P2A by xuyuzhu

VIEWS: 4 PAGES: 6

									                 TUESDAY, OCTOBER 7, 2003
               POSTER SESSIONS: 3:00–4:30 p.m.
                            * Author presenting Paper

Session: P2A
                      CONTRAST AGENTS III
                          Chair: P. Burns
                     Sunnybrook Health Science

P2A-1
    CHARACTERISATION OF NOVEL MICROBUBBLE
              CONTRAST AGENTS
R. J. ECKERSLEY*, C. A. SENNOGA, R. C. CAMPBELL, and M. J. K. BLOM-
LEY, Imperial College, London, UK.
Corresponding e-mail: r.eckersley@imperial.ac.uk

An exciting recent development in ultrasound microbubble contrast agent tech-
nology is their extension from non-specific diagnostic tools to targeted and ther-
apeutic agents. This process involves the addition of large molecules such as
ligands or DNA segments to the microbubbles. The aim of this work was to
evaluate the effects of these additional components on the acoustic properties
and the stability of microbubbles. Novel encapsulated microbubbles were pro-
duced in our laboratory with shell materials containing albumin or phospholipid.
In each case both targeted, conjugated bubbles and simple unconjugated ver-
sions were manufactured. Laboratory made microbubbles were compared to
similar commercially produced microbubbles. The attenuation coefficient was
measured with a broadband single element transducer using a substitution ap-
                                                                         r
proach and the backscatter was measured with a Toshiba PowerVision 8000.
Samples of each bubble type were sized from photographs taken through a
standard light microscope. The unconjugated laboratory bubbles were found
to behave comparably to their commercial equivalents. For example, albumin
                                                                  r
based bubbles were of equal stability and echogenicity to Optison . After conju-
gation albumin bubbles showed significantly lower echogenicity after 5 minutes
of exposure. Further investigation with bubbles conjugated with plasmid DNA
with additional cross-linking of the albumin shell was found to improve both the
echogenicity and the stability of the bubbles. The backscatter was no longer
significantly different to the unconjugated equivalent [33±6dB (mean±1s.d.)
unconjugated versus 38±8dB conjugated at 3MHz with MI=0.2]. While the
stability, measured from temporal changes in the attenuation spectra, improved
from a half-life of 300±20s for the control sample to 520±10s for conjugated
bubbles. For the lipid bubbles improvement in stability was also recorded upon
conjugation with PEG-COOH. This work demonstrates that the acoustic char-
acterisation of novel bubbles is crucial in refining the manufacturing process.
The results presented show that conjugation of large molecules into the bubble

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can affect the behaviour of the bubbles. The approaches employed in this work
allow testing of chemical hypotheses in the design of novel targeted agents.
Robert Eckersley is supported by the IRC-MIAS consortium funded jointly by the EPSRC and
the MRC, UK. Charles Sennoga is supported by NTRAC




P2A-2
   EFFECT OF BUBBLE SIZE DISTRIBUTION ON
NONLINEAR SCATTERING FROM MICROBUBBLES AT
             HIGH FREQUENCIES
D. E. GOERTZ, M. E. FRIJLINK, A. BOUAKAZ, C. T. CHIN, N. DE JONG,
and A. F. W. VAN DER STEEN, Erasmus MC, Rotterdam.
Corresponding e-mail: d.goertz@erasmusmc.nl

