Quantitative measurements of second harmonic Doppler using ultrasound contrast agents

Quantitative measurements of second harmonic and first harmonic Doppler were carried out using two ultrasound contrast agents, Albunex and FS069. The RMS amplitudes of the Doppler shift spectra were measured as a function of the concentration of the agents, frequency and transmitted acoustic pressure. The results showed that, for a given lot of contrast agent investigated, FS069 was able to produce higher levels of first and, especially, second harmonic signals compared to Albunex. Under the same experimental conditions, the RMS Doppler amplitude (RDA) of FS069 was 3.8 +/- 0.8 dB higher than Albunex at first harmonic and 12.6 +/- 0.8 dB higher at second harmonic. The ratio of the second harmonic to first harmonic RDA, which we called R2/R1, decreases at a rate of 7 dB/MHz for both agents with increasing frequency. The difference in the value of R2/R1 between FS069 and Albunex at any frequency was approximately 4.5 dB. R2/R1 was found to increase linearly as a function of the transmitted acoustic pressure for both agents. Simulations using the Rayleigh-Plesset equation show a decrease of R2/R1 at a rate of 5 dB/MHz. Comparison of experimental results with theory indicates that the shell elasticity parameter may be an increasing function of the mean diameter of the bubbles.