Ultrasound contrast agents (UCAs) are small microbubbles filled with gas. Because of their scattering properties, UCAs enhance the diagnostic capabilities of ultrasonic imaging. UCAs are associated with therapeutic or enhancing therapeutic applications of ultrasound and with possible adverse bioeffects. Quantification of the in vivo concentration of microbubbles is therefore essential to establishing a dose/effect response for therapeutics and for quantifying other bioeffects. The concentration of UCAs is hypothesized to be proportional to the magnitude of the ultrasonic backscattered power spectrum. To demonstrate the ability to quantify UCAs from ultrasonic backscatter, several experiments were conducted. All experiments were conducted with FDA approved Definity® contrast agents and were performed in vitro, i.e., within a beaker or within a perfusion phantom, or in vivo, i.e., within the auricular artery of a rabbit. Estimates of the UCA concentration were obtained by comparing estimates of the backscattered power spectrum corresponding to the scattering from UCAs. A Monte Carlo technique was used to estimate the UCA concentration in vitro by minimizing the mean square error between the estimated power spectrum and the theoretical power spectrum. Samples of the Definity mixture were also extracted and analyzed under a fluorescence microscope and hemacytometer to obtain the size distribution and concentration of microbubbles optically for comparison with the ultrasound estimates. In both the in vitro and in vivo experiments, the linear relationship between the UCA concentration and magnitude of the ultrasonic backscattered power spectrum was demonstrated. Additionally, with the Monte Carlo technique, the UCA concentration and mean microbubble radius was estimated to within 12.3% and 8.48% of the optically measured values, respectively.
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Quantification of Ultrasound Contrast Agents Using High-Frequency Ultrasound