Contrast enhanced ultrasound (CEU) is the application of ultrasound contrast agents to traditional medical sonography. Ultrasound contrast agents are gas-filled microbubbles that are administered intravenously to the systemic circulation. Microbubbles have a high degree of echogenicity, which is the ability of an object to reflect the ultrasound waves. The echogenicity difference between the gas in the microbubbles and the soft tissue surroundings of the body is immense. Thus, ultrasonic imaging using microbubble contrast agents enhances the ultrasound backscatter, or reflection of the ultrasound waves, to produce a unique sonogram with increased contrast due to the high echogenicity difference. Contrast enhanced ultrasound can be used to image blood perfusion in organs, measure blood flow rate in the heart and other organs, and has other applications as well. A baby in its mothers womb, viewed in a sonogram Ultrasound is sound with a frequency greater than the upper limit of human hearing, approximately 20 kilohertz/20,000 Hertz. ... Medical ultrasonography (sonography) is an ultrasound-based diagnostic imaging technique used to visualize internal organs, their size, structure and any pathological lesions. ... The circulatory system or cardiovascular system is the organ system which circulates blood around the body of most animals. ... Biological tissue is a substance made up of cells that perform a similar function. ... Backscatter is the reflection of light, radar, radio, or other electromagnetic waves directly back to the direction they came from. ... A sonogram may refer to the following: A diagnostic medical image created using (ultrasound) echo equipment, see sonography. ... Perfusion is a physiological term that refers to the process of nutritive delivery of arterial blood to a capillary bed in the biological tissue. ... Blood flow is the flow of blood in the cardiovascular system. ... The heart and lungs (from an older edition of Grays Anatomy) The heart (Latin cor) is a hollow, muscular organ that pumps blood through the blood vessels by repeated, rhythmic contractions. ...

Targeting ligands that bind to receptors characteristic of intravascular diseases can be conjugated to microbubbles, enabling the microbubble complex to accumulate selectively in areas of interest, such as diseased or abnormal tissues. This form of molecular imaging, known as targeted contrast enhanced ultrasound, will only generate a strong ultrasound signal if targeted microbubbles bind in the area of interest. Targeted contrast enhanced ultrasound can potentially have many applications in both medical diagnostics and medical therapeutics. However, the targeted technique has not yet been approved for clinical use; it is currently under preclinical research and development. In chemistry, a ligand is an atom, ion or functional group that is bonded to one or more central atoms or ions, usually metals generally through coordinate covalent bond. ... Receptor may refer to: In telecommunication, a receiver. ... This page is a candidate to be moved to Wiktionary. ... Diagnosis (from the Greek words dia = by and gnosis = knowledge) is the process of identifying a disease by its signs, symptoms and results of various diagnostic procedures. ... Look up Therapy in Wiktionary, the free dictionary Therapy (in Greek: θεραπεία) or treatment is the attempted remediation of a health problem, usually following a diagnosis. ...

Microbubble Contrast Agents

General Features

There are a variety of microbubbles contrast agents. Microbubbles differ in their shell makeup, gas core makeup, and whether or not they are targeted.

• Microbubble Shell: selection of shell material determines how easily the microbubble is taken up by the immune system. A more hydrophilic material tends to be taken up more easily, which reduces the microbubble residence time in the circulation. This reduces the time available for contrast imaging. The shell material also affects microbubble mechanical elasticity. The more elastic the material, the more acoustic energy it can withstand before bursting (McCulloch et al., 2000). Currently, microbubble shells are composed of albumin, galactose, lipid, or polymers (Lindner, 2004).

• Microbubble Gas Core: The gas core is the most important part of the ultrasound contrast microbubble because it determines the echogenicity. When gas bubbles are caught in an ultrasonic frequency field, they compress, oscillate, and reflect a characteristic echo- this generates the strong and unique sonogram in contrast enhanced ultrasound. Gas cores can be composed of air, or heavy gases like perfluorocarbon, octafluoropropane, or nitrogen (Lindner, 2004). Heavy gases are less water-soluble so they are less likely to leak out from the microbubble to impair echogenicity (McCulloch et al., 2000). Therefore, microbubbles with heavy gas cores are likely to last longer in circulation.

