Introduction
Ultrasound scans are one of the few primary diagnostic images and the most predominantly used techniques in medicine. The reason for which this diagnostic method is preferred is because of its features that provide advantages to the users as well as the person diagnosing. The benefits of ultrasound imaging techniques include safety while performing the procedure as it is non-invasive, and the images can be viewed immediately. Ultrasound imaging techniques are used in diagnosis and ultrasound-mediated therapy, where it is used for diagnosing cancer of the thyroid, stomach, and breast and treating inflammatory conditions like osteoarthritis and rheumatoid arthritis. Here, microbubbles are tiny, bubbles-like particles filled with gaseous substances employed to carry contrast materials used in ultrasounds to examine a particular area of the body.
What Are Microbubbles?
Microbubbles are bubble shells that enclose a core of gasses, where the microbubbles are composed of nitrogen, air, and a perfluorocarbon-making core. The shell of the microbubble is made up of proteins, polymers, and lipids. Here, these microbubbles in ultrasound imaging act as a contrast agent, enhancing the image's quality and the echo of the waves, as well as the therapeutic agents in ultrasound-mediated therapy. The contrast is achieved by exposing these microbubbles to a 1 to 7 m (mean diameter) frequency under an ultrasound range of 2 to 15 MHZ ( megahertz). When exposed to a particular frequency, these microbubbles emit a phenomenon of resistance that, in turn, increases the image contrast. In the case of therapeutic applications of ultrasound, the efficacy is achieved by a combined process of sonoporation and cavitation seen while combining the microbubbles with the ultrasound.
What Are the Types of Microbubbles?
The microbubbles are available commercially in sizes ranging from one to ten micrometers. As these microbubbles consist of an outer shell and an inner core of gasses, manufacturing even the smallest microbubbles in a uniform size is easily possible. These smaller-sized microbubbles of elastics can circulate in the circulatory system, even passing through the thinnest capillary vessels. Their difference in the type of commercially available microbeads is that they vary according to the shell materials, weight, and based on their solubility. Some of the commercially available microbubble brands include the following.
- Levovist: These microbubbles are the first-generation microbubbles used in ultrasound as contrast agents. The shells of these microbubbles are biocompatible and are composed of 99.9 percent galactose, while their core is composed of air mixed with 0.1 percent palmitic acid. These Levovist microbubbles send harmonic signals during the procedure while reducing the signals of the noises emitted. Levovist microbubbles also act as a transducer in situations with low acoustic power. This type of microbubble cannot be easily destroyed and requires high-intensity acoustic powers during imaging.
- Optison: Option microbubbles are named so because of their octafluoropropane core, which is then covered with a protein shell made of human albumin. The other components, like galactose, are mixed with albumin to provide the microbubble with consistent structural stability. As these microbubbles are made up of albumin, the Kupffer cells eat them up easily due to phagocytosis. However, these microbubbles help in differentiating cancer cells from normal cells.
- Sonovue: These types of microbubbles are made up of sulfur hexafluoride (SF6) as the core material, and the shell is made up of a single layer of phospholipid, which has a very low solubility rate. Sonovue microbubbles also have a decent stability rate when in contact with various surfactants like phospholipids, palmitic acid, and phospholipids. Due to this, microbubbles are used to examine peripheral blood, which requires long term stability.
- Definity: The definite microbubbles comprise multiple lipids on the outer shell and an inner core made of octafluoropropane. It enables usage in areas with low acoustic power modes as the higher lipid density in the shells shows higher instability.
- Sonazid: The Sonazid microbubbles comprise a perfluorobutane core covered in a lipid shell. These perfluorocarbons show a very low reactivity rate compared to the other microbubbles and show a strong bonding of the carbon and fluorine ions. Also, these Sonazoid microbubbles are used in diagnosing tumors of the liver where they react similarly to the optics on microbubbles reacting with the Kupffer cells.
What Is the Theory of Microbubble Usage in the Ultrasound?
These microbubbles were originally made to enhance the contrast of the images obtained by ultrasound imaging, to distinguish the vessels, and to reduce the image noise and signals in the background. The microbubbles are in the following steps:
- Cavitation: Cavitation is a process that produces high and extreme temperatures that cause the microbubbles to expand and later burst, causing cavitation at the site of a clot or tissue. This increase in the membrane permeability caused by cavitation boosts the efficiency and gene delivery of the medication. However, as this technique is not mostly preferred and is highly unpredictable, it is preferred only in certain diagnostic procedures.
- Sonoporation Effect: Sonoporation is a gene delivery technology that has the potential to potentially be used in gene therapy. Sonoporation, a targeted drug delivery system, and non-viral gene transfection, offers a fresh approach with promising potential. Sonoporation improves adeno-associated viral (AAV) endocytosis (this process was originally called phagocytosis, where the cells inside the body engulf the bacterial cell), which enhances gene transfer efficiency. However, no sonoporation clinical trials have been reported since it has proven unsuitable for accurate and precise gene transfer.
Conclusion:
Microbubbles are used non-linearly to amplify the ultrasound images and increase the wave frequency. Due to the high echogenicity of these bubbles, it is easier to administer them to the circulatory system depending on the size, where the size of the microvasculature targets a specific area to be examined. Microbubbles are also used in therapeutic areas to cross the blood-brain barrier, tumors, cardiovascular anomalies, etc. Hence, it is one of the best ways to be considered or included in the clinical practice while performing scans because it provides an area-specific targeted approach without disturbing the adjacent approximating structures.
