Affordable stereotactic-guided focused ultrasound device for tunable drug delivery to the mouse brain

Abstract

Focused ultrasound combined with microbubble (FUS+MB)-mediated blood brain barrier (BBB) opening is not only a promising technique for clinical applications but also a powerful tool for preclinical neuroscience and neuro-oncology research. However, existing FUS systems are expensive and lack the flexibility of modulating BBB opening volume, which prevents a broader research community from adopting the FUS+MB technique in preclinical studies. To address the challenge, we developed a low cost (∼$100), mini FUS transducer with the capability to modulate BBB opening size that can be readily integrated with a standard stereotaxic frame for mouse. Specifically, we manufactured in-house mini FUS transducers with three frequencies (1.5, 3.0, and 6.0 MHz), and quantified BBB opening and targeting accuracy at varying pressures (0.20 to 0.81 MPa). The volume of FUS+MB-induced BBB opening was evaluated using both contrast-enhanced MRI and Evans blue extravasation. Our results showed that we can achieve varying amount of Evans blue delivery and BBB opening size by modulating the transducer frequency and acoustic pressure. Additionally, the amount of Evans blue delivery and BBB opening had a significant linear correlation with the cavitation index (defined by the ratio between acoustic pressure and frequency). We believe that this stereotaxic-guided FUS system will lower the barrier for adopting the FUS technique in a broader research community.