Effect of scattered pressures from oscillating microbubbles on neuronal activity in mouse brain under transcranial
Zhiwei Cui1, Dapeng Li1, Shanshan Xu1
1The Key Laboratory of Biomedical Information Engineering of the Ministry of Education, Department of Biomedical Engineering, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, China.
Abstract:
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.
Insights
Microbubbles (MBs) enhance neuronal activity during transcranial focused ultrasound stimulation. Pulsating MBs generate scattered pressures that contribute to this effect, revealing a key mechanism for ultrasound neuromodulation.
Area of Science:
- Neuroscience
- Acoustic Physics
- Biomedical Engineering
Background:
- Microbubbles (MBs) are known to influence neuronal activity during sonication.
- The precise mechanisms by which MBs affect neuronal responses to ultrasound remain unclear.
Purpose of the Study:
- To numerically model scattered pressures from pulsating MBs in the mouse brain.
- To investigate the effect of MBs on neuronal activity during transcranial focused ultrasound stimulation.
- To elucidate the role of MB-generated scattered pressures in ultrasound neuromodulation.
Main Methods:
- Developed a numerical model to calculate summed scattered pressures (Psummed_scat) from lipid-encapsulated MBs.
- Experimentally quantified neuronal activity using immunofluorescence assays (c-fos).
- Determined the pressure difference (ΔP) required for equivalent neuronal activation with and without MBs.
Main Results:
- Psummed_scat accounted for approximately half of the ΔP under "compression-only" MB response.
- A critical acoustic pressure triggered a sudden increase in Psummed_scat.
- This critical pressure correlated with a rapid enhancement in experimental ΔP.
Conclusions:
- Additional scattered pressures from pulsating MBs are a likely mechanism influencing neuronal activity during transcranial focused ultrasound.
- This finding advances the understanding of ultrasound-mediated neuromodulation.
- Highlights the importance of MB dynamics in focused ultrasound applications.
