High-speed video microscopy and numerical modeling of bubble dynamics near a
surface of urinary stone
Yuri A. Pishchalnikov
, William M. Behnke-Parks
, Kevin Schmidmayer
, Kazuki Maeda
, Tim Colonius
, Thomas W.
Kenny
, and
Daniel J. Laser
Citation:
The Journal of the Acoustical Society of America
146
, 516 (2019); doi: 10.1121/1.5116693
View online:
https://doi.org/10.1121/1.5116693
View Table of Contents:
https://asa.scitation.org/toc/jas/146/1
Published by the
Acoustical Society of America
High-speed video microscopy and numerical modeling of bubble
dynamics near a surface of urinary stone
Yuri A.
Pishchalnikov,
1,
a)
William M.
Behnke-Parks,
1
Kevin
Schmidmayer,
2
Kazuki
Maeda,
2,
b)
Tim
Colonius,
2
Thomas W.
Kenny,
3
and Daniel J.
Laser
1
1
Applaud Medical, Incorporated, 953 Indiana Street, San Francisco, California 94107, USA
2
Division of Engineering and Applied Science, California Institute of Technology, Pasadena,
California 91125, USA
3
Department of Mechanical Engineering, Stanford University, Stanford, California 94305, USA
(Received 4 March 2019; revised 21 June 2019; accepted 26 June 2019; published online 26 July
2019)
Ultra-high-speed video microscopy and numerical modeling were used to assess the dynamics of
microbubbles at the surface of urinary stones. Lipid-shell microbubbles designed to accumulate on
stone surfaces were driven by bursts of ultrasound in the sub-MHz range with pressure amplitudes
on the order of 1 MPa. Microbubbles were observed to undergo repeated cycles of expansion and
violent collapse. At maximum expansion, the microbubbles’ cross-section resembled an ellipse
truncated by the stone. Approximating the bubble shape as an oblate spheroid, this study modeled
the collapse by solving the multicomponent Euler equations with a two-dimensional-axisymmetric
code with adaptive mesh refinement for fine resolution of the gas-liquid interface. Modeled bubble
collapse and high-speed video microscopy showed a distinctive circumferential pinching during the
collapse. In the numerical model, this pinching was associated with bidirectional microjetting nor-
mal to the rigid surface and toroidal collapse of the bubble. Modeled pressure spikes had ampli-
tudes two-to-three orders of magnitude greater than that of the driving wave. Micro-computed
tomography was used to study surface erosion and formation of microcracks from the action of
microbubbles. This study suggests that engineered microbubbles enable stone-treatment modalities
with driving pressures significantly lower than those required without the microbubbles.
V
C
2019 Acoustical Society of America
.
https://doi.org/10.1121/1.5116693
[CCC]
Pages: 516–531
I. INTRODUCTION
Mechanical action of engineered microbubbles in response
to acoustic excitation is increasingly used in medical applica-
tions, such as for targeted destruction of biomineralizations.
1
–
3
To promote preferential action on a target, the bubble shell can
be engineered to facilitate accumulation of micr
obubbles on
the surfaces of targets.
1
,
2
To target and treat urinary stones,
Ramaswamy
et al.
1
proposed placing engineered microbubbles
in the urinary tract or kidney, where the bubbles can
accumu-
late on exposed surf
aces of stones (Fig.
1
). The accumulated
microbubbles then can be energized by one or more energy
sources to mechanically erode, pit, and fragment the stone.
1
,
4
,
5
With a pulsed laser energy source, a recent
in vitro
study
has shown that adding stone-surface-accumulating (SSA)
microbubbles increased the rate of erosion, pitting, and frag-
mentation of model stones by
70%.
4
Other studies have
shown that SSA microbubbles can be placed in the urinary
tract cystoscopically and energized by an extracorporeal
acoustic energy source.
5
The use of ultrasound with wide
beam widths (several centimeters) reduces the burden of pre-
cise image guidance (Fig.
1
) and, with a cystoscopic delivery
of SSA microbubbles, can be performed in diverse clinical
settings including the urologist office.
In shock wave lithotripsy, urinary stones are broken
with focused shock pulses with pressure amplitudes of
15–150 MPa.
6
Recent
in vitro
experiments have shown that
urinary stones can be broken by bursts of focused ultrasound
with center frequencies in a sub-MHz range and amplitudes
of several MPa.
7
Preliminary experiments with SSA micro-
bubbles suggest that model and urinary stones can be broken
by acoustic bursts with pressure amplitudes at the upper lev-
els of diagnostic ultrasound (1.2
6
0.2 MPa, 0.3–1 MHz).
5
In
these experiments, the stones were implanted in a porcine
model and treated by wide beam-width ultrasound with no
evidence of urothelium damage and renal parenchymal hem-
orrhage on histological and gross anatomical examination of
post-procedure ureters and kidneys.
5
These encouraging results suggest a need to better
understand the dynamics and the mechanical action of SSA
microbubbles at these driving conditions. In this work,
we used bursts of ultrasound with central frequencies of
0.42 MHz and amplitudes of 1.4
6
0.4 MPa. The dynamics
of microbubbles was studied using high-speed video micros-
copy at a frame rate of up to 10
10
6
fps, capturing com-
plete expansion-collapse cycles of the bubbles. The observed
geometry of bubbles at their maximum expansion was used
as the initial shape for the numerical modeling of the col-
lapse. For modeling, we solved the multicomponent Euler
equations using a two-dimensional (2 D)-axisymmetric code
with adaptive time step and mesh refinement algorithms for
fine resolution of the gas-liquid interface and shock fronts.
