Submicron ultrasound contrast agents are gas-filled, double-walled microspheres with a diameter smaller than 1 μm that rupture when exposed to ultrasound energy at megahertz frequencies. These agents differ from traditional ultrasound contrast microbubbles in that the submicron bubbles may serve as extravascular agents. They are small enough to travel through the lymphatic system and to be extravasated from tumor neovasculature. The detection of these agents is limited by their hard shell, which requires high-pressure ultrasound insonation for shell rupture and excitation of the gas bubble. After shell rupture, the gas diffuses rapidly from submicron sized agents. The optimal processing of each echo is important.

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.

Tissue-specific ultrasound contrast agents improve the image contrast resolution through differential uptake. The concentration of microbubble contrast agents within the vasculature, reticulo-endothelial, or lymphatic systems produces an effective passive targeting of these areas. Other contrast media concepts include targeted drug delivery via contrast microbubbles.
Tissue-specific ultrasound contrast agents are injected intravenously and taken up by specific tissues or they adhere to specific targets such as venous thrombosis. These effects may require minutes to several hours to reach maximum effectiveness. By enhancing the acoustic differences between normal and diseased tissues, these tissue-specific agents improve the detectability of abnormalities.
Some microbubbles accumulate in normal hepatic tissue; some are phagocytosed by Kupffer cells in the reticuloendothelial system and others may stay in the sinusoids. Liver tumors without normal Kupffer cells can be identified by the lack of the typical mosaic color pattern of the induced acoustic emission. The hepatic parenchymal phase, which may last from less than an hour to several days, depending on the specific contrast medium used, may be imaged by bubble-specific modes such as stimulated acoustic emission (color Doppler using high MI) or pulse inversion imaging.

(MRgFUS) Magnetic resonance guided focused ultrasound is a surgical procedure that uses high intensity focused ultrasound waves to destroy tissue in combination with magnetic resonance imaging (MRI), which guides the treatment.
With focused ultrasound waves uterine fibroids are heated and destroyed (ablated) inside the MRI device , allowing the physician to plan, monitor and control the treatment with temperature sensitive images while it is in progress.

See also High Intensity Focused Ultrasound, and Interventional Ultrasound.

A transducer is a device, usually electrical or electronic, that converts one type of energy to another. Most transducers are either sensors or actuators. A transducer (also called probe) is a main part of the ultrasound machine. The transducer sends ultrasound waves into the body and receives the echoes produced by the waves when it is placed on or over the body part being imaged.
Ultrasound transducers are made from crystals with piezoelectric properties. This material vibrates at a resonant frequency, when an alternating electric current is applied. The vibration is transmitted into the tissue in short bursts. The speed of transmission within most soft tissues is 1540 m/s, producing a transit time of 6.5 ms/cm. Because the velocity of ultrasound waves is constant, the time taken for the wave to return to the transducer can be used to determine the depth of the object causing the reflection.
The waves will be reflected when they encounter a boundary between two tissues of different density (e.g. soft tissue and bone) and return to the transducer. Conversely, the crystals emit electrical currents when sound or pressure waves hit them (piezoelectric effect). The same crystals can be used to send and receive sound waves; the probe then acts as a receiver, converting mechanical energy back into an electric signal which is used to display an image. A sound absorbing substance eliminates back reflections from the probe itself, and an acoustic lens focuses the emitted sound waves. Then, the received signal gets processed by software to an image which is displayed at a monitor.
Transducer heads may contain one or more crystal elements. In multi-element probes, each crystal has its own circuit. The advantage is that the ultrasound beam can be controlled by changing the timing in which each element gets pulsed. Especially for cardiac ultrasound it is important to steer the beam.
Usually, several different transducer types are available to select the appropriate one for optimal imaging. Probes are formed in many shapes and sizes. The shape of the probe determines its field of view.
Transducers are described in megahertz (MHz) indicating their sound wave frequency. The frequency of emitted sound waves determines how deep the sound beam penetrates and the resolution of the image. Most transducers are only able to emit one frequency because the piezoelectric ceramic or crystals within it have a certain inherent frequency, but multi-frequency probes are also available.
See also Blanking Distance, Damping, Maximum Response Axis, Omnidirectional, and Huygens Principle.