Abstract
Noninvasive methods for enhancing the brain drug delivery has been pursued for years. Previously we developed a new MR-guided focused ultrasound (FUS)-based technique, which can achieve targeted brain hyperthermia for heat-triggered drug release and simultaneously open the blood–brain barrier safely for drug penetration. However, the underline mechanisms were unclear. This study aimed to explore the mechanisms for the enhanced FUS brain tissue hyperthermia with microbubbles via numerical modeling in COMSOL. The acoustic wave equation was employed to describe the FUS propagation. A bubble dynamics equation was adopted for calculating the stable bubble oscillations under FUS exposures. A modified bioheat transfer equation was utilized to compute the heating, with various heating sources including FUS, microbubble acoustic emission (MAE), and viscous dissipation (VD). The microbubbles were randomly distributed within the focal region. The sonication time was 6s with an initial temperature of 41°C. The average temperature in the focal region were 41.65°C, 42.24°C, 42.98°C, and 43.59°C for FUS alone, FUS + MAE, FUS + VD, and FUS + MAE + VD, respectively. Compared with the FUS alone, both MAE and VD made significant contributions to the heating with additional temperature increases of 47.6% and 67.2%, respectively.
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