8
,
9
a)
Electronic mail: yuri.pishchalnikov@applaudmedical.com
b)
Present address: Department of Mechanical Engineering, University of
Washington, Seattle, WA 98195, USA.
516 J. Acoust. Soc. Am.
146
(1), July 2019
V
C
2019 Acoustical Society of America
0001-4966/2019/146(1)/516/16/$30.00
The use of a 2 D code instead of a one-dimensional (1D)
spherical model
10
–
16
was motivated by the present and previ-
ous observations showing that oscillations of microbubbles
can be highly nonspherical.
2
,
17
–
25
Hsiao and Chahine
26
modeled a shelled microbubble
subjected to one cycle of 2.5-MHz ultrasound at 1 MPa. The
modeling showed nonspherical deformations due to the pres-
ence of a nearby rigid boundary and, depending on the stand-
off distance, one of the following dynamics of the collapse:
(1) a single reentrant jet, (2) a ring-type reentrant jet, and (3)
a pinching of the bubble.
26
Here, we report experimental
observations of a circumferential pinching and the numerical
modeling showing that the pinching propels two microjets
directed away and toward the rigid boundary. When hitting
the boundary, the jet was either a single reentrant jet or a
ring-type jet, depending on the amount of gas modeled in the
bubble.
The present paper is organized as follows. Section
II
describes the experimental arrangement to record the
dynamics of microbubbles at the surface of urinary stones.
Section
III
presents experimental results showing that micro-
bubbles, driven by
1.5 MPa, expand up to about 60
l
min
diameter, and acquire the shape resembling an oblate spher-
oid. Section
IV
describes the numerical modeling of the col-
lapse showing the circumferential pinching and the
formation of the two microjets (Sec.
IV E
). The pressure
generated by the collapsing microbubble at the rigid wall
(Sec.
IV F
) exceeded the driving pressure by two-to-three
orders of magnitude. Section
V
shows micro-computed
tomography of urinary stones before and after the action of
SSA microbubbles illustrating surface erosion and formation
of microcracks. The significance and limitations of this work
are discussed in Sec.
VI
. The
Appendix
describes numerical
details, including an illustration of the adaptive mesh refine-
ment (AMR) algorithm.
II. MATERIALS AND METHODS
A. SSA microbubbles and urinary stones
SSA microbubbles (Applaud Medical, Inc.) were made
of perfluoroalkane gas (C
4
F
10
) encapsulated by lipid shells
engineered to accumulate on stone surfaces.
1
The lipid shells
incorporate polyethylene glycol structures and synthetic
pyrophosphate analogs, collectively functioning to minimize
interaction with the urothelium and facilitate accumulation
on stone surfaces. The size distribution of the microbubbles
was measured with a Coulter counter (Multisizer 4e Coulter
Cell Analyzer, Beckman Coulter, Indianapolis, IN) using an
aperture size of 30
l
m in diameter. The mean diameter of
the microbubbles was [mean
6
standard deviation (SD)]
1.19
6
0.04
l
m.
These experiments were conducted with surgically
retrieved urinary stones. The chemical composition of stones
was determined by Fourier-transform infrared spectroscopy
and was mostly calcium oxalate monohydrate. Specifically,
the surface of the stone shown in the inset of Fig.
2(b)
con-
tained 90% calcium oxalate monohydrate, 5% calcium oxa-
late dihydrate, and 5% apatite; the interior contained 70%
calcium oxalate monohydrate, 10% calcium oxalate dihy-
drate, and 20% apatite.
To position the stone in the focus of a microscope, the
stone was glued with a small amount of a Loctite Super Glue
to a tip of 0.25-mm thin coverslip (clear vinyl plastic,
18
18
0.25 mm, VWR International, PA) as shown in the
inset of Fig.
2(b)
. The stone was then kept in water for several
weeks for hydration. The hydrated stone was positioned in the
water tank (Fig.
2
) and aligned at the focus of the microscope
using an XYZ-micrometer stage (Thorlabs Inc., NJ).
B. Test tank
The test tank was three-dimensionally (3 D) printed from a
thermoplastic material (acrylonitrile butadiene styrene) and cov-
ered with a waterproof coating (Marine Grade Epoxy 109
Medium, Tap Plastics, CA). For imaging with the inverted
microscope, the bottom of the tank had a glass port (75
25
1 mm microscope slide, VistaVision, VWR International,
LLC, Radnor, PA) glued along its edges to the bottom of the
tank (Fig.
2
). The tank was filled with six liters of water
(PURELAB Chorus 1 for Life Science Applications, ELGA,
Veolia Water Solutions and Technologies, UK) with an electri-
cal resistivity of 18.2 MOhm-cm and the ultrafiltration to parti-
clesizelessthan0.05
l
m. The water remained in the tank for
several days and was in equilibrium with atmospheric gases.
During the experiments, the temperature of the water slowly
increased from
23
Cto
28
C due to the heating by intense
light used for the high-speed imaging.
C. Light sources
We used both continuous and flashlight illumination. The
continuous lighting was provided with a fluorescence illumina-
tion system EXFO X-cite 120 (XE120, Photonic Solutions
Inc., Mississauga, Ontario, CA). This light source uses a 120-
W Metal Halide lamp coupled to a liquid lightguide. The end
of this lightguide was positioned at about 1 cm above the stone
and provided back light to the stone (Fig.
2
).
