Ultrasound in Med. & Biol., Vol. 29, No. 5, pp.

687– 694, 2003

Copyright © 2003 World Federation for Ultrasound in Medicine & Biology
Printed in the USA. All rights reserved
0301-5629/03/$–see front matter

doi:10.1016/S0301-5629(03)00027-9

● Original Contribution

THE BEHAVIOUR OF INDIVIDUAL CONTRAST AGENT

MICROBUBBLES

V. SBOROS, C. M. MORAN, S. D. PYE and W. N. MCDICKEN

Department of Medical Physics and Medical Engineering, University of Edinburgh, Edinburgh, UK

(Received 22 July 2002; in final form 31 December 2002)

Abstract—In recent years, our knowledge of the behaviour of ultrasonic microbubble contrast agents has
improved substantially through in vitro experiments. However, there has been a tendency to use high concen-
trations of contrast agents in suspension, so that ultrasonic backscatter data are generated by a cloud of
microbubbles. Such experiments involve a variety of assumptions with validity that is open to question. In
addition, high concentrations of microbubbles cannot be used to understand the behaviour of individual
microbubble scatterers. This paper proposes a technique that minimises the number of assumptions that need to
be made to interpret in vitro experimental data. The basis of the technique is a dilute suspension of microbubbles
that makes single scattering events distinguishable. A commercial scanner was used to collect radio frequency
(RF) data from suspensions of two different contrast agents, Quantison™ and Definity. Backscatter data were
collected over a range of acoustic pressures. It was found that Definity provided a constant number of scattering
events per unit volume of suspension for almost all applied acoustic pressures. Quantison™ demonstrated an
increasing number of scattering events per unit volume with increasing acoustic pressure. Below 0.6 MPa,
Quantison™ scatterers were not individually detectable and provided levels of backscatter similar to those of a
blood-mimicking fluid, which suggests that Quantison™ microbubbles had almost linear scattering behaviour. At
acoustic pressures greater than 0.6 MPa, both agents appeared to provide echoes from free bubbles. The change
in the number of scatterers per unit volume with acoustic pressure cannot be demonstrated using high
concentrations of contrast agent. (E-mail: Vassilis.Sboros@ed.ac.uk) © 2003 World Federation for Ultrasound
in Medicine & Biology.

Key Words: Contrast agent, Definity, Microbubble, Quantison™.

INTRODUCTION bubble, and the destruction mechanisms, as well as ra-

Even though ultrasound (US) contrast agents (UCAs)
have been introduced in clinical routine, their potential is
far from fulfilled. Experimental work has improved the
understanding of the interaction between contrast micro-
bubbles and the US beam, but the effort to accomplish
this is by no means complete. In this context, in vivo as
well as in vitro studies are required to assist in optimising
the use of UCAs. In vitro work is essential in providing
basic scientific information that can then be applied to in
vivo studies.
Acoustic pressure variations can change the nature
of the spherical motion of a contrast bubble from linear
to nonlinear. Bubble destruction occurs at higher pres-
sures and may take various forms. The influence of the
shell material and the gas content on the motion of the
Address correspondence to: Vassilis Sboros, Department of
Medical Physics, Royal Infirmary of Edinburgh, 1 Lauriston Place,
EH3 9YW, UK. E-mail: Vassilis.Sboros@ed.ac.uk
diation force effects, become observable with the use of
high-speed cameras in microscopy (Dayton et al. 1997;
Wu and Tong 1998; Dayton et al. 1999). However, the
behaviour of contrast bubbles in different acoustic pres-
sure fields has not been thoroughly investigated. In terms
of backscatter dependence on acoustic pressure, some
publications do not establish differences between con-
trast and linear scatterer behaviour (Chang et al. 1996;
Shi et al. 1999; Shi and Forsberg 2000; Krishna et al.
1999). Of course, there is also experimental evidence
that shows that the acoustic pressure-dependence of the
backscatter of US contrast agents (UCAs) is different
from that of linear scatterers (Krishna and Newhouse
1997; Morgan et al. 1998; Shi et al. 1999; Shi and
Forsberg 2000; Frinking and de Jong 1998). Different
transducer characteristics, contrast self-attenuation, con-
trast decay and nonlinear propagation are some of the
problems encountered in these studies. The dependence
of the scattering behaviour of contrast microbubbles on

