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
N1 - Funding Information:
The authors wish to gratefully acknowledge Dr. Peter Frinking from Bracco Research for an insightful discussion. This research was supported by NIH R01-EB009066 and R21-CA139173 to MAB.
PY - 2010/6
Y1 - 2010/6
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
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U2 - 10.1016/j.ultrasmedbio.2010.03.015
DO - 10.1016/j.ultrasmedbio.2010.03.015
M3 - Article
C2 - 20447755
AN - SCOPUS:77953585956
SN - 0301-5629
VL - 36
SP - 935
EP - 948
JO - Ultrasound in Medicine and Biology
JF - Ultrasound in Medicine and Biology
IS - 6
ER -