An Optimized Miniaturized Ultrasound Transducer for Transcranial Neuromodulation

Abstract

Transcranial ultrasound stimulation (TUS) is a young neuromodulation technology, which uses ultrasound to achieve non-invasive stimulation or inhibition of deep intracranial brain regions, with the advantages of non-invasive, deep penetration, and high resolution. It is widely considered to be one of the most promising techniques for probing brain function and treating brain diseases. In preclinical studies, developing miniaturized transducers to facilitate neuromodulation in freely moving small animals is critical for understanding the mechanism and exploring potential applications. In this article, a miniaturized transducer with a half-concave structure is proposed. Based on the finite element simulation models established by PZFlex software, several ultrasound transducers with different concave curvatures were designed and analyzed. Based on the simulation results, half-concave focused ultrasonic transducers with curvature radii of 5 mm and 7.5 mm were fabricated. Additionally, the emission acoustic fields of the ultrasonic transducers with different structures were characterized at their thickness resonance frequencies of 1 MHz using a multifunctional ultrasonic test platform built in the laboratory. To verify the practical ability for neuromodulation, different ultrasound transducers were used to induce muscle activity in mice. As a result, the stimulation success rates were (32 ± 10)%, (65 ± 8)%, and (84 ± 7)%, respectively, by using flat, #7, and #5 transducers, which shows the simulation and experimental results have a good agreement and that the miniaturized half-concave transducer could effectively converge the acoustic energy and achieve precise and effective ultrasonic neuromodulation.

Keywords: FEM simulation; converge acoustic energy; half-concave structure; neuromodulation; ultrasonic transducer.

FIGURE 1

Schematic diagram of the neural regulation process.

FIGURE 2

Electrical impedance and phase plots of pic255.

FIGURE 3

The impedances of different curvatures of piezoelectric element.

FIGURE 4

Simulation structure: (A) The half-concave ultrasonic transducer and (B). The plane ultrasonic transducer.

FIGURE 5

Emission acoustic field in the simulation.

FIGURE 6

(A) Manufacture process of dimpling, (B) the structure diagram of the half-concave ultrasonic transducer, (C) dimpled pic255 piezoelectric ceramic, and (D) the packaged ultrasonic transducers.

FIGURE 7

Emission acoustic field in the experiment.

FIGURE 8

(A) Normalized acoustic field after transmitting through the skull by simulation. (B) Normalized lateral acoustic field distribution of different transducers by simulation at a maximum acoustic pressure point. (C) The normalized acoustic pressure distribution of the focal area in the X-Y plane. (D) The relative position of the skull and different transducers.

FIGURE 9

(A) Schematic diagram of in vivo mouse EMG recordings using ultrasound neuromodulation to the motor cortex. (B) Example sync pulses (orange) and EMG responses (blue) resulting from sonication with sham, flat transducer, focused transducer #7.5, and #5 at 1.6 MPa. (C) Representative EMG signals induced by a single trial, zooming from (B). (D) The success rate of ultrasound evoked responses and the response latencies (E) sonicated by sham, flat, focused transducer #7.5, and #5 (N = 6, 20 trials/animal, *p < 0.05, **p < 0.01, one-way ANOVA with post-hoc Tukey test. All statistically significant differences are shown).