687
688 Ultrasound in Medicine and Biology
acoustic pressure has not been the focal point in most of
the above studies.
The above obstacles should not be a serious source
of problems in the study of microbubble behaviour. The
quantitative criterion “microbubble density less than that
required to cause shadowing” is often quoted in the
literature (Krishna and Newhouse 1997). This is usually
higher than 10 microbubbles per mL of suspension.
Multiple scattering and bubble interactions have been
assumed insignificant, but there is evidence which sug-
gests that both phenomena might be underestimated
(Soetanto and Chan 2000; Parlitz et al. 1999). But there
is a more fundamental complication that is intrinsic to
the use of high microbubble concentrations. The distri-
bution of microbubble responses is not a statistically
normal distribution of responses, as has usually been
assumed. Quantison™ microbubbles, for example, have
a dual behaviour and scatter US either as free gas bubbles
or as highly damped encapsulated bubbles (Sboros et al.
2001). The scattering and absorption cross-sections of
UCAs have been central to theoretical investigations and
their experimental assessment has always been a goal.
Even when the response of a region-of-interest (ROI) is
measured and there are no further calculations to analyse
the data, it is common to assume a normal distribution of
microbubble behaviour in the discussion of the results.
Studies with Quantison™ suspensions were limited in
quantifying the backscatter of the agent (Finking and de
Jong 1998; Frinking et al. 1999). Even for other contrast
microbubbles where the duality of Quantison™ is not
present, it is difficult to justify the assumption of a
normal distribution of responses.
Very diluted contrast suspensions are employed in
the present study, to isolate single scattering events from
two different contrast agents and to assess the usefulness
of such an approach. There are two immediate advan-
tages of doing so: 1. the attenuation becomes negligible
and, therefore, does not need to be measured or calcu-
lated and 2. single scatterers can be counted and a quan-
titative estimate of the scattering cross-section can be
obtained. The principal disadvantage of this approach is
the loss of signals that are at or below noise level and can
only be registered collectively at high microbubble con-
centrations. A range of acoustic pressures typical of
diagnostic scanning were used to assess their effect on
contrast backscatter phenomena.
MATERIALS AND METHODS
Technique
The same experimental technique was used as in
previous communications (Sboros et al. 2000b, 2001).
Suspensions of contrast agents were scanned at 3-MHz
Volume 29, Number 5, 2003
centre frequency using an Ultramark 9 (UM9) ultrasonic
scanner (Advanced Technology Laboratories, Bothell,
WA). The nominal transmit power ranged from 2.24% to
100% of maximum output power and the focal distance
was 4.25 cm. This corresponded to a range of 0.27 MPa
to 1.52 MPa peak negative pressure at 3 cm from the
probe, which was the centre of the ROI. The experiments
were performed in triggered imaging mode. Single
frames were triggered, via the ECG lead, using a pulse
generator (Philips PM5705). Complete RF sector frames
were collected and images were reconstructed using a
moving average filter. The image analysis software writ-
ten in the Department of Medical Physics (University of
Edinburgh, UK) were used to calculate the RF backscat-
ter power of subregions within an ROI. The subregions
were defined by thresholding the pixel intensity. In other
words, the average RF intensity of an ROI was calculated
for those pixels that had higher pixel intensity value than
a preset threshold. This allowed the calculation of aver-
age intensities excluding background noise.
The experimental protocol
The contrast agents used in this experiment were
Definity (DuPont Pharmaceutical Co., Waltham, MA),
and Quantison™ (Quadrant Healthcare, Nottingham,
UK). The concentrations used were low enough to enable
individual scatterers to be distinguished in the ultrasonic
image and high enough to obtain the highest possible
number density to increase sample size and minimise the
variability of the measurements.
To achieve this, both agents were diluted; 3 ␮L of
Definity were introduced in a beaker with 100 mL of
sterile water and mixed for 1 min using a magnetic
stirrer. Of that suspension, 50 ␮L were introduced into
the tank, which contained 200 mL of sterile water, giving
approximately 7.5 bubbles per mL (⬎ 1 ␮m) of suspen-
sion. A period of 30 s mixing was allowed before the
acquisition of five triggered frames each separated by 1 s.
For Quantison™, 5 ␮L were introduced into a beaker
with 100 mL sterile water and, from that suspension, 250
␮L were introduced into the tank (94 bubbles larger than
1 ␮m per mL of suspension). The experiment was re-
peated at each of eight acoustic pressures, 5 times for
Definity and 8 times for Quantison™.
No measures were taken to control the air content of
the suspensions. The decay of the either agent is not
significantly affected by air content (Sboros et al. 2000a).
Both agents were also inspected in suspension under a
phase microscope (Olympus IX50, Tokyo, Japan). All
the microbubbles from both agent suspensions appeared to
be separated from each other and no clustering was ob-
served.
 Individual contrast microbubbles ● V. SBOROS et al. 689

