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. In order 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 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 to 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.

Nanobubbles for enhanced ultrasound imaging of tumors

“…Second, some time is necessary for the permeation and aggregation of the NBs; this requirement explains why the TTP of the NBs was later than that of the control MBs, which were too large to fit through the endothelial gaps. Third, because of their small size, the NBs were expected to absorb high-frequency ultrasound to a greater degree than their scattering at the fundamental frequency; 26 thus, the NBs exhibited a lower peak intensity in this study. Finally, their small size and PEGylated lipid shells helped the NBs escape from the mononuclear phagocyte system.…”

Engineering optically triggered droplets for photoacoustic imaging and therapy

“…This would result in a loss of core mass leading to a slightly smaller vaporized bubble. Nevertheless, the size distribution is well-maintained through the condensation and laser induced vaporization process; an important feature of the agents for dual mode imaging applications where strong scattering from the vaporized droplet population is desired [34,35].…”

Effects of high-fat diet and losartan on renal cortical blood flow using contrast ultrasound imaging

“…Subsequent studies have been performed in rat (13,31,41), rabbit (59), dog (63,64,68), swine (24,69), mouse (55,57), and isolated organs (54). Contrast ultrasound imaging of the kidney is not in widespread clinical use, although studies have demonstrated potential utility for evaluation of focal abnormalities (46) and in identifying rejection following renal transplant (14,27,28).…”