Increases in the pressure output of diagnostic ultrasound scanners have prompted interest in establishing thresholds for bioeffects in many organs including the lungs and intestines on mammals. For example, thresholds for extravasation of blood cells into the alveolar spaces in murine lung were first reported by Child et al. [Child SZ, et al. Ultrasound Med. Biol. 1990; 16:817-825]. The damage, which increased markedly with exposure level, was present as subcapsular petechiae near the pleural surface. Subsequently, thresholds for lung damage from pulsed diagnostic ultrasound have been determined in neonatal mice, neonatal pig, rat, rabbit, and pig. Ultrasonically induced petechial hemorrhage has also been demonstrated in the mouse intestine. In all of these animal systems, pockets of gas are activated during ultrasonic exposure. Indeed, Holland et al. detected inertial cavitation events produced in vivo in rat lung exposed to 44-MHz pulsed Doppler using a 30-MHz, pulse-echo ultrasound system [Holland CK, et al. Ultrasound Med. Biol., in press]. Based on these observations, we hypothesize that the damage to lung in meditated by inertial cavitation and seek to establish such a casual relationship. In addition, exogenous echo contrast agents which consist of microbubbles could nucleate cavitation in vivo. Organs which normally do not contain stabilized gas bubbles, such as liver, might exhibit similar damage from exposure to diagnostic ultrasound if echo contrast agents are utilized. Through in vivo experiments in a rat model, we plan to extend the knowledge base of pressure thresholds for ultrasound-induced lung, to examine the severity of damage under suprathreshold conditions and to explore the potential bioeffects in liver which contain an echo contrast agent. Using the 30-MHz ultrasound system to detect inertial cavitation, we plan to determine the relationship between cavitational activity and damage in lung tissue from exposure to pulses of diagnostic ultrasound. The use of perfluorocarbon liquids to replace the breathing gas in the rat will demonstrate the importance of gas-filled alveolar sacs in the observed damage due to ultrasound exposure. These proposed studies of the consequences of gas body activation associated with aerated lung tissue containing an echo contrast agent represent an important instance of cavitation relevant to clinical practice. Our findings will clarify the potential risks involved in the use of diagnostic ultrasound scanners near aerated lung or in the presence of an echo contrast agent.