Fig. 1. (a) Reconstructed image frame for Definity. The pixel intensity was calculated for the rectangle ROI (which was
also used in the rest of this paper). (b) Threshold 1 was employed and most of the pixels in the frame became blue. Those
pixels had higher amplitude than the threshold, and the analysis package would calculate the average pixel intensity for
the pixels inside the ROI. The threshold is the square root of the average pixel intensity of an identical ROI of a tank
filled with sterile water. Similarly in (c) and (d) Where thresholds 2 and 3 were used (square root of average pixel
intensity of two different are facts of the tank filled with sterile water). The images were the same frame at 0.58 MPa
peak negative pressure.

Data analysis
Number of scatterers. The number of scatterers was
counted manually in a specified ROI in each image. The
ROI used was identical to that used previously (Sboros et
al. 2000b) and was 2.9 ⫾ 0.05 cm long and 1.4 ⫾ 0.05
cm wide. The tip of a 0.2-mm needle hydrophone (Pre-
cision Acoustics, Dorchester, UK) was used as a point
scatterer to assess the ultrasonic slice width. The scanner
gain was adjusted to obtain an average pixel intensity
from the tip of the hydrophone similar to the brightest
contrast microbubble. The slice width of the beam was
defined for the purposes of the present study to be equal
to the distance (across the slice width) at which the tip of
the hydrophone was visible on the scanner’s monitor.
This distance was found to be 1.50 ⫾ 0.05 cm. There-
fore, the volume of the ROI was 6.2 ⫾ 0.3 cm. This
allowed an estimation of the number of microbubbles per
unit volume imaged in the ROI to be compared with the
known concentration (7.5 or 94 microbubbles/mL).
The measurement of backscatter. The average RF
intensity was calculated for the ROI. The analysis pack-
age installed on a Sun workstation was modified to allow
the selection of a threshold pixel amplitude to calculate
the average RF intensity of the pixels that had higher
amplitude than that threshold. The RF intensity was
measured using four different thresholds produced by the
following procedure. The tank was filled with sterile
water and was allowed to settle until no air bubbles or
artefacts could be seen on the monitor. A frame was
captured at each acoustic pressure. Three intensities from
three different ROIs were calculated. The first one was
from the ROI mentioned above and the square root of the
magnitude of the backscatter intensity was set to be
threshold 1. The second and third ROIs were set over two
different intensity backscattering artefacts appearing in
each frame. Their spatial peak intensities were still lower
than those from individual microbubble backscatter in-
tensities. The respective square roots of those intensities
were threshold 2 and threshold 3. Both those artefacts
were air bubbles, visualised in the wall of the tank. They
provided very low echoes because they were almost
outside the scan plane, but the echoes were significant
when compared with those from single scatterers. The
fourth threshold was set to zero to include background
noise in the mean pixel intensity calculation (threshold
4). After having set the threshold amplitude, all the
pixels that would be included in the average pixel inten-
sity calculation were displayed blue in the image. Figure
1b shows the pixels that were included in the calculation
of the average pixel intensity using threshold 1. Figure 1c
and d shows the pixels that had amplitudes above thresh-
old 2 and threshold 3. It is obvious that threshold 4 would
create a completely blue image and, therefore, it is not
690 Ultrasound in Medicine and Biology Volume 29, Number 5, 2003

Fig. 2. Reconstructed frames for scatterer counting. The number of scatterers inside the rectangular ROI is stated in each
frame. The particular frames were chosen to have numbers of scatterers close to the average for all acquisitions at each
peak negative pressure. Definity showed a particularly constant number of scatterers at different acoustic pressures, but
Quantison™ showed an increasing number of scatterers with increasing acoustic pressure. Note that the number of
microbubbles in the suspension was 7.5 microbubbles/mL for Definity (⬃ 46 microbubbles in the ROI), and 94
microbubbles/mL for Quantison™ (⬃ 580 in the ROI). Note also that, at 0.79 MPa, there are two larger scatterers that
are probably air bubbles.

