C. D. Clark

Maxwell's equations-based dynamic laser-tissue interaction model

Since its invention in the early 1960s, the laser has been used as a tool for surgical, therapeutic, and diagnostic purposes. To achieve maximum effectiveness with the greatest margin of safety it is important to understand the mechanisms of light propagation through tissue and how that light affects living cells. Lasers with novel output characteristics for medical and military applications are too often implemented prior to proper evaluation with respect to tissue optical properties and human safety. Therefore, advances in computational models that describe light propagation and the cellular responses to laser exposure, without the use of animal models, are of considerable interest. Here, a physics-based laser-tissue interaction model was developed to predict the dynamic changes in the spatial and temporal temperature rise during laser exposure to biological tissues. Unlike conventional models, the new approach is grounded on the rigorous electromagnetic theory that accounts for wave interference, polarization, and nonlinearity in propagation using a Maxwells equations-based technique.

Limiting mechanism for NIR laser retinal damage

Near-infrared (NIR) laser exposures to the retina are affected by intraocular absorption, chromatic aberration and retinal absorption. We present the latest results of retinal exposure to wavelengths between 1.0 to 1.319 micrometers and show how the trends for long-pulse exposure are dramatically affected by intraocular absorption in the anterior portion of the eye.

Modeling of Surface Thermodynamics and Damage Thresholds in the IR and THz Regime

The Air Force Research Lab has developed a configurable, two-dimensional, thermal model to predict laser-tissue interactions, and to aid in predictive studies for safe exposure limits. The model employs a finite-difference, time-dependent method to solve the two-dimensional cylindrical heat equation (radial and axial) in a biological system construct. Tissues are represented as multi-layer structures, with optical and thermal properties defined for each layer, are homogeneous throughout the layer. Multiple methods for computing the source term for the heat equation have been implemented, including simple linear absorption definitions and full beam propagation through finite-difference methods. The model predicts the occurrence of thermal damage sustained by the tissue, and can also determine damage thresholds for total optical power delivered to the tissue. Currently, the surface boundary conditions incorporate energy loss through free convection, surface radiation, and evaporative cooling. Implementing these boundary conditions is critical for correctly calculating the surface temperature of the tissue, and, therefore, damage thresholds. We present an analysis of the interplay between surface boundary conditions, ambient conditions, and blood perfusion within tissues.

Theoretical and experimental bioeffects research for high-power terahertz electromagnetic energy

Historically, safety analyses for radio frequency emission and optical laser exposures have been designed to define the threshold level for tissue damage. To date, no experimental studies have documented damage thresholds to living tissues in the terahertz (THz) range of electromagnetic frequencies (0.1 - 10 THz). Exposure limits exist as extrapolated estimates at the extreme bounds of current occupational safety standards for lasers and radio frequency sources. Therefore, due to the lack of published data on the safety of terahertz emissions, an understanding of the bioeffects of tissue exposures to terahertz beams is necessary. The terahertz frequency band represents an intermediate range in which both optical and radiofrequency methods of theory and experimentation can be selectively employed and compared for consistency. We report on work recently completed to reconcile the theoretical methods of optical and radio-frequency radiative transport modeling, while additionally discussing preliminary theoretical estimates of damage thresholds to skin tissue from terahertz energy and work planned to validate these findings experimentally.

On the probability summation model for laser-damage thresholds

Abstract. This paper explores the probability summation model in an attempt to provide insight to the model’s utility and ultimately its validity. The model is a statistical description of multiple-pulse (MP) damage trends. It computes the probability of n pulses causing damage from knowledge of the single-pulse dose–response curve. Recently, the model has been used to make a connection between the observed n−1/4 trends in MP damage thresholds for short pulses (<10u2009u2009μs) and experimental uncertainties, suggesting that the observed trend is an artifact of experimental methods. We will consider the correct application of the model in this case. We also apply this model to the spot-size dependence of short pulse damage thresholds, which has not been done previously. Our results predict that the damage threshold trends with respect to the irradiated area should be similar to the MP damage threshold trends, and that observed spot-size dependence for short pulses seems to display this trend, which cannot be accounted for by the thermal models.

Evidence of thermal additivity during short laser pulses in an in vitro retinal model

Laser damage thresholds were determined for exposure to 2.5-ms 532-nm pulses in an established in vitro retinal model. Single and multiple pulses (10, 100, 1000) were delivered to the cultured cells at three different pulse repetition frequency (PRF) values, and overt damage (membrane breach) was scored 1 hr post laser exposure. Trends in the damage data within and across the PRF range identified significant thermal additivity as PRF was increased, as evidenced by drastically reduced threshold values (< 40% of single-pulse value). Microthermography data that were collected in real time during each exposure also provided evidence of thermal additivity between successive laser pulses. Using thermal profiles simulated at high temporal resolution, damage threshold values were predicted by an in-house computational model. Our simulated ED50 value for a single 2.5-ms pulse was in very good agreement with experimental results, but ED50 predictions for multiple-pulse trains will require more refinement.