Optison, a FDA-approved microbubble made by GE Healthcare, has an albumin shell and octafluoropropane gas core. The second FDA-approved microbubble, Levovist, made by Schering, has a lipid/galactose shell and an air core. (Lindner, 2004) The immune system is the system of specialised cells and organs that protect an organism from outside biological influences. ... The adjective hydrophilic describes something that likes water (from Greek hydros = water; philos = friend). ... You may be looking for albumen, or egg white. ... Galactose (also called brain sugar) is a type of sugar found in dairy products, in sugar beets and other gums and mucilages. ... Figure 1: Structure of a Lipid. ... A polymer is a long, repeating chain of atoms, formed through the linkage of many molecules called monomers. ... Sine waves of various frequencies; the lower waves have higher frequencies than those above. ... Fluid Dynamics Compressibility (physics) is a measure of the relative volume change of fluid or solid as a response to a pressure (or mean stress) change: . For a gas the magnitude of the compressibility depends strongly on whether the process is adiabatic or isothermal, while this difference is small in... Air is a name for the mixture of gases present in the Earths atmosphere. ... Perfluorocarbons (or PFCs) are compounds derived from hydrocarbons by replacement of hydrogen atoms by fluorine atoms. ... This article is in need of attention from an expert on the subject. ... This article does not cite its references or sources. ... The United States Food and Drug Administration is the government agency responsible for regulating food, dietary supplements, drugs, cosmetics, medical devices, biologics and blood products in the United States. ... GE Heathcare is a unit of General Electric worth approximately 14 billion US dollars. ... Schering Aktiengesellschaft was founded in 1851 and is a research-centered pharmaceutical company, employing more than 26. ...

Regardless of the shell or gas core composition, microbubble size is fairly uniform. They lie within in a range of 1-4 micrometres in diameter. That makes them smaller than red blood cells, which allows them to flow easily through the circulation as well as the microcirculation.

Targeted Microbubbles

Targeted microbubbles are under preclinical development. They retain the same general features as untargeted microbubbles, but they are outfitted with ligands that bind specific receptors expressed by cell types of interest, such as inflamed cells or cancer cells. Current microbubbles in development are composed of a lipid monolayer shell with a perflurocarbon gas core. The lipid shell is also covered with a polyethylene glycol (PEG) layer. PEG prevents microbubble aggregation and makes the microbubble more non-reactive. It temporarily “hides” the microbubble from the immune system uptake, increasing the amount of circulation time, and hence, imaging time (Klibanov, 2005). In addition to the PEG layer, the shell is modified with molecules that allow for the attachment of ligands that bind certain receptors. These ligands are attached to the microbubbles using carbodiimide, maleimide, or biotin-streptavidin coupling (Klibanov, 2005). Biotin-streptavidin is the most popular coupling strategy because biotin’s affinity for streptavidin is very strong and it is easy to label the ligands with biotin. Currently, these ligands are monoclonal antibodies produced from animal cell cultures that bind specifically to receptors and molecules expressed by the target cell type. Since the antibodies are not humanized, they will elicit an immune response when used in human therapy. Humanizing antibodies is an expensive and time-intensive process, so it would be ideal to find an alternative source of ligands, such as synthetically manufactured targeting peptides that perform the same function, but without the immune issues. Chemical structure of the polymeric polyethylene glycol Polyethylene glycol (PEG) and polyethylene oxide (PEO) are polymers having an identical structure except for chain length and end groups, and are the most commercially important polyethers. ... In chemistry, a ligand is an atom, ion or functional group that is bonded to one or more central atoms or ions, usually metals generally through co-ordinate covalent bond. ... Receptor may refer to: In telecommunication, a receiver. ... A carbodiimide is a functional group consisting of the formula N=C=N. Carbodiimides hydrolyze to form ureas, which makes them rarely found in nature. ... Maleimides are a group of organic compounds with a 2,5-pyrroledione skeleton. ... Biotin, also known as vitamin H or B7 and C10H16N2O3S (Biotin; Coenzyme R, Biopeiderm), is a water-soluble B-complex vitamin which is composed of an ureido ring fused with a tetrahydrothiophene ring. ... Streptavidine (more commonly spelled streptavidin) is a tetrameric protein purified from Streptomyces avidinii that binds very tightly to the vitamin biotin with a dissociation constant (Kd) of ~ 10^(–15) M. This is one of the strongest biochemical interactions known, and is widely taken advantage of in scientific laboratories. ... Monoclonal antibodies (mAb) are antibodies that are identical because they were produced by one type of immune cell, all clones of a single parent cell. ... Peptides are the family of molecules formed from the linking, in a defined order, of various amino acids. ...