included in Fig. 1. The normalised backscatter was cal- onstrated approximately constant scatterer number at all
culated as in Sboros et al (2001). The four different acoustic pressures, apart from the lowest one. Quanti-
thresholds were compared by means of normalised son™ scatterers did not exceed the noise level of the two
backscatter. lowest pressures and demonstrated an increasing number
The ratio of the normalised backscatter (for a se- of scatterers with the increase of acoustic pressure.
lected threshold) to the number of scatterers in the ROI The calculation of the volume of the ROI allowed an
gives the normalised backscatter per scatterer. This cal- approximate calculation of the concentration of observed
culation was averaged over all frames captured at each
acoustic pressure. Because the bubble concentration was
very low, a small number of very large scatterers ap-
peared in some of the images, caused probably by im-
purities (usually air bubbles). Those frames could distort
the calculation of the normalised backscatter per bubble.
For this reason, those frames were not used in the cal-
culation of normalised backscatter.

RESULTS
Figure 2 shows reconstructed frames at two different
acoustic pressures for Definity and Quantison™. The
number of scatterers refers to the counts inside the rect-
angular ROI. The frames displayed in Fig. 2 were chosen
to have a number of scatterers close to the average for
that acoustic pressure.
The numbers of scatterers in the ROI at different
acoustic pressures are illustrated in Fig. 3. Definity dem-
Fig. 3. Number of scatterers counted in the ROI vs. peak
negative pressure. Definity provided constant counts at most
acoustic pressures and only the two lowest acoustic pressures
had lower counts. Quantison™ showed an increase of the
number of scatterers with the increase of acoustic pressure that
settled at the two maximum acoustic pressures.
 Individual contrast microbubbles ● V. SBOROS et al.
Fig. 4. The ratio of observed scatterers per unit volume to the
concentration of bubbles is plotted vs. peak negative pressure
for (a) Definity and (b) Quantison™. This ratio was close to
one for most acoustic pressures for Definity, but it did not
exceed 8% for Quantison™.
scatterers per unit volume. The expected concentration of
the introduced contrast was calculated, knowing the con-
centration of bubbles in the vial given by each manufac-
turer. Using this number, Definity would have 7.5 mi-
crobubbles per mL of suspension in the tank and Quan-
tison™, 94. The ratio of the concentration of scatterers
(microbubbles that were seen to scatter and were ac-
counted for) to the expected concentration of micro-
bubbles was shown vs. the acoustic pressure in Fig. 4a
for Definity and, in Fig. 4b, for Quantison™. The ratio
for Definity was close to one for most acoustic pressures.
This means that all of the microbubbles were observed as
scatterers that exceeded noise levels individually. For
Quantison™, not more than 8% of the microbubbles
were observed as scatterers.
The calculated normalised backscatter per scatterer
was plotted against acoustic pressure in Fig. 5a for
Definity and, in Fig. 5b, for Quantison™. Of 200 frames
for Definity, 12 were considered to have impurities (such
as air bubbles shown in Fig. 1 at 0.79 MPa for Quanti-
son™) and, therefore, they were not used in the calcu-
lation of the normalised backscatter per scatterer. For
Quantison™, 52 of 180 frames were considered to have
similar problems, which is significantly more than for the
691
Fig. 5. Average backscatter per scatterer plotted against peak
negative pressure for (a) Definity and (b) Quantison™. (---) All
the data; (—) data after rejecting the frames that had impurities.
6% of the frames of the original data were rejected for Definity
and 29% for Quantison™.
Definity frames. The difference in the gases of those two
agents might explain this occurrence. Definity vials con-
tain perfluorocarbon, and Quantison™ vials contain air,
which may be the reason for the formation of bigger air
bubbles. The dashed lines are the average normalised
backscatter per scatterer for all data, and the solid lines
are the average normalised backscatter per scatterer for
the data that did not seem to have any impurities.
The display of error bars in Fig. 5 would affect its
clarity and, therefore, the percent SD of the normalised
backscatter per scatterer was plotted in Fig. 6. Dashed
lines refer to the calculation that included all the data and
the solid lines refer to the calculation that excluded the
data with impurities. The solid lines are at lower values
than the dashed ones. Definity did not show significant
difference because the frames that were found to have
impurities were only 6% of the total amount of frames.
For Quantison™, the difference between the two curves
was greater, because the frames with impurities were
almost 30% of the total number of frames. The SD
seemed to decrease with increasing acoustic pressure for
Quantison™, perhaps because the lower acoustic pres-
692 Ultrasound in Medicine and Biology Volume 29, Number 5, 2003

