “
High-Intensity Focused Ultrasound for the Treatment of Liver Tumours
,”
Ultrasonics
,
42
(
1
), pp.
931
935
.
3.
Zhang
,
L.
, and
Wang
,
Z.-B.
,
2010
, “
High-Intensity Focused Ultrasound Tumor Ablation: Review of Ten Years of Clinical Experience
,”
Front. Med. China
,
4
(
3
), pp.
294
302
.
4.
Napoli
,
A.
,
Anzidei
,
M.
,
Ciolina
,
F.
,
Marotta
,
E.
,
Marincola
,
B. C.
,
Brachetti
,
G.
,
Di Mare
,
L.
,
Cartocci
,
G.
,
Boni
,
F.
, and
Noce
,
V.
,
2013
, “
MR-Guided High-Intensity Focused Ultrasound: Current Status of an Emerging Technology
,”
Cardiovasc. Interventional Radiol.
,
36
(
5
), pp.
1190
1203
.
5.
Chen
,
W.-S.
,
Lafon
,
C.
,
Matula
,
T. J.
,
Vaezy
,
S.
, and
Crum
,
L. A.
,
2003
, “
Mechanisms of Lesion Formation in High Intensity Focused Ultrasound Therapy
,”
Acoust. Res. Lett. Online
,
4
(
2
), pp.
41
46
.
6.
Takegami
,
K.
,
Kaneko
,
Y.
,
Watanabe
,
T.
,
Watanabe
,
S.
,
Maruyama
,
T.
,
Matsumoto
,
Y.
, and
Nagawa
,
H.
,
2005
, “
Heating and Coagulation Volume Obtained With High-Intensity Focused Ultrasound Therapy: Comparison of Perflutren Protein-Type A Microspheres and MRX-133 in Rabbits 1
,”
Radiology
,
237
(
1
), pp.
132
136
.
7.
Umemura
,
S.-I.
,
Kawabata
,
K.-I.
, and
Sasaki
,
K.
,
2005
, “
In Vivo Acceleration of Ultrasonic Tissue Heating by Microbubble Agent
,”
IEEE Trans. Ultrason. Ferroelectr. Freq. Control
,
52
(
10
), pp.
1690
1698
.
8.
Tung
,
Y.-S.
,
Liu
,
H.-L.
,
Wu
,
C.-C.
,
Ju
,
K.-C.
,
Chen
,
W.-S.
, and
Lin
,
W.-L.
,
2006
, “
Contrast-Agent-Enhanced Ultrasound Thermal Ablation
,”
Ultrasound Med. Biol.
,
32
(
7
), pp.
1103
1110
.
9.
Luo
,
W.
,
Zhou
,
X.
,
Ren
,
X.
,
Zheng
,
M.
,
Zhang
,
J.
, and
He
,
G.
,
2007
, “
Enhancing Effects of SonoVue, a Microbubble Sonographic Contrast Agent, on High-Intensity Focused Ultrasound Ablation in Rabbit Livers In Vivo
,”
J. Ultrasound Med.
,
26
(
4
), pp.
469
476
.
10.
Luo
,
W.
,
Zhou
,
X.
,
He
,
G.
,
Li
,
Q.
,
Zheng
,
X.
,
Fan
,
Z.
,
Liu
,
Q.
,
Yu
,
M.
,
Han
,
Z.
, and
Zhang
,
J.
,
2008
, “
Ablation of High Intensity Focused Ultrasound Combined With SonoVue on Rabbit VX2 Liver Tumors: Assessment With Conventional Gray-Scale US, Conventional Color/Power Doppler US, Contrast-Enhanced Color Doppler US, and Contrast-Enhanced Pulse-Inversion Harmonic US
,”
Ann. Surg. Oncol.
,
15
(
10
), pp.
2943
2953
.
11.
Coussios
,
C.
,
Farny
,
C.
,
Ter Haar
,
G.
, and
Roy
,
R.
,
2007
, “
Role of Acoustic Cavitation in the Delivery and Monitoring of Cancer Treatment by High-Intensity Focused Ultrasound (HIFU)
,”
Int. J. Hyperthermia
,
23
(
2
), pp.
105
120
.
12.
