Femtosecond laser lithotripsy: feasibility and ablation mechanism.

Light emitted from a femtosecond laser is capable of plasma-induced ablation of various materials. We tested the feasibility of utilizing femtosecond-pulsed laser radiation (lambda=800 nm, 140 fs, 0.9 mJ/pulse) for ablation of urinary calculi. Ablation craters were observed in human calculi of greater than 90% calcium oxalate monohydrate (COM), cystine (CYST), or magnesium ammonium phosphate hexahydrate (MAPH). Largest crater volumes were achieved on CYST stones, among the most difficult stones to fragment using Holmium:YAG (Ho:YAG) lithotripsy. Diameter of debris was characterized using optical microscopy and found to be less than 20 microm, substantially smaller than that produced by long-pulsed Ho:YAG ablation. Stone retropulsion, monitored by a high-speed camera system with a spatial resolution of 15 microm, was negligible for stones with mass as small as 0.06 g. Peak shock wave pressures were less than 2 bars, measured by a polyvinylidene fluoride (PVDF) needle hydrophone. Ablation dynamics were visualized and characterized with pump-probe imaging and fast flash photography and correlated to shock wave pressures. Because femtosecond-pulsed laser ablates urinary calculi of soft and hard compositions, with micron-sized debris, negligible stone retropulsion, and small shock wave pressures, we conclude that the approach is a promising candidate technique for lithotripsy.

In vivo histological evaluation of a novel ablative fractional resurfacing device.

BACKGROUND AND OBJECTIVES: A novel carbon dioxide (CO(2)) laser device employing ablative fractional resurfacing was tested on human skin in vivo for the first time. STUDY DESIGN/MATERIALS AND METHODS: An investigational 30 W, 10.6 microm CO(2) laser system was focused to a 1/e(2) spot size of 120 microm to generate an array of microscopic treatment zones (MTZ) in human forearm skin. A range of pulse energies between 5 and 40 mJ was tested and lesion dimensions were assessed histologically using hematoxylin and eosin. Wound healing of the MTZ's was assessed immediately-, 2-day, 7-day, 1-month, and 3-month post treatment. The role of heat shock proteins was examined by immunohistochemistry. RESULTS: The investigational CO(2) laser system created a microscopic pattern of ablative and thermal injury in human skin. The epidermis and part of the dermis demonstrated columns of thermal coagulation that surrounded tapering ablative zones lined by a thin eschar layer. Changing the pulse energy from 5 to 30 mJ resulted in a greater than threefold increase in lesion depth and twofold increase in width. Expression of heat shock protein (hsp)72 was detected as early as 2 days post-treatment and diminished significantly by 3 months. In contrast, increased expression of hsp47 was first detected at 7 days and persisted at 3 months post-treatment. CONCLUSION: The thermal effects of a novel investigational ablative CO(2) laser system utilizing fractional resurfacing were characterized in human forearm skin. We confirmed our previous ex vivo findings and show for the first time in-vivo, that a controlled array of microscopic treatment zones of ablation and coagulation could be deposited in human skin by varying treatment pulse energy. Immunohistochemical studies of heat shock proteins revealed a persistent collagen remodeling response lasting at least 3 months. We successfully demonstrated the first in-vivo use of ablative fractional resurfacing (AFR) treatment on human skin.

The effects of pulse energy variations on the dimensions of microscopic thermal treatment zones in nonablative fractional resurfacing.

BACKGROUND AND OBJECTIVES: We examined the effects of pulse energy variations on the dimensions of microscopic thermal injury zones (MTZs) created on human skin ex vivo and in vivo using nonablative fractional resurfacing. MATERIALS AND METHODS: A Fraxel SR laser system emitting at 1,550 nm provided an array of microscopic spots at variable densities. Pulse energies ranging from 4.5 to 40 mJ were tested on human abdominal skin ex vivo and in vivo. Tissue sections were stained with hematoxylin and eosin (H&E) or nitro blue tetrazolium chloride (NBTC) and MTZ dimensions were determined. Ex vivo and in vivo results were compared. Dosimetry analyses were made for the surface treatment coverage calculation as a function of pulse energy and collagen coagulation based on H&E stain or cell necrotic zone based on NBTC stain. RESULTS: Each MTZ was identified by histological detection of a distinct region of loss of tissue birefringence and hyalinization, representing collagen denaturation and cell necrosis within the irradiated field immediately, 1, 3, and 7 days after treatment. At high pulse energies, the MTZ depth could exceed 1 mm and width approached 200 microm as assessed by H&E. NBTC staining revealed viable interlesional tissue. In general, no statistically significant difference was found between in vivo and ex vivo depth and width measurements. CONCLUSIONS: The Fraxel SR laser system delivers pulses across a wide range of density and energy levels. We determined that increases in pulse energy led to increases in MTZ depth and width without compromising the structure or viability of interlesional tissue.

Ex vivo histological characterization of a novel ablative fractional resurfacing device.

