Biophysical mechanisms responsible for pulsed low-level laser excitation of neural tissue

摘要

Background/Objective: The traditional method of stimulating neural activity has been based on electrical methods and remains the gold standard to date despite inherent limitations. We have previously shown a new paradigm to in vivo neural activation based on pulsed infrared light, which provides a contact-free, spatially selective, artifact-free method without incurring tissue damage that may have significant advantages over electrical stimulation in a variety of diagnostic and therapeutic applications. The goal of this study was to investigate the physical mechanism of this phenomenon, which we propose is a photo-thermal effect from transient tissue temperature changes resulting in direct or indirect activation of transmembrane ion channels causing propagation of the action potential. Methods: Rat sciatic nerve preparation was stimulated in vivo with the Holmium: YAG laser (2.12μm), Free Electron Laser (2.1 μm), Alexandrite laser (690nm), and the prototype for a solid state commercial laser nerve stimulator built by Aculight (1.87μm) to determine contributions of photobiological responses from laser tissue interactions, including temperature, pressure, electric field, and photochemistry, underlying the biophysical mechanism of stimulation. Single point temperature measurements were made with a microthermocouple adjacent to the excitation site, while an infrared camera was used for 2-D radiometry of the irradiated surface. Displacement from laser-induced pressure waves or thermoelastic expansion was measured using a PS-OCT system. Results: Results exclude a direct photochemical, electric field, or pressure wave effect as the mechanism of optical stimulation. Measurements show relative small contributions from thermoelastic expansion (300 nm) with the laser parameters used for nerve stimulation. The maximum change in tissue temperature is about 9℃ (average increase of 3.66℃) at stimulation threshold radiant exposures. Conclusion: Neural activation with pulsed laser-light occurs by a transient thermally induced mechanism. Future experiments will reveal if this effect is through direct membrane interaction or facilitated through an indirect effect leading to membrane depolarization.