A Low-complexity Programmable Ultrasound Stimulation System: Design and Safety Evaluation.

Abstract

Accurate control, monitoring of acoustic power, and flexible waveform generation are essential for safe and reproducible transcranial focused ultrasound (tFUS) neuromodulation, which is not comprehensively supported by existing benchtop platforms. This work presents a low-complexity and programmable tFUS stimulation system. The system integrates a direct digital synthesis module, a DAC-controlled programmable DC-DC supply, a full-bridge driver, and an impedance matching network to achieve flexible waveform generation and efficient transducer excitation. Acoustic power is monitored using a nonuniform discrete Fourier transform method at the driving frequency. Direct amplitude regulation enables highly linear pressure control up to 4.85 MPa. Impedance matching raised the maximum peak-to-peak excitation voltage from 86 V to 206 V (×2.4) and reduced total harmonic distortion (THD) by 19.19 dB. The power monitor achieves <5% error for outputs above 3 W. In vivo safety was evaluated in mice using both acute (single 20-min exposure) and chronic (21-day, 20-min/day) protocols. Four stimulation groups at $\mathrm{I_{SPPA}}$ = 40 W/cm² with duty cycles from 1.8% to 14.4% ($\mathrm{I_{SPTA}}$ = 0.72-5.76 W/cm²) were compared with sham and controls. Behavioral outcomes and histological analysis revealed no abnormalities under these conditions. The $\mathrm{I_{SPTA}}$ range corresponds to one to eight times the FDA guideline limit, thereby encompassing and extending typical safety margins in neuromodulation studies. These results demonstrate the feasibility of the proposed platform, with validation at both the circuit level and through preclinical safety studies.