Kripfgans
,
O. D.
,
Fowlkes
,
J. B.
,
Miller
,
D. L.
,
Eldevik
,
O. P.
, and
Carson
,
P. L.
,
2000
, “
Acoustic Droplet Vaporization for Therapeutic and Diagnostic Applications
,”
Ultrasound Med. Biol.
,
26
(
7
), pp.
1177
1189
.
13.
Zhang
,
M.
,
Fabiilli
,
M. L.
,
Haworth
,
K. J.
,
Padilla
,
F.
,
Swanson
,
S. D.
,
Kripfgans
,
O. D.
,
Carson
,
P. L.
, and
Fowlkes
,
J. B.
,
2011
, “
Acoustic Droplet Vaporization for Enhancement of Thermal Ablation by High Intensity Focused Ultrasound
,”
Acad. Radiol.
,
18
(
9
), pp.
1123
1132
.
14.
Kopechek
,
J.
,
Park
,
E.
,
Mei
,
C.-S.
,
McDannold
,
N.
, and
Porter
,
T.
,
2013
, “
Accumulation of Phase-Shift Nanoemulsions to Enhance MR-Guided Ultrasound-Mediated Tumor Ablation In Vivo
,”
J. Healthcare Eng.
,
4
(
1
), pp.
109
126
.
15.
Moyer
,
L. C.
,
Timbie
,
K. F.
,
Sheeran
,
P. S.
,
Price
,
R. J.
,
Miller
,
G. W.
, and
Dayton
,
P. A.
,
2015
, “
High-Intensity Focused Ultrasound Ablation Enhancement In Vivo Via Phase-Shift Nanodroplets Compared to Microbubbles
,”
J. Ther. Ultrasound
,
3
(
1
), p.
7
.
16.
Kripfgans
,
O. D.
,
Zhang
,
M.
,
Fabiilli
,
M. L.
,
Carson
,
P. L.
,
Padilla
,
F.
,
Swanson
,
S. D.
,
Mougenot
,
C.
, and
Fowlkes
,
J. B.
,
2014
, “
Acceleration of Ultrasound Thermal Therapy by Patterned Acoustic Droplet Vaporization
,”
J. Acoust. Soc. Am.
,
135
(
1
), pp.
537
544
.
17.
Phillips
,
L. C.
,
Puett
,
C.
,
Sheeran
,
P. S.
,
Dayton
,
P. A.
,
Miller
,
G. W.
, and
Matsunaga
,
T. O.
,
2013
, “
Phase-Shift Perfluorocarbon Agents Enhance High Intensity Focused Ultrasound Thermal Delivery With Reduced Near-Field Heating
,”
J. Acoust. Soc. Am.
,
134
(
2
), pp.
1473
1482
.
18.
Kopechek
,
J. A.
,
Zhang
,
P.
,
Burgess
,
M. T.
, and
Porter
,
T. M.
,
2011
, “
Synthesis of Phase-Shift Nanoemulsions With Narrow Size Distributions for Acoustic Droplet Vaporization and Bubble-Enhanced Ultrasound-Mediated Ablation
,”
J. Visualized Exp.
,
13
(
67
), p.
e4308
.
19.
Zhang
,
P.
,
Kopechek
,
J. A.
, and
Porter
,
T. M.
,
2013
, “
The Impact of Vaporized Nanoemulsions on Ultrasound-Mediated Ablation
,”
J. Ther. Ultrasound
,
1
(
2
), epub.
20.
Zhu
,
M.
,
Jiang
,
L.
,
Fabiilli
,
M. L.
,
Zhang
,
A.
,
Fowlkes
,
J. B.
, and
Xu
,
L. X.
,
2013
, “
Treatment of Murine Tumors Using Acoustic Droplet Vaporization-Enhanced High Intensity Focused Ultrasound
,”
Phys. Med. Biol.
,
58
(
17
), pp.
6179
6191
.
21.
Kopechek
,
J. A.
,
Park
,
E.-J.
,
Zhang
,
Y.-Z.
,
Vykhodtseva
,
N. I.
,
McDannold
,
N. J.
, and
Porter
,
T. M.
,
2014
, “
Cavitation-Enhanced MR-Guided Focused Ultrasound Ablation of Rabbit Tumors In Vivo Using Phase Shift Nanoemulsions
,”
Phys. Med. Biol.
