An Ultrasound-Guided Hemispherical Phased Array for Microbubble-Mediated Ultrasound Therapy

Goal: To develop a low-cost magnetic resonance imaging (MRI)-free transcranial focused ultrasound (FUS) system for microbubble-mediated therapy. Methods: A 128-element 11 MHz array for skull localization was integrated within a 256-module multi-frequency (306/612/1224 kHz) dual-mode phased array. The system's transcranial transmit and receive performance was evaluated with ex-vivo human skullcaps using phase aberration corrections calculated from computed tomography (CT)-based simulations via ultrasound-based (USCT) and landmark-based (LMCT) registrations, and a gold-standard fixed source emitter (FSE)-based method. Results: Displacement and rotation registration errors of 1.4 ± 0.4 mm and 2.1 ± 0.2$^\circ $ were obtained using USCT, resulting in sub-millimeter transmit targeting errors driven at 306 kHz (0.9 ± 0.2 mm) and 612 kHz (0.9 ± 0.3 mm), and source localization errors of 1.0 ± 0.3 mm and 0.6 ± 0.2 mm at receive frequencies of 306 kHz and 612 kHz, respectively (mean ± SD). Similar errors were obtained using LMCT and no significant differences between these two approaches were found on either transmit (p = 0.64/0.99) or receive (p = 0.45/0.36) at 306 kHz/612kHz. During volumetric multi-point exposures, approximately 70% and 60% of the transmit frames in which microbubble activity was detected via FSE were recovered using USCT when imaging at the second-harmonic and half-harmonic, respectively, compared to 60% and 69% using LMCT. Conclusion: This low-cost ultrasound-guided transcranial FUS system affords USCT skull registration with accuracy comparable to LMCT methods. Significance: Such systems have great potential to advance the adoption of microbubble-mediated FUS brain therapy by improving access to the technology.