Fig. 6. Percent SD of the normalised backscatter per scatterer

for (. . .) the original data and (—) for the data without any
impurities. The small number of rejected frames for Definity
provided similar SDs for both data sets. Quantison™ showed a
higher rejection rate and, therefore, the deviations showed
greater improvement for the data without impurities. The de-
creasing tendency of percent SD with increasing acoustic pres-
sure for Quantison™ was, perhaps, associated with the increas-
ing number of scatterers.

sure provided a lower number densities of scatterers (i.e.,

increased random error). Definity showed a stable per-
cent SD over the range of acoustic pressures used.
The results produced by using the four different
thresholds are plotted in Fig. 7a for Definity and, in Fig.
7b, for Quantison™. All the thresholds provided similar
values of normalised backscatter per scatterer. For Quan-
tison™, none of the thresholds produced significantly
different values. Definity demonstrated a significantly
lower level of normalised backscatter per scatterer for
threshold 3 when compared with thresholds 1 and 2. All
the other comparisons demonstrated insignificant differ-
ences between them. The calculation of normalised back-
scatter per scatterer was optimal when threshold 2 was
used. At the lowest acoustic pressure used for Quanti-
son™, an elevation of the normalised backscatter per
scatterer is observed in Fig. 7b for thresholds 1 and 0.
This might be due to the very low count of scatterers
(lowest in Fig. 3), which made the contribution of the
background significant when using those two thresholds.
Figure 7 illustrates the insignificant contribution of the
background to the vast majority of the calculations. For
all the above reasons, threshold 2 was considered to be
optimal for the calculation of normalised backscatter per
scatterer.
The result of the previous analysis leads to Fig. 8.
The normalised backscatter per scatterer was plotted
against peak negative pressure for the two agents, after
the use of threshold 2 and rejecting the frames that had
impurities. At low acoustic pressures, Definity seemed to
have a higher normalised backscatter per scatterer. At
Fig. 7. Normalised backscatterer per scatterer plotted against
acoustic pressure. The four threshold levels provided different
levels of backscatter for (a) Definity and (b) Quantison™. The
difference between the thresholds was almost insignificant
(perhaps with the exception of threshold 3 for Definity).
Threshold 2 was found to be optimal for extracting the nor-
malised backscatter per scatterer.
high acoustic pressures, both agents become almost iden-
tical. Both agents have a linearly increasing normalised
backscatter per scatterer with acoustic pressure.
DISCUSSION
Number of scatterers
Microscopic investigation demonstrated that the mi-
crobubbles from both agents do not cluster and keep well
apart. This alone does not mean that the distance between
two microbubbles in suspension was enough to allow
separate registration of their echoes. However, the high
dilution of all contrast samples made sure that the aver-
age distance between two microbubbles was larger than
the axial and lateral resolutions of the system. Moreover,
the fact that the number of the counted Definity scatterers
was similar to the expected number strongly suggests
that the registration of scattering events could only be
attributed to individual microbubbles. The higher con-
 Individual contrast microbubbles ● V. SBOROS et al.
Fig. 8. Normalised backscatter per scatterer against acoustic
pressure. Definity showed higher values at low acoustic pres-
sures, which became similar for both agents at high acoustic
pressures. The relationship between normalised backscatter per
scatterer and acoustic pressure was linear for both Definity and
Quantison™.
centration for Quantison™ was due to its dual backscat-
tering behaviour, but it is more difficult to be certain that
the scattering events belong to single microbubbles. The
low backscattering microbubbles that have near linear
scatterer echoes cannot be registered individually and
higher concentrations are needed to detect backscatter
signals at acoustic pressures lower than 0.6 MPa. The
scattering events that appear at acoustic pressures above
0.6 MPa provide lower or equal levels of backscatter
compared with those of single Definity microbubbles
(Fig. 8). This strongly suggests that the scattering events
from Quantison™ cannot be attributed to more than one
microbubble.
There was a large difference in the number of scat-
terers counted using the manual technique between
Definity and Quantison™. The first agent provided an
almost constant number of scatterers over the range of
acoustic pressures used but, for Quantison™, scatterers
first appeared in the image at 0.69 MPa peak negative
pressure and showed an increase in number with increas-
ing acoustic pressure. Approximate calculation shows
that most Definity bubbles were strongly backscattering,
but only a small percentage of the Quantison™ bubbles
