Abstract
Transcranial focused ultrasound (tFUS) is an emerging, non-invasive therapeutic approach for neurological conditions. However, its development is hindered by the skull, which serves as a significant acoustic barrier. Although small animal models have been used extensively to study tFUS, the impact of the skull in these models remains poorly understood. To address this knowledge gap, this study experimentally examined the attenuation and defocusing effects of two ex vivo rat skulls on acoustic pressure fields at therapeutically relevant frequencies. Using three focused ultrasound transducers operating between 1 and 2.25 MHz, we evaluated the impact of rat skull characteristics, location of the focus, and frequency on ultrasound transmission loss, full width at half maximum (FWHM), and focal location. The results demonstrated that skull thickness and morphology substantially influence attenuation and defocusing. Higher frequencies, while offering sharper focus, also led to increased attenuation and defocusing. Furthermore, the position of the focus relative to the skull had a minimal effect on the outcomes. Overall, the presence of the rat skull resulted in a 50 - 88% reduction in focal intensity, a focal broadening of 1 - 53%, and a focal shift of -1.6 - 2.1 mm. These findings provide critical insights that can enhance the precision and efficacy of tFUS in preclinical applications using rats as a small animal model.