Ultrasound Contrast Agents Microbubbles Intro • 'Contrast Agents' in Ultrasound News (15) •
Microbubbles filled with air or inert gases are used as contrast agents in ultrasound imaging. Compression and rarefaction created by an ultrasound wave insonating a gas-filled microbubble along with the mechanical index of the ultrasonic beam lead to volume pulsations of the bubbles, and it is this change that results in the signal enhancement. Microbubbles have diameters from 1 μm to 10 μm and a thin flexible or rigid shell composed of albumin, lipid, or polymer confining a gas such as nitrogen, or a perfluorocarbon. These microbubbles can cross the pulmonary capillaries and have a serum half-life of a few minutes. Microbubbles in the 1-10 μm range have their resonance at the frequencies used in diagnostic ultrasound (1−15MHz). Smaller bubbles resonate at higher frequencies. Caused by this coincidence, they are such effective reflectors. The intrinsic compressibility of microbubbles is approximately 17,000 times more than water, and they are very strong scatterers of ultrasound. Under acoustic pressure the vibrating bubble radius may have a conventional linear response or a harmonic non-linear response. Microbubbles usually increase the Doppler signal amplitude by up to 30 dB. • View NEWS results for 'Microbubbles' (12). Further Reading: Basics:
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A microbubble shell, designed to reduce diffusion into the blood, can be stiff (e.g., denatured albumin) or more flexible (phospholipid), varying in thickness from 10-200 nm. The shell stabilizes against dissolution and coalescence with additional materials at the gas-liquid interface. This material can be an elastic solid shell that enhances stability by supporting a strain to counter the effect of surface tension. Also a surfactant, or a combination of two or more, improves the stability by a high reduction of the surface tension at the interface. Current ultrasound contrast agents are micron-sized bubbles with a stabilizing shell. Further Reading: Basics: News & More:
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The gas in microbubbles is highly compressible and, when subjected to the alternating compression and refraction pressures that constitute an ultrasound pulse, microbubbles oscillate at their natural frequency at which they resonate most strongly. This is determined by their size but is also influenced by the composition of the filling gas. Air, sulfur hexafluoride, nitrogen, and perfluorochemicals are used as filling gases. Most newer ultrasound contrast agents use perfluorochemicals because of their low solubility in blood and high vapor pressure. By substituting different types of perfluorocarbon gases for air, the stability and plasma longevity of the agents have been markedly improved, usually lasting more than five minutes. •
The persistence of microbubbles is depended of the shell stability and the density of the gas. This is defined by the equation: (R x d)/(DIFS x constsat) where R is the bubble radius, d the gas density, DIFS the gas diffusivity and constsat the saturation constant. Microbubbles are stabilized with thin coatings of substances such as palmitic acid or by encapsulation in microspheres made with albumin, lipids, or polymers. Low-solubility low-diffusibility gases dramatically improve the persistence. Most recently developed ultrasound contrast agents combine these two approaches to prolong contrast enhancement. Persistence is also a type of temporal smoothing used in both gray scale and color Doppler imaging. Successive frames are averaged as they are displayed to reduce the variations in the image between frames, hence lowering the temporal resolution of the image. •
(AE) Induced acoustic emission is an effect of ultrasound contrast agents, presenting the interaction between the agent and the incident ultrasound wave. Microbubbles break down in high-amplitude diagnostic ultrasound energy. The bubble rupture produces a transient pressure wave, which results in a characteristic mosaic pattern from tissues containing the agent. It is important to note that the color patterns of induced acoustic emission do not represent flow signals. As far as the laws of mathematics refer to reality, they are not certain; and as far as they are certain, they do not refer to reality. - Albert Einstein |