Generation of ultraharmonics in surfactant based ultrasound contrast agents: use and advantages

A unique distinction between surfactant stabilized ultrasound contrast agent ST68 and water (or tissue), is the enhanced ability of the agent to generate non-linear frequencies such as sub-harmonics (f0/2), higher harmonics (2fo, 3fo, 4fo,...), and ultraharmonics (3f0/2, Sf0/2, 7f0/2,...), when insonated with fundamental frequency f0. Currently, second harmonics (2f0) have been predominantly researched, to exploit the diagnostic benefits of the contrast-specific non-linear imaging. However, we found that at normal imaging pressures (100 kPa-1 MPa), ST68 agent-generated second harmonic enhancements dropped to approximately 8 dB at 100 kPa and approximately 2 dB at 1 MPa. Moreover, at these pressures water (or tissue) produced strong second harmonics due to non-linear propagation. Ultraharmonics and sub-harmonics on the other hand, were generated only by the agent, and were not produced due to the non-linear propagation of ultrasound in either water or tissue. Additionally, ultraharmonic (3f0/2) enhancements of approximately 23 dB at 100 kPa, approximately 35 dB at 0.5 MPa and approximately 41dB at 1.1 MPa for ST68-PFC, offer much greater signal to noise ratio than higher harmonics.