BACKGROUND AND OBJECTIVES: We introduce a novel CO(2) laser device that utilizes ablative fractional resurfacing for deep dermal tissue removal and characterize the resultant thermal effects in skin. STUDY DESIGN/MATERIALS AND METHODS: A prototype 30 W, 10.6 microm CO(2) laser was focused to a 1/e(2) spot size of 120 microm and pulse duration up to 0.7 milliseconds to achieve a microarray pattern in ex vivo human skin. Lesion depth and width were assessed histologically using either hematoxylin & eosin (H&E) or lactate dehydrogenase (LDH) stain. Pulse energies were varied to determine their effect on lesion dimensions. RESULTS: Microarrays of ablative and thermal injury were created in fresh ex vivo human skin irradiated with the prototype CO(2) laser device. Zones of tissue ablation were surrounded by areas of tissue coagulation spanning the epidermis and part of the dermis. A thin condensed lining on the interior wall of the lesion cavity was observed consistent with eschar formation. At 23.3 mJ, the lesion width was approximately 350 microm and depth 1 mm. In this configuration, the cavities were spaced approximately 500 microm apart and interlesional epidermis and dermis demonstrated viable tissue by LDH staining. CONCLUSION: A novel prototype ablative CO(2) laser device operating in a fractional mode was developed and its resultant thermal effects in human abdominal tissue were characterized. We discovered that controlled microarray patterns could be deposited in skin with variable depths of dermal tissue ablation depending on the treatment pulse energy. This is the first report to characterize the successful use of ablative fractional resurfacing as a potential approach to dermatological treatment.

Laser-induced transepidermal elimination of dermal content by fractional photothermolysis.

The wound healing process in skin is studied in human subjects treated with fractional photothermolysis. In-vivo histological evaluation of vacuoles formed over microthermal zones (MTZs) and their content is undertaken. A 30-W, 1550-nm single-mode fiber laser system delivers an array of 60 microm or 140 microm 1e2 incidence microbeam spot size at variable pulse energy and density. Treatments span from 6 to 20 mJ with skin excisions performed 1-day post-treatment. Staining with hematoxylin and eosin demonstrates an intact stratum corneum with vacuolar formation within the epidermis. The re-epithelialization process with repopulation of melanocytes and keratinocytes at the basal layer is apparent by 1-day post-treatment. The dermal-epidermal (DE) junction is weakened and separated just above zones of dermal coagulation. Complete loss of dermal cell viability is noted within the confines of the MTZs 1-day post-treatment, as assessed by lactate dehydrogenase. All cells falling outside the irradiation field remain viable. Content within the epidermal vacuoles stain positively with Gomori trichrome, suggesting a dermal origin. However, the positive staining could be due to loss of specificity after thermal alteration. Nevertheless, this dermal extrusion hypothesis is supported by very specific positive staining with an antihuman elastin antibody. Fractional photothermolysis creates microthermal lesions that allow transport and extrusion of dermal content through a compromised DE junction. Some dermal material is incorporated into the microepidermal necrotic debris and shuttled up the epidermis to eventually be exfoliated through the stratum corneum. This is the first report of a nonablative laser-induced transport mechanism by which dermal content can be predictably extruded biologically through the epidermis. Thus, treatment with the 1550-nm fiber laser may provide the first therapeutic option for clinical indications, including pigmentary disorders such as medically recalcitrant melasma, solar elastosis, as well as depositional diseases such as mucinosis and amyloidosis.

Erbium: YAG laser lithotripsy mechanism.

PURPOSE: We tested the hypothesis that the mechanism of long pulse erbium:YAG laser lithotripsy is photothermal. MATERIALS AND METHODS: Human urinary calculi were placed in deionized water and irradiated with erbium:YAG laser energy delivered through a sapphire optical fiber. Erbium:YAG bubble dynamics were visualized with Schlieren flash photography and correlated to acoustic emissions measured by a polyvinylidene fluoride needle hydrophone. The sapphire fiber was placed either parallel or perpendicular to the calculus surface to assess the contribution of acoustic transients to fragmentation. Stones were irradiated using desiccated stone irradiated in air, hydrated stone irradiated in air and hydrated stone irradiated in water. Ablation crater sizes were compared. Uric acid stones were irradiated in water and the water was assayed for cyanide. RESULTS: During the early phase of vapor bubble expansion, acoustic transients had minimal effects on calculus fragmentation. Fragmentation occurred due to direct absorption of laser energy transmitted to the calculus through the vapor channel between the sapphire fiber tip and calculus. The forward axial expansion of the bubble occurred more rapidly than the radial expansion. A parallel oriented fiber on the calculus surface produced no fragmentation but generated larger amplitude acoustic transients compared to perpendicular orientation. In perpendicular orientation the erbium:YAG laser did not generate any collapse acoustic waves but fragmentation occurred. Crater width was greatest for desiccated stones irradiated in air (p <0.03). Cyanide production increased as erbium:YAG irradiation of uric acid calculi increased, (r2 = 0.98). CONCLUSIONS: The erbium:YAG laser fragments stones through a photothermal mechanism.