A Transmit-Receive Phased Array for Microbubble-Mediated Focused Ultrasound Brain Therapy in Small Animals.

Abstract

Focused ultrasound (FUS) combined with circulating microbubbles (MBs) can be employed for non-invasive, localized agent delivery across the blood-brain barrier (BBB). Previous work has demonstrated the feasibility of clinical-scale transmit-receive phased arrays for performing transcranial therapies under MB imaging feedback. This study aimed to design, construct, and evaluate a dual-mode phased array for MB-mediated FUS brain therapy in small animals. A 256-element sparse hemispherical array (100 mm diameter) was fabricated by installing 128 PZT cylinder transmitters (f₀ = 1.16 MHz) and 128 broadband PVDF receivers within a 3D-printed scaffold. The transmit array's focal size at the geometric focus was 0.8 mm × 0.8 mm × 1.7 mm, with a 31 mm/27 mm (lateral/axial) steering range. The receive array's point spread function was 0.6 mm × 0.6 mm × 1.5 mm (1.16 MHz source) at the geometric focus, and sources were localized up to 30 mm/16 mm (lateral/axial) from geometric focus. The array was able to spatially map MB cloud activity in 3D throughout a vessel-mimicking phantom at sub-, ultra-, and second-harmonic frequencies. Preliminary in-vivo work demonstrated its ability to induce localized BBB permeability changes under 3D sub-harmonic MB imaging feedback in a mouse model. Small form factor transmit-receive phased arrays enable acoustic imaging-controlled FUS and MB-mediated brain therapies with high targeting precision required for rodent studies. Dual-mode phased arrays dedicated for small animal use will facilitate high-throughput studies of FUS-mediated BBB permeability enhancement to explore novel therapeutic strategies for future clinical application.