Optoacoustic brain stimulation at submillimeter spatial precision

Abstract

Low-intensity ultrasound is an emerging modality for neuromodulation. Yet, transcranial neuromodulation using low-frequency piezo-based transducers offers poor spatial confinement of excitation volume, often bigger than a few millimeters in diameter. In addition, the bulky size limits their implementation in a wearable setting and prevents integration with other experimental modalities. Here, we report spatially confined optoacoustic neural stimulation through a miniaturized Fiber-Optoacoustic Converter (FOC). The FOC has a diameter of 600 μm and generates omnidirectional ultrasound wave locally at the fiber tip through the optoacoustic effect. We show that the acoustic wave generated by FOC can directly activate individual cultured neurons and generate intracellular Ca 2+ transients. The FOC activates neurons within a radius of 500 μm around the fiber tip, delivering superior spatial resolution over conventional piezo-based low-frequency transducers. Finally, we demonstrate direct and spatially confined neural stimulation of mouse brain and modulation of motor activity in vivo.

Transcranial focused ultrasound stimulation with high spatial resolution

“…Recently, a new method using optoacoustics demonstrated motor neuromodulation in mice at a submillimeter spatial resolution. However, this technique is highly invasive as it required insertion of a fiber directly into the brain [39]. Therefore, there is still a challenge to achieve high spatial resolution in the axial direction for noninvasive ultrasound neuromodulation.…”

Mirroring Action Potentials: Label‐Free, Accurate, and Noninvasive Electrophysiological Recordings of Human‐Derived Cardiomyocytes

“…After the invention of patch-clamp, [1] awarded with the Noble prize in 1991, many complementary approaches have been developed to meet this challenge. They include microelectrode arrays (MEA), [2,3] CMOS nanoelectrode array (CNEA), [4] calcium imaging, [5,6] voltage-sensing optical (VSO) platforms [7] or impedance spectroscopy, [8] and others. However, each approach presents specific advantages as well as it suffers from intrinsic limitations.…”

A fiber optoacoustic emitter with controlled ultrasound frequency for cell membrane sonoporation at submillimeter spatial resolution

“…In our previous work, an optical fiber coated with ZnO/Epoxy and Graphite/Epoxy was developed, serving as an optoacoustic guide for sub-millimeter tumor localization and intuitive surgical guidance [ 32 ]. To study the involvement of cochlear pathway in the ultrasound induced brain stimulation, the fiber based optoacoustic emitter was used for spatially confined neuron stimulation of mouse brain in vivo [ 33 ], showing powerful capability of understanding the bio-interface mechanism. Notably, none of the reported fiber based optoacoustic devices in the literature delivered central sub-MHz frequencies with controllability.…”