It has been shown that nonlinear scattering can be produced from current con-
trast agents at high frequencies (15-30 MHz). Subharmonic (SH), ultrahar-
monic (UH), and second harmonic (SecH) emissions can be stimulated, though
the latter are affected by nonlinear propagation. Such scattering has recently
been exploited by a novel high frequency nonlinear B-scan and flow imaging
system. The origin of nonlinear scattering at high frequencies has yet to be
established, though it is hypothesized to be associated with a subpopulation of
small bubbles. This study was undertaken to establish the effects of bubble size
on nonlinear scattering at high frequencies. Simulations were performed using
a modified Herring bubble model at a 20 MHz transmit frequency. Nonlinear
propagation effects were accounted for using KZK modeling. The results suggest
that bubbles with diameters on the order of 1.4-1.8 microns produce SHs and
UHs most efficiently, while bubbles on the order of 0.7-0.8 microns are most
suitable for SecH scattering. These findings were investigated experimentally
with a flow cell system located at the focus of a PVDF transducer. Experiments
were conducted at 20 MHz as a function of pressure and bandwidth (10-25%),
with the native size distribution of the experimental agent BR-14 (Bracco Re-
search, Geneva) and when larger bubbles were excluded using porous membrane
mechanical filtering. When a 2 micron pore filter is used to remove bubbles >2
microns (>90% of the volume fraction) the total received signal diminishes by
only 5-8 dB. For this filtered population, the ratios of the SH, UH, and SecH to
fundamental scattering improve by 6, 4, and 4 dB respectively. This suggests
the majority of nonlinear scattering is associated with bubbles <2 microns in
diameter. When bubbles >1 micron are preferentially filtered out, the received
power decreases by 8-11 dB, depending on pressure. The ratios of the SH, UH,
and SecH to fundamental scattering improve by 3, 2, and 7 dB respectively.
Much of the SH and UH signals are therefore derived from 1-2 micron filtered
bubbles, while SecH scattering is strongest below 1 micron. These results sug-
gest that agents comprised entirely of bubbles <2 microns in diameter should
improve signal strength and nonlinear scattering at high frequencies.
This work was supported by STW and NWO


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P2A-3
  A STUDY ON AN EVALUATION METHOD OF SHELL
   CHARACTERISTICS OF ULTRASOUND CONTRAST
       AGENT USING A HIGH-SPEED CAMERA
N. KUDO*, K. OKADA, and K. YAMAMOTO, Graduate School of Engineering,
Hokkaido University, Sapporo, Japan.
Corresponding e-mail: kudo@bme.eng.hokudai.ac.jp

New methods for ultrasound contrast imaging that use amplitude-encoded ul-
trasound pulses have recently been developed. In these methods, it is important
to understand various behaviors of bubbles exposed to ultrasound with different
pulse pressures. In order to study the pressure dependence of bubble behav-
ior, it is necessary to observe the behavior of one bubble exposed to multiple
pulses, since bubble behavior strongly depends not only on the pressure of the
ultrasound pulse to which the bubble is exposed but also on bubble size. How-
ever, in our previous observation system, after one bubble had been exposed to
one pulse, the bubble disappeared from a microscope field of view by acous-
tic streaming and could not be used for the next observation. To resolve this
problem, the high-speed observation system was improved to generate pulses
that had various pressures at a repetition rate of several tens of microseconds,
and trigger timing of each frame of a high-speed photograph was synchronized
to the pulse release. The interval of pulse sequence was sufficiently short, and
                                                                           r
distances of bubble movement in this time interval were small. Levovist was
used in experiments, and the center frequency of ultrasound pulses was set at
1 MHz. A microbubble was exposed to five ultrasound pulses with different
pressures (normalized pressures of 1.0, 1.2, 1.4, 1.6 and 1.8 with a pulse in-
terval of 40 microseconds). The total frame number of the high-speed camera
was 24, and 5 frames were assigned to each pulse (4 frames to the last pulse).
It was found that the amplitudes of bubble oscillation generally increased with
increase in pulse pressure. However, amplitude of oscillation increased rapidly
at a certain pressure in many cases, and it was thought that a strong nonlinear
relationship exists between pressure of ultrasound pulse and amplitude of radial
oscillation of a microbubble. The findings suggest that this nonlinear nature
should be considered in amplitude-coded contrast imaging methods.
This research was partially supported by a grant-in-aid for scientific research from the Ministry
of Education, Science, Sports and Culture, Japan and also supported by a research fund from
the Japan Society of Ultrasound in Medicine.