How Contrast Enhanced Ultrasound Works

There are two forms of contrast enhanced ultrasound, untargeted (used in the clinic today) and targeted (under preclinical development). The two methods slightly differ from each other.

Untargeted CEU

Untargeted microbubbles, such as the aforementioned Optison or Levovist, are injected intravenously into the systemic circulation in a small bolus. The microbubbles will remain in the systemic circulation for a certain period of time. During that time, ultrasound waves are directed on the area of interest. When microbubbles in the blood flow past the imaging window, the microbubbles’ compressible gas cores oscillate in response to the high frequency sonic energy field, as described in the ultrasound article. The microbubbles reflect a unique echo that stands in stark contrast to the surrounding tissue due to the orders of magnitude mismatch between microbubble and tissue echogenicity. The ultrasound system converts the strong echogenicity into a contrast-enhanced image of the area of interest. In this way, the bloodstream’s echo is enhanced, thus allowing the clinician to distinguish blood from surrounding tissues. Fluid Dynamics Compressibility (physics) is a measure of the relative volume change of fluid or solid as a response to a pressure (or mean stress) change: . For a gas the magnitude of the compressibility depends strongly on whether the process is adiabatic or isothermal, while this difference is small in... A baby in its mothers womb, viewed in a sonogram Ultrasound is sound with a frequency greater than the upper limit of human hearing, approximately 20 kilohertz/20,000 Hertz. ... Echo may refer to: Echo (mythology), a nymph from Greek mythology. ... Red blood cells (erythrocytes) are present in the blood and help carry oxygen to the rest of the cells in the body Blood is a circulating tissue composed of fluid plasma and cells (red blood cells, white blood cells, platelets). ...

Targeted CEU

Targeted contrast enhanced ultrasound works in a similar fashion, with a few alterations. Microbubbles targeted with ligands that bind certain molecular markers that are expressed by the area of imaging interest are still injected systemically in a small bolus. Microbubbles theoretically travel through the circulatory system, eventually finding their respective targets and binding specifically. Ultrasound waves can then be directed on the area of interest. If a sufficient number of microbubbles have bound in the area, their compressible gas cores oscillate in response to the high frequency sonic energy field, as described in the ultrasound article. The targeted microbubbles also reflect a unique echo that stands in stark contrast to the surrounding tissue due to the orders of magnitude mismatch between microbubble and tissue echogenicity. The ultrasound system converts the strong echogenicity into a contrast-enhanced image of the area of interest, revealing the location of the bound microbubbles (Klibanov, 1999). Detection of bound microbubbles may then show that the area of interest is expressing that particular molecular, which can be indicative of a certain disease state, or identify particular cells in the area of interest. A baby in its mothers womb, viewed in a sonogram Ultrasound is sound with a frequency greater than the upper limit of human hearing, approximately 20 kilohertz/20,000 Hertz. ...

Applications of Contrast Enhanced Ultrasound

Untargeted contrast enhanced ultrasound is currently applied in echocardiography. Targeted contrast enhanced ultrasound is being developed for a variety of medical applications. An echocardiogram. ...

Untargeted CEU

Untargeted microbubbles like Optison and Levovist are currently used in echocardiography.

• Organ Edge Delineation: microbubbles can enhance the contrast at the interface between the tissue and blood. A clearer picture of this interface gives the clinician a better picture of the structure of an organ. Tissue structure is crucial in echocardiograms, where a thinning, thickening, or irregularity in the heart wall indicates a serious heart condition that requires either monitoring or treatment.
• Blood Volume and Perfusion: contrast enhanced ultrasound holds the promise for (1) evaluating the degree of blood perfusion in an organ or area of interest and (2) evaluating the blood volume in an organ or area of interest. When used in conjunction with Doppler Ultrasound, microbubbles can measure myocardial flow rate to diagnose valve problems. And the relative intensity of the microbubble echoes can also provide a quantitative estimate on blood volume.

This is a disambiguation page — a navigational aid which lists other pages that might otherwise share the same title. ...

