Effects of contrast agent infusion rates on thresholds for tissue damage produced by single exposures of high-intensity ultrasound

Abstract

Stabilized microbubble ultrasound contrast agents (UCA) have potential to aid tissue ablation during ultrasound surgery by enhancing both cavitational and thermal damage mechanisms. Previously, we showed UCA infused at a rate of 1 L/kg/min prior to ultrasound exposure could reduce the total energy required to produce tissue damage by up to two orders of magnitude. In this paper, we evaluate thresholds for macroscopic tissue damage with UCA infusion rates (IR) of 0.1, 0.3, 1, 3, and 10 L/kg/min to determine IR potentially effective for ultrasound therapy. Canine kidneys were surgically externalized and insonified with single exposures of focused ultrasound. Incident exposures were 1.44 MHz tone bursts, either 250 ms in duration with intensity between 500 W/cm 2 and 3200 W/cm 2 , or 100 s to 1 s in duration with intensity equal to 3200 W/cm 2 . Probabilities of tissue damage occurrence were determined for each set of exposure conditions (intensity, duration, and IR). A threshold intensity and threshold duration, defined as the quantities for which tissue damage occurred with probability equal to 0.5, were estimated for each IR. Results show that, as IR increased from 0.1 to 10 L/kg/min, the threshold intensity decreased by up to a factor of 3, and threshold duration decreased by up to a factor of 200. Microbubble introduction at IR up to 10 L/kg/min thus may be effective in aiding ultrasound therapy.

High-intensity focused ultrasound: past, present, and future in neurosurgery

“…Ultrasound contrast agents, such as preformed microbubbles, amplify focal heating during sonication and have been used to reduce the time-averaged power needed during transcranial FUS ablation. 79 In a study on rabbits, McDannold et al 60 demonstrated that the administration of a microbubble-based ultrasound contrast agent reduced the acoustic power needed to induce lesions to less than one-tenth of what is required to produce thermal lesions without the contrast agents.…”

Cavitation-Enhanced Thermal Effects and Applications

“…They showed that these MBs significantly lowered the threshold for tissue damage: Both the required intensity and exposure duration were reduced when MBs were present. They also evaluated the threshold for macroscopic tissue damage with MB infusion rates (IR) to determine is the level that was effective for HIFU ablation in the kidneys of adult female dogs (Tran et al 2005). In this study, canine kidneys were exposed to HIFU with 1.44-MHz tone bursts.…”

Magnetic Resonance–Guided Focused Ultrasound Surgery

“…One method of improving the safety profile of cavitation is with the administration of microbubbles, which are commonly used as an ultrasound imaging contrast agent. In this instance, lower power ultrasound can be delivered to achieve similar cavitation effects, because one is not relying on ultrasound-induced nucleation of gas bubbles within the tissue 26-30 .…”