Identifying optimal parameters for infrared neural stimulation in the peripheral nervous system

Abstract

Significance: Infrared neural stimulation (INS) utilizes pulsed infrared light to selectively elicit neural activity without exogenous compounds. Despite its versatility in a broad range of biomedical applications, no comprehensive comparison of factors pertaining to the efficacy and safety of INS such as wavelength, radiant exposure, and optical spot size exists in the literature. Aim: Here, we evaluate these parameters using three of the wavelengths commonly used for INS, 1450 nm, 1875 nm, and 2120 nm. Approach: In an in vivo rat sciatic nerve preparation, the stimulation threshold and transition rate to 100% activation probability were used to compare the effects of each parameter. Results: The pulsed diode lasers at 1450 nm and 1875 nm had a consistently higher ( $\sim 1.0J/{\mathrm{cm}}^2$ ) stimulation threshold than that of the Ho:YAG laser at 2120 nm ( $\sim 0.7J/{\mathrm{cm}}^2$ ). In addition, the Ho:YAG produced a faster transition rate to 100% activation probability compared to the diode lasers. Our data suggest that the superior performance of the Ho:YAG is a result of the high-intensity microsecond spike at the onset of the pulse. Acute histological evaluation of diode irradiated nerves revealed a safe range of radiant exposures for stimulation. Conclusion: Together, our results identify measures to improve the safety, efficacy, and accessibility of INS technology for research and clinical applications.

Keywords: clinical translation; efficacy; in vivo; infrared neural stimulation; neurophotonics; peripheral nerves.

Fig. 1

Experimental setup for in vivo INS of the rat sciatic nerve. The laser source was coupled directly into a multimode optical fiber positioned over the nerve. The nerve was stimulated optically and CMAPs were recorded from the soleus muscle using a modular data acquisition system.

Fig. 2

Spot size measurements made using IR beam profiler fitted to a Gaussian distribution (solid lines). Maximum intensities are modulated for clear visualization. ${\mathrm{S}\text{pot Size}}_{500}=528.5\mu \mathrm{m}$, $R^2=0.9989$; ${\mathrm{S}\text{pot Size}}_{800}=802.1\mu \mathrm{m}$, $R^2=0.9993$; ${\mathrm{S}\text{pot Size}}_{1000}=1003\mu \mathrm{m}$, $R^2=0.9986$.

Fig. 3

AUC-normalized temporal pulse shapes from Ho:YAG and diode lasers. (a) AUC-normalized temporal pulse shapes from a regular Ho:YAG and $350\mu \mathrm{s}$ diode pulse. (b) AUC-normalized temporal pulse shape from a spikeless Ho:YAG pulse. Pulse traces were taken with amplified, InGaAs detector (PDA10D, Thorlabs, Newton, New Jersey).

Fig. 4

Stimulation threshold remains constant across every spot size for a given wavelength while the Ho:YAG consistently produces a $H_{50}$ lower than that of both laser diode systems. ($H_{50}\pm \mathrm{SEM}$, $n=5$).

Fig. 5

Effects of pulse width on $H_{50}$. (a) Pulse width does not significantly alter the $H_{50}$ for diode lasers ($H_{50}\pm \mathrm{SEM}$, $n=\mathrm{5,}500\mu \mathrm{m}$ spot size). (b) $H_{50}$ of the Ho:YAG laser is lower than that of the diode lasers at equal pulse widths ($H_{50}\pm \mathrm{SEM}$, $n=5$, ${\tau }_p=350\mu \mathrm{s}$, $500\mu \mathrm{m}$ spot size).

Fig. 6

Difference in activation probabilities between diode and Ho:YAG lasers. (a) CDFs fitted to all samples from diode and Ho:YAG lasers for a given set of parameters. (${\lambda }_{5\mathrm{ms}}=1875\mathrm{nm}$, ${\text{S}\text{pot Size}}_{5\mathrm{ms}}=1000\mu \mathrm{m}$; ${\lambda }_{2\mathrm{ms}}=1470\mathrm{nm}$, ${\text{S}\text{pot Size}}_{2\mathrm{ms}}=500\mu \mathrm{m}$; ${\lambda }_{350\mu \mathrm{s}}=1470\mathrm{nm}$, ${\lambda }_{2\mathrm{ms}}=1470\mathrm{nm}$, ${\text{S}\text{pot Size}}_{350\mu \mathrm{s}}=500\mu \mathrm{m}$; ${\lambda }_{\mathrm{Ho}:\mathrm{YAG}}=2120\mathrm{nm}$, ${\text{S}\text{pot Size}}_{\mathrm{Ho}:\mathrm{YAG}}=500\mu \mathrm{m}$). (b) The transition rate ($m_{\text{peak}}$) of diode lasers at various pulse widths and Ho:YAG laser at $350\mu \mathrm{s}$ pulse width ($m_{\text{peak}}\pm \mathrm{SEM}$, $n=5$). A larger $m_{\text{peak}}$ corresponds to a steeper transition in activation probability.

Fig. 7

The effects of spikeless Ho:YAG pulse on stimulation efficacy. (a) Spikeless pulses produced a greater $H_{50}$ than the unaltered Ho:YAG pulse (${\mathrm{H}}_{50}\pm \mathrm{SEM}$, $n=5$) (b) Fitted CDFs to all data for the spikeless Ho:YAG, unaltered Ho:YAG, and diode lasers. (c) The transition rate ($m_{\text{peak}}$) of the spikeless Ho:YAG, unaltered Ho:YAG, and diode lasers ($m_{\text{peak}}\pm \mathrm{SEM}$, $n=5$). For all experiments: $\text{spot size}=500\mu \mathrm{m}$, ${\lambda }_{\text{Diode}}=1470\mathrm{nm}$, ${\tau }_p=350\mu \mathrm{s}$. NS, spikeless.

Fig. 8

Representative irradiated nerve slices stained with toluidine blue. (a) Negative control, no stimulation. (b) Positive control: $6\mathrm{J}/{\mathrm{cm}}^2$ at 1450 nm light. Red ellipse indicates region of myelin disruption. (c) $3.08\mathrm{J}/{\mathrm{cm}}^2$ irradiation at 1450 nm. (d) $3.15\mathrm{J}/{\mathrm{cm}}^2$ irradiation at 1875 nm.