Harmonic imaging was originally developed for microbubble contrast agents in the early 90s under the assumption that tissue is linear and all harmonic echoes are generated by the bubbles. In fact, tissue, like bubbles, is a nonlinear medium. Whereas the harmonic echoes from bubbles have their origins in nonlinear scattering, those from tissue are a result of nonlinear propagation. The clinical benefits of tissue harmonic imaging are reduced reverberation noise and overall clutter level, improved border delineation, increased contrast resolution, and reduced phase aberration artifacts. To a large extend these benefits are explained by the properties of nonlinear propagation of the transmitted ultrasonic pulses in the tissue.
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Michalakis A. Averkiou (2002) studied this question.
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