Optically-generated focused ultrasound for noninvasive brain stimulation with ultrahigh precision

Abstract

High precision neuromodulation is a powerful tool to decipher neurocircuits and treat neurological diseases. Current non-invasive neuromodulation methods offer limited precision at the millimeter level. Here, we report optically-generated focused ultrasound (OFUS) for non-invasive brain stimulation with ultrahigh precision. OFUS is generated by a soft optoacoustic pad (SOAP) fabricated through embedding candle soot nanoparticles in a curved polydimethylsiloxane film. SOAP generates a transcranial ultrasound focus at 15 MHz with an ultrahigh lateral resolution of 83 µm, which is two orders of magnitude smaller than that of conventional transcranial-focused ultrasound (tFUS). Here, we show effective OFUS neurostimulation in vitro with a single ultrasound cycle. We demonstrate submillimeter transcranial stimulation of the mouse motor cortex in vivo. An acoustic energy of 0.6 mJ/cm2, four orders of magnitude less than that of tFUS, is sufficient for successful OFUS neurostimulation. OFUS offers new capabilities for neuroscience studies and disease treatments by delivering a focus with ultrahigh precision non-invasively.

Photoacoustic: A Versatile Nongenetic Method for High-Precision Neuromodulation

“…The mechanical index of the PA stimulation was found to be less than 1, below the FDA-approved value of 1.9 (FDA-2017-D-5372). Experimentally, our results have confirmed no tissue damage observed in vivo used in the photoacoustic brain stimulation. , …”

“…The PA approach offers the merits of being non-contacting with a high penetration depth via ultrasound as well as high spatial precision and multiplexing capacity via photons. Enabled by chemical synthesis and material design, we have designed different materials and devices as highly efficient PA transducers, including fiber-based photoacoustic emitters, ,,− PA films, PA nanoparticles, and optically driven focused ultrasound . They have been applied as implants minimally invasive, and noninvasive neural interfaces for different applications.…”

Force-Based Neuromodulation

“…Photoacoustic nanoparticles represent a less invasive alternative, although the penetration depth of 1030 nm light remains limited in biological tissue . The use of injections or implants may be overcome by the externally placed optoacoustic transducers; however, this method lacks the spatial precision of the FOC and PAN technologies …”

“…19 The use of injections or implants may be overcome by the externally placed optoacoustic transducers; however, this method lacks the spatial precision of the FOC and PAN technologies. 70 Besides photoacoustic neuromodulation, the interaction of light with molecules that undergo photoisomerization upon irradiation offers a fundamentally different mechanism to mechanically modulate neural activity. This mechanism, which is known as photoswitchable molecular actuation, is based on a well-known phenomenon in which the mechanical perturbation of membranes can modulate neural activity by directly modifying the membrane potential.…”

High-precision photoacoustic neural modulation uses a non-thermal mechanism

“…In 2020, Jiang et al reported the development of a fiber optoacoustic emitter 14 capable of sub-millimeter neurostimulation both in vitro and in vivo. In addition to the fiber device, other modalities were also developed for different applications, including biocompatible optoacoustic films for neural regeneration 15 , photoacoustic nanotransducers 16 for single cell stimulation, and optically generated focused ultrasound for transcranial brain stimulation 17 .…”