The potential for thermal damage posed by microbubble ultrasound contrast agents

The development of coated microbubble ultrasound contrast agents for use in imaging applications and as carriers in drug and gene delivery applications has intensified the need for a clear understanding of their behaviour and potential bioeffects. Previous studies have focused on the risks posed by unencapsulated bubbles as representing the "worst case scenario". They have concluded that the risk of thermal damage should be minimal provided the threshold for inertial cavitation is not exceeded. However, these treatments have ignored the heating effects due to viscous dissipation in the coatings of contrast agent particles. Simulations indicate that the temperature rise due to this process may be sufficient to generate harmful bioeffects even under conventionally "safe" insonation conditions. The implications of these findings and strategies for addressing the risks posed by contrast agents are discussed.