,
59
(
13
), pp.
3465
3481
.
22.
Li
,
F.
,
Feng
,
R.
,
Zhang
,
Q.
,
Bai
,
J.
, and
Wang
,
Z.
,
2006
, “
Estimation of HIFU Induced Lesions In Vitro: Numerical Simulation and Experiment
,”
Ultrasonics
,
44
(
Supplement
), pp.
e337
e340
.
23.
Liu
,
X.
,
Li
,
J.
,
Gong
,
X.
, and
Zhang
,
D.
,
2006
, “
Nonlinear Absorption in Biological Tissue for High Intensity Focused Ultrasound
,”
Ultrasonics
,
44
(
Supplement
), pp.
e27
e30
.
24.
Solovchuk
,
M.
,
Sheu
,
T. W.-H.
, and
Thiriet
,
M.
,
2015
, “
Multiphysics Modeling of Liver Tumor Ablation by High Intensity Focused Ultrasound
,”
Commun. Comput. Phys.
,
18
(
4
), pp.
1050
1071
.
25.
Tamura
,
Y.
,
Tsurumi
,
N.
, and
Matsumoto
,
Y.
,
2011
, “
Numerical Simulation of Cavitation in Ultrasound Field
,”
Tenth International Symposium on Therapeutic Ultrasound
(
ISTU
), Tokyo, Japan, June 9–12, pp. 431–436.
26.
Okita
,
K.
,
Sugiyama
,
K.
,
Ono
,
K.
,
Takagi
,
S.
, and
Matsumoto
,
Y.
,
2011
, “
Numerical Study of the Effective Combination of Microbubbles and Ultrasound in HIFU Therapy
,”
Tenth International Symposium on Therapeutic Ultrasound
(
ISTU
), Tokyo, Japan, June 9–12, pp. 437–442.
27.
Lauterborn
,
W.
,
1976
, “
Numerical Investigation of Nonlinear Oscillations of Gas Bubbles in Liquids
,”
J. Acoust. Soc. Am.
,
59
(
2
), pp.
283
293
.
28.
Keller
,
J. B.
, and
Miksis
,
M.
,
1980
, “
Bubble Oscillations of Large Amplitude
,”
J. Acoust. Soc. Am.
,
68
(
2
), pp.
628
633
.
29.
Prosperetti
,
A.
, and
Lezzi
,
A.
,
1986
, “
Bubble Dynamics in a Compressible Liquid—Part 1: First-Order Theory
,”
J. Fluid Mech.
,
168
, pp.
457
478
.
30.
Dayton
,
P. A.
,
Morgan
,
K. E.
,
Klibanov
,
A. L.
,
Brandenburger
,
G. H.
, and
Ferrara
,
K. W.
,
1999
, “
Optical and Acoustical Observations of the Effects of Ultrasound on Contrast Agents
,”
IEEE Trans. Ultrason. Ferroelectr. Freq. Control
,
46
(
1
), pp.
220
232
.
31.
de Jong
,
N.
,
Frinking
,
P. J.
,
Bouakaz
,
A.
,
Goorden
,
M.
,
Schourmans
,
T.
,
Jingping
,
X.
, and
Mastik
,
F.
,
2000
, “
Optical Imaging of Contrast Agent Microbubbles in an Ultrasound Field With a 100-MHz Camera
,”
Ultrasound Med. Biol.
,
26
(
3
), pp.
487
492
.
32.
Chavrier
,
F.
,
Chapelon
,
J.
,
Gelet
,
A.
, and
Cathignol
,
D.
,
2000
, “
Modeling of High-Intensity Focused Ultrasound-Induced Lesions in the Presence of Cavitation Bubbles
,”
J. Acoust. Soc. Am.
,
108
(
1
), pp.
432
440
.
33.
Curiel
,
L.
,
Chavrier
,
F.
,
Gignoux
,
B.
,
Pichardo
,
S.
,
Chesnais
,
S.
, and
Chapelon
,
J.
,
2004
, “
Experimental Evaluation of Lesion Prediction Modelling in the Presence of Cavitation Bubbles: Intended for High-Intensity Focused Ultrasound Prostate Treatment
,”
Med. Biol. Eng. Comput.
,
42
(
1
), pp.
44
54
.
34.
