Frequency and concentration dependence of the backscatter coefficient of the ultrasound contrast agent Albunex®

A broadband ultrasonic measurement system has been utilized to characterize the concentration and frequency dependence of in vitro suspensions of Albunex® microspheres at concentrations ranging from 1.7×105 to 2.1×107 microspheres/mL and over a bandwidth of 1–16 MHz. The apparent backscattered power (not compensated for effects due to attenuation) was shown to increase with dose for lower concentrations of microspheres, but then to decrease rapidly with increasing concentration where attenuation effects become significant. Measurements of signal loss demonstrated that the attenuation grew exponentially with increasing concentration, so that a doubling of the number of microspheres led to a doubling of the value of the attenuation coefficient measured in dB/cm. This relationship was demonstrated over the entire system bandwidth. Compensation of the apparent backscattered power for the attenuation yielded the backscatter transfer function. This quantity was shown to be linearly proportional to concentration, so that a doubling of the number of microspheres led to a 3-dB increase in the backscatter transfer function. A broadband data reduction technique was used to further reduce the data to backscatter coefficient, an absolute parameter describing the intrinsic scattering efficiency of the Albunex® microsphere suspensions. The backscatter coefficient was shown to be linearly proportional to microsphere concentration at all concentrations investigated and over all the usable bandwidth. This suggests that, with appropriate compensation for attenuation and equipment parameters, perfusion or flow quantification techniques which assume a linear dependence of backscatter with contrast agent concentration should be applicable. The backscatter coefficient exhibits a rapid rise with frequency below 3 MHz, and appears to approach a frequency independent limit above 3 MHz. The relationships of the attenuation coefficient and backscatter transfer function to concentration were generally consistent with predictions from a simple scattering model. These relationships appear to be valid within the usable bandwidth of our measurement system for all concentrations investigated.