The side lighting was provided with a flashlamp
WRF300 (Hadland Imaging, LLC, Santa Cruz, CA). This
spark-discharge lamp produced a light pulse with the dura-
tion of about 10
l
s. The spark light was delivered through a
separate liquid lightguide illuminating the side of the stone
proximal to the incoming acoustic waves (Fig.
2
).
FIG. 1. (Color online) The concept of treating urinary stones with SSA micro-
bubbles driven by an extracorporeal source of ultrasound: (a) general view and
(b)–(d) zoomed-in view of a urinary stone in the ureter. Gas-filled microbub-
bles are introduced into the urinary tract and accumulate at the surface of the
urinary stone (b); the accumulated microbubbles are excited with ultrasound (c)
and erode, pit, and fragment the stone facilitating its passage (d).
J. Acoust. Soc. Am.
146
(1), July 2019
Pishchalnikov
etal.
517
D. High-speed video microscopy
Images were captured with a high-speed camera HPV-
X2 (Shimadzu, Kyoto, Japan) operated in one of two modes.
In the full-pixel (FP) mode, the camera captures 128 frames of
400- by 250-pixels at a rate up to 5 Mfps. In the half-pixel
(HP) mode, the camera captures every other pixel in a checker-
board pattern, interpolating the images into 400- by 250-pixel
frames and recording 256 frames at rates up to 10 Mfps.
Exposures were 110 ns at 5 Mfps and 50 ns at 10 Mfps.
Magnification was achieved using a microscope (Nikon
Eclipse TS100) with a 4
objective (4
/0.13 PhL DL, WD
16.4, Nikon Plan Fluor), a 2.5
projection lens (Nikon CF
PL2.5
), and a 34-cm extension tube (Fig.
2
). The numerical
aperture of the objective was 0.13 giving the diffraction-limited
depth of field of 43
6
12
l
m and lateral resolution of 2
6
0.5
l
m.
This diffraction-limited lateral resolution of the objective was
considered in choosing the magnification of the projection lens
and the length of the extension tube. These optical elements were
chosen to have a camera resolution of 1
l
m/pixel.
In post-processing, recorded images were digitally
enlarged (3
by resampling with preserving details in
Adobe Photoshop), rotated, and cropped. The acoustic radia-
tion force was directed approximately from right to left in
these images (Fig.
4
,
Mm. 1
, and
Mm. 2
). The buoyant force
was directed into the image plane (Fig.
2
).
E. Driving acoustic field
Driving acoustic waves were generated with a custom-
made piezoelectric transducer (Sonic Concepts, Inc., Bothell,
WA) positioned at
9 cm from the proximal surface of the uri-
nary stone (Fig.
2
). The active element of the transducer was
made of a piezoelectric plate (72.3
30.3
3.18 mm) divided
into eight elements and connected in pairs. In these experi-
ments, each pair was powered by one of four power amplifiers
(AP-400B, ENI, USA). The frequency and duration of the
acoustic bursts were computer controlled with a specially
designed signal generator, allowing us to trigger the HS-
camera with TTL pulses while reproducing the frequency mod-
ulationusedintheclinic
5
and also to study other driving
regimes. In this work, the transducer was driven with a fre-
quency set of 400, 400, 433, and 433 kHz, generating acoustic
bursts with a center frequency of 416.5 kHz and
30
l
s dura-
tion of the envelope (Fig.
4
).
The spatial characteristics of the acoustic beam (Fig.
3
)
were measured using a needle hydrophone (HNR-0500, Onda
Inc., Sunnyvale, CA) with a diameter of the sensitive element of
0.5 mm. The acoustic field was scanned with a 2-mm step using
an XYZ-positioning system assembled with three motorized lin-
ear slides (X-LSM150A, Zaber Technologies, Vancouver, BC,
Canada). The motion of the positioning system was controlled
by a computer through the RS-232 link with a program wr
itten
in Python, which was also used to acquire hydrophone data
recorded by a digital oscilloscope (HDO
4024 Teledyne, LeCroy
Corp., NY). These measurements were conducted in a
35
27
20 cm tank with acrylic walls acoustically isolated
with sheets of absorptive material 1-cm thick (Aptflex F28,
Precision Acoustics, UK) providing echo reduction greater than
25 dB. The tank was filled with 14 liters of water degassed with
a pinhole degasser [ref JASA cain] to 1.1
6
0.5 mg/l (measured
with a dissolved oxygen meter DO 6
þ
, Eutech Instruments,
Singapore). To prevent the damage of the Onda hydrophone,
the spatial characteristics of the acoustic beam were measured
at low amplitudes and are shown normalized on the maximum
pressure
P
max
found among the scans in the three orthogonal
planes (Fig.
3
). At the position of the stone (
Z
¼
90 mm), the
FIG. 2. (Color online) Experimental setup: (a) schematic diagram and (b) view in the tank. A urinary stone was positioned in the focus of an inverted mic
ro-
scope (dotted rectangle). The optical path from the stone to the high-speed camera (HS-camera) is shown in the diagram by arrows and dashed lines with t
he
glass elements (lenses and prisms) shaded in gray. Bubbles were driven with bursts of ultrasound produced by a piezoelectric transducer positioned a
t9cm
from the proximal surface of the urinary stone. The inset in (b) shows a photograph of the urinary stone (bottom right). More general views of the setup a
re
shown in POMA (Ref.
27
).
518 J. Acoust. Soc. Am.
146
(1), July 2019
Pishchalnikov
etal.
acoustic beam had the cross section with the
6-dB width of
30 mm and the height of
60 mm (solid contour lines, Fig.
