Kin F. Chan

Laser-induced transepidermal elimination of 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.

Holmium:YAG laser lithotripsy: A dominant photothermal ablative mechanism with chemical decomposition of urinary calculi

Evidence is presented that the fragmentation process of long‐pulse Holmium:YAG (Ho:YAG) lithotripsy is governed by photothermal decomposition of the calculi rather than photomechanical or photoacoustical mechanisms as is widely thought. The clinical Ho:YAG laser lithotriptor (2.12 μm, 250 μs) operates in the free‐running mode, producing pulse durations much longer than the time required for a sound wave to propagate beyond the optical penetration depth of this wavelength in water. Hence, it is unlikely that shock waves are produced during bubble formation. In addition, the vapor bubble induced by this laser is not spherical. Thus the magnitude of the pressure wave produced at cavitation collapse does not contribute significantly to lithotripsy.

Fractional Deep Dermal Ablation Induces Tissue Tightening

Due to the significant risk profile associated with traditional ablative resurfacing, a safer and less invasive treatment approach known as fractional deep dermal ablation (FDDA™) was recently developed. We report the results of the first clinical investigation of this modality for treatment of photodamaged skin.

A perspective on laser lithotripsy: the fragmentation processes

This paper describes in simple terms the physics of laser-calculus interactions and introduces a method with which physicians can understand or evaluate the application of any new laser technique for use in lithotripsy or other medical fields. Tissue optical properties and laser parameters govern the mechanism(s) of fragmentation of urinary or biliary calculi. Laser pulse energies for clinical lithotripsy range from Q0 = 20 mJ to 2 J for short-pulsed lasers to long-pulsed lasers, respectively. Lasers with short pulse durations (i.e., less than a few microseconds) fragment calculi by means of shockwaves following optical breakdown and plasma expansion of ionized water or calculus compositions or by cavitation collapse, thus manifesting a photoacoustical effect. Laser-tissue interactions involving dominant photomechanical or photoacoustical effects are usually stress confined. Long-pulsed lasers (i.e., >100 microsec), on the other hand, generate minimal acoustic waves, and calculi are fragmented by temperatures beyond the thresholds for vaporization of calculus constituents, melting, or chemical decomposition.

ERBIUM:YAG VERSUS HOLMIUM:YAG LITHOTRIPSY

PURPOSE We test the hypothesis that erbium:YAG (Er:YAG) lithotripsy is more efficient than holmium:YAG (Ho:YAG) lithotripsy. MATERIALS AND METHODS Human calculi composed of greater than 97% calcium oxalate monohydrate and cystine were studied. Calculi were irradiated in water using Er:YAG or Ho:YAG lasers. Er:YAG lithotripsy was done with a 425 microm sapphire optical fiber at a pulse energy of 50 mJ at 10 Hz. Ho:YAG lithotripsy was performed with a 365 microm low hydroxy optical fiber at a pulse energy of 500 mJ at 10 Hz or a 425 microm sapphire optical fiber at a pulse energy of 50 mJ at 10 Hz. Fragmentation was defined as the initial stone mass minus the final dominant fragment mass and normalized for incident laser fluence (energy per unit area of fiber tip). RESULTS Mean fragmentation plus or minus standard deviation for calcium oxalate monohydrate was 38 +/- 27 mg for Er:YAG and 22 +/- 6 for Ho:YAG (low hydroxy silica fiber) versus 5 +/- 1 for Ho:YAG (sapphire fiber, p = 0.001). When fragmentation was normalized for incident laser fluence given different optical fiber sizes, mean fragmentation efficiency was 53.6 +/- 38.7 g-microm2/J for Er:YAG lithotripsy compared with 22.6 +/- 6.4 for Ho:YAG (low hydroxy silica fiber) lithotripsy (p = 0.04). Mean cystine fragmentation was 15 +/- 3 mg for Er:YAG versus 9 +/- 1 for Ho:YAG (sapphire fiber, p = 0.0005). CONCLUSIONS Er:YAG lithotripsy is more efficient than Ho:YAG lithotripsy.

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.

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.

Free electron laser ablation of urinary calculi: an experimental study

Infrared laser ablation of urinary calculi was investigated as a function of wavelength to determine the relation of ablation threshold fluences, ablation depths, and optical absorption. A simple photothermal ablation model was employed to examine this relationship. Human urinary calculi composed of >95% uric acid, >95% cystine, >95% calcium oxalate monohydrate (COM), and >90% magnesium ammonium phosphate hexahydrate (MAPH) were used. Various wavelengths between 2.1 and 6.5 /spl mu/m were selected to perform threshold fluence and ablation depth measurements. The laser source for this study was the tunable pulsed infrared free electron laser (FEL) at Vanderbilt University. Experimental results indicated a correlation of threshold fluence and ablation depth to the optical absorption properties of the calculi. When calculus optical absorption increased, the threshold fluences decreased. Although the ablation depths increased with calculus optical absorption, results indicated that in certain calculi the ablation depth was affected by optical attenuation through the ablation plume. These observations were in agreement with the photothermal ablation model, but fractures in striated calculi at higher optical absorptions indicated the contribution of a photomechanical mechanism.

Dynamics of pulsed holmium:YAG laser photocoagulation of albumen.

The pulsed holmium:YAG laser (lambda = 2.12 microm, tau(p) = 250 micros) has been investigated as a method for inducing localized coagulation for medical procedures, yet the dynamics of this process are not well understood. In this study, photocoagulation of albumen (egg white) was analysed experimentally and results compared with optical-thermal simulations to investigate a rate process approach to thermal damage and the role of heat conduction and dynamic changes in absorption. The coagulation threshold was determined using probit analysis, and coagulum dynamics were documented with fast flash photography. The nonlinear computational model, which included a Beers law optical component, a finite difference heat transfer component and an Arrhenius equation-based damage calculation, was verified against data from the literature. Moderate discrepancies between simulation results and our experimental data probably resulted from the use of a laser beam with an irregular spatial profile. This profile produced a lower than expected coagulation threshold and an irregular damage distribution within a millisecond after laser onset. After 1 ms, heat conduction led to smoothing of the coagulum. Simulations indicated that dynamic changes in absorption led to a reduction in surface temperatures. The Arrhenius equation was shown to be effective for simulating transient albumen coagulation during pulsed holmium:YAG laser irradiation. Greater understanding of pulsed laser-tissue interactions may lead to improved treatment outcome and optimization of laser parameters for a variety of medical procedures.

Immunohistochemical evaluation of the heat shock response to nonablative fractional resurfacing

Despite the emergence of nonablative fractional resurfacing (NFR) as a new therapeutic modality for skin photoaging, little is known about the molecular events that underlie the heat shock response to different treatment parameters. Human subjects are treated with a scanned 1550-nm fractional laser at pulse energies spanning 6 to 40 mJ and a 140-μm spot size. The heat shock response is assessed immunohistochemically immediately through 7 days posttreatment. At the immediately posttreatment time point, we observe subepidermal clefting in most sections. The basal epidermis and dermal zones of sparing are both found to express HSP47, but not HSP72. By day 1, expression of HSP72 is detected throughout the epidermis, while that of HSP47 remains restricted to the basal layer. Both proteins are detected surrounding the dermal portion of the microscopic treatment zone (MTZ). This pattern of expression persists through day 7 post-NFR, although neither protein is found within the MTZ. Immediately posttreatment, the mean collagen denaturation zone width is 50 μm at 6 mJ, increasing to 202 μm at 40 mJ. The zone of cell death exceeds the denaturation zone by 19 to 55% over this pulse energy range. The two zones converge by day 7 posttreatment.