Optimization of microbubble side-scattering signal analysis for efficient cavitation dosimetry

Abstract

In this study microbubble (MB) cavitation signal analysis was performed in both pressure and exposure duration domains of the acoustic field with the aim to optimize current cavitation dosimetry model by the application of signal processing. The discrete wavelet transform is applied to denoise the non-stationary US signals. For the development of universal cavitation dosimetry model and unification of cavitation dosimetry protocols, we have defined the optimal frequency range to be associated with the highest values of differential inertial cavitation dose (ICD). At our experimental conditions, it was evaluated to be 1.5–1.8 MHz, as ICD, quantified in this frequency band, is clearly distinguished from ICD of other frequency ranges. The explicitly high RMS values, obtained in 1.5–1.8 MHz frequency range, not only allow to track MB dynamics with the highest accuracy but also perform sonoporation optimization in exposure duration scale by RMS decrease to the background level. For sonoporation temporal dosimetry we have introduced “MB survival time” - the estimate, based on system output characteristics and directly related to sonoporation outcome. The rate of “MB survival time” has high correlation (R = 0.85, p < 0.05) with pre-existing index, ICD, and therefore, implies a possibility to be used for dosimetric applications for US-mediated drug and gene delivery. The rate of “MB survival time” is a time-dependent measure, which implies universal result reproducibility, as it is possible to relate absolute values of time-dependent indexes to particular in vitro/in vivo bioeffects.