Characterization of individual submicron perfluorocarbon gas bubbles by ultrasonic backscatter




Characterization of individual submicron perfluorocarbon gas bubbles by ultrasonic backscatter

Characterization of individual submicron
perfluorocarbon gas bubbles by ultrasonic
backscatter
E. Carr Everbacha)
Department of Engineering, Swarthmore College, 500 College Avenue, Swarthmore, PA 19081-1397
ceverba1@swarthmore.edu
Damir B. Khismatullin
Department of Biomedical Engineering, Duke University, Durham, NC 27708-0281
damir@duke.edu
John T. Flaherty
Transkaryotic Therapies Inc., 700 Main Street, Cambridge, MA 02139
jflaherty@tktx.com
Ronald A. Roy
Department of Aerospace and Mechanical Engineering, Boston University, 110 Cummington Street, Boston,
MA 02215
ronroy@bu.edu
Abstract: Measurements were undertaken to determine the unknown
microbubble-size distribution of a dodecafluoropentane (DDFP) emulsion
consisting of 1012 droplets/ml in surfactant-stabilized water. The acoustic
backscatter of 2-microsecond-duration tonebursts of 30-MHz focused ultrasound
was measured from the emulsion as it moved in a coaxial flow. Calibration
for the system was accomplished using 3-mm-radius polystyrene spheres,
using a linear scattering model and literature values for polystyrene. Applying
viscous linear scattering theory to the backscatter data from individual DDFP
bubbles allowed inversion of the radius–backscatter relation. A mean microbubble
radius of 130 nm was inferred for the DDFP population.
© 2005 Acoustical Society of America
PACS numbers: 43.30.Gv, 43.35.Yb, 43.80.Vj
Date Received: January 23, 2005 Date Accepted: April 29, 2005
1. Introduction
Determining the size distribution of preparations of microbubbles is an ongoing challenge in
fields as diverse as oceanography1 and biomedical ultrasound.2 Various methods have been
employed to interrogate large populations of microbubbles and yield ensemble-averaged
parameters3 that, in turn, provide information about bubble-size distributions. Methods that
interrogate a single bubble at a time avoid these pitfalls,4–6 although optical methods and
Coulter counters have low sensitivity for bubbles smaller than about 1-mm radius.
Of great interest in biomedicine is the characterization of echocontrast agents used in
biomedical ultrasound applications such as cardiology.7 Of interest here are emulsions of
dodecafluoropentane (DDFP) droplets used in echocontrast agents8 such as Echogen™. Since
the boiling temperature for this Material is approximately 28–30 7C at 1 atmosphere pressure,
individual droplets will be superheated at body temperature (37 7C). If a nucleation mechanism
allows some droplets to boil and hence become bubbles, the low solubility of DDFP will allow
the bubbles to persist in the circulatory system and provide sustained ultrasonic contrast.
a)Corresponding author.
Everbach et al.: Acoustics Research Letters Online [DOI: 10.1121/1.1901734] Published Online 24 June 2005
175 ARLO 6(3), July 2005 1529-7853/05/6(3)/175/7/$22.50 © 2005 Acoustical Society of America 175

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    Characterization of individual submicron perfluorocarbon gas bubbles by ultrasonic backscatter

    Characterization of individual submicron perfluorocarbon gas bubbles by ultrasonic backscatter

    Characterization of individual submicron
    perfluorocarbon gas bubbles by ultrasonic
    backscatter
    E. Carr Everbacha)
    Department of Engineering, Swarthmore College, 500 College Avenue, Swarthmore, PA 19081-1397
    ceverba1@swarthmore.edu
    Damir B. Khismatullin
    Department of Biomedical Engineering, Duke University, Durham, NC 27708-0281
    damir@duke.edu
    John T. Flaherty
    Transkaryotic Therapies Inc., 700 Main Street, Cambridge, MA 02139
    jflaherty@tktx.com
    Ronald A. Roy
    Department of Aerospace and Mechanical Engineering, Boston University, 110 Cummington Street, Boston,
    MA 02215
    ronroy@bu.edu
    Abstract: Measurements were undertaken to determine the unknown
    microbubble-size distribution of a dodecafluoropentane (DDFP) emulsion
    consisting of 1012 droplets/ml in surfactant-stabilized water. The acoustic
    backscatter of 2-microsecond-duration tonebursts of 30-MHz focused ultrasound
    was measured from the emulsion as it moved in a coaxial flow. Calibration
    for the system was accomplished using 3-mm-radius polystyrene spheres,
    using a linear scattering model and literature values for polystyrene. Applying
    viscous linear scattering theory to the backscatter data from individual DDFP
    bubbles allowed inversion of the radius–backscatter relation. A mean microbubble
    radius of 130 nm was inferred for the DDFP population.
    © 2005 Acoustical Society of America
    PACS numbers: 43.30.Gv, 43.35.Yb, 43.80.Vj
    Date Received: January 23, 2005 Date Accepted: April 29, 2005
    1. Introduction
    Determining the size distribution of preparations of microbubbles is an ongoing challenge in
    fields as diverse as oceanography1 and biomedical ultrasound.2 Various methods have been
    employed to interrogate large populations of microbubbles and yield ensemble-averaged
    parameters3 that, in turn, provide information about bubble-size distributions. Methods that
    interrogate a single bubble at a time avoid these pitfalls,4–6 although optical methods and
    Coulter counters have low sensitivity for bubbles smaller than about 1-mm radius.
    Of great interest in biomedicine is the characterization of echocontrast agents used in
    biomedical ultrasound applications such as cardiology.7 Of interest here are emulsions of
    dodecafluoropentane (DDFP) droplets used in echocontrast agents8 such as Echogen™. Since
    the boiling temperature for this Material is approximately 28–30 7C at 1 atmosphere pressure,
    individual droplets will be superheated at body temperature (37 7C). If a nucleation mechanism
    allows some droplets to boil and hence become bubbles, the low solubility of DDFP will allow
    the bubbles to persist in the circulatory system and provide sustained ultrasonic contrast.
    a)Corresponding author.
    Everbach et al.: Acoustics Research Letters Online [DOI: 10.1121/1.1901734] Published Online 24 June 2005
    175 ARLO 6(3), July 2005 1529-7853/05/6(3)/175/7/$22.50 © 2005 Acoustical Society of America 175