Distinguishing Photoacoustic and Photothermal Neuron Stimulation Through Quantitative Mapping Spatiotemporal Field Evolution
Deming Li, Andrew Cheng, Xinrui Gong, Haoxin Huang, Yueming Li, Yifan Zhu, Edward A. Nelson, Ji-Xin Cheng, Guo Chen, Chen Yang
2026 · 10.64898/2026.06.02.729635
Abstract
Neuromodulation is a rapidly advancing strategy for modulating brain function and treating neurological disorders, yet the mechanisms of optical neural stimulation remain incompletely understood. A central challenge is that photoacoustic (PA) and photothermal (PT) effects are typically generated simultaneously and evolve on overlapping spatial and temporal scales, making their contributions to neuronal activation difficult to distinguish. Here, we overcome this limitation by integrating two carbon-based emitters with a spatial-offset pump-probe imaging platform to distinguish PA and PT neuromodulation through direct mapping of spatiotemporal field evolution. The two emitters produce nearly identical thermal fields while exhibiting a 26-fold difference in acoustic output, enabling decoupled comparison of thermal and acoustic contributions. To directly characterize the physical fields, we establish a spatial-offset pump-probe imaging system capable of visualizing both temperature and pressure evolution, confirming matched thermal profiles between the two emitters. Neuronal stimulation experiments further show that neurons are markedly more responsive to PA stimulation than to PT stimulation. Beyond resolving a longstanding mechanistic question, this work demonstrates the enhanced efficiency of PA stimulation and provides general guidance for designing high-performance optical neural interfaces.
Abstract via europepmc.
Exposures
Exposure 1: Fiber optoacoustic emitters (candle soot CSFOE and carbon nanotube CNTFOE) on cultured cortical neurons
Target: cultured neurons — “GCaMP6f-labeled primary neurons (DIV 10-13) cultured on a glass-bottom dish”
Device: custom-built · candle soot fiber optoacoustic emitter (CSFOE) and carbon nanotube fiber optoacoustic emitter (CNTFOE) ✓
| Waveform | other patterned | |
|---|---|---|
| Fundamental frequency (kHz) | 18,720, 6,990swept | ✓✓✓⚑ |
| Pulse duration (ms) | not reported | ⚑ |
| Pulse repetition frequency (Hz) | 2,500 | ✓✓✓ |
| Duty cycle (%) | not reported | |
| Sonication duration (s) | 0.1, 0.2swept | ✓✓✓⚑ |
| Free-field pressure (kPa) | 210.3, 15.58swept | ✓✓✓⚑ |
|---|---|---|
| Free-field Isppa (W/cm²) | not reported | |
| Free-field Ispta (W/cm²) | not reported | |
| In-situ estimate | not applicable | |
| In-situ pressure (kPa) | not applicable | |
| In-situ Isppa (W/cm²) | not applicable | |
| In-situ Ispta (W/cm²) | not applicable |
Optoacoustic transients generated by 3 ns, 1030 nm laser pulses at a 2.5 kHz repetition rate, delivered as 100 ms trains (16.4 uJ/pulse) and 200 ms trains (51.8 mW) with the fiber tip 0 to 150 um from the neurons. Not an ultrasound transducer; acoustic output is single-cycle optoacoustic transients.
Flags from extraction
exposures[0].fundamental_frequency_khz— Optoacoustic emitters, not a conventional transducer; central frequencies 18.72 MHz (CSFOE) and 6.99 MHz (CNTFOE) from FFT of hydrophone signals, listed in that order.exposures[0].free_field.pressure_kpa— Peak-to-peak pressure measured by hydrophone in water about 300 um from the fiber tip, CSFOE first then CNTFOE, at different laser energies (4.08 and 12.29 uJ/pulse); SOPPI field measurements at 100 um are in arbitrary units.exposures[0].timing.sonication_duration_s— 100 ms in the first stimulation experiment and 200 ms in the distance experiment; the quote supports 100 ms (200 ms is in a following sentence).exposures[0].timing.pulse_duration_ms— 3 ns is the laser pulse width, not an acoustic pulse duration; left not_reported.n_subjects— Culture/dish counts not given; N values are neurons per condition (e.g. 20 and 17).exposures[0].timing.waveform— Laser pulse train producing nanosecond optoacoustic transients.