3
).
Selected measurements were conducted with another
needle hydrophone (Y-104, Sonic Concepts, Inc., Bothell,
WA). In particular, this hydrophone was used to measure
pressure traces at the driving amplitudes (Fig.
4
) in the focus
of the microscope at the position of the stone (Fig.
2
). For
these measurements, the stone was replaced with the sensi-
tive tip of the Y-104 hydrophone—the 1.5-mm diameter
ceramic crystal enclosed in a 3-mm metal tube. As the diam-
eter of the tip was comparable with the acoustic wavelength
(
k
3.6 mm), the hydrophone’s sensitivity depended on its
orientation. The angular response of the hydrophone was
measured and taken into account, increasing the uncertainty
of pressure measurements to
30%.
The pressure traces recorded in the HS-camera test
tank at the position of the stone were combined with the
HS-camera images into multimedia frames using programs
written in LabVIEW (National Instruments, Austin, TX) and
converted into movies with the H.264-video format using
QuickTime Pro 7 (Fig.
4
,
Mm. 1
, and
Mm. 2
). In these
movies, representative hydrophone traces (dark blue) were
superimposed on several waveforms (light blue) showing
shot-to-shot variability. The vertical arrow shows the timing
of the HS-camera with the uncertainty of 0.2
l
s. Time
t
¼
0
was positioned at the start of implosion of the largest solitary
bubble.
F. Micro-computed tomography
Micro-computed tomography (micro-CT) of urinary stones
(Fig.
9
) was used to assess the stone damage produced by the
SSA microbubbles. The micro-CT images were acquired with
a high-resolution X-ray tomography (MicroXCT-200, Xradia,
FIG. 3. (Color online) Spatial characteristics of the acoustic beam: (a) 3D Cartesian coordinate system with the orientation of
X
,
Y
, and
Z
axes for beam plots;
(b)–(d) normalized pressure amplitudes
P
/
P
max
in three orthogonal planes. The surface of the transducer was at
Z
¼
0. An
XY
-scan at
Z
¼
90 mm (d) shows the
cross section of the beam at the position of the stone. Pressure contour lines at half amplitude (solid lines) show the
6-dB dimensions of the acoustic beam.
J. Acoust. Soc. Am.
146
(1), July 2019
Pishchalnikov
etal.
519
Inc., Pleasanton, CA) before and after the action of SSA
microbubbles.
III. EXPERIMENTAL RESULTS
Bubble dynamics at the surface of a urinary stone is
shown in movies
Mm. 1
and
Mm. 2
. The movie
Mm. 1
was
recorded with the HS-camera in FP mode at 5 Mfps and pro-
vides full resolution images although at the slower frame
rate than
Mm. 2
, which was recorded in HP mode capturing
every other pixel at 10 Mfps.
Mm. 1.
Bubble dynamics at the surface of a urinary stone
recorded in FP mode at 5 Mfps and 110-ns exposure.
This is a file of type “mov” (8.8 Mb).
Mm. 2.
Bubble dynamics at the surface of a urinary stone
recorded in HP mode at 10 Mfps and 50-ns exposure.
This is a file of type “mov” (9.6 Mb).
During the first two acoustic cycles in these movies
(
3.4
<
t
<
0.8
l
s) the microbubbles expanded to a larger
maximum size from the first to the second cycle, concomi-
tant with increasing driving pressure. The second collapse
(
0.8
l
s) produced a cluster of bubbles. Bubbles in clusters
varied in shape, size, and standoff distance, merging with
other bubbles. Here, we focus on the collapse of a solitary
bubble starting from its maximum expansion (
t
0 – 0.8
l
s,
Mm. 1
and
Mm. 2
).
At maximum expansion [Fig.
4(a)
and
t
¼
0,
Mm. 1–Mm. 2
], the bubbles were nonspherical with a
cross-section resembling an ellipse truncated by the
stone [Fig.
5(a)
]. Average major and minor axes of 16
bubbles were measured to be 2
Ry
¼
51
6
9
l
mand
2
Rx
¼
39
6
6
l
m[Fig.
5(b)
]. The bubbles had an eccentric-
ity
¼
ffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffi
1
ð
Rx
=
Ry
Þ
2
q
of 0.63
6
0.08 and centers located
at
h
¼
12
6
3
l
m from the stone. This standoff distance
h
was used to model the collapse of the largest bubbles
approximating their initial shape as an oblate spheroid
18
with dimensions of 2
Ry
¼
62
l
mand2
Rx
¼
40
l
m.
IV. NUMERICAL MODELING
A. Governing equations
The collapse of a microbubble was modeled by solving
the multicomponent Euler equations with a 2D-axisymmetric
FIG. 4. (Color online) Three frames from movie
Mm. 1
showing a microbubble at the surface of a urinary stone at three moments in time: (a)
t
¼
0—bubble is at its maximum expansion, and (b) and (c) during the collapse. Bottom panels show driving acoustic pressure. The upper plot shows an
enlargement of two acoustic cycles. The timing of the HS-camera is indicated by the vertical arrow pointing to a circle on the pressure trace. The circl
eis
bounded by two vertical cursors encompassing the 0.2-
l
s interval between the frames. These HS-camera frames were recorded in FP mode at 5 Mfps
with an exposure of 0.11
l
s.
FIG. 5. (Color online) Geometry of microbubbles at their maximum expan-
sion: (a) approximation of bubble’s shape as an oblate spheroid; (b) mea-
surements of major 2
Ry
and minor 2
Rx
axes for 16 bubbles. The bubbles
had an eccentricity
of 0.63
6
0.08.
