WFUMB safety symposium on echo-contrast agents:: In vitro bioeffects

This chapter has reviewed in vitro research on bioeffects of ultrasound in the presence of contrast agent gas bodies. This wide ranging research includes research with whole blood and other cell suspensions, cell monolayers and phagocytic cells. Cellular effects include sonoporation, DNA transfer, hemolysis, monolayer cell detachment, DNA damage and cell killing both by membrane disruption and by apoptosis. Bioeffects on cells in suspension appear to result from inertial cavitation and broadband emissions appear to provide a dosimetric monitor. Bioeffects on cells in monolayers occur at PRPAs less than the inertial cavitation threshold, and appear to result from near-boundary shear stress generated on the cell membranes. Some reports have demonstrated potential applications of ultrasound contrast agents for therapy, such as DNA transfer by sonoporation for gene therapy. Other studies have been oriented toward potential adverse consequences of contrast aided diagnostic ultrasound, which has been emphasized in this chapter. Determinations of apparent thresholds for bioeffects are important for risk avoidance, and values of some reported thresholds are plotted in Fig. 1. Thresholds for killing of monolayer cells in contact with contrast agent gas bodies appear to be proportional to frequency with p/f ≈ 0.06 MPa/MHz. Although this threshold function may represent the lowest exposure for cell killing, it should be noted that sublethal bioeffects (e.g., sonoporation) may occur at even lower exposure levels. Above the apparent thresholds, effects typically increase rapidly with the square or higher power of the PRPA, and in proportion to the contrast agent concentration. In vitro results with clinical scanners have established that micro-scale cellular bioeffects can be produced by diagnostic ultrasound in the presence of contrast agent gas bodies. © 2007 World Federation for Ultrasound in Medicine & Biology.