(PII) Pulse inversion imaging (also called phase inversion imaging) is a non-linear imaging method specifically made for enhanced detection of microbubble ultrasound contrast agents. In PII, two pulses are sent in rapid succession into the tissue; the second pulse is a mirror image of the first. The resulting echoes are added at reception. Linear scattering of the two pulses will give two echoes which are inverted copies of each other, and these echoes will therefore cancel out when added.
Linear scattering dominates in tissues. Echoes from linear scatterers such as tissue cancel, whereas those from gas microbubbles do not. Non-linear scattering of the two pulses will give two echoes which do not cancel out completely due to different bubble response to positive and negative pressures of equal magnitude. The harmonic components add, and the signal intensity difference between non-linear and linear scatterers is therefore increased. The resulting images show high sensitivity to bubbles at the resolution of a conventional image.
In harmonic imaging, the frequency range of the transmitted pulse and the received signal should not overlap, but this restriction is less in pulse inversion imaging since the transmit frequencies are not filtered out, but rather subtracted. Broader transmit and receive bandwidths are therefore allowed, giving shorter pulses and improved axial resolution, hence the alternative term wideband harmonic imaging. Many ultrasound machines offer some form of pulse inversion imaging.

See also Pulse Inversion Doppler, Narrow Bandwidth, Dead Zone, Ultrasound Phantom.

Rayleigh scattering is the backscattering of ultrasound from blood. The echoes detected from blood are created through interference between scattered wavelets from numerous point scatterers. Rayleigh Scatterers are objects whose dimensions are much less than the ultrasound wavelength. Rayleigh scattering increases with frequency raised to the 4th power and provides much of the diagnostic information from ultrasound. Doubling the ultrasonic frequency makes the echoes from blood 16 times as strong. The intensity of the backscattered echoes is proportional to the total number of scatterers, which means that the echo amplitude is proportional to the square root of the total number of scatterers.
At normal blood flow, the number of point scatterers in blood is proportional to the number of red blood cells. When blood flow is turbulent, or accelerating fast (e.g. in a stenosis), the number of inhomogeneities in the red blood cell concentration will increase.

See also Scattered Echo.

(UCA / USCA) Ultrasonography is the most commonly performed diagnostic imaging procedure. The introduction of sonographic contrast media into routine practice modifies the use of ultrasound in a variety of clinical applications. USCAs consist of microbubbles filled with air or gases and can be classified according to their pharmacokinetics. Among the blood pool agents, transpulmonary ultrasound contrast agents offer higher diagnostic potential compared to agents that cannot pass the pulmonary capillary bed after a peripheral intravenous injection. In addition to their vascular phase, some USCAs can exhibit a tissue- or organ-specific phase.
The sonogram image quality is improved either by decreasing the reflectivity of the undesired interfaces or by increasing the backscattered echoes from the desired regions.

Different types of ultrasound contrast agents:
Ultrasound contrast agents act as echo-enhancers, because of the high different acoustic impedance at the interface between gas and blood. The enhanced echo intensity is proportional to the change in acoustical impedance as the sound beam crosses from the blood to the gas in the bubbles.

The ideal qualities of an ultrasound contrast agent:
A typical ultrasound contrast agent consists of a thin flexible or rigid shell composed of albumin, lipid, or polymer confining a gas such as nitrogen, or a perfluorocarbon. The choice of the microbubble shell and gas has an important influence on the properties of the agent.
Current generations of microbubbles have a diameter from 1 μm to 5 μm. The success of these agents is mostly dependent on the small size and on the stability of their shell, which allows passage of the microbubbles through the pulmonary circulation. Microbubbles must be made smaller than the diameter of capillaries or they would embolize and be ineffective and perhaps even dangerous.
The reflectivity of these microbubbles is proportional to the fourth power of a particle diameter but also directly proportional to the concentration of the contrast agent particles themselves.
Ultrasound contrast agents produce unique acoustic signatures that allow to separate their signal from tissue echoes and to depict whether they are moving or stationary. This enables the detection of capillary flow and of targeted microbubbles that are retained in tissues such as normal liver.
The new generation of contrast media is characterized by prolonged persistence in the vascular bed which provides consistent enhancement of the arterial Doppler signal. Contrast agents make it also possible to perform dynamic and perfusion studies. Targeted contrast imaging agents are for example taken up by the phagocytic cell systems and thus have liver/spleen specific effects.

See also Ultrasound Contrast Agent Safety, Adverse Reaction, Tissue-Specific Ultrasound Contrast Agent, and Bubble Specific Imaging.

From Lantheus Medical Imaging.
Activated DEFINITY® Injectable Suspension is indicated for use in patients with suboptimal echocardiograms to opacify the left ventricular chamber and to improve the delineation of the left ventricular endocardial border. The perflutren lipid microspheres exhibit lower acoustic impedance than blood and enhance the intrinsic backscatter of blood.
Echocardiography with Definity produced more detailed images of the heart in difficult-to-image patients versus echocardiography alone, and images obtained with the contrast agent provided a more accurate assessment of segmental wall motion compared with unenhanced images.

See also Coherent Contrast Imaging.

In August 2001 DuPont Pharmaceuticals Company received FDA approval.

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.
The disadvantage of this microbubbles produced by agitation, was that the air quickly leak from the thin bubble shell into the blood, where it dissolved. In addition, the small bubbles that were capable of traversing the capillary bed did not survive long enough for imaging because the air quickly dissipated into the blood. Aside from agitated saline, also hydrogen peroxide, indocyanine green dye, and iodinated contrast has been tested. The commercial development of contrast agents began in the 1980s with greatest effort to the stabilization of small microbubbles.

The development generations by now:
To pass through the lung capillaries and enter into the systemic circulation, microspheres should be less than 10 μm in diameter. Air bubbles in that size range persist in solution for only a short time; too short for systemic vascular use.
The first developed agent was Echovist (1982), which enabled the enhancement of the right heart. The second generation of echogenic agents, sonicated 5% human albumin-containing air bubbles (Albunex), were capable of transpulmonary passage but often failed to produce adequate imaging of the left heart. Both Albunex and Levovist utilize air as the gas component of the microbubble.
In the 1990s newer developed agents with fluorocarbon gases and albumin, surfactant, lipid, or polymer shells have an increased persistence of the microspheres. This smaller, more stable microbubble agents, and improvements in ultrasound technology, have resulted in a wider range of application including myocardial perfusion.

See also First Generation USCA, Second Generation USCA, and Third Generation USCA.