When specifically looking for a defect such as this, small air bubbles can be used as a contrast medium and injected intravenously, where they travel to the right side of the heart.
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The test would be positive for an abnormal communication if the bubbles are seen passing into the left side of the heart. Normally, they would exit the heart through the pulmonary artery and be stopped by the lungs. This form of bubble contrast medium is generated on an ad hoc basis by the testing clinician by agitating normal saline e. There are a variety of microbubble contrast agents.
Microbubbles differ in their shell makeup, gas core makeup, and whether or not they are targeted. Regardless of the shell or gas core composition, microbubble size is fairly uniform. They lie within 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 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 perfluorocarbon 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. These ligands are attached to the microbubbles using carbodiimide , maleimide , or biotin-streptavidin coupling. 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. There are two forms of contrast-enhanced ultrasound, untargeted used in the clinic today and targeted under preclinical development.
- Contrast-enhanced ultrasound.
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The two methods slightly differ from each other. Untargeted microbubbles, such as the aforementioned SonoVue, 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. 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.
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The ultrasound system converts the strong echogenicity into a contrast-enhanced image of the area of interest. 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. The patient had an aortic stent graft placed remotely that was being followed by serial unenhanced CTs as a result of renal failure.
The unenhanced CT is provided in B. Reproduced with permission from Barr RG. Guidelines for the use of CEUS in characterization of liver lesions 4 , 8 , 19 and in nonhepatic uses have been published. A review of the principles of CEUS is important. This is beyond the scope of this article, but several excellent resources available. Additionally, Bracco Diagnostics Inc can help in locating training opportunities. To develop a CEUS program, you need to contact your referring physicians to inform them that CEUS is now available and discuss appropriate patients for referral.
Lumason is contraindicated in patients with history of hypersensitivity reactions to sulfur hexafluoride lipid microsphere components or to any of the inactive ingredients in Lumaso. Lumason is pregnancy category B. Lumason should only be used during pregnancy if clearly needed. It is not known whether Lumason is excreted in human milk. Caution should be exercised when Lumason is administered to a nursing woman. Serious cardiopulmonary reactions, including fatalities, have rarely occurred during or shortly following administration of UCAs.
The adverse event rate has been reported at 0. The risk of serious reactions may be increased in patients with unstable cardiopulmonary conditions. As with all facilities administering contrast agents, cardiopulmonary resuscitation personnel and equipment should be readily available. Currently there is not a current procedural terminology code specific for CEUS of the abdomen. Codes that can be used are liver ultrasound or if performed as part of a complete abdominal ultrasound liver, common bile duct, gallbladder, pancreas, spleen, kidneys, and the upper abdominal aorta and inferior vena cava.
For renal CEUS, can be used for a complete retroperitoneal exam, or for a limited retroperitoneal exam. Payers may or may not allow this code for contrast administration. Lumason can only be billed with Q injection, sulfur hexafluoride lipid microspheres , per milliliter. Developing a CEUS program in your department can be very rewarding, because it provides improved diagnostic information to referring physicians and improved care for your patients. Volume 36 , Issue 6.
The full text of this article hosted at iucr. If you do not receive an email within 10 minutes, your email address may not be registered, and you may need to create a new Wiley Online Library account. If the address matches an existing account you will receive an email with instructions to retrieve your username. Journal of Ultrasound in Medicine Volume 36, Issue 6. Technical Innovation Free Access. Richard G. Tools Request permission Export citation Add to favorites Track citation. Share Give access Share full text access. Share full text access. Please review our Terms and Conditions of Use and check box below to share full-text version of article.
What Are Microbubbles? Figure 1 Open in figure viewer PowerPoint. Figure 2 Open in figure viewer PowerPoint. Figure 3 Open in figure viewer PowerPoint. Figure 4 Open in figure viewer PowerPoint. Two Sets of Hands Two sets of hands are needed: the sonographer to perform the study and a second person to inject the contrast followed by the saline flush.
Perform Unenhanced Examination Before injecting contrast, a standard ultrasound examination should be performed initially.
Figure 5 Open in figure viewer PowerPoint. Figure 6 Open in figure viewer PowerPoint. Report Study As with all contrast examinations, the report should include details of the contrast administered, the number of injections, and the dose of each injection. Dosage The recommended dose of Lumason for an adult patient is 2.
Figure 7 Open in figure viewer PowerPoint. Figure 8 Open in figure viewer PowerPoint. Figure 9 Open in figure viewer PowerPoint. Kidney For indeterminate renal masses, absence of flow is indicative of a benign lesion. Figure 10 Open in figure viewer PowerPoint. Figure 11 Open in figure viewer PowerPoint. Figure 12 Open in figure viewer PowerPoint.
Related Enhancing the Role of Ultrasound with Contrast Agents
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