Holt
,
R. G.
,
Roy
,
R. A.
,
Thomas
,
C. R.
,
Farny
,
C.
,
Wu
,
T.
,
Yang
,
X.
, and
Edson
,
P.
,
2006
, “
Therapeutic Bubbles: Basic Principles of Cavitation in Therapeutic Ultrasound
,”
Fifth International Symposium on Therapeutic Ultrasound
(
ISTU
), Boston, MA, Oct. 27–29, pp. 13–17.
35.
Wu
,
T.
,
Roy
,
R. A.
, and
Holt
,
R. G.
,
2006
, “
Thermal Lesion Development in Bubble‐Mediated HIFU: Modeling
,”
Therapeutic Ultrasound: Fifth International Symposium on Therapeutic Ultrasound
(
ISTU
), Boston, MA, Oct. 27–29, pp. 333–337.
36.
Fabiilli
,
M. L.
,
Haworth
,
K. J.
,
Fakhri
,
N. H.
,
Kripfgans
,
O. D.
,
Carson
,
P. L.
, and
Fowlkes
,
J. B.
,
2009
, “
The Role of Inertial Cavitation in Acoustic Droplet Vaporization
,”
IEEE Trans. Ultrason. Ferroelectr. Freq. Control
,
56
(
5
), pp.
1006
1017
.
37.
Lo
,
A. H.
,
Kripfgans
,
O. D.
,
Carson
,
P. L.
,
Rothman
,
E. D.
, and
Fowlkes
,
J. B.
,
2007
, “
Acoustic Droplet Vaporization Threshold: Effects of Pulse Duration and Contrast Agent
,”
IEEE Trans. Ultrason. Ferroelectr. Freq. Control
,
54
(
5
), pp.
933
946
.
38.
Commander
,
K. W.
, and
Prosperetti
,
A.
,
1989
, “
Linear Pressure Waves in Bubbly Liquids: Comparison Between Theory and Experiments
,”
J. Acoust. Soc. Am.
,
85
(
2
), pp.
732
746
.
39.
Church
,
C. C.
,
1995
, “
The Effects of an Elastic Solid Surface Layer on the Radial Pulsations of Gas Bubbles
,”
J. Acoust. Soc. Am.
,
97
(
3
), pp.
1510
1521
.
40.
Qiao
,
Y.
,
Zong
,
Y.
,
Yin
,
H.
,
Chang
,
N.
,
Li
,
Z.
, and
Wan
,
M.
,
2014
, “
Spatial and Temporal Observation of Phase-Shift Nano-Emulsions Assisted Cavitation and Ablation During Focused Ultrasound Exposure
,”
Ultrason. Sonochem.
,
21
(
5
), pp.
1745
1751
.
41.
Chen
,
H.
,
Li
,
X.
, and
Wan
,
M.
,
2006
, “
Spatial–Temporal Dynamics of Cavitation Bubble Clouds in 1.2 MHz Focused Ultrasound Field
,”
Ultrason. Sonochem.
,
13
(
6
), pp.
480
486
.
42.
Lo
,
A. H.
,
Kripfgans
,
O. D.
,
Carson
,
P. L.
, and
Fowlkes
,
J. B.
,
2006
, “
Spatial Control of Gas Bubbles and Their Effects on Acoustic Fields
,”
Ultrasound Med. Biol.
,
32
(
1
), pp.
95
106
.
43.
Reznik
,
N.
,
Seo
,
M.
,
Williams
,
R.
,
Bolewska-Pedyczak
,
E.
,
Lee
,
M.
,
Matsuura
,
N.
,
Gariepy
,
J.
,
Foster
,
F. S.
, and
Burns
,
P. N.
,
2011
, “
Optical Fluorescence Studies of Perfluorocarbon Droplet Vaporization
,”
IEEE International Ultrasonics Symposium
(
ULTSYM
), Orlando, FL, Oct. 18–21, pp. 2424–2427.
44.
Reznik
,
N.
,
Seo
,
M.
,
Williams
,
R.
,
Bolewska-Pedyczak
,
E.
,
Lee
,
M.
,
Matsuura
,
N.
,
Gariepy
,
J.
,
Foster
,
F. S.
, and
Burns
,
P. N.
,
2012
, “
Optical Studies of Vaporization and Stability of Fluorescently Labelled Perfluorocarbon Droplets
,”
Phys. Med. Biol.
