Linear acoustic propagation in a medium with respect to ultrasound would result if the shape and amplitude of the signal at any point in the medium were proportional to the input excitation. However, tissue exhibits a nonlinear property with respect to ultrasound propagation, resulting in the shape and amplitude of the acoustic signal changing as it propagates into the tissue. Specifically, ultrasound propagation in nonlinear tissue results in pulse and beam distortion, harmonic generation, and saturation of acoustic pressure. This is caused by the fact that, as a sinusoidal signal of a single frequency is generated and transmitted into a non-linear medium, the signal will distort as it propagates because the compression phase velocity of the signal is greater than the velocity of the rarefaction phase. This effect will result in distortion of the wave as it propagates so that a “sawtooth” or “N”-shaped wave is generated, which has frequencies at harmonic multiples of the fundamental frequency. Since tissue attenuation increases with frequency, the higher harmonics will be attenuated, leaving an attenuated low-frequency signal at greater depths. Investigation of generation of harmonics in water by ultrasound imaging systems began in the 1970s and 1980s.103–105 Use of nonlinear acoustics in medical imaging systems accelerated in the 1990s with primarily two applications: tissue harmonics and ultrasound contrast agents.
Tissue harmonic imaging was investigated in the 1990s by several groups.106,107 and was commonly available in clinical ultrasound systems by the late 1990s. Two competing effects characterize ultrasound propagation in nonlinear media such as tissue. Increasing harmonics with propagation distance leads to increased absorption. The latter reduces pressure amplitude and harmonic generation. Since tissue heating is a consequence of absorption, nonlinear effects enhance tissue heating as compared to the heating that would have occurred at the fundamental propagation frequency.108,109
Tissue harmonic imaging is typically implemented by filtering out the fundamental ultrasound frequency of the received beam. Second harmonic images have been shown to often improve contrast and resolution as compared to images generated by the fundamental frequency. These advantages result from multiple improvements, such as narrower beamwidth, reduced sidelobes, reduced reverberations and multiple scattering, reduced grating lobes, and increased dynamic range.107,110 This is primarily due to the fact that these unwanted signals are mainly incoherent and are small in amplitude. Thus, they do not generate harmonics and can be filtered out in the second harmonic image.111 In addition, since harmonics are proportional to the square of the fundamental pressure, increasing the acoustic input pressure will generate a disproportionate increase in the second harmonic, compared to the situation in which the medium is linear and no harmonics are generated (Fig. 2).