Correlation of Escherichia coli inactivation with histotripsy bubble cloud size

Abstract

Bacterial loads can be effectively reduced with cavitation-mediated focused ultrasound, or histotripsy. Our previous in vitro work with Escherichia coli (E. coli) established strong trends of bactericide with increasing peak negative pressure amplitude, pulse length, PRF, and treatment time. The current study correlates bactericide as a function of the histotripsy bubble cloud size produced for these treatment parameters at several frequencies. Histotripsy was applied to E. coli suspensions in 10-ml sample vials at 810 kHz, 1.2 MHz, or 3.25 MHz for 40 min. Separately, cavitation was recorded using a Photron Fastrax high-speed camera for acoustic parameters equivalent to those used in the E. coli studies. The images were used to quantify the maximum size of each bubble cloud, with the assumption that the cloud was axially symmetric around the propagation direction. A strong linear relationship exists between log kill versus cloud size (R2 = 0.96). Remarkably, across all variables studied, the log-reduction in viable bacteria exhibited a direct proportional relationship with the dimensions of the bubble cloud. This strong correlation between bacterial reduction and cavitation bubble cloud size could have significance for clinical applications where bacteria cannot easily be sampled. [Work supported by NIH R01AR080120 and R01EB023910.]