Thermal and damage data from multiple microsecond pulse trains at 532nm in an in vitro retinal model

An artificially pigmented retinal pigment epithelial (RPE) cell model was used to study the damage rates for exposure to 1, 10, 100, and 1,000 230-μs laser pulses at 532 nm, at two different concentrations of melanosome particles (MPs) per cell. Multiple pulses were delivered at pulse repetition rates of 50 and 99 pulses per second. Standard fluorescence viability indicator dyes and the method of microthermography were used to assess damage and thermal responses, respectively. Although frame rate during microthermography was more than five times slower than the duration of laser pulses, thermal information was useful in refining the BTEC computational model for simulating high-resolution thermal responses by the pigmented cells. When we temporally sampled the thermal model output at a rate similar to our microthermography, the resulting thermal profiles for multiple pulses resembled the thermal experimental profiles. Complementary to the thermal simulations, our computer-generated thresholds were in good agreement with the in vitro data. Findings are examined within the context of common exposure limit definitions in the national and international laser safety standards.

Visualization of thermal lensing induced image distortion using Zemax ray tracing and BTEC thermal modeling

In recent years, several studies have been investigating the impact of thermal lensing in ocular media on the visual function. These studies have shown that when near-infrared (NIR) laser energy (1319 nm) is introduced to a human eye, the heating of the eye can be sufficient to alter the index of refraction of the media leading to transient changes in the visible wavefront through an effect known as thermal lensing, while remaining at a safe level. One of the main limitations of experimentation with human subjects, however, is the reliance on a subject’s description of the effect, which can vary greatly between individuals. Therefore, a computational model was needed that could accurately represent the changes of an image as a function of changes in the index of refraction. First, to model changes in the index of refraction throughout the eye, a computational thermal propagation model was used. These data were used to generate a comprehensive ray tracing model of the human eye using Zemax ( Radiant Zemax Inc, Redmond WA) via a gradient lens surface. Using this model, several different targets have been analyzed which made it possible to calculate real-world visual acuity so that the effect of changes in the index of refraction could be related back to changes in the image of a visual scene.

Predicted multiple-pulse thermal damage thresholds and exposure limits

We report on the first of a series of modeling studies examining multiple-pulse damage thresholds in the retina. This effort focuses on near-infrared wavelength (1064nm – 1350nm) point source (small spot) thermal damage thresholds, but some general properties of multiple pulse exposures are obtained. We analyze the threshold trends as a function of wavelength, pulse width, inter-pulse spacing, and number of pulses, spanning a large parameter space.The rules used for determining multiple-pulse maximum permissible exposures (MPEs) in the current ANSI Z136.1 standard are evaluated, and we show that the MPE trends to not follow the damage threshold trends for many pulse train configurations, leading to large variations in the safety factor. We investigate a system for setting multiple-pulse MPEs that more closely follows the damage threshold trends, and also propose changes to the current multiple-pulse MPE rules.

Spatially-correlated microthermography maps threshold temperature in laser-induced damage

We measured threshold temperatures for cell death resulting from short (0.1 – 1.0 s) 514-nm laser exposures using an in vitro retinal model. Real-time thermal imaging at sub-cellular resolution provided temperature information that was spatially correlated with cells at the boundary of cell death, as indicated by post-exposure fluorescence images. Our measurements indicated markedly similar temperatures, not only around individual boundaries (single exposure), but among all exposures of the same duration in a laser irradiance-independent fashion. Two different methods yielded similar threshold temperatures with low variance. Considering the experimental uncertainties associated with the thermal camera, an average peak temperature of 53 ± 2 °C was found for laser exposures of 0.1, 0.25, and 1.0 s. Additionally, we found a linear relationship between laser exposure duration and time-averaged integrated temperature. The mean thermal profiles for cells at the boundary of death were assessed using the Arrhenius rate law using three different parameter sets (frequency factor and energy of activation) found in the literature.We measured threshold temperatures for cell death resulting from short (0.1 – 1.0 s) 514-nm laser exposures using an in vitro retinal model. Real-time thermal imaging at sub-cellular resolution provided temperature information that was spatially correlated with cells at the boundary of cell death, as indicated by post-exposure fluorescence images. Our measurements indicated markedly similar temperatures, not only around individual boundaries (single exposure), but among all exposures of the same duration in a laser irradiance-independent fashion. Two different methods yielded similar threshold temperatures with low variance. Considering the experimental uncertainties associated with the thermal camera, an average peak temperature of 53 ± 2 °C was found for laser exposures of 0.1, 0.25, and 1.0 s. Additionally, we found a linear relationship between laser exposure duration and time-averaged integrated temperature. The mean thermal profiles for cells at the boundary of death were assessed using the Arrheniu...