,
57
(
21
), pp.
7205
7217
.
45.
Del Grosso
,
V.
, and
Mader
,
C.
,
1972
, “
Speed of Sound in Pure Water
,”
J. Acoust. Soc. Am.
,
52
(
5B
), pp.
1442
1446
.
46.
Pinkerton
,
J.
,
1947
, “
A Pulse Method for the Measurement of Ultrasonic Absorption in Liquids: Results for Water
,”
Nature
,
160
(
4056
), pp.
128
129
.
47.
Takegami
,
K.
,
Kaneko
,
Y.
,
Watanabe
,
T.
,
Maruyama
,
T.
,
Matsumoto
,
Y.
, and
Nagawa
,
H.
,
2004
, “
Polyacrylamide Gel Containing Egg White as New Model for Irradiation Experiments Using Focused Ultrasound
,”
Ultrasound Med. Biol.
,
30
(
10
), pp.
1419
1422
.
48.
Cui
,
S. T.
,
Siepmann
,
J. I.
,
Cochran
,
H. D.
, and
Cummings
,
P. T.
,
1998
, “
Intermolecular Potentials and Vapor–Liquid Phase Equilibria of Perfluorinated Alkanes
,”
Fluid Phase Equilib.
,
146
(
1
), pp.
51
61
.
49.
Kandadai
,
M. A.
,
Mohan
,
P.
,
Lin
,
G.
,
Butterfield
,
A.
,
Skliar
,
M.
, and
Magda
,
J. J.
,
2010
, “
Comparison of Surfactants Used to Prepare Aqueous Perfluoropentane Emulsions for Pharmaceutical Applications
,”
Langmuir
,
26
(
7
), pp.
4655
4660
.
50.
Yang
,
X.
, and
Church
,
C. C.
,
2005
, “
A Model for the Dynamics of Gas Bubbles in Soft Tissue
,”
J. Acoust. Soc. Am.
,
118
(
6
), pp.
3595
3606
.
51.
Kripfgans
,
O. D.
,
Fabiilli
,
M. L.
,
Carson
,
P. L.
, and
Fowlkes
,
J. B.
,
2004
, “
On the Acoustic Vaporization of Micrometer-Sized Droplets
,”
J. Acoust. Soc. Am.
,
116
(
1
), pp.
272
281
.
52.
Sheeran
,
P. S.
,
Wong
,
V. P.
,
Luois
,
S.
,
McFarland
,
R. J.
,
Ross
,
W. D.
,
Feingold
,
S.
,
Matsunaga
,
T. O.
, and
Dayton
,
P. A.
,
2011
, “
Decafluorobutane as a Phase-Change Contrast Agent for Low-Energy Extravascular Ultrasonic Imaging
,”
Ultrasound Med. Biol.
,
37
(
9
), pp.
1518
1530
.
53.
Radhakrishnan
,
K.
,
Holland
,
C. K.
, and
Haworth
,
K. J.
,
2016
, “
Scavenging Dissolved Oxygen Via Acoustic Droplet Vaporization
,”
Ultrason. Sonochem.
,
31
, pp.
394
403
.
54.
Watkin
,
N.
,
Ter Haar
,
G.
, and
Rivens
,
I.
,
1996
, “
The Intensity Dependence of the Site of Maximal Energy Deposition in Focused Ultrasound Surgery
,”
Ultrasound Med. Biol.
,
22
(
4
), pp.
483
491
.
55.
Bailey
,
M. R.
,
Couret
,
L. N.
,
Sapozhnikov
,
O. A.
,
Khokhlova
,
V. A.
,
ter Haar
,
G.
,
Vaezy
,
S.
,
Shi
,
X.
,
Martin
,
R.
, and
Crum
,
L. A.
,
2001
, “
Use of Overpressure to Assess the Role of Bubbles in Focused Ultrasound Lesion Shape In Vitro
,”
Ultrasound Med. Biol.
,
27
(
5
), pp.
695
708
.
56.
Unga
,
J.
, and
Hashida
,
M.
,
2014
, “
Ultrasound Induced Cancer Immunotherapy
,”
Adv. Drug Delivery Rev.
,
72
, pp.
144
153
.
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