Harmonic imaging relies on detection of harmonics of the transmitted frequency produced by bubble oscillation. This method is widely available on ultrasound scanners and uses the same array transducers as conventional imaging. A major limitation of the use of ultrasound contrast agents is the problem that signals from the microbubbles are mixed with those from tissue. Echoes from solid tissue and red blood cells are suppressed by harmonic imaging.
In harmonic mode, the system transmits at one frequency, but is tuned to receive echoes preferentially at double that frequency, and the second harmonic echoes from the place of the bubble. Typically, the transmit frequency lies between 1.5 and 3 MHz and the receive frequency is selected by means of a bandpass filter whose center frequency lies between 3 and 6 MHz.
Color Doppler and real-time harmonic spectral Doppler modes have also been implemented and show a level of tissue motion suppression not available in conventional modes.

See also Harmonic B-Mode Imaging, and Harmonic Power Doppler.

The earliest introduction of vascular ultrasound contrast agents (USCA) was by Gramiak and Shah in 1968, when they injected agitated saline into the ascending aorta and cardiac chambers during echocardiographic to opacify the left heart chamber. Strong echoes were produced within the heart, due to the acoustic mismatch between free air microbubbles in the saline and the surrounding blood.

A linear probe contains one or more acoustic linear array transducer elements arranged in a line to send pulses of sound into a material. The linear array gives a large probe surface (footprint) and near field. In Doppler mode, a linear probe operates a subset of its elements as a linear phased array and can thus steer the Doppler beam at a selected angle to the imaging beam. This is a popular configuration for peripheral vascular and perivascular scanning.

Standard scanners allow visualizing microbubbles on conventional gray scale imaging in large vascular spaces. In the periphery, more sensitive techniques such as Doppler or non-linear gray scale modes must be used because of the dilution of the microbubbles in the blood pool. Harmonic power Doppler (HPD) is one of the most sensitive techniques for detecting ultrasound contrast agents.
Commonly microbubbles are encapsulated or otherwise stabilized to prolong their lifetime after injection. These bubbles can be altered by exposure to ultrasound pulses. Depending on the contrast agent and the insonating pulse, the changes include deformation or breakage of the encapsulating or stabilizing material, generation of free gas bubbles, reshaping or resizing of gas volumes.
High acoustic pressure amplitudes and long pulses increase the changes. However, safety considerations limit the pressure amplitude and long pulses decrease spatial resolution. In addition, lowering the pulse frequency increases destruction of contrast bubbles. However, at low insonation power levels, contrast agent particles resist insonation without detectable changes. Newer agents are more reflective and will usually allow gray scale imaging to be used with the advantages of better spatial resolution, fewer artifacts and faster frame rates.

Feasible imaging methods with advantages in specific acoustic microbubble properties:
Resonating microbubbles emit harmonic signals at double their resonance frequency. If a scanner is modified to select only these harmonic signals, this non-linear mode produces a clear image or trace. The effect depends on the fact that it is easier to expand a bubble than to compress it so that it responds asymmetrically to a symmetrical ultrasound wave. A special array design allows to perform third or fourth harmonic imaging. This probe type is called a dual frequency phased array transducer.

See also Bubble Specific Imaging.

Usually, multiple probes are used because most transducers are only able to emit one frequency because the piezoelectric ceramic or crystals within it have a certain inherent frequency.
Multi-frequency probes have multiple crystals with different frequencies and the desired specific frequency can be selected. Advanced probes can emit sound waves at different frequencies for the near and far fields. The disadvantage is that multi-frequency (multifrequency) probes have slower frame rates and therefore they are only useful for imaging of static structures.

See also Dual Frequency Phased Array Transducer and Tri-Frequency Probe.