Does the use of contrast (ultrasound contrast agent) increase the risk of cavitation in ultrasound imaging?

From the Guidelines

Yes, using contrast agents in ultrasound does increase the risk of cavitation, as they can act as nucleation sites for cavitation, and the risk increases with higher acoustic power and lower ultrasound frequencies. The use of contrast agents in ultrasound imaging introduces microbubbles that enhance image quality by improving the reflection of sound waves. However, these microbubbles can also lead to cavitation, which is the formation and collapse of gas-filled bubbles in a liquid when exposed to ultrasound waves. During cavitation, the microbubbles oscillate, expand, and potentially collapse violently in response to the pressure changes from ultrasound waves, generating localized high temperatures, pressure waves, and free radicals that can potentially damage nearby tissues.

The mechanical index (MI) is an indicator of the likelihood of cavitation, and it is recommended to keep the MI below 0.4 to minimize cavitation risk while still obtaining adequate image enhancement 1. Studies have shown that higher MI values are associated with an increased risk of deleterious structural effects, such as extravasations of erythrocytes into the retinal layers, erosion of the corneal surface, and disruption of retinal layer organisation 1. In contrast, studies that assessed MI values below 0.3 generally found either nil adverse effects or reversible changes on histology.

Key points to consider when using contrast agents in ultrasound imaging include:

• The risk of cavitation increases with higher acoustic power and lower ultrasound frequencies
• The mechanical index (MI) is an indicator of the likelihood of cavitation
• Keeping the MI below 0.4 is generally recommended to minimize cavitation risk
• Higher MI values are associated with an increased risk of deleterious structural effects
• The use of contrast agents can improve image quality, but it is essential to balance this with the potential risks of cavitation.

It is essential to follow the recommendations of medical safety authorities, such as the US-FDA and the British Medical Ultrasound Society (BMUS), which have set maximum MI values for ophthalmic ultrasound applications to minimize the risk of cavitation 1. By understanding the risks and benefits of using contrast agents in ultrasound imaging, clinicians can make informed decisions to optimize image quality while minimizing the risk of adverse effects.

From the Research

Ultrasound Contrast Agents and Cavitation Risk

• The use of ultrasound contrast agents, such as microbubbles, can increase the risk of cavitation in ultrasound imaging 2, 3, 4.
• Cavitation occurs when the microbubbles oscillate and eventually collapse, producing a strong mechanical stress that can enhance tissue permeability and increase the extravasation of drugs from the blood into the cytoplasm or interstitium 3, 4.
• High-intensity focused ultrasound (HIFU) surgery and lithotripsy have been investigated as means of increasing the speed and efficacy of treatment using controlled cavitation 2.
• The risk of cavitation can be minimized by using a mechanical index of < 0.4, which preserves the microbubbles and is not typically associated with substantial bioeffects 4.

Safety of Ultrasound Contrast Agents

• Ultrasound contrast agents have a proven safety record based on over two decades of use, with adverse effects being less common than CT/MR contrast agents 4, 5.
• Rare adverse reactions, such as anaphylactic shock, have been observed, but these can be managed with a comprehensive emergency plan and rescue measures 5.
• The safety of sulfur hexafluoride microbubbles has been investigated in a retrospective analysis of 30,222 cases, with no patient deaths reported as a result of adverse reactions 5.

Mechanisms of Cavitation

• The motion of microbubbles increases the permeability of both individual cell membranes and the endothelium, thus enhancing therapeutic uptake 2.
• Inertial cavitation and destruction of microbubbles can produce a strong mechanical stress that enhances tissue permeability and increases the extravasation of drugs from the blood into the cytoplasm or interstitium 3.
• Stable cavitation by high-frequency ultrasound can mildly increase tissue permeability without causing damage, even at high acoustic pressures 3.