V. COMPARISON OF ZnGeP 2 OPTICAL PARAMETRIC OSCILLATOR AND
5.2: Introduction
The ultimate goal of medical laser ablation is to remove a defined amount of material in an efficient manner while doing the least amount of collateral (thermal or mechanical) damage possible. To this end, two classes of laser sources have been examined;
specifically, lasers in the ultraviolet and the infrared have been studied since they are both highly absorbed in water and thus tissue [1]. Due to the mutagenic potential of ultraviolet lasers; however, lasers in the infrared hold more promise for medical applications [1]. Traditionally, the investigation of mid-infrared tissue ablation has been centered at 2.1 µm (Ho:YAG) and 2.94 µm (Er:YAG) because these wavelengths are easily obtainable through conventional laser sources. The thermal damage associated with these lasers, especially the free-running lasers which have 100-250 µs pulse durations has been quite significant, since they are not thermally confined. While q- switching these lasers leads to thermal confinement, the absorption coefficient at 2.94 is also extremely high (1 µm penetration depth), which leads to a great deal of thermal diffusion out of the irradiated zone which leads to thermal damage as well [2-5]. Due to the shortcomings of these wavelengths, the need for laser source around 6 µm is evident.
Investigations in the infrared have recently been centered on two specific wavelengths, 6.1 and 6.45 µm. These wavelengths coincide with the amide-I and amide-II absorption bands of protein respectively[1]. In addition, these wavelengths coincide with the bending mode of water, which has a peak absorption at 6.1 µm[1]. At these two wavelengths, energy is coupled into the protein matrix as well as the bound and unbound water within the tissue. It has been postulated that some of the energy imparted to the tissue is coupled into the protein matrix causing conformational changes which then
reduces the structural integrity of the tissue allowing for tissue removal with less collateral damage when compared with other wavelengths [6]. Recently Edwards et al.
have described a model for cornea comprised of superheated saline surrounded by collagen fibers in which the temperature and pressure of these saline layers increases until the outer protein layers mechanically fail. At 6.45 µm the collagen becomes brittle due to denaturation and fractures when marginally stressed, leading to less collateral damage compared with other wavelengths[7]. Biophysical investigations with a Mark-III free electron laser (FEL), tuned to 6.45 µm in wavelength have demonstrated minimal collateral damage and high ablation yield (removal of material) in ocular and neural tissues [7-12].
The Mark-III FEL has been used successfully in human neurosurgery and ophthalmic surgery based on these findings [8-10, 13-16]. While the use of this wavelength of light produced by the FEL has shown much promise for surgical applications, further advances are limited due the high overhead related with the use of the FEL. Further in depth investigation and widespread clinical use requires the development of alternative laser sources in the mid-infrared (6-8 µm); however, the role the unique pulse structure of the FEL plays in the efficient removal of soft tissue with minimal collateral damage has not be clearly defined.
Currently several different sources are under investigation as potential FEL replacements. This includes a strontium vapor laser, based on metal vapor laser technology, a nonlinear optical parametric oscillator based on an Nd:YAG pumped ZnGeP2 crystal (ZGP-OPO), and an Er:YAG pumped AgGaSe2 OPO[17-24]. Of these potential alternative sources, only the ZGP-OPO currently is sufficiently reliable and has
enough energy per pulse (~250 µJ) to reach three times the ablation threshold for water and soft tissue at the wavelengths of interest given a ~60 µm spot size. In addition a great deal of research has been carried out by this author involving changing the native structure of the FEL micropulse and is discussed in chapters 3 and 4 of this dissertation.
The results of this research suggest that the micropulse structure of the FEL is not important to the process of soft-tissue ablation.
This paper focuses on the comparison of the Mark-III FEL with the ZGP-OPO at 6.1, 6.45, and 6.73 µm (similar water absorption compared to 6.45 µm without protein absorption) in wavelength with a similar spot size. The ablation threshold of both water and mouse dermis was determined at the three wavelengths of interest with both laser sources. The 6.1 µm wavelength was chosen due to the location of the water peak and the amide-I absorption band at this wavelength. The 6.45 µm wavelength was chosen due to its location at the amide-II absorption band with one tenth the absorption in water as seen at 6.1 µm. Additionally, 6.73 µm was chosen for comparison because it has roughly the same water absorption as 6.45 µm with minimal protein absorption. The efficiency of both lasers with their differing pulse structures was also examined on 90% w/w gelatin and mouse dermis. In addition, bright-field (pump-probe) imaging was performed to analyze the dynamics seen in the ablation plume for both laser sources. This research will provide much insight into the possibility of using a ZGP:OPO as an alternative to the FEL for medical applications.
From an ablation physics point of view, the pulse durations of both laser sources are thermally confined, but not stress-confined (FEL micropulse is stress-confined, see Table 5.1). This suggests that both sources should operate in a similar manner with respect to
6.1 um 6.45 um 6.73 um
Absorption Coefficient (1/mm) 270 82 62
Penetration Depth (mm) 0.0037 0.0122 0.0161
Thermal Confinement Time (s) 2.29E-05 2.48E-04 4.34E-04 Stress Confinement Time (s) 2.405E-09 7.919E-09 1.047E-08
FEL micropulse (s) 1.00E-12 1.00E-12 1.00E-12
FEL macropulse (s) 5.00E-06 5.00E-06 5.00E-06
ZGP-OPO (s) 1.00E-07 1.00E-07 1.00E-07
Table 5.1 This table summarizes the relevant ablation parameters for the FEL and the ZGP-OPO for the three wavelengths used.
the ablation threshold and the ablation efficiency. The 100 nanosecond pulse of the ZGP- OPO suggests that the ablation dynamics from the sub-ablative phase, development of the vapor plume, and material ejection will be similar to that seen with the 5 microsecond FEL macropulse while occurring on a much shorter timescale[25]. Each of these was examined in depth by the proceeding research.