Ultrasound-induced cell lysis and sonoporation enhanced by contrast agents

The enhancement of ultrasound-induced cell destruction, lysis, and sonopora tion in low cell concentration suspensions (2 x 10(5)/mL) by the presence o f contrast agents (gas bubble to cell ratio = 230) was demonstrated using c ervical cancer cells (HeLa S3) suspensions containing micron-size denatured albumin microspheres filled with air (Albunex(R)) or octafluoropropane (Op tison(TM)). The suspensions were insonificated by 2-MHz continuous or tone burst ultrasound in near field. The spatial peak-pressure amplitude was 0.2 MPa. The enhancement of cell destruction due to Optison(TM) was shown to b e much higher than that due to Albunex(R) for similar bubble concentration and ultrasound conditions. For tone burst exposures, significant lysis and sonoporation only occurred in the presence of a contrast agent. The majorit y of the bioeffects observed occured in the first 5 min of exposure. The re lationship between the enhancement of bioeffects and duty cycle of tone bur st ultrasound appears to indicate that both stable gas spheres of contrast agents and cavitation nuclei created by the disruption of the gas spheres p lay a significant role in causing the bioeffects. (C) 1999 Acoustical Socie ty of America. [S0001-4966(99)02205-5].