(CPS) Contrast pulse sequencing is a technique to exploit contrast agent properties with series of three pulses that differ in phase and amplitude. CPS allows bubble specific imaging with non-linear fundamental and higher order harmonics, low MI, and extremely high microbubble-to-tissue background ratio.

See also Ultrasound Contrast Agent Safety.

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.

(HPD) Harmonic power Doppler is currently one of the most sensitive techniques for detecting ultrasound contrast agents. HPD works by transmitting multiple pulses toward the object to be imaged and detecting the pulse-to-pulse changes in the received echo signals.
Second harmonic bandbass filtering is applied to the received signals to exploit the non-linear behavior of scattering from bubbles (clutter). Harmonic power Doppler operates best at high output levels because of increased contrast destruction, and pulse amplitudes close to the maximum allowed are used much of the time.
With a high mechanical index, non-linear propagation of the sound will cause significant harmonic components from tissue, and the contrast agent to tissue ratio will decrease.
Also called Harmonic Power Angio. See also Multiple Frame Trigger.

MRX 408 is an investigational thrombus-specific ultrasound contrast agent for clot detection and sonothrombolysis enhancement. Targeted contrast imaging with this GPIIb receptor-targeted ultrasound contrast agent demonstrated better visualization of thrombus within AV fistulae.
MRX 408 is available (ImaRx LLC) with a mean radius of 1.0 mm and a standard deviation of 0.8 mm.

(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.