Optimizing Laser-Tissue Interactions to Improve Targeting during Infrared Neural Inhibition

Abstract

Pulsed infrared lasers have been leveraged for inducing temperature mediated block of the propagation of neural signals in a technique called infrared neural inhibition (INI). INI has been shown to selectively block small diameter axons at lower temperatures, and thus has been hypothesized as a potential novel technique to alleviate of chronic pain. While non-damaging in acute trials, current temperature rises required for INI are problematic for sustained use. Better targeting of neurons in the bulk tissue may be able to take advantage of the native laser-tissue interactions and result in less extraneous heating. It has been hypothesized that there is a relationship between the length of axon heated, defined as the block length (BL), and the temperature threshold for INI, and optimizing the BL targeted may reduce the temperature threshold. In this dissertation, a joint optical-thermal computational model was used to aid the understanding of laser heating during INI and assess how optical scattering affects the induced temperature distribution. This analysis demonstrates that there is a non-negligible effect of optical scattering on the maximum temperature rise and 1/e thermal penetration depth, and that a Monte Carlo simulation of photon propagation is needed to properly predict the light distribution during INI. The presence of a BL effect was then established in a proof-of-principle study comparing INI thresholds for one and two adjacent irradiation optical fibers placed along nerves. Subsequent exploration of the parameter space of viable BL using laser heating was explored to optimize this phenomenon. Interrogation of a range of BLs revealed two distinct temperature trend regimes and that a minimum in the temperature threshold for INI occurs at the intersection of these two regimes (~1.15 mm of heating along axons). This minimum in temperature motivates that the BL can be optimized during INI. Computational modeling can be used to optimize laser irradiation to target the proper BL. Utilizing predictive modeling and optimized BL may serve to reduce INI temperature thresholds to a level suitable for long-term application, aiding in its clinical potential.