A High-Frequency Phased Array System for Transcranial Ultrasound Delivery in Small Animals

Existing systems for applying transcranial focused ultrasound (FUS) in small animals produce large focal volumes relative to the size of cerebral structures available for interrogation. The use of high ultrasonic frequencies can improve targeting specificity; however, the aberrations induced by rodent calvaria at megahertz frequencies severely distort the acoustic fields produced by single-element focused transducers. Here, we present the design, fabrication, and characterization of a high-frequency phased array system for transcranial FUS delivery in small animals. A transducer array was constructed by micromachining a spherically curved PZT-5H bowl (diameter = 25 mm, radius of curvature = 20 mm, fundamental frequency = 3.3 MHz) into 64 independent elements of equal surface area. The acoustic field generated by the phased array was measured at various target locations using a calibrated fiber-optic hydrophone, both in free-field conditions as well as through ex vivo rat skullcaps with and without hydrophone-assisted phase aberration corrections. Large field-of-view acoustic field simulations were carried out to investigate potential grating lobe formation. The focal beam size obtained when targeting the array's geometric focus was 0.4 mmx0.4 mmx2.6 mm in water. The array can steer the FUS beam electronically over cylindrical volumes of 4.5 mm in diameter and 6 mm in height without introducing grating lobes. Insertion of a rat skullcap resulted in substantial distortion of the acoustic field (p
_no
corrs
= 24 ± 4% p
_water
); however, phase corrections restored partial focal quality (p
_skull
corrs
= 31 ± 3% p
_water
). Using phase corrections, the array is capable of generating a trans-rat skull peak negative focal pressure of up to ~2.0 MPa, which is sufficient for microbubble-mediated blood-brain barrier permeabilization at this frequency.