IV. THE EFFECT OF FREE ELECTRON LASER PULSE STRUCTURE ON THE
4.2: Introduction
The ultimate goal of soft tissue laser ablation is the removal of a well defined volume of material while leaving the remaining tissue around the ablation site viable. In order to achieve this, it is necessary to determine the laser parameters that will both ablate tissue with a relatively high efficiency, while leaving minimal collateral damage. Laser sources in the ultraviolet and infrared are both good candidates due to their absorption in biological tissue; however, the mutagenic potential of ultraviolet light precludes their use in most applications. Therefore, a great deal of focus has been centered on lasers in the mid-infrared. At mid-infrared wavelengths, specifically, 6.1 and 6.45 µm, light is absorbed by both water and protein. Studies have shown that lasers operating at these wavelengths produce efficient ablation with minimal collateral damage, due to a proposed weakening of the structural integrity of the tissue matrix before explosive vaporization takes place.
The Vanderbilt Mark-III Free Electron Laser (FEL) operating at 6.45 µm in wavelength first demonstrated the ablation of soft tissue in a highly efficient manner with minimal collateral damage (<40 µm) in 1994 [1]; however, the mechanism of this efficient ablation has not been fully understood to date. In the ten years since this landmark discovery, a great deal of research has gone into the study of soft tissue ablation at both 6.1 and 6.45 µm using the FEL for possible clinical applications, including eight human surgeries. The success of the Mark-III FEL for clinical applications has been
limited; however, due to the large overhead and difficult implementation of an FEL as a clinical laser system.
Transition of this technology to more conventional, smaller, laser sources is needed for further advancement. Only recently alternative laser sources, covering the wavelengths of interest, have started to be developed. Our lab is currently investigating two promising sources: an Er:YAG pumped zinc germanium phosphide optical parametric oscillator (ZGP-OPO) and a strontium vapor laser based on metal vapor laser technology. While these lasers operate at the same wavelength as the FEL, their pulse structures vary significantly from the native FEL pulse structure. In order for these lasers to replace the FEL as a viable clinical tool, the role of pulse structure in the ablation mechanism needs to be more completely understood.
The Mark-III FEL is a unique pulsed laser source. The gain medium of this laser is a series of short pulses of electrons that are accelerated to relativistic speeds and interact briefly with light stored within the laser cavity [2], the output radiation is consequently a series of short pulses (about 1 ps), repeated at the electron beam repetition rate of 2.856 GHz. The micropulse train is maintained for up to 5 microseconds, providing a total of over 10,000 micropulses per macropulse. During any given micropulse, the instantaneous power can be up to several megawatts; however, the low duty cycle keeps the average power during the macropulse below ~ 20 kilowatts. Since most solid state or gas lasers have a much simpler pulse structure (often quasi-continuous for tens of nanoseconds), comparison of the FEL with more traditional lasers, even while operating at the same wavelength is quite complicated. It is essential, for continued research into alternative sources for the FEL, to determine which of these features are
important, be it the high-intensity or high repetition rate of the micropulse or the high average power during the macropulse.
An analysis of the effect of pulse structure at 6.1 and 6.45 µm involves using the FEL with a different pulse structure using a pulse stretcher as described in chapter 3.
This offers us the ability to analyze the effect of vastly different pulse structures from the native FEL pulse on the process of ablation, while still using the same system and keeping all other parameters constant. The FEL allows us to collect valuable data that will specify the parameters necessary to help bridge the gap between the multimillion- dollar FEL and much cheaper and efficient bench top laser sources, as they become available.
Previous studies have shown that changing the pulse structure of the FEL from 1 to 200 ps and thus reducing the peak irradiance of the micropulse by 200 times had little or no effect on both the ablation threshold radiant exposure and the ablated crater depth for a defined radiant exposure. This study focuses on the ablation mechanism at 6.1 and 6.45 µm with a careful emphasis on the role of the FEL pulse structure. Three separate experiments were performed to gain insight into this mechanism. The first was a careful analysis of the ablation plume dynamics for a 1 ps micropulse compared with a 200 ps micropulse as seen through bright-field (pump-probe) analysis. The second experiment was a histological analysis of corneal and dermal tissue to determine whether there is less thermal damage associated with one micropulse duration versus another. The final set of experiments involved the use of mass spectrometric analysis to determine whether or not amide bond breakage could occur in the proteins present in tissue as a result of direct absorptions of mid-infrared light into the amide I and amide II absorption bands, which
correspond to 6.1 and 6.45 µm respectively. This has been a question for many years since Edwards et al. published their proposed mechanism of FEL ablation at 6.45 µm[1, 3]. Edwards et al. suggested that a partitioning of energy at this wavelength was occurring in which the protein structure was being comprised by the light prior to the explosive vaporization taking place, which led to a reduction in the mechanical and thermal damage to soft tissues [4]. While this mechanism was proposed, and the FEL community has been working under this hypothesis, little research has been performed to confirm it. In an effort to determine whether a chemical change is taking place at the protein level, prior to explosive vaporization, we used mass spectrometry to determine the existence, or extent of amide bond breakage in protein due to FEL irradiation at 6.1 or 6.45 µm. These experiments will lead to a better understanding of the laser parameters necessary for alternative laser sources to have success as replacements for the FEL with increased clinical relevance.