Machine Learning Assisted Optimization Framework for Designing Transcranial Focused Ultrasound Phased Array Transducer for Deep Brain Neuromodulation in Mice

Transcranial focused ultrasound is an emerging noninvasive neuromodulation technique offering high spatial precision and deep penetration. However, in deep brain neuromodulation in mice, the skull base attenuates the signal, distorting the focal region and creating off target peaks. This study presents a machine learning driven simulation framework to optimize a bowl-shaped phased array transducer design for hypothalamic targeting and compares its performance with that of time-reversal phase conjugation and a single-element baseline. A computed tomography based mouse head model was used for full-wave acoustic simulations with a fixed bowl geometry (10 mm aperture, 6 mm radius of curvature). Designs were evaluated across various parameters, including operating frequency (0.2 to 1.5 MHz), active element count (16, 32, 64, 128), and element diameter (300 to 550 micron). The evaluation employed four metrics: the presence of a -3 dB focal region within the hypothalamic area, axial focal length defined by the -3 dB full-width at half maximum, focal fragmentation measured by the -3 dB blob count, and targeting displacement. Random Forest surrogate models were trained in simulation outputs and paired with the Non-dominated Sorting Genetic Algorithm II to reduce computational costs during multi-objective optimization. The forward-excitation-optimized phased-array design (0.73 MHz, 128 elements, 381 micron; element diameter) achieved a focal region at the hypothalamic target with a full width at half maximum of 0.67 mm, a blob count of 1, and a targeting displacement of 0.38 mm when placed 1 mm below the nominal position. Time-reversal phase conjugation further improved confinement and targeting (full width at half maximum: 0.59 mm; displacement: 0.37 mm). Limitations include reliance on a single mouse anatomy, and incorporating additional CT-derived anatomies should enhance generalizability across strains, ages, and sexes.