Microbubble cavitation in low-intensity focused ultrasound stimulation: A multi-scale computational study

Area of Science:

• Biomedical Engineering
• Acoustic Physics
• Computational Modeling

Background:

• Low-intensity transcranial focused ultrasound (LIFUS) with microbubbles (MBs) shows promise for non-invasive brain stimulation and blood-brain barrier (BBB) opening.
• Previous studies often examined ultrasound propagation and MB dynamics separately, hindering the establishment of safe acoustic thresholds due to skull distortions and nonlinear MB behavior.

Purpose of the Study:

• To develop a multi-scale computational model integrating 3D LIFUS simulations with MB dynamics.
• To investigate the impact of skull anatomy on LIFUS-induced MB cavitation.
• To establish safe and effective acoustic thresholds for LIFUS applications.

Main Methods:

• Developed a multi-scale computational model combining 3D LIFUS simulations with Marmottant equation-based MB dynamics.
• Utilized 3D human skull models from CT/MRI data for LIFUS simulations at 250 and 500 kHz.
• Quantified stable (V_SC) and inertial cavitation (V_IC) volumes for clinically relevant MB sizes.

Main Results:

• Skull-induced distortions enlarged cavitation volumes and advanced cavitation onset compared to free water.
• Skull attenuation reduced acoustic pressures by 75%-85%, leading to smaller cavitation volumes.
• Skull attenuation elevated the inertial cavitation threshold by approximately 3-5 fold.

Conclusions:

• Skull anatomy critically influences LIFUS and MB cavitation, with distortions significantly affecting outcomes.
• Multi-scale modeling provides a basis for understanding LIFUS effects and optimizing BBB opening.
• Findings support the development of safer and more effective LIFUS-based therapeutic applications.