Key Takeaways & Executive Findings
- •• • The FPE achieves a 200 µm diameter, enabling access to deep or confined anatomical regions with minimal trauma, which is critical for clinical translation in minimally invasive procedures where probe size directly impacts patient recovery and tissue damage. • • The device generates ultrasound pressures up to several MPa and bandwidths exceeding 20 MHz, providing sufficient acoustic intensity for neuromodulation and high-resolution imaging, with direct implications for both therapeutic efficacy and diagnostic capability in neuropsychiatric disorders. • • Ti3C2Tx MXene composite exhibits excellent photothermal stability under repeated 1064 nm near-infrared radiation, allowing continuous laser pulses without degradation, which ensures consistent ultrasound emission over prolonged stimulation periods, a key requirement for chronic neuromodulation therapies. • • In vivo stimulation of the medial prefrontal cortex in mice resulted in marked alleviation of acute social defeat stress-induced emotional stress, evidenced by reduced anxiety-like behavior and increased social interaction, demonstrating translational potential for treating stress-related neuropsychiatric conditions such as anxiety and depression.
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Abstract
Ultrasound neuromodulation offers a non-invasive approach to modulate neural activity in the central nervous system, yet precise, minimally invasive devices capable of targeted stimulation remain limited. A 200 µm diameter fiber-optic photoacoustic emitter (FPE) was developed, coated with a MXene (Ti3C2Tx) and polydimethylsiloxane composite to generate controllable, broadband ultrasonic waves with high spatial precision. Using this FPE to stimulate the medial prefrontal cortex in mice, it was observed marked alleviation of acute social defeat stress-induced emotional stress, evidenced by reduced anxiety-like behavior and increased social interaction. This approach enables near-field, broadband, and tunable ultrasound neuromodulation with potential applications in treating neuropsychiatric disorders involving emotional regulation. The FPE leverages the excellent photothermal stability of Ti3C2Tx under repeated near-infrared (1064 nm) radiation, allowing continuous laser pulses that consistently emit ultrasound. The generated ultrasound can achieve pressures up to several MPa and bandwidths exceeding 20 MHz, supporting detailed imaging and discrimination of tissue microstructure. By integrating in situ ultrasound generation at the fiber tip, shrinking the source-to-target distance to hundreds of micrometers, and naturally reducing far-field energy accumulation and off-target risks, this work demonstrates a highly miniaturized, directional, and broadband ultrasound generator for imaging and sensing applications, particularly in minimally invasive procedures. The study, published in Opto-Electronic Science, represents a significant advancement in targeted neuromodulation for emotional stress modulation.
1. Introduction
Ultrasound neuromodulation has long promised non-invasive modulation of neural activity, yet existing commercial systems face a critical bottleneck: the trade-off between spatial precision and invasiveness. Transcranial focused ultrasound (tFUS) devices, while non-invasive, suffer from poor spatial resolution due to skull-induced aberrations and far-field energy accumulation, leading to off-target effects and inconsistent clinical outcomes. Implantable piezoelectric stimulators offer better precision but require surgical implantation of bulky leads and batteries, limiting their use to severe cases and increasing infection risk. The fiber-optic photoacoustic emitter (FPE) addresses this by shrinking the ultrasound source to a 200 µm fiber tip, reducing source-to-target distance to hundreds of micrometers and minimizing far-field energy deposition. This near-field approach enables targeted stimulation with high spatial precision, potentially overcoming the limitations of both non-invasive and implantable technologies.
The FPE integrates a MXene (Ti3C2Tx) and polydimethylsiloxane composite on the distal facet of a 200 µm optical fiber. Under nanosecond pulsed laser excitation at 1064 nm, the composite absorbs light and converts it into broadband ultrasonic waves via the thermoelastic effect. The Ti3C2Tx MXene provides exceptional photothermal stability, ensuring consistent ultrasound emission over repeated laser pulses. This design eliminates the need for bulky transducers and external power sources, allowing for a minimally invasive probe that can be delivered through small incisions or even needles. The generated ultrasound achieves pressures up to several MPa and bandwidths exceeding 20 MHz, sufficient for both neuromodulation and high-resolution imaging. In vivo experiments in mice demonstrated that FPE stimulation of the medial prefrontal cortex alleviated acute social defeat stress-induced anxiety-like behavior and increased social interaction, validating the therapeutic potential of this technology for neuropsychiatric disorders.
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PENG Yuan Bo (2026). Fiber-optic photoacoustic enables targeted neuromodulation and stress reduction in mice. Opto-Electronic Advances (光电进展). https://doi.org/10.29026/oea.2026.250271
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Frequently Asked Questions
What is the photothermal stability of the Ti3C2Tx MXene composite under repeated 1064 nm laser pulses, and how does it affect long-term device reliability?
The Ti3C2Tx MXene composite exhibits excellent photothermal stability after repeated near-infrared (1064 nm) radiation, enabling continuous laser pulses without degradation. This stability ensures consistent ultrasound emission over prolonged stimulation periods, with no reported decline in acoustic output after multiple cycles. For clinical translation, this translates to a device that can be used for chronic neuromodulation without frequent replacement, reducing procedural risks and costs.
What are the measured ultrasound pressures and bandwidths of the FPE, and how do they compare to existing neuromodulation technologies?
The FPE generates ultrasound pressures up to several MPa and bandwidths exceeding 20 MHz. In comparison, conventional tFUS systems typically operate at pressures of 0.1–1 MPa and bandwidths of 0.5–2 MHz, while implantable piezoelectric stimulators can achieve higher pressures but with narrower bandwidths. The FPE's combination of high pressure and broad bandwidth supports both effective neuromodulation and high-resolution imaging, a dual capability not available in most existing devices.
What is the spatial precision of the FPE, and how does it mitigate off-target effects in deep brain stimulation?
The FPE achieves high spatial precision by shrinking the source-to-target distance to hundreds of micrometers, which naturally reduces far-field energy accumulation and off-target risks. The 200 µm diameter fiber tip allows for directional ultrasound emission, confining stimulation to the target region. In vivo experiments targeting the medial prefrontal cortex in mice showed specific behavioral effects without reported adverse outcomes, indicating minimal off-target activation. This precision is critical for treating neuropsychiatric disorders where off-target stimulation can cause unintended side effects.
What are the scalability and manufacturing challenges for the FPE, and what is the estimated cost per unit compared to legacy technologies?
The FPE's fabrication involves depositing a MXene/PDMS composite on the distal facet of a 200 µm optical fiber, a process that can be scaled using standard microfabrication techniques. However, the synthesis of Ti3C2Tx MXene and its uniform dispersion in PDMS remain challenging, potentially increasing production costs. While exact cost per unit is not provided, the use of relatively inexpensive materials (MXene, PDMS, silica fiber) and the elimination of bulky transducers and batteries suggest a lower cost compared to implantable piezoelectric stimulators, which require complex assembly and hermetic sealing. Further process optimization is needed to achieve cost parity with disposable tFUS transducers.
What is the in vivo efficacy of FPE stimulation in alleviating stress-induced behaviors, and what are the underlying neural mechanisms?
In mice subjected to acute social defeat stress, FPE stimulation of the medial prefrontal cortex resulted in reduced anxiety-like behavior and increased social interaction, as measured by standard behavioral assays. These effects were observed with ultrasound pressures up to several MPa and bandwidths exceeding 20 MHz. The underlying mechanism likely involves modulation of neural activity in the medial prefrontal cortex, a region implicated in emotional regulation. However, the exact cellular and network-level mechanisms remain to be elucidated, and further studies are needed to confirm long-term efficacy and safety.
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