Enhancement of ultrasonically-induced hemolysis by perfluorocarbon-based compared to air-based echo-contrast agents

Hemolysis induced by ultrasonic activation of various contrast-agent gas bodies was investigated. Canine whole blood, with high concentrations of the agents held in 1 mm thick chambers, was exposed in the nearfield of a 2.4-MHz ultrasound beam in a 37 degrees C water bath. Sterile phosphate buffered saline (PBS) served as a control agent without gas bodies. Albunex (Mallinckrodt Medical, St. Louis, MO) and Levovist (Schering AG, Berlin, Germany) represented the air-based contrast agents. The experimental agents FS069 (Optison, Molecular Biosystems Inc., San Diego, CA) and modified MRX-130 (ImaRx Pharmaceutical Corp., Tucson, AZ) represented perfluorocarbon-based contrast agents. No significant ultrasonically-induced hemolysis was detected for the PBS or Levovist suspensions. After 1 s continuous exposure, ultrasonically-induced hemolysis was significant for Albunex at 0.4 MPa or higher pressure amplitudes, for FS069 at 0.2 MPa and for modified MRX-130 at 0.4 MPa. Hemolysis found after pulsed exposure with 10 micros pulses and 1 ms pulse repetition period was significant for Albunex, FS069 and modified MRX-130 above thresholds of 1.1 MPa, 0.57 MPa and 1.6 MPa, respectively. FS069 led to more hemolysis after pulsed mode exposures of 1 s duration or longer than did Albunex. Reduced concentrations of gas bodies gave increased thresholds and reduced hemolysis. These results indicate that improvements in persistence of contrast agents, which increase their clinical utility, may also enhance the potential for cavitational bioeffects.