P2A-4
IMPROVED FRAME RATE BY REDUCTION OF BUBBLE
    DESTRUCTION USING NONLINEAR CODED
               EXCITATIONS
C. T. CHIN*, J. BORSBOOM, and N. DE JONG, Erasmus Medical Centre,
Rotterdam, The Netherlands.
Corresponding e-mail: c.chin@erasmusmc.nl

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Previously, a nonlinear coded excitation method based on chirps was proposed
for contrast imaging. Theoretical and experimental results suggested that it
offers higher signal-to-noise and contrast-to-tissue ratios without increasing MI.
However, this gain in sensitivity roughly scales with transmitted energy per fir-
ing. If the higher transmitted energy of chirps results in proportionally more
destruction of contrast bubbles, any sensitivity gain would be diminished in vivo
where blood flow often limits replenishment of contrast bubbles. This study
investigates the destructive effects of normal and chirp pulses in an in vitro flow
setup.
   A 0.12% solution of an experimental agent BR14 (Bracco Research SA,
Geneva) was fed thru a 10mm channel in an agar gel at 3ml/sec. Ultrasound was
fired from a 3.5MHz, 65% bandwidth, 13mm aperture unfocussed transducer
thru the channel. The amplitude was varied from MI = 0.01 to 0.1. PRF was
varied from 10 to 1000 Hz. Normal and chirp pulses were created at 2.0MHz
and 45% bandwidth with Gaussian windows. The chirp has 10dB more energy
than a pulse with the same peak amplitude. Attenuation of the ultrasound as
detected by a needle hydrophone behind the channel was related to the concen-
tration of the agent. Thus, measured attenuation indicates the balance between
destruction by each firing and replenishment by the in-flow.
   Destruction was minimal at low MI and PRF, resulting in the maximal at-
tenuation of 10dB. As PRF was increased, more bubbles were destroyed and
measured attenuation was decreased. When compared at equal amplitude and
PRF, chirps were attenuated slightly less than pulses (typically 0-2dB), indi-
cating that chirps are marginally more destructive than normal pulses of equal
peak amplitude. When the data was plotted to show average transmitted power
(product of PRF and pulse energy) as a function of measured attenuation. It
was found that chirps allow 3-8dB more transmitted power than normal pulses
at equal destruction levels.
   Previous studies indicated that nonlinear coded excitation imaging may allow
a 66% reduction of MI while delivering equivalent sensitivity and resolution. The
present study suggests that this reduced MI offers a tangible benefit in bubble
destruction and may allow up to a 3-fold increase in frame rate.
This project is supported by The Technology Foundation STW of the Netherlands. C. T. Chin
is supported by Fundamenteel Onderzoek der Materie of the Netherlands.


P2A-5
 A NEWTONIAN INTERFACIAL RHEOLOGICAL MODEL
      OF ULTRASOUND CONTRAST AGENTS
K. SARKAR*1 , D. CHATTERJEE1 , W. T. SHI2 , and F. FORSBERG2 , 1 Depart-
ment of Mechanical Engineering, University of Delaware, 2 Department of Radi-
ology, Thomas Jefferson University.
Corresponding e-mail: sarkar@me.udel.edu

A proper characterization with a reliable model of ultrasound contrast agents is
critical for developing improved agents and associated imaging protocols. Our
hypothesis is that a model for contrast agent, if it retains the essential physics,

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will offer applicability over a wide range of acoustic pressure amplitudes and
frequencies. Specifically, we will be able to predict their nonlinear response.
We have developed a new complex interface model of the encapsulation of a
microbubble contrast agent. The interface has zero thickness and an intrinsic
Newtonian rheology with surface tension γ and surface dilatational viscosity κs .
A modified Rayleigh-Plesset equation with these parameters was obtained. A
                                                 a
rationale for the present interface model vis-`-vis ones with a layer of nonzero
thickness lies in the anisotropy and the inhomogeneity (in thickness direction) in
the detail structure of the encapsulation. The characteristic parameters of the
model were determined by comparing in vitro attenuation data for a number of
contrast agents (Albunex, Optison, Sonazoid, and Quantison). The linearized
dynamics was used to match data from a controlled set of experiments per-
formed at smaller pressure amplitudes (<0.1MPa). The determined model was
investigated for its ability to predict the nonlinear response at higher amplitudes
(>1.0 MPa). We performed such a validation study for two test cases: Optison
(Mallinckrodt, St Loius, MO) with γ=0.9 N/m, κs =0.08 msP and Sonazoid
(Amersham Health, Oslo, Norway) with γ= 0.6N/m, κs =0.01 msP. In contrast
to existing models, the new model captured the distinct characteristics of sub-
harmonic emissions—initiation and rapid growth—for these agents. A detail
parametric study of the bubble behavior showed that the encapsulation dras-
tically reduces the influence of resonance frequency on scattering cross-section
suggesting possible means of improvement in imaging at off-resonant frequen-
cies. The present model seems to be a reliable descriptor of contrast agent
behaviors, and therefore, may be used to characterize different agents and to
design next generation agents by tuning the model parameters.
Department of Defense, University of Delware Research Foundation

