Harmonic B-mode imaging takes advantage of the non-linear oscillation of microbubbles. During harmonic imaging, the sound signal is transmitted at a frequency of around 1.5 to 2.0 MHz and received at twice this frequency. The microbubbles also reflect waves with wavelengths different from the transmitted one, the detectors can be set to receive only the latter ones and create only images of the contrast agent.
Using bandpass filters the transmitted frequency is separated from the received signal to get improved visualization of vessels containing ultrasound contrast agents (USCAs). The signal to noise ratio during the presence of microbubbles in tissue is four- to fivefold higher at the harmonic compared with the basic frequency.
Using harmonic B-mode imaging, harmonic frequencies produced by the ultrasound propagation through tissue have to be taken into account. The tissue reflection produces only a small amount harmonic energy compared to USCAs, but has to be removed by background subtraction for quantitative evaluation of myocardial perfusion.

See also Non-linear Propagation.

Power modulation is a non-linear method, based on a multi-pulse technique where the acoustic amplitude (and hence power) of the transmitted pulses is changed. Full and half amplitudes pulses are used to induce changes in the response of the contrast agent. The received echoes from the emitted half amplitude pulse are adjusted with the full amplitude pulse and this pairs of pulses are subtracted. Power modulation is used to separate contrast agent echoes at low mechanical index, allowing real-time perfusion imaging.
Power modulation can be used with a low frequency wide band transducer to increase the depth and transmit the sound beam homogenous allowing ultraharmonic imaging.

Quantison, consisting of air-filled microbubbles with stiff and rigid human serum albumin shells, is an investigational ultrasound contrast agent for the assessment of coronary artery disease.
The stiff shell inhibits the bubbles from oscillating and decrease non-linear scattering. Quantison is capable of long lasting cavity contrast and myocardial opacification using intermittent imaging.

Superharmonic imaging uses higher harmonics like third and fourth harmonic to increase the contrast to tissue ratio compared to a second harmonic imaging mode. Second harmonic imaging is better than fundamental imaging, but has limited capabilities to discriminate between tissue and microbubbles, caused by the non-linear propagation of ultrasound.

Microbubbles filled with air or inert gases are used as contrast agents in ultrasound imaging. Compression and rarefaction created by an ultrasound wave insonating a gas-filled microbubble along with the mechanical index of the ultrasonic beam lead to volume pulsations of the bubbles, and it is this change that results in the signal enhancement.
Microbubbles have diameters from 1 μm to 10 μm and a thin flexible or rigid shell composed of albumin, lipid, or polymer confining a gas such as nitrogen, or a perfluorocarbon. These microbubbles can cross the pulmonary capillaries and have a serum half-life of a few minutes. Microbubbles in the 1-10 μm range have their resonance at the frequencies used in diagnostic ultrasound (1−15MHz). Smaller bubbles resonate at higher frequencies. Caused by this coincidence, they are such effective reflectors.
The intrinsic compressibility of microbubbles is approximately 17,000 times more than water, and they are very strong scatterers of ultrasound. Under acoustic pressure the vibrating bubble radius may have a conventional linear response or a harmonic non-linear response. Microbubbles usually increase the Doppler signal amplitude by up to 30 dB.