520 J. Acoust. Soc. Am.
146
(1), July 2019
Pishchalnikov
etal.
code. Specifically, the code models the gas and the liquid as a
two-phase compressible flow using the following system of
equations:
28
@
a
1
@
t
þ
u
$
a
1
¼
ld
p
@
ð
a
1
q
1
Þ
@
t
þ
$
a
1
q
1
u
ðÞ
¼
0
@
ð
a
2
q
2
Þ
@
t
þ
$
a
2
q
2
u
ðÞ
¼
0
@
ð
q
u
Þ
@
t
þ
$
q
u
u
þ
P
I
¼
0
@
ð
a
1
q
1
e
1
Þ
@
t
þ
$
a
1
q
1
e
1
u
ðÞ
þ
a
1
p
1
$
u
¼
l
p
I
d
p
@
ð
a
2
q
2
e
2
Þ
@
t
þ
$
a
2
q
2
e
2
u
ðÞ
þ
a
2
p
2
$
u
¼
l
p
I
d
p
:
8
>
>
>
>
>
>
>
>
>
>
>
>
>
>
>
>
>
>
>
>
>
>
<
>
>
>
>
>
>
>
>
>
>
>
>
>
>
>
>
>
>
>
>
>
>
:
(1)
Here,
a
1
and
a
2
are the volume fractions of the gas and
the liquid; vector
u
is the velocity of the flow. The gas and the
liquid are governed by their equations of state
e
k
¼
e
k
ð
q
k
;
p
k
Þ
,
where
q
k
,
e
k
and
p
k
are the density, the internal energy, and the
pressure of phase
k
. The gas in the bubble obeys the ideal-gas
equation of state with
c
gas
¼
1
:
1 (the ratio of specific heats
c
for C
4
F
10
is 1.07).
14
The water obeys the stiffened-gas equation
of state with
c
water
¼
6.12 and
p
1
;
water
¼
3
:
43
10
8
Pa.
29
The
gas-liquid mixture has the density
q
¼
a
1
q
1
þ
a
2
q
2
. Likewise,
the pressure
P
in the gas-liquid mixture is the sum of partial
pressures
a
1
p
1
and
a
2
p
2
.
The right-hand side of Eq.
(1)
describes the relaxation
of pressure between the phases, where
d
p
p
1
p
2
,a
coefficient
l
determines the speed of relaxation (section
1
of the
Appendix
), and interfacial pressure
p
I
is
z
2
p
1
þ
z
1
p
2
=
z
1
þ
z
2
.Here
z
k
¼
q
k
c
k
is the acoustic impedance of
the phase
k
with
c
k
being the speed of sound of the corre-
sponding phase.
Due to
p
1
6
¼
p
2
, the total-energy equation of the mixture
is replaced by the internal-energy equation for each phase.
Nevertheless, the mixture-total-energy equation of the sys-
tem can be written in the usual form
@
ð
q
E
Þ
@
t
þ
$
ð
q
E
þ
P
ðÞ
u
Þ¼
0
;
(2)
where
E
¼ð
e
þ
1
=
2
Þjj
u
jj
2
and
e
are the total and internal
energies. Although Eq.
(2)
may appear redundant (as the
internal-energy equations are solved for both phases), it is
important to ensure the energy conservation and, hence, to
preserve a correct treatment of shocks.
The system of equations
(1)
was solved with a two-
substepapproach(section
1
of the
Appendix
)usingadap-
tive time steps and an AMR algorithm (section
3
of the
Appendix
). In comparison with the numerical modeling in
POMA,
27
the use of an improved system of equations
(1)
allows us to take into account expansion and compression
of each phase in mixture regions. This improvement and
the use of the AMR algorithm (section
3
of the
Appendix
)
allowed us to increase the accuracy of the results, includ-
ing the spatial and time resolution of gas-liquid interfaces
and shock fronts.
B. Initial and boundary conditions (BCs)
To reduce the computation time and needed resources,
the dynamics of the collapsing bubble was modeled with
the following simplifications. First, the model was axi-
symmetric, although the experiments showed some appar-
ent divergency from axial symmetry, in part, due to
the irregular surface of urinary stones [inset in Fig.
2(b)
,
Fig.
9
]. Second, the wave scattering by the irregular
surface of the urinary stone was not modeled in this work
and the stone was modeled as a rigid plane. Third, the
absolute pressure far from the bubble was assumed to be a
constant
P
1
.
The assumption of a constant pressure
P
1
was an
approximation as the driving acoustic pressure varied during
the growth-collapse cycle of the bubbles (Fig.
4
,
Mm. 1
, and
Mm. 2
). The time for bubbles to reach their maximum size
varied from bubble to bubble and increased as the bubbles
grew from cycle to cycle (
Mm. 1
and
Mm. 2
). Here, we
model the bubble that reached its maximum size at
t
¼
0,
which was about 45 degrees into the positive pressure phase
of the driving acoustic wave (
0
:
3
t
0
:
9
l
s, Fig.
4
,
Mm.
1
and
Mm. 2
). The time-average pressure of this “sinusoidal”
half-cycle during the time of the collapse (0
t
0
:
9
l
s)
was about 0.7 of the amplitude of the driving acoustic wave.
