[PUBLICATION] Numerical modeling of ultrasound propagation in the inner ear for sonoporation-mediated drug delivery

Abstract

To date, no treatment has been developed for targeted delivery to the inner ear (IE). Sonoporation, a promising drug delivery method, increases the permeability of round window membranes (RWMs), enhancing drug diffusion to the IE. A dedicated ultrasound protocol is essential to treat IE pathologies in combination with sonoporation. In situ acoustic pressure (AP) measurements cannot be used for RWM sonoporation because of the heterogeneous anatomy of the temporal bone. This study aimed to model ultrasound propagation in the IE to ensure adequate AP for RWM sonoporation. The impact of the position of the ultrasound probe relative to the RWM on AP as well as potential temperature increases caused by tissue/ultrasound interaction were investigated. Using MATLAB®, a surgical procedure was simulated based on the computed tomography scans of sheep heads (14 IEs). An ultrasound probe (12.7 mm in diameter, 1 MHz) with a degassed water-filled adapter was placed in front of the RWM. Mechanical properties, such as tissue density, sound speed, and ultrasound attenuation, were computed. Ultrasound propagation was simulated using k-wave. Standing waves can double the AP locally; however, the final AP is comparable to a free water field map when accounting for microbubble-induced attenuation. The angle and distance of the probe relative to the RWM have minimal effect on the AP; the main effect is caused by centering the probe on the RWM. No significant thermal elevation was observed. The developed computational model paves the way for designing an optimal and safe ultrasound protocol for sonoporation-mediated drug delivery into the IE.