High frequency attenuation measurements of lipid encapsulated contrast agents

Abstract

A number of recent studies have indicated the potential of ultrasound contrast agent imaging at high ultrasound frequencies. However, the acoustic properties of microbubbles at frequencies above 10 MHz remain poorly understood at present. In this study we characterize the high frequency attenuation properties of (1) BR14, (2) BR14 that has been mechanically filtered (1 and 2 lm pore sizes) to exclude larger bubbles, and (3) the micron to submicron agent BG2423. A narrowband pulse-echo substitution method is employed with a series of four transducers covering the frequency range from 2 to 50 MHz. For BR14, attenuation decreases rapidly from 2 to 10 MHz and then more gradually from 10 to 50 MHz. For 2 lm filtration, the attenuation peaks between 10 and 15 MHz. For 1 lm filtration, attenuation continues to rise until 50 MHz. The agent BG2423 exhibits a diffuse attenuation peak in the range of 15-25 MHz and remains high until 50 MHz. These results demonstrate a strong influence of bubble size on high frequency attenuation curves, with bubble diameters of 1-2 lm and below having more pronounced acoustic activity at frequencies above 10 MHz.

Ultrabubble: A Laminated Ultrasound Contrast Agent with Narrow Size Range

“…[6] Thus, methods are now sought to stabilize lipid capsules and produce a homogeneous size distribution. [4,5,[7][8][9][10] This has been demonstrated by Pancholi et al, [4] who produced bubbles of 5.12 mm, and by Talu et al, [9] with even smaller standard deviation of 0.2 mm. However, these contrast agents work on the principle that their compressible gas core scatters incident acoustic waves more efficiently than surrounding blood and tissue, [11] and other materials may be more suitable to trap microbubbles that will provide ultrasound contrast.…”

“…[1] However, the challenge is not insignificant: the ideal capsule diameter is between 1-4 mm, safe for passage through the pulmonary capillary bed, [2,3] whereas the current lipid capsules normally have a broad size distribution. [3][4][5] Furthermore, although lipid preparations can be stored in the lyophilized state, they generally become acoustically inactive a few hours after reconstitution. [6] Thus, methods are now sought to stabilize lipid capsules and produce a homogeneous size distribution.…”

P2A-3 High Frequency Attenuation and Size Distribution Measurements of Definity and Manipulated Definity Populations

“…The details of the apparatus and processing can be found in [12]. A series of four commercially available transducers was used to cover the range of 2-50 MHz.…”

“…To date very little work has been done to measure attenuation at high ultrasound frequencies (>10 MHz). In [12] the 2 to 50 MHz attenuation properties of the experimental lipid encapsulated agents BR14 and the BG2423 were measured. The small bubble agent BG2423 was found to exhibit an increase in attenuation with frequency until reaching a diffuse peak in the range of 15 to 25 MHz.…”

On-chip targeted single cell sonoporation with microbubble destruction excited by surface acoustic waves

“…2(c), the attenuation of microbubbles increases with the excited frequency and the microbubbles have significant acoustic activity within the range 23 MHz-26 MHz, which is consistent with the results of phospholipid coated microbubbles. 22 Since the mean diameter of these microbubbles is just 0.91 lm, the acoustic backscattering is relatively weak and the attenuation spectrum does not show a particularly strong resonance. 23,24 The results suggest that the microbubbles are more active and likely to initiate cavitation at 23-26 MHz when the ultrasonic waves have sufficient intensity.…”