In the experiments, the driving acoustic wave was a superpo-
sition of sine waves at two frequencies giving the free-field
pressure amplitude of 1.4
6
0.4 MPa (Fig.
4
,
Mm. 1
, and
Mm. 2
). The pressure at the urinary stone was higher
by
50%
30
due to constructive interference of the incident
and scattered waves, increasing the pressure amplitude to
2.1 MPa. This amplitude gave the time-average value for
the absolute pressure during the collapse (0
t
0
:
9
l
s) of
P
1
¼
1.55 MPa. This time-average pressure was assumed to
be spatially uniform within the computational domain
(768
768
l
m, Fig.
10
), which was much smaller than
the spatial characteristics of the driving acoustic beam (e.g.,
6-dB zone of 3
6 cm, Fig.
3
).
The initial pressure in the bubble
P
0
depended on the
amount of gas and vapor in the bubble. To bracket the
range of possible behaviors, we modeled the collapse
with two initial gas pressures:
P
01
¼
10 Pa and
P
02
¼
100 kPa. The pressure
P
01
would occur in the bubble
polytropically expanded from a nucleus with an initial
radius of
1.2
l
m to the maximum size observed in
the high-speed image (
Rx
¼
20
l
m,
Ry
¼
31
l
m, and
h
¼
12
l
m, Fig.
5
) if vaporization, condensation, and gas
diffusion were negligible. The pressure
P
02
would occur
in the expanded bubble if vaporization, condensation,
and gas diffusion were infinitely fast. The pressure
P
02
overestimates the pressure and amount of gas in the bub-
ble, potentially cushioning the collapse. In the experi-
ments, the pressure in the expanded bubble (
t
0) was
between
P
01
and
P
02
.
The initial density of gas in the bubble was
q
01
¼
2
:
78
10
4
kg
=
m
3
at
P
01
,and
q
02
¼
1
:
2kg
=
m
3
(density of air
at
10–35
C) for
P
02
. The initial density of water was
q
1
¼
1000 kg
=
m
3
. BCs and the computational domain
(Fig.
10
) are described in section
2
of the
Appendix
.
J. Acoust. Soc. Am.
146
(1), July 2019
Pishchalnikov
etal.
521
C. Numerical movies of collapsing bubbles
Numerical results are shown in
Mm. 3
and
Mm. 4
.
Mm. 3.
Modeling of the collapse with the initial gas pressure
of
P
01
¼
10 Pa. This is a file of type “mov” (9.4 Mb).
Mm. 4.
Modeling of the collapse with the initial gas pressure
of
P
02
¼
100 kPa. This is a file of type “mov” (9.3 Mb).
The content of these movies is illustrated in Fig.
6
, show-
ing a representative frame from
Mm. 3
. In both movies, the top
left panels show pressure in color on a logarithmic scale rang-
ing from 1 kPa (blue) to 0.5 GPa (red). Pressures outside of this
range are shown either in dark red (
>
0.5GPa)orindarkblue
(
<
1 kPa). The color image is overlaid by the volume fraction
of gas shown in black and white, with an opacity function to
render translucent surfaces. The black shows regions of high
gas content. The opaqueness decreases with volume fraction
until the gas volume fraction is zero (100% liquid) depicted as
100% transparent.
The bottom left panels in Fig.
6
,
Mm. 3
, and
Mm. 4
show numerical schlieren
u
of mixture-density gradients
u
¼
exp
ba
ðÞ
gas
þ
ba
ðÞ
water
k
$
q
k
k
$
q
jj
max
!
;
(3)
where
b
is a scaling factor for simultaneous visualization of
waves in both fluids (
b
gas
¼
20 and
b
water
¼
200).
31
Thick lines in these images suggest the position of the
bubble-water interface. Thin lines typically show moving
fronts of pressure waves. The different contrast of shock
fronts in these movies show that the bubble with smaller
amount of gas (
P
01
,
Mm. 3
) produced stronger shocks than
the bubble with the larger amount of gas (
P
02
,
Mm. 4
). The
difference in contrast of shocks is also seen in Figs.
8(a)–8(b)
showing the final stages of the collapse. These results support
the notion that the gas in the bubble cushions the collapse,
so that bubbles with smaller amount of gas produce stronger
collapses.
D. Numerical modeling and experimental observations
Both experimental [Fig.
7(a)
] and numerical [Fig.
7(b)
]
images showed a distinctive circumferential narrowing of
the bubble (
t
0.4 – 0.7
l
s), indicating greater bubble-wall
velocities toward the axis of symmetry of the bubble. Figure
7(c)
shows bubble-wall velocities
v
1
(squares) and
v
2
(circles) measured at the moving points 1 (square) and 2 (cir-
cle) indicated in the inset. Numerical velocities are shown
for both initial gas pressures by thin (
P
01
) and thick (
P
02
)
lines. Both bubbles had similar dynamics but the bubble
with smaller amount of gas (
P
01
) developed greater bubble-
wall velocities and collapsed faster than the bubble with
P
02
.
The averaged bubble-wall velocities measured in HS-camera
images during the final stage of the collapse (
t
>
0.6
l
s,
squares and circles) were in between the numerical curves.
This behavior might be expected as in the experiments the
gas pressure at
t
¼
0 was between
P
01
and
P
02
.
E. Circumferential pinching and microjets
Both experimental (dots) and numerical (lines) veloci-
ties show that the bubble-wall velocity directed toward the
axis of symmetry of the bubble
v
1
was greater than the
FIG. 6. (Color online) Frame
t
¼
0.726
l
s from
Mm. 3
showing the moment when the jet hits the rigid wall (located at the left boundary, Fig.
