Effect of scattered pressures from oscillating microbubbles on neuronal activity in mouse brain under transcranial focused ultrasound stimulation.

Previous studies have indicated that the presence of microbubbles (MBs) during sonication has an impact on neuronal activity, while the underlying mechanisms remain to be revealed. In this study, a model for the scattered pressures produced by the pulsating lipid-encapsulated MBs in mouse brain was developed to numerically investigate the effect of MBs on neuronal activity during transcranial focused ultrasound stimulation. The additional summed scattered pressure (Psummed_scat) from the oscillating MBs was calculated from the model. The level of neuronal activity was experimentally verified using an immunofluorescence assay with antibodies against c-fos. The pressure difference (ΔP) between acoustic pressures at which the same level of neuronal activity is excited by ultrasound stimulation with and without MBs was obtained from the experiments. The results showed that Psummed_scat accounts for about half of the ΔP when the MBs experience a "compression-only" response. The Psummed_scat suddenly increased at a critical acoustic pressure, around which a rapid enhancement of ΔP obtained from experiment also occurred. This work suggested that the additional scattered pressures from pulsating MBs are probably a mechanism that affects neuronal activity under transcranial focused ultrasound stimulation.