P2A-6
  MICRO BUBBLE AGGREGATION BY INTERFERENCE
  OF INCIDENT AND THE SECONDARY ULTRASONIC
     WAVES AND ITS APPLICATION TO BUBBLE
               CHARACTERIZATION
Y. YAMAKOSHI*, N. MASUDA, and N. CHELLY, Faculty of Engineering,
Gunma University.
Corresponding e-mail: yamakosi@el.gunma-u.ac.jp

An ultrasonic wave assisted micro bubble trapping may be a promising technol-
ogy in a future drug delivery system. In the micro bubble trapping by ultrasonic
waves, it is often observed that the bubbles are aggregated and they grow up to
a certain size. The aggregated bubble size depends, for example, on the ultra-
sonic wave frequency and the bubble characteristics. In this paper, micro bubble
aggregation inside the ultrasonic wave field is evaluated both theoretically and
numerically. We consider the case where bubbles are in an interference sound
field which is produced by a plane ultrasonic wave in z direction and the sec-
ondary ultrasonic waves radiated from the bubbles on (x,y) plane. It is derived
that the secondary Bjerknes force makes aggregated bubbles if the relative phase

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between the secondary ultrasonic wave from the center bubble and the radial
oscillation of newly coming bubble is between -90 to 90 degrees. Under this
condition, the radius of the aggregated bubbles is determined by the ultrasonic
wave frequency and the relative phase. Based on the model, numerical analysis
is carried out. The Bjerknes force over (x,y) plane is evaluated for two or more
bubbles cases. The stability of a couple of aggregated bubbles is also discussed.
The experiments are done for the bubbles which are produced by an ultrasonic
contrast agent “Levovist” (Schering, A.G. Germany) and the bubbles with rel-
ative hard PVC shell. The frequency of the ultrasonic wave is from 2.5MHz
to 7.5MHz. The sound pressure is up to 200 kPa. The aggregated bubble
size and the micro bubble trapping pattern around the center bubble are well
in agreement with the numerical estimation. As an application of the bubble
aggregation by ultrasonic waves, characterization of secondary ultrasonic wave
radiation from the aggregated bubble is proposed. This method estimates the
relative phase of secondary ultrasonic waves by measuring the bubble aggrega-
tion pattern. This gives useful information in considering the bubble motion due
to the interactive force between the neighboring bubbles.


Session: P2B
            TISSUE CHARACTERIZATION II
                   Chair: J. Miller
                 Washington University

P2B-1
  DETECTION OF CALCIFIED VESSELS IN BREAST
TISSUE BY VIBRO-ACOUSTOGRAPHY: IMPLICATIONS
 ON DIAGNOSIS OF CORONARY ARTERY DISEASES
A. ALIZAD*, M. FATEMI, D. H. WHALEY, and J. F. GREENLEAF, Mayo
Clinic/Foundation.
Corresponding e-mail: aza@mayo.edu

Background: The relationship between breast arterial calcification and coro-
nary artery calcification and stenosis is currently an area of active research. It
has been suggested in the literature that calcified arteries in the breast may be
positively correlated with coronary artery disease. The efficacy of x-ray mam-
mography, the main breast imaging method, is greatly reduced in radiologially
dense breasts. In a recent study, we have shown that vibro-acoustography (VA),
a novel noninvasive imaging technique that is based on the dynamic response of
the object to a vibrating force, can detect microcalcifications in breast regardless
of breast density. This method uses the radiation force of ultrasound to vibrate
the tissue at a low (kHz) frequency and records the resulting acoustic field to
produce an image that is related to the hardness of the tissue. Here, we study
application of VA in detecting calcified arteries in breast tissue. Objective: To
evaluate the performance of VA in detecting calcified breast arteries. Method:

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