10
). Left panel
shows pressure in color overlaid by the volume fraction of gas (top) and schlieren of mixture-density gradients (bottom). Right panel shows maximum p
ressure
at the rigid wall. For this figure, the movie frame was modified by enlarging the pressure plot, adding some annotations, and drawing the initial positio
n of the
bubble wall (
t
¼
0, dashed ellipse).
522 J. Acoust. Soc. Am.
146
(1), July 2019
Pishchalnikov
etal.
velocity
v
2
directed toward the stone (Fig.
7
). This dispro-
portion led to the circumferential pinching of the bubble,
splitting it into two parts. The distal-to-stone part of the
bubble was smaller than the proximal part and collapsed
first (
Mm. 3
and
Mm. 4
,Fig.
8
). The collapse was intensi-
fied by a pressure surge with an amplitude of
1.23 GPa at
P
01
and
0.37 GPa at
P
02
. This pressure surge was pro-
duced by the converging flow of liquid when it collided at
the axis of symmetry of the bubble (0.719
l
sin
Mm. 3
and
0.763
l
sin
Mm. 4
). The collision formed two axial micro-
jets directed away and toward the stone. The reentrant jet
hitting the stone was either a single (
P
01
) or a ring-type
(
P
02
)jet(Fig.
8
). This jet had the velocity
v
jet
shown in
Fig.
7(c)
with the maximum of 4117 m/s at
P
01
and
1164 m/s at
P
02
.
F. Pressure at the rigid wall
The impact of the reentrant microjet on the stone pro-
duced a hydraulic shock with the water-hammer pressure of
0.65 GPa at
P
01
and
0.5 GPa at
P
02
seen as the first pres-
sure spikes at
y
¼
0inFig.
8(c)
. This water-hammer pressure
was followed by a longer somewhat triangular pulse with the
stagnation pressure of
0.3 GPa at
P
01
and
0.2 GPa at
P
02
[
y
¼
0, Fig.
8(c)
].
The impact of the microjet hitting the stone was intensi-
fied by the pressure waves radiated by the collapse of the
distal part of the bubble (0.721
l
sin
Mm. 3
and 0.769
l
sin
Mm. 4
, frames 3 in Fig.
8
). These pressure waves also
intensified the collapse of the main part of the bubble located
proximal to the rigid surface. This proximal bubble toroidally
collapsed (frames 4–6, Fig.
8
) producing pressure waves
at the stone with local maximums initially located at
y
6.2
l
mat
P
01
(0.748
l
s,
Mm. 3
)and
y
9
l
mat
P
02
(0.798
l
s,
Mm. 4
).
The pressure waves radiated by the toroidal collapse
converged toward the axis of symmetry of the bubble, pro-
ducing the overall maximum pressure at the stone at
P
01
(0.75
l
s,
Mm. 3
). As the toroidal bubble collapsed from
the periphery radiating multiple waves (frame 6 in Fig.
8
,
Mm. 3
and
Mm. 4
), the location of the maximum pressure
was slightly off-axis and not seen in Fig.
8(c)
.Themaxi-
mum pressure determined along the entire surface of the
stone—rather than at specified locations as in Fig.
8(c)
—is
shown on the right panel in Fig.
6
,
Mm. 3
and
Mm. 4
.
The maximum pressure reached 6.88 GPa at
P
01
(0.75
l
s,
Mm. 3
) and 1.32 GPa at
P
02
(
Mm. 4
).
At
P
02
, the greater amount of gas in the bubble cush-
ioned the collapse, so that the pressure waves radiated by
the toroidal collapse of the proximal bubble were not as
strong as at
P
01
(frame 6 in Fig.
8
,
t
0.798
l
s,
Mm. 4
).
These pressure waves collapsed the daughter bubbles that
were produced by the distal bubble. In turn, the collapse
of these daughter bubbles radiated pressure waves that
drove the rebound of the bubble at the stone surface near
the axis. The collapse of this rebounding bubble produced
the overall maximum pressure at the stone surface at
P
02
(1.32 GPa at 0.843
l
s,
Mm. 4
).
FIG. 7. (Color online) Collapse of a
microbubble at the surface of urinary
stone. (a) HS-camera sequence of
images recorded at 10 Mfps (
t
¼
0.1
– 0.8
l
s,
Mm. 2
). (b) Frames with
0.1-
l
s step from the numerical model-
ing with
P
02
(
t
¼
0.1 – 0.8
l
s,
Mm. 4
).
Bubble-wall profiles are also shown in
the inset of Fig.
8(c)
for both
P
01
(top)
and
P
02
(bottom). (c) Bubble-wall
velocities
v
1
(squares) and
v
2
(circles)
at points 1 and 2 (inset). Error bars
show measurement uncertainties (ver-
tical) and HS-camera exposure time of
50 ns (horizontal). Numerical veloci-
ties are shown by thin (
P
01
) and thick
(
P
02
) lines. At the end of the traces
(
t
0.72
l
sat
P
01
and
t
0.764
l
sat
P
02
), the converging flow of liquid
v
1
forms the axial microjets toward and
away from the stone (
Mm. 3
and
Mm.
4
) with jet velocities
v
jet
toward the
stone reaching 4117 m/s at
P
01
and
1164 m/s at
P
02
.
J. Acoust. Soc. Am.
146
(1), July 2019
Pishchalnikov
etal.