Targeted CEU

• Inflammation: in inflammatory diseases such as Crohn’s disease, atherosclerosis, and even heart attacks, the inflamed blood vessels specifically express certain receptors like VCAM-1, ICAM-1, E-selectin. If microbubbles are targeted with ligands that bind these molecules, they can be used in contrast echocardiography to detect the onset of inflammation. Early detection allows the design of better treatments.
• Cancer: cancer cells also express a specific set of receptors, mainly receptors that encourage angiogenesis, or the growth of new blood vessels. If microbubbles are targeted with ligands that bind receptors like VEGF, they can non-invasively and specifically identify areas of cancers.
• Gene Delivery: Vector DNA can be conjugated to the microbubbles. Microbubbles can be targeted with ligands that bind to receptors expressed by the cell type of interest. When the targeted microbubble accumulates at the cell surface with its DNA payload, ultrasound can be used to burst the microbubble. The force associated with the bursting may temporarily permeablize surrounding tissues and allow the DNA to more easily enter the cells.
• Drug Delivery: drugs can be incorporated into the microbubble’s lipid shell. The microbubble’s large size relative to other drug delivery vehicles like liposomes may allow a greater amount of drug to be delivered per vehicle. By targeted the drug-loaded microbubble with ligands that bind to a specific cell type, microbubble will not only deliver the drug specifically, but can also provide verification that the drug is delivered if the area is imaged using ultrasound.

Inflammation is the first response of the immune system to infection or irritation and may be referred to as the innate cascade. ... A myocardial infarction occurs when an atherosclerotic plaque slowly builds up in the inner lining of a coronary artery and then suddenly ruptures, totally occluding the artery and preventing blood flow downstream. ... Inflammation is the first response of the immune system to infection or irritation and may be referred to as the innate cascade. ... When normal cells are damaged beyond repair, they are eliminated by apoptosis. ... Angiogenesis is the physiological process involving the formation of new blood vessels from pre-existing vessels. ... Vascular endothelial growth factor or VEGF is an important signal protein involved in angiogenesis. ... Gene therapy using an Adenovirus vector. ... A Vector DNA is a small piece of DNA containing regulatory and coding sequences of interest. ... A liposome is a spherical vesicle with a membrane composed of a phospholipid bilayer used to deliver drugs or genetic material into a cell. ...

Recent Microbubble Targeting History

Microbubbles can be used in various contrast enhanced ultrasound applications, as shown above. The area of greatest area of promise and growth lies in targeted contrast enhanced ultrasound. Current microbubble targeting strategies produce low adhesion efficiencies at high vessel shear stresses of physiological relevance. This means that only a small fraction of microbubbles injected into the test subject actually binds to the molecular markers of interest (Takalkar et al., 2004). This is one of the main issues preventing targeted contrast enhanced ultrasound’s jump from bench to bedside.

There has been an increasing interest in the biomedical research community to enhance the adhesion efficiency of microbubble contrast agents in order to realize targeted contrast enhanced ultrasound’s immense diagnostic and therapeutic potentials. Scientists have outfitted microbubbles with monoclonal antibodies that bind endothelial markers of inflammation, specifically the cell adhesion molecules P-selectin, ICAM-1, and VCAM-1. They showed that these complexes enable targeted ultrasound imaging of inflammation (Lindner, 2004). But, the aforementioned efficiency of microbubble adhesion to the molecular target was poor and a large fraction of microbubbles that bound to the target rapidly detached, especially at high shear stresses of physiological relevance (Takalkar et al., 2004). Effective contrast-enhanced ultrasound requires efficient microbubble binding at the area of imaging interest (Klibanov, 1999). Biomedical Research involves thorough investigation of any matter related to the domain of living or biological Systems. ... The endothelium is the layer of thin, flat cells that lines the interior surface of blood vessels, forming an interface between circulating blood in the lumen and the rest of the vessel wall. ... Selectins are a family of cell-surface adhesion molecules of leukocytes and endothelial cells. ... Intercellular adhesion molecules (ICAMs) are molecules that promote adhesion between cells. ... Inflammation is the first response of the immune system to infection or irritation and may be referred to as the innate cascade. ...

