Ultrasound waves are created at harmonics of the delivered frequency. Subharmonic imaging uses the harmonic oscillation of a system at a frequency that is a simple fraction of its fundamental frequency. The subharmonic response frequencies has half of the fundamental frequency. The second subharmonic has a half fundamental frequency of one half the frequency, and so on.

See also Harmonic Imaging and Superharmonic Imaging.

The fundamental frequency is the natural or resonant frequency of a system and the first harmonic of a system's oscillation.

See also Subharmonic Imaging.

Harmonic is an oscillation of a system at a frequency that is a simple multiple of its fundamental frequency. The fundamental frequency of a sinusoidal oscillation is called the first harmonic. The second harmonic has a frequency doubled that of the fundamental.

See also Fundamental Imaging, Harmonic Imaging, Subharmonic Imaging and Superharmonic Imaging.

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.

(MI) The mechanical index is an estimate of the maximum amplitude of the pressure pulse in tissue. It is an indicator of the likelihood of mechanical bioeffects (streaming and cavitation). The mechanical index of the ultrasound beam is the amount of negative acoustic pressure within a ultrasonic field and is used to modulate the output signature of US contrast agents and to incite different microbubble responses.
The mechanical index is defined as the peak rarefactional pressure (negative pressure) divided by the square root of the ultrasound frequency.
The FDA ultrasound regulations allow a mechanical index of up to 1.9 to be used for all applications except ophthalmic (maximum 0.23). The used range varies from 0.05 to 1.9.
At low acoustic power, the acoustic response is considered as linear. At a low MI (less than 0.2), the microbubbles undergo oscillation with compression and rarefaction that are equal in amplitude and no special contrast enhanced signal is created. Microbubbles act as strong scattering objects due to the difference in impedance between air and liquid, and the acoustic response is optimized at the resonant frequency of a microbubble.
At higher acoustic power (MI between 0.2-0.5), nonlinear oscillation occurs preferentially with the bubbles undergoing rarefaction that is greater than compression. Ultrasound waves are created at harmonics of the delivered frequency. The harmonic response frequencies are different from that of the incident wave (fundamental frequency) with subharmonics (half of the fundamental frequency), harmonics (including the second harmonic response at twice the fundamental frequency), and ultra-harmonics obtained at 1.5 or 2.5 times the fundamental frequency. These contrast enhanced ultrasound signals are microbubble-specific.
At high acoustic power (MI greater than 0.5), microbubble destruction begins with emission of high intensity transient signals very rich in nonlinear components. Intermittent imaging becomes needed to allow the capillaries to be refilled with fresh microbubbles. Microbubble destruction occurs to some degree at all mechanical indices. A mechanical index from 0.8 to 1.9 creates high microbubble destruction. The output signal is unique to the contrast agent.