523
V. DAMAGE ON THE STONE SURFACE: REMOVAL
OF STONE MATERIAL AND FORMATION OF
MICROCRACKS
Micro-CT images of a urinary stone before and after the
action of SSA microbubbles showed removal of stone mate-
rial and formation of microcracks (Fig.
9
). Specifically,
arrows 1–8 point to places of removed material in the 3 D
rendered surface of the stone [Fig.
9(a)
], whereas arrows 10
and 11 point to the formation of microcracks visible in the
cross sections of the stone [Figs.
9(b)
and
9(c)
].
VI. DISCUSSION
The combination of HS-video microscopy and numerical
modeling employed here showed a pronounced difference
between the previously reported dynamics of initially spherical
bubbles
22
–
25
,
27
and the dynamics of the SSA microbubbles at
the surface of urinary stones. The SSA microbubbles expanded
nonspherically (
Mm. 1
and
Mm. 2
) and, at their maximum
expansion, acquired the shape similar to an oblate spheroid
[Figs.
4(a)
and
7(a)
]. Approximating the cross-section of bub-
bles as an ellipse truncated by the plane rigid surface [Fig.
5(a)
], we modeled the collapse of the microbubbles at the sur-
face of urinary stones. Both the numerical modeling and the
experimental observations showed a circumferential constric-
tion pinching the bubbles (Figs.
7
–
8
,
Mm. 1–Mm. 4
). The
pinching was absent in the collapse of the initially spherical
bubbles as shown in Fig.
8
in POMA.
27
Furthermore, whereas for the initially spherical bubbles
the axial jet originated from the distal surface of the bub-
ble,
22
–
25
,
27
the circumferential pinching of the SSA micro-
bubble split the bubble into two parts producing two axial
microjets directed away and toward the stone. The reentrant
jet hitting the stone was either a single (
P
01
,
Mm. 3
)ora
ring-type (
P
02
,
Mm. 4
) jet. The velocity of this jet
v
jet
reached 4117 m/s at
P
01
and 1164 m/s at
P
02
[Fig.
7(c)
], sup-
porting the notion that microjets can reach high subsonic or
even supersonic speeds.
23
,
24
The quantitative verification of the predicted velocities
of these microjets requires fine spatial (
1
l
m) and temporal
FIG. 8. (Color online) Final stages of
the collapse for two initial gas pres-
sures: (a)
P
01
¼
10 Pa (
Mm. 3
) and (b)
P
02
¼
100 kPa (
Mm. 4
). These movie
frames were cropped to the width of
18.5
l
m and show the following
moments: (1) last frame shown in Fig.
7(b)
before the collapse, (2) circumfer-
ential pinching split the bubble into
two parts producing a pressure surge
and forming two microjets directed
away and toward the stone, (3) distal
bubble collapsed radiating pressure
waves, (4) microjet hit the surface, (5)
the microjet diverged reaching periph-
ery of the proximal bubble, and (6) the
proximal bubble collapsed radiating
shock waves. Plot (c) shows pressure
vs time at four radial distances
y
along
the rigid surface. The inset shows
bubble-wall profiles for
P
01
(top) and
P
02
(bottom) at steps of 0.1
l
s from 0
to 0.7
l
s, i.e., to the first frame shown
in (a) and (b). As gas in the bubbles
was cushioning the collapse, the bub-
ble with
P
02
collapsed later and pro-
duced smaller pressure than the bubble
with
P
01
. Maximum pressures were
associated with shorter pulses of
1ns
and seen near the axis of symmetry of
the bubbles. Longer pulses had dura-
tion of
10–30 ns and were seen both
at
y
¼
0 and at greater distances off-
axis. Within a 10-
l
m radius from the
axis, the peak pressure produced by the
bubbles exceeded 150 MPa, i.e., was
two orders of magnitude greater than
the driving pressure.
524 J. Acoust. Soc. Am.
146
(1), July 2019
Pishchalnikov
etal.
(
1 ns) resolutions (Fig.
8
,
Mm. 3
and
Mm. 4
), both of
which are experimentally difficult. The numerical frames
(Fig.
8
) are shown with frame rates up to one billion frames
per second. The fastest frame rate of our state-of-the-art
camera was 10
10
6
fps (
Mm. 2
). Although there are cam-
eras that can record a small number (8–15) of frames at rates
up to 200
10
6
fps, capturing the exact moment of collapse
is difficult even with laser-nucleated bubbles
32
and it is
practically impossible with the microbubbles at the surface
of urinary stones reported in this work. The main reason is
that the bubbles are never exactly the same, and tiny varia-
tions in bubble’s size shifts the moment of collapse, making
the capturing of the fine details during the short moment of
the collapse technically challenging. Some verification of
the numerical model can be provided by comparison with
other accepted models and analytical solutions (see section
4
of the
Appendix
). The comparison shows a good agree-
ment with the established models and analytical solutions,
supporting the trustworthiness of the present numerical
results.
It has been suggested that the velocity of microjets is
increased by the reflection of the driving wave from the solid
surface.
24
Here, we showed that microjets produced by SSA
microbubbles were also accelerated by the pressure surge
when the circumferential flow collides on the axis of symme-
try of the bubble (frame 2, Fig.
8
). Even though short-lived,
FIG. 9. (Color online) Micro-computed
tomography of a urinary stone before
and after the action of SSA microbub-
bles: (a) 3D rendering of the surface,
(b)–(c) 2D cross sections A and B.
Numbered arrows point to removal of
stone material (1–9, 12) and formation
of microcracks (10, 11).
J. Acoust. Soc. Am.
146
(1), July 2019
Pishchalnikov
etal.
525