Leukocytes possess high adhesion efficiencies, partly due to a dual-ligand selectin-integrin cell arrest system (Eniola et al., 2003). One ligand:receptor pair (PSGL-1:selectin) has a fast bond on-rate to slow the leukocyte and allows the second pair (integrin:immunoglobulin superfamily), which has a slower on-rate but slow off-rate to arrest the leukocyte, kinetically enhancing adhesion. White Blood Cells is also the name of a White Stripes album. ... Selectins are a family of cell-surface adhesion molecules of leukocytes and endothelial cells. ... An integrin, or integrin receptor, is an integral membrane protein in the plasma membrane of cells. ... P-selectin glycoprotein ligand-1 is a protein receptor found on white blood cells and endothelial cells that binds to P-selectin (P stands for platelet). ... Schematic of antibody binding to an antigen An antibody is a protein complex used by the immune system to identify and neutralize foreign objects like bacteria and viruses. ...

Several research groups have taken advantage of this concept. Eniola and Hammer at the University of Pennsylvania applied dual-ligand targeting of distinct receptors to polymer microspheres for drug delivery and reported an increase in microsphere binding (Eniola and Hammer, 2005). Similarly, Weller and colleagues at the University of Pittsburgh used microbubbles targeted to bind two distinct receptors and showed increased microbubble adhesion strength (Weller et al., 2005). Biomimcry of the leukocyte’s selectin-integrin cell arrest system has also been investigated in the context of improving microbubble adhesion efficiency at the University of Virginia (Rychak et al., 2005). All three research groups showed that dual-targeted microbubbles showed enhanced adhesion compared to single-targeted microbubbles. Though this strategy markedly improves upon prior adhesion, it is still less than ideal. The adhesion efficiency must be higher to allow clinical use of targeted contrast enhanced ultrasound. The University of Pennsylvania (Penn is the nickname used by the university itself; UPenn is also common) is a private, nonsectarian, research university located in Philadelphia, Pennsylvania. ... The University of Pittsburgh is a state-related, doctoral/research university in Pittsburgh, Pennsylvania. ... Website Virginia. ...

Advantages of Contrast Enhanced Ultrasound

On top of the strengths mentioned in the medical sonography entry, contrast enhanced ultrasound adds these additional advantages: Medical ultrasonography (sonography) is an ultrasound-based diagnostic imaging technique used to visualize internal organs, their size, structure and any pathological lesions. ...

• The body is 90% water, and therefore, acoustically homogeneous. Blood and surrounding tissues have similar echogenicities, so it is also difficult to clearly discern the degree of blood flow, perfusion, or the interface between the tissue and blood using traditional ultrasound (Lindner, 2004).
• Ultrasound imaging allows real-time evaluation of blood flow (Lindner et al., 2002).
• Ultrasonic molecular imaging is safer than molecular imaging modalities such as radionuclide imaging because it does not involve radiation (Lindner et al., 2002).
• Alternative molecular imaging modalities, such as MRI, PET, and SPECT are very costly. Ultrasound, on the other hand, is very cost-efficient and widely available (Klibanov, 1999).
• Since microbubbles can generate such strong signals, a lower intravenous dosage is needed, micrograms of microbubbles are needed compared to milligrams for other molecular imaging modalities such as MRI contrast agents (Klibanov, 1999).
• Targeting strategies for microbubbles are versatile and modular. Targeting a new area only entails conjugating a new ligand.

Radiocontrast agents (or simply contrast agents) are compounds used to improve the visibility of internal bodily structures in an X-ray image. ... The mri are a fictional alien species in the Faded Sun Trilogy of C.J. Cherryh. ... Pets and humans often contribute toward the happiness of the other in a pet relationship. ... SPECT (Single Photon Emission Computed Tomography) is a nuclear medicine tomographic imaging technique using gamma rays. ...

Disadvantages of Contrast Enhanced Ultrasound

In addition to the weaknesses mentioned in the medical sonography entry, contrast enhanced ultrasound suffers from the following disadvantages: Medical ultrasonography (sonography) is an ultrasound-based diagnostic imaging technique used to visualize internal organs, their size, structure and any pathological lesions. ...

• Microbubbles don’t last very long in circulation. They have low circulation residence times because they either get taken up by immune system cells or get taken up by the liver or spleen even when they are coated with PEG (Klibanov, 1999).
• Ultrasound produces more heat as the frequency increases, so the ultrasonic frequency must be carefully monitored.
• Microbubbles burst at low ultrasound frequencies and at high mechanical indices (MI), which is the measure of the acoustic power output of the ultrasound imaging system. Increasing MI increases image quality, but there are tradeoffs with microbubble destruction. Microbubble destruction could cause local microvasculature ruptures and hemolysis (Klibanov, 2005).
• Targeting ligands can be immunogenic, since current targeting ligands used in preclinical experiments are derived from animal culture (Klibanov, 2005).
• Low targeted microbubble adhesion efficiency, which means a small fraction of injected microbubbles bind to the area of interest (Takalkar et al., 2004). This is one of the main reasons that targeted contrast enhanced ultrasound remains in the preclinical development stages.

