Abstract
Recently, our group developed a synergistic brain drug delivery method to achieve simultaneous transcranial hyperthermia and localized blood-brain barrier opening via MR-guided focused ultrasound (MRgFUS). In a rodent model, we demonstrated that the ultrasound power required for transcranial MRgFUS hyperthermia was significantly reduced by injecting microbubbles (MBs). However, the specific mechanisms underlying the power reduction caused by MBs remain unclear. The present study aims to elucidate the mechanisms of MB-enhanced transcranial MRgFUS hyperthermia through numerical studies using the finite element method. The microbubble acoustic emission (MAE) and the viscous dissipation (VD) were hypothesized to be the specific mechanisms. Acoustic wave propagation was used to model the FUS propagation in the brain tissue, and a bubble dynamics equation for describing the dynamics of MBs with small shell thickness was used to model the MB oscillation under FUS exposures. A modified bioheat transfer equation was used to model the temperature in the rodent brain with different heat sources. A theoretical model was used to estimate the bubble shell's surface tension, elasticity, and viscosity losses. The simulation reveals that MAE and VD caused a 40.5% and 52.3% additional temperature rise, respectively. Compared with FUS only, MBs caused a 64.0% temperature increase, which is consistent with our previous animal experiments. Our investigation showed that MAE and VD are the main mechanisms of MB-enhanced transcranial MRgFUS hyperthermia.