Effect of microbubble size on fundamental mode high frequency ultrasound imaging in mice

Shashank Sirsi, Jameel Feshitan, James Kwan, Shunichi Homma, Mark Borden

Research output: Contribution to journalArticle

98 Citations (Scopus)

Abstract

High-frequency ultrasound imaging using microbubble (MB) contrast agents is becoming increasingly popular in pre-clinical and small animal studies of anatomy, flow and vascular expression of molecular epitopes. Currently, in vivo imaging studies rely on highly polydisperse microbubble suspensions, which may provide a complex and varied acoustic response. To study the effect of individual microbubble size populations, microbubbles of 1-2 μm, 4-5 μm and 6-8 μm diameter were isolated using the technique of differential centrifugation. Size-selected microbubbles were imaged in the mouse kidney over a range of concentrations using a Visualsonics Vevo 770 ultrasound imaging system (Visualsonics, Toronto, Ontario, Canada) with a 40-MHz probe in fundamental mode. Results demonstrate that contrast enhancement and circulation persistence are strongly dependent on microbubble size and concentration. Large microbubbles (4-5 and 6-8 μm) strongly enhanced the ultrasound image with positive contrast, while 1-2 μm microbubbles showed little enhancement. For example, the total integrated contrast enhancement, measured by the area under the time-intensity curve (AUC), increased 16-fold for 6-8 μm diameter microbubbles at 5 × 107 MB/bolus compared with 4-5 μm microbubbles at the same concentration. Interestingly, 1-2 μm diameter microbubbles, at any concentration, did not measurably enhance the integrated ultrasound signal at tissue depth, but did noticeably attenuate the signal, indicating that they had a low scattering-to-attenuation ratio. When concentration matched, larger microbubbles were more persistent in circulation. However, when volume matched, all microbubble sizes had a similar circulation half-life. These results indicated that dissolution of the gas core plays a larger role in contrast elimination than filtering by the lungs and spleen. The results of this study show that microbubbles can be tailored for optimal contrast enhancement in fundamental mode imaging.

Original languageEnglish (US)
Pages (from-to)935-948
Number of pages14
JournalUltrasound in Medicine and Biology
Volume36
Issue number6
DOIs
StatePublished - Jun 1 2010

Fingerprint

Microbubbles
mice
Ultrasonography
augmentation
Ontario
spleen
anatomy
kidneys
Canada
half life
lungs
animals
elimination
dissolving
attenuation
acoustics
probes
curves
scattering
gases

Keywords

  • Absorption
  • Circulation persistence
  • Contrast agent
  • Diameter
  • Kidney
  • Scattering cross-section

ASJC Scopus subject areas

  • Radiological and Ultrasound Technology
  • Biophysics
  • Acoustics and Ultrasonics

Cite this

Effect of microbubble size on fundamental mode high frequency ultrasound imaging in mice. / Sirsi, Shashank; Feshitan, Jameel; Kwan, James; Homma, Shunichi; Borden, Mark.

In: Ultrasound in Medicine and Biology, Vol. 36, No. 6, 01.06.2010, p. 935-948.

Research output: Contribution to journalArticle

Sirsi, Shashank ; Feshitan, Jameel ; Kwan, James ; Homma, Shunichi ; Borden, Mark. / Effect of microbubble size on fundamental mode high frequency ultrasound imaging in mice. In: Ultrasound in Medicine and Biology. 2010 ; Vol. 36, No. 6. pp. 935-948.
@article{79422d1cd2164063b74234a84922658c,
title = "Effect of microbubble size on fundamental mode high frequency ultrasound imaging in mice",
abstract = "High-frequency ultrasound imaging using microbubble (MB) contrast agents is becoming increasingly popular in pre-clinical and small animal studies of anatomy, flow and vascular expression of molecular epitopes. Currently, in vivo imaging studies rely on highly polydisperse microbubble suspensions, which may provide a complex and varied acoustic response. To study the effect of individual microbubble size populations, microbubbles of 1-2 μm, 4-5 μm and 6-8 μm diameter were isolated using the technique of differential centrifugation. Size-selected microbubbles were imaged in the mouse kidney over a range of concentrations using a Visualsonics Vevo 770 ultrasound imaging system (Visualsonics, Toronto, Ontario, Canada) with a 40-MHz probe in fundamental mode. Results demonstrate that contrast enhancement and circulation persistence are strongly dependent on microbubble size and concentration. Large microbubbles (4-5 and 6-8 μm) strongly enhanced the ultrasound image with positive contrast, while 1-2 μm microbubbles showed little enhancement. For example, the total integrated contrast enhancement, measured by the area under the time-intensity curve (AUC), increased 16-fold for 6-8 μm diameter microbubbles at 5 × 107 MB/bolus compared with 4-5 μm microbubbles at the same concentration. Interestingly, 1-2 μm diameter microbubbles, at any concentration, did not measurably enhance the integrated ultrasound signal at tissue depth, but did noticeably attenuate the signal, indicating that they had a low scattering-to-attenuation ratio. When concentration matched, larger microbubbles were more persistent in circulation. However, when volume matched, all microbubble sizes had a similar circulation half-life. These results indicated that dissolution of the gas core plays a larger role in contrast elimination than filtering by the lungs and spleen. The results of this study show that microbubbles can be tailored for optimal contrast enhancement in fundamental mode imaging.",
keywords = "Absorption, Circulation persistence, Contrast agent, Diameter, Kidney, Scattering cross-section",
author = "Shashank Sirsi and Jameel Feshitan and James Kwan and Shunichi Homma and Mark Borden",
year = "2010",
month = "6",
day = "1",
doi = "10.1016/j.ultrasmedbio.2010.03.015",
language = "English (US)",
volume = "36",
pages = "935--948",
journal = "Ultrasound in Medicine and Biology",
issn = "0301-5629",
publisher = "Elsevier USA",
number = "6",