The liver is one of the largest internal organs of the human body. ... The spleen is a ductless, vertebrate gland that is not necessary for life but is closely associated with the circulatory system, where it functions in the destruction of old red blood cells and removal of other debris from the bloodstream, and also in holding a reservoir of blood. ... Hemolysis (alternative spelling haemolysis) is the excessive breakdown of red blood cells. ...

See Also

• ultrasound
• sonography
• medical imaging
• medical ultrasonography
• echocardiography
• Doppler effect

A baby in its mothers womb, viewed in a sonogram Ultrasound is sound with a frequency greater than the upper limit of human hearing, approximately 20 kilohertz/20,000 Hertz. ... Night writing was a system of code that used symbols of twelve dots (2 wide and 6 high) designed by Charles Barbier in response to Napoleons demand for a code that soldiers could use to communicate silently and without light at night. ... Medical imaging is the process by which physicians evaluate an area of the subjects body that is not normally visible. ... Medical ultrasonography (sonography) is an ultrasound-based diagnostic imaging technique used to visualize internal organs, their size, structure and any pathological lesions. ... An echocardiogram. ... Sound waves emanating from an ambulance moving to the right. ...

References

1. Eniola, A.O., and D.A. Hammer. 2005. In vitro characterization of leukocyte mimetic for targeting therapeutics to the endothelium using two receptors. Biomaterials. 26: 7136-44.
2. Eniola, A.O., P.J. Willcox, and D.A. Hammer. 2003. Interplay between rolling and firm adhesion elucidated with a cell-free system engineered with two distinct receptor-ligand pairs. Biophys. J. 85: 2720-31.
3. Klibanov, A.L. 2005. Ligand-carrying gas-filled microbubbles: ultrasound contrast agents for targeted molecular imaging. Bioconjug Chem. 16: 9-17.
4. Klibanov, A.L. 1999. Targeted delivery of gas-filled microspheres, contrast agents for ultrasound imaging. Adv Drug Deliv Rev. 37: 139-157.
5. Lindner, J.R. 2004. Microbubbles in medical imaging: current applications and future directions. Nat Rev Drug Discov. 3: 527-32.
6. Lindner, J.R., A.L. Klibanov, and K. Ley. Targeting inflammation, In: Biomedical aspects of drug targeting. (Muzykantov, V.R., Torchilin, V.P., eds.) Kluwer, Boston, 2002; pp. 149-172.
7. McCulloch, M., C. Gresser, S. Moos, J. Odabashian, S. Jasper, J. Bednarz, P. Burgess, D. Carney, V. Moore, E. Sisk, A. Waggoner, S. Witt, and D. Adams. Ultrasound contrast physics: A series on contrast echocardiography, article 3. J Am Soc Echocardiogr. 13: 959-67.
8. Rychak J.J., A.L. Klibanov, W. Yang, B. Li, S. Acton, A. Leppanen, R.D. Cummings, and K. Ley. "Enhanced Microbubble Adhesion to P-selectin with a Physiologically-tuned Targeting Ligand," 10th Ultrasound Contrast Research Symposium in Radiology, San Diego, CA, March 2005.
9. Takalkar, A.M., A.L. Klibanov, J.J. Rychak, J.R. Lindner, and K. Ley. 2004. Binding and detachment dynamics of microbubbles targeted to P-selectin under controlled shear flow. J. Contr. Release. 96: 473-482.
10. Weller, G.E., F.S. Villanueva, E.M. Tom, and W.R. Wagner. 2005. Targeted ultrasound contrast agents: In vitro assessment of endothelial dysfunction and multi-targeting to ICAM-1 and sialyl Lewis(x). Biotechnol. Bioeng. 92: 780-8.

External Links

• Optison Information from GE Healthcare
• Levovist Data Sheet from New Zealand Medicines and Medical Devices Safety Authority
• Schering Diagnostics Webpage
• GE Healthcare on Ultrasound Contrast Media
• The American Society of Echocardiography
• The Contrast Zone at the American Society of Echocardiography