Response of multicell spheroids to 1-MHz ultrasonic irradiation: cavitation-related damage

The response of EMT6/Ro single cells and multicell spheroids (150-800 microns diameter) to 1-MHz ultrasonic irradiation was determined for intensities of 0-5 W/cm2 for 1-5 min. Damage was assessed by evaluating both lysis and survival of individual spheroid cells, growth of whole spheroids, and the physical integrity of whole spheroids by histological and scanning electron microscopic techniques. The surviving fraction of spheroid cells was higher than that of single cells, and several of the intensity-duration combinations showed a statistically significant correlation between resistance to ultrasound and increased spheroid size. This resistance with size was also found in spheroid growth experiments. Histological sections showed that both peripheral and internal damage occur. The relationship of spheroid damage to studies of effects on tissues and possible therapeutic use of nonthermal ultrasound are discussed.