[Paper Review] Optically-generated focused ultrasound for noninvasive brain stimulation with ultrahigh precision

Yue‐Ming Li, Ying Jiang+10 more|arXiv (Cornell University)|Apr 19, 2022

Pain Management and Treatment4 citations

TL;DR

This study introduces optically-generated focused ultrasound (OFUS) using a soft optoacoustic pad (SOAP) made of candle soot nanoparticles in a curved polydimethylsiloxane film, achieving 83 µm lateral resolution—two orders of magnitude finer than conventional transcranial focused ultrasound (tFUS). The method enables non-invasive, submillimeter precision stimulation of the mouse motor cortex with only 0.6 mJ/cm² acoustic energy, four orders of magnitude lower than tFUS, demonstrating ultrahigh-precision neuromodulation for neuroscience and therapeutic applications.

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 um, 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/cm^2, 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.

Motivation & Objective

• To develop a non-invasive brain stimulation method with submillimeter spatial precision for advanced neuroscience research.
• To overcome the limited spatial resolution (typically millimeter-scale) of current non-invasive neuromodulation techniques.
• To reduce the acoustic energy required for effective stimulation, minimizing tissue damage risks.
• To enable precise targeting of specific neural circuits in the brain without surgical intervention.
• To demonstrate feasibility of optically-generated focused ultrasound (OFUS) in both in vitro and in vivo models.

Proposed method

• The OFUS system uses a soft optoacoustic pad (SOAP) fabricated by embedding candle soot nanoparticles into a curved polydimethylsiloxane film to generate ultrasound via photothermal effect.
• Laser irradiation of the SOAP generates localized thermal expansion, producing highly focused ultrasound waves at 15 MHz.
• The curved geometry of the SOAP enables beam focusing through acoustic lensing, achieving sub-100 µm lateral resolution.
• The system is designed for transcranial application, allowing non-invasive delivery of ultrasound through the skull.
• Acoustic energy is minimized by optimizing nanoparticle distribution and laser pulse duration to achieve effective stimulation with only 0.6 mJ/cm².
• In vivo validation uses optogenetic and electrophysiological assays to confirm precise motor cortex activation in mice.

Experimental results

Research questions

• RQ1 Can optically-generated focused ultrasound achieve sub-100 µm lateral resolution in transcranial brain stimulation?
• RQ2 Is it possible to achieve effective neuromodulation with acoustic energy four orders of magnitude lower than conventional tFUS?
• RQ3 Can OFUS enable precise, non-invasive stimulation of specific brain regions like the motor cortex in vivo?
• RQ4 What is the minimum acoustic energy required for reliable neural activation using OFUS?
• RQ5 Can OFUS be used to stimulate neural circuits with spatial precision sufficient for mapping functional brain circuits?

Key findings

• The OFUS system achieved a lateral resolution of 83 µm, which is two orders of magnitude finer than conventional transcranial focused ultrasound (tFUS).
• Neurostimulation was successfully demonstrated in vitro using only a single ultrasound cycle, indicating high temporal precision.
• In vivo stimulation of the mouse motor cortex achieved submillimeter precision, with targeted activation confirmed via electrophysiological recordings.
• The required acoustic energy for effective stimulation was 0.6 mJ/cm²—four orders of magnitude lower than typical tFUS applications.
• The soft optoacoustic pad (SOAP) enabled efficient, non-invasive transcranial ultrasound focusing without damaging the skull or surrounding tissue.
• The OFUS system demonstrated stable and repeatable performance across multiple trials, supporting its potential for clinical and research applications.