Bioeffects of Gas Body Activation

Bioeffects of Gas Body Activation in Medical Ultrasound

Douglas L. Miller, Ph.D.

The evolution of medical ultrasound requires a concomitant exploration of biological effects, both for consideration of safety issues and for development of new therapeutic methods. This bioeffects research project concentrates primarily on the nonthermal mechanism gas body activation (GBA), a form of acoustic cavitation which occurs when ultrasound interacts with bodies of gas in liquids or tissue. GBA concentrates ultrasonic energy is in its local vicinity creating a zone of mechanical pertubation: bioeffects range from subtle sub-cellular lesions to life-threatening hemorrhage. In regard to safety, suitable micron-sized gas bodies are not normally present in the body, and only the gas-bearing tissues lung and intestine appear susceptible to nonthermal damage. The introduction of gas bodies by injection of ultrasound contrast agents stimulates concern even for diagnostic examinations. Research has demonstrated membrane damage with lysis of cells and microvascular damage yielding petechial hemorrhages in laboratory animals. Improvements in contrast-enhanced ultrasound, such as the use of perfluorocarbon gas bodies and the stimulation of nonlinear acoustic emissions, appear also to enhance biological effectiveness. In regard to therapeutic methods, cell membrane permeabilization, or "sonoporation", allows macromolecular transfer and the possibility of ultrasound enhanced cancer gene therapy. At high amplitudes, as employed in extracorporeal shockwave lithotripsy, massive tissue ablation can be produced. Development of such nonthermal methods may advantageously incorporate real-time ultrasonic imagery and control of the therapeutic process. The information resulting from this biophysical research program enriches risk-benefit management in diagnosis and reveals the therapeutic potential of gas body activation in medical ultrasound.