}

TY - JOUR

T1 - Effect of microbubble size on fundamental mode high frequency ultrasound imaging in mice

AU - Sirsi, Shashank

AU - Feshitan, Jameel

AU - Kwan, James

AU - Homma, Shunichi

AU - Borden, Mark

PY - 2010/6/1

Y1 - 2010/6/1

N2 - High-frequency ultrasound imaging using microbubble (MB) contrast agents is becoming increasingly popular in pre-clinical and small animal studies of anatomy, flow and vascular expression of molecular epitopes. Currently, in vivo imaging studies rely on highly polydisperse microbubble suspensions, which may provide a complex and varied acoustic response. To study the effect of individual microbubble size populations, microbubbles of 1-2 μm, 4-5 μm and 6-8 μm diameter were isolated using the technique of differential centrifugation. Size-selected microbubbles were imaged in the mouse kidney over a range of concentrations using a Visualsonics Vevo 770 ultrasound imaging system (Visualsonics, Toronto, Ontario, Canada) with a 40-MHz probe in fundamental mode. Results demonstrate that contrast enhancement and circulation persistence are strongly dependent on microbubble size and concentration. Large microbubbles (4-5 and 6-8 μm) strongly enhanced the ultrasound image with positive contrast, while 1-2 μm microbubbles showed little enhancement. For example, the total integrated contrast enhancement, measured by the area under the time-intensity curve (AUC), increased 16-fold for 6-8 μm diameter microbubbles at 5 × 107 MB/bolus compared with 4-5 μm microbubbles at the same concentration. Interestingly, 1-2 μm diameter microbubbles, at any concentration, did not measurably enhance the integrated ultrasound signal at tissue depth, but did noticeably attenuate the signal, indicating that they had a low scattering-to-attenuation ratio. When concentration matched, larger microbubbles were more persistent in circulation. However, when volume matched, all microbubble sizes had a similar circulation half-life. These results indicated that dissolution of the gas core plays a larger role in contrast elimination than filtering by the lungs and spleen. The results of this study show that microbubbles can be tailored for optimal contrast enhancement in fundamental mode imaging.

AB - High-frequency ultrasound imaging using microbubble (MB) contrast agents is becoming increasingly popular in pre-clinical and small animal studies of anatomy, flow and vascular expression of molecular epitopes. Currently, in vivo imaging studies rely on highly polydisperse microbubble suspensions, which may provide a complex and varied acoustic response. To study the effect of individual microbubble size populations, microbubbles of 1-2 μm, 4-5 μm and 6-8 μm diameter were isolated using the technique of differential centrifugation. Size-selected microbubbles were imaged in the mouse kidney over a range of concentrations using a Visualsonics Vevo 770 ultrasound imaging system (Visualsonics, Toronto, Ontario, Canada) with a 40-MHz probe in fundamental mode. Results demonstrate that contrast enhancement and circulation persistence are strongly dependent on microbubble size and concentration. Large microbubbles (4-5 and 6-8 μm) strongly enhanced the ultrasound image with positive contrast, while 1-2 μm microbubbles showed little enhancement. For example, the total integrated contrast enhancement, measured by the area under the time-intensity curve (AUC), increased 16-fold for 6-8 μm diameter microbubbles at 5 × 107 MB/bolus compared with 4-5 μm microbubbles at the same concentration. Interestingly, 1-2 μm diameter microbubbles, at any concentration, did not measurably enhance the integrated ultrasound signal at tissue depth, but did noticeably attenuate the signal, indicating that they had a low scattering-to-attenuation ratio. When concentration matched, larger microbubbles were more persistent in circulation. However, when volume matched, all microbubble sizes had a similar circulation half-life. These results indicated that dissolution of the gas core plays a larger role in contrast elimination than filtering by the lungs and spleen. The results of this study show that microbubbles can be tailored for optimal contrast enhancement in fundamental mode imaging.

KW - Absorption

KW - Circulation persistence

KW - Contrast agent

KW - Diameter

KW - Kidney

KW - Scattering cross-section

UR - http://www.scopus.com/inward/record.url?scp=77953585956&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77953585956&partnerID=8YFLogxK

U2 - 10.1016/j.ultrasmedbio.2010.03.015

DO - 10.1016/j.ultrasmedbio.2010.03.015

M3 - Article

C2 - 20447755

AN - SCOPUS:77953585956

VL - 36

SP - 935

EP - 948

JO - Ultrasound in Medicine and Biology

JF - Ultrasound in Medicine and Biology

SN - 0301-5629

IS - 6

ER -