Efficacy and predictability of soft tissue ablation using a prototype Raman-shifted alexandrite laser.

Previous research showed that mid-infrared free-electron lasers could reproducibly ablate soft tissue with little collateral damage. The potential for surgical applications motivated searches for alternative tabletop lasers providing thermally confined pulses in the 6- to-7-µm wavelength range with sufficient pulse energy, stability, and reliability. Here, we evaluate a prototype Raman-shifted alexandrite laser. We measure ablation thresholds, etch rates, and collateral damage in gelatin and cornea as a function of laser wavelength (6.09, 6.27, or 6.43 µm), pulse energy (up to 3 mJ/pulse), and spot diameter (100 to 600 µm). We find modest wavelength dependence for ablation thresholds and collateral damage, with the lowest thresholds and least damage for 6.09 µm. We find a strong spot-size dependence for all metrics. When the beam is tightly focused (~100-µm diameter), ablation requires more energy, is highly variable and less efficient, and can yield large zones of mechanical damage (for pulse energies>1 mJ). When the beam is softly focused (~300-µm diameter), ablation proceeded at surgically relevant etch rates, with reasonable reproducibility (5% to 12% within a single sample), and little collateral damage. With improvements in pulse-energy stability, this prototype laser may have significant potential for soft-tissue surgical applications.

Miniature forward-imaging B-scan optical coherence tomography probe to guide real-time laser ablation.

BACKGROUND AND OBJECTIVE: Investigations have shown that pulsed lasers tuned to 6.1 µm in wavelength are capable of ablating ocular and neural tissue with minimal collateral damage. This study investigated whether a miniature B-scan forward-imaging optical coherence tomography (OCT) probe can be combined with the laser to provide real-time visual feedback during laser incisions. STUDY DESIGN/METHODS AND MATERIALS: A miniature 25-gauge B-scan forward-imaging OCT probe was developed and combined with a 250 µm hollow-glass waveguide to permit delivery of 6.1 µm laser energy. A gelatin mixture and both porcine corneal and retinal tissues were simultaneously imaged and lased (6.1 µm, 10 Hz, 0.4-0.7 mJ) through air. The ablation studies were observed and recorded in real time. The crater dimensions were measured using OCT imaging software (Bioptigen, Durham, NC). Histological analysis was performed on the ocular tissues. RESULTS: The combined miniature forward-imaging OCT and mid-infrared laser-delivery probe successfully imaged real-time tissue ablation in gelatin, corneal tissue, and retinal tissue. Application of a constant number of 60 pulses at 0.5 mJ/pulse to the gelatin resulted in a mean crater depth of 123 ± 15 µm. For the corneal tissue, there was a significant correlation between the number of pulses used and depth of the lased hole (Pearson correlation coefficient = 0.82; P = 0.0002). Histological analysis of the cornea and retina tissues showed discrete holes with minimal thermal damage. CONCLUSIONS: A combined miniature OCT and laser-delivery probe can monitor real-time tissue laser ablation. With additional testing and improvements, this novel instrument has the future possibility of effectively guiding surgeries by simultaneously imaging and ablating tissue.

Comparing an optical parametric oscillator (OPO) as a viable alternative for mid-infrared tissue ablation with a free electron laser (FEL).

Beneficial medical laser ablation removes material efficiently with minimal collateral damage. A Mark-III free electron laser (FEL), at a wavelength of 6.45 µm has demonstrated minimal damage and high ablation yield in ocular and neural tissues. While this wavelength has shown promise for surgical applications, further advances are limited by the high overhead for FEL use. Alternative mid-infrared sources are needed for further development. We compared the FEL with a 5-µs pulse duration with a Q-switched ZGP-OPO with a 100-ns pulse duration at mid-infrared wavelengths. There were no differences in the ablation threshold of water and mouse dermis with these two sources in spite of the difference in their pulse structures. There was a significant difference in crater depth between the ZGP:OPO and the FEL. At 6.1 µm, the OPO craters are eight times the depth of the FEL craters. The OPO craters at 6.45 and 6.73 µm were six and five times the depth of the FEL craters, respectively. Bright-field (pump-probe) images showed the classic ablation mechanism from formation of a plume through collapse and recoil. The crater formation, ejection, and collapse phases occurred on a faster time-scale with the OPO than with the FEL. This research showed that a ZGP-OPO laser could be a viable alternative to FEL for clinical applications.

The effect of free-electron laser pulse structure on mid-infrared soft-tissue ablation: ablation metrics.

Pulsed mid-infrared (6.45 microm) radiation has been shown to cut soft tissue with minimal collateral damage (<40 microm); however, the mechanism of ablation has not been elucidated to date. The goal of this research was to examine the role of the unique pulse structure of the Vanderbilt Mark-III free-electron laser (FEL) and its role in the efficient ablation of soft tissue with minimal collateral damage. The effect of the picosecond micropulse was examined by running the native FEL pulse structure through a pulse stretcher in order to increase the micropulse length from 1 ps up to approximately 200 ps. This allowed us to determine whether or not the picosecond train of micropulses played any role in the ablation process. The ablation threshold was determined for water and mouse dermis for each micropulse length. While the results of the analysis showed a statistically significant difference between 1 and 200 ps, the average per cent difference amounts to only 28% and is not proportional to the 200-fold drop in peak irradiance. The ablation efficiency was also measured on gelatin and mouse dermis for the different micropulse lengths. A small but statistically significant difference was observed between 1 and 200 ps, with the 200 ps pulse being more efficient on gelatin, and with the opposite trend for mouse dermis. We have shown that there is a small effect of micropulse duration of the FEL on the ablation process; however, this effect is negligible between 1 and 200 ps given that there is a 200-fold decrease in peak intensity. These results suggest that as we move forward in developing alternative laser sources for tissue ablation to replace the FEL, the picosecond micropulse structure is not a critical parameter that needs to be duplicated.

The effect of free-electron laser pulse structure on mid-infrared soft-tissue ablation: biological effects.

Previous studies have shown that changing the pulse structure of the free electron laser (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 microm with an emphasis on the role of the FEL pulse structure. Three different experiments were performed to gain insight into this mechanism. The first was an analysis of the ablation plume dynamics observed for a 1 ps micropulse compared with a 200 ps micropulse as seen through bright-field analysis. Negligible differences are seen in the size, but not the dynamics of ablation, as a result of this imaging. 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. No significant difference was seen in the extent of thermal damage on either canine cornea or mouse dermis for the micropulse durations studied at either wavelength. The final set of experiments involved the use of mass spectrometry to determine whether 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. This analysis showed that there was no amide bond breakage due to irradiation at 6.45 microm on protein.