Miniaturized optically generated Bessel beam ultrasound for volumetric transcranial brain stimulation

Noninvasive stimulation of small, variably shaped brain subregions is crucial for advancing our understanding of brain functions. Current ultrasound neuromodulation faces two major trade-offs when targeting brain subregions: miniaturization versus volumetric control and spatial resolution versus transcranial capability. Here, we present an optically generated Bessel beam ultrasound (OBUS) device designed to overcome these limitations. This miniaturized device, measuring 2.33 millimeters in diameter, delivers a column-shaped field achieving a lateral resolution of 152 micrometers and an axial resolution of 1.93 millimeters, enabling targeting of brain subregions with an elongated volume of tissue activation. Immunofluorescence imaging of mouse brain slices confirms its ability to stimulate cells at depths up to 2.1 millimeters. In addition, OBUS outperforms conventional Gaussian ultrasound in transcranial transmission efficiency and beam shape preservation. Electrophysiological recordings and functional MRI captured rodent brain responses evoked by OBUS, demonstrating OBUS's ability to noninvasively activate neural circuits in intact brains. This technology offers expanded possibilities for studying brain functions with precision and volumetric control.