appeared as individually detectable scatterers (not more
than 8%). It is already known that Quantison™ has a
much thicker coating compared with Definity and that
this coating is not usually destroyed after insonation
(Johnson 1997). This suggests that the gas may leak out
of the coating to create a free bubble. The fact that more
bubbles did that with increasing acoustic pressure is
consistent with this explanation because higher acoustic
pressures could cause leakage of bubbles with more
robust coating. Furthermore, the creation of free bubbles
may have occurred for Definity at high acoustic pres-
693
sures, where the normalised backscatter per scatterer was
almost identical to that of Quantison™. The two agents
are different in nature in both gas and shell material. The
almost identical behaviour of the two agents at high
pressures suggests that they release similar free bubbles.
Limitations of the study
It was difficult to provide an accurate assessment of
the backscatter intensity of the scatterers. We addressed
some problems in an empirical way. Impurities that were
probably air bubbles were difficult to define. The aim
was to identify a scattering feature in the image that was
much larger in size than the rest of the scatterers (at least
double). The rejection of those images significantly re-
duced the variability of the measurement of the nor-
malised backscatter per scatterer. The reason why Quan-
tison™ showed a greater percentage of frames with
impurities is unknown. Whatever the reason, reconstruc-
tion of RF data proved to be crucial to the outcome of
this study by facilitating the detection of artefacts and
unwanted echoes. It is also likely to be necessary for
studies that intend to measure scattering cross-section.
The procedure employed resulted in calculating the
normalised backscatter per scatterer and plotting this
against peak negative pressure. Figure 8 illustrates the
linearity between acoustic pressure and normalised back-
scatter per scatterer above 0.6 MPa. Hence,
N ⬵ c XP ⫺, (1)
where N is the normalised backscatter per scatterer, cx is
the slope provided by the linear fit for the (X) agent and
P⫺ is the peak negative pressure.
Assuming the same field for the normalising and the
contrast suspensions, and also that the backscatter inten-
sity of the Orgasol威 particles in the normalising suspen-
sion was approximately equal to the product of their
number in the ROI, their scattering cross-section and the
incident US intensity,
Ii n CA␴ CA
N⫽ ⬵ , (2)
NI i n nor␴ nor
where Ii is the backscatter intensity per scatterer from the
contrast agent, NIi is the backscatter intensity from the
normalising suspension, nCA is the number of counted
contrast agent scatterers, nnor is the number of scatterers
in the normalising suspension, ␴CA is the average scat-
tering cross-section of the contrast agent scatterers and
␴nor is the average scattering cross-section of the parti-
cles of the normalising suspension. Combining eqns (1)
and (2), the average scattering cross-section of the con-
trast agent is:
694 Ultrasound in Medicine and Biology
n nor
␴ CA ⬇ ␴ c P⫺ (3)
n CA nor X
and, because nnor, nCA, ␴nor, and Cx are constant, the
average scattering cross-section of either contrast agents
is proportional to the peak negative pressure.
Definity provided an outlier to the linear trend at the
lowest acoustic pressure. The concentration of observer-
counted scatterers was very similar to the concentration
of bubbles (Fig. 4a), which suggests that any systematic
error in manually counting the scatterers was almost
negligible at most acoustic pressures. Furthermore, the
generally insignificant differences provided by the cal-
culations of normalised backscatter by the different
thresholds strongly suggests that the manual counting
of the scatterers was not underestimating their num-
ber. Therefore, the counted number of scatterers for
the lowest acoustic pressure was correct and is prob-
ably due to the lower sensitivity of the system at that
pressure.
It is difficult to draw conclusions for the behaviour
of Definity at low acoustic pressures, however, because
only one point in the plot cannot be used to infer the
behaviour of the agent at low acoustic pressures.
SUMMARY
The behaviours of two different types of contrast
agents have been explored by means of very diluted
suspensions of contrast microbubbles. The high dilution
allowed detection of single scattering events of the mi-
crobubbles, and it was found that the number of these
events for Quantison™ was dependent on acoustic pres-
sure. The scattering cross-section of the detected micro-
bubbles was proportional to acoustic pressure. This was
demonstrated for both agents, despite their different shell
composition and gas. There was also good evidence that,
above a certain acoustic pressure (around 0.6 MPa), free
bubbles were released from both agents. Further studies
of this type will be useful in accurately quantifying
contrast agent backscatter.
Volume 29, Number 5, 2003
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