A series of experiments were conducted <i>in vivo</i> on porcine skin to determine the ED50 damage thresholds for 1214 nm continuous wave laser irradiation. These results provide new information for refinement of Maximum Permissible Exposure (MPE). The study employed exposure durations of 1 sec, 3 sec, and 10 seconds with nominal spot diameters of 6 mm, 8 mm and 10 mm and as a function of laser power. The effect of each irradiation was evaluated acutely, one hour after exposure, and 24 hours post exposure. Probit analysis was conducted to estimate the dose for 50% probability of laser-induced damage (ED50); Damage was defined as persistent redness at the site of irradiation for the pig skin after 24 hours. The results indicated that Maximum Permissible Exposure (MPE) limits should be lowered for the laser beam diameters larger than 6 mm.
Optical changes in skin blood flow due to the presence of glycerol were measured from a two-dimensional map of blood
flow in skin blood vessels with a dynamic imaging technique using laser speckle. In this study a dorsal skin-flap window
was implanted on the hamster skin with and without a hyper-osmotic agent i.e. glycerol. The hyper-osmotic drug was
delivered to the skin through the open dermal end of the window model. A two-dimensional map of blood flow in skin
blood vessels were obtained with very high spatial and temporal resolution by imaging the speckle pattern with a CCD
camera. Preliminary studies demonstrated that hyper-osmotic agents such as glycerol not only make tissue temporarily
translucent, but also reduce blood flow. The blood perfusion was measured every 3 minutes up to 36-60 minutes after
diffusion of anhydrous glycerol. Small capillaries blood flow reduced significantly within 3-9 minutes. Perfusion rate in
lager blood vessels i.e. all arteries and some veins decreased (speckle contrasts increased from 0.0115 to 0.384) over
time. However, the blood flow in some veins reduced significantly in 36 minutes. After 24 hours the blood perfusion
further reduced in capillaries. However, the blood flow increased in larger blood vessels in 24 hours compared to an hour
after application of glycerol. For further investigation the speckle contrast measurement were verified with color
Doppler optical coherence tomography.
To support refinement of the Maximum Permissible Exposure (MPE) safety limits, a series of experiments were
conducted in vivo on Dutch Belted rabbit corneas to determine corneal minimum visible lesion thresholds for 2.0 &mgr;m
continuous-wave laser irradiation. Single pulse radiant exposures were made at specified pulse durations of 0.1 sec, 0.25
sec, 0.5 sec, 1.0 sec, 2.0 sec and 4.0 seconds for spot 1/e<sup>2</sup> diameters of 1.17 mm and 4.02 mm. Lesions were placed in rows without overlap on rabbit cornea. The effect of each irradiation was evaluated within one minute post exposure
and the final determination of lesion formation was made using a slit lamp one hour post exposure. Threshold lesions
were defined as the presence of a superficial surface whitening one hour after irradiation. Probit analysis was conducted
to estimate the dose for 50% probability (ED50) of laser-induced damage. Approximately 20 different radiant exposures
were made for each exposure duration-spot size combination. At the threshold level, the diameters of barely visible
opaque white lesions were smaller than the Gaussian 1/e<sup>2</sup> beam diameter. In selected survival animals, most of the
threshold lesions were still visible 24 hours after exposure. The average lesion radius was approximately 0.4 ± 0.12 mm
diameter for the 1.17 mm spot size and 1.0 ± 0.20 mm diameter for the 4.02 mm spot size. The exposure duration
dependence of threshold average radiant exposure was described by an empirical power law equation: Threshold radiant
exposure[J/cm2] = a x exposure duration[s] <sup>b</sup>, experimentally derived coefficient <i>a</i> was 9.79 and <i>b</i> was 0.669 for the
1.17 mm spot diameter; values of <i>a</i> and <i>b</i> were 4.57 and 0.456 respectively for the 4.02 spot diameter. Based on the
experimental data and the empirical power law, the safety factors which were defined as threshold radiant exposure
divided by MPE values were predicted for the 2.0 &mgr;m wavelength at various exposure durations and spot diameters.
The minimum limit of the safety factor was approximately a factor of four for both 4.02 mm and 1.17 mm spot
diameters. Due to the very sharp boundary and small uncertainties of damage threshold determination, it is suggesting
that a factor of 4 "padding" is adequate and safety standard may not need to be changed.
The aim of this study was to determine the histopathologic effect on the skin of 2.0 &mgr;m wavelength laser with various
exposure conditions 48 hours after irradiation.
Histological sections of lesions were created at, below and beyond the threshold for grossly apparent thermal lesions.
These lesions were studied to 1)identify and define the microscopically apparent threshold lesions, 2)determine the
mechanisms producing the gross and microscopic threshold lesions in the skin, and 3)map the extent and severity of the
Grossly apparent threshold lesion were defined as persistent surface redness at 48 hours. Histologically, these lesions
showed relatively severe thermal damage in both the epidermis and the dermis. Damage included death and necrosis of
the epidermal cells and endothelial necrosis, intravascular thrombosis as well as perivascular edema and inflammation
in dermal blood vessels. The collagen bundles below the epidermis were slightly swollen but there was no change in
birefringence image intensity. For each threshold lesion, three quantitative parameters were measured to map the extent
of thermal damage: 1) the width of necrotic epidermis, 2) the depth measured from the epidermal/dermal junction to the
deepest extent of thrombosis, and 3) the depth measured from the epidermal/dermal junction to the deepest extent of
perivascular inflammation and edema. Birefringence change of dermal collagen which occurred at powers above
threshold was another measurable damage marker which indicated coagulation of collagen bundles.
These quantitative histopathologic data for skin damage associated with the transient temperature profiles and
irradiation parameters provided important information to mathematically derive rate process coefficients for thermal
damage and formulate mathematical tissue damage models for each cutaneous damage effect.
An optical-thermal-damage model of the skin under laser irradiation is developed by using finite-element modeling software (FEMLAB 3.1, Comsol, Incorporated, Burlington, Massachusetts). The general model simulates light propagation, heat generation, transient temperature response, and thermal damage produced by a radically symmetric laser beam of normal incidence. Predictions from the model are made of transient surface temperatures and the thermal damage on a pigskin surface generated by 2000-nm laser irradiation, and these predictions are compared to experimental measurements. The comparisons validate the model predictions, boundary conditions, and optical, thermal, and rate process parameters. The model enables the authors to verify the suitability of the American National Standards Institute (ANSI) maximum permissible exposure (MPE) standard for a wavelength of 2000 nm with exposure duration from 0.1 to 1 s and 3.5-mm beam diameter. Compared with the ANSI MPE standard, however, the MPE values predicted by the model are higher for exposure durations less than 0.1 s. The model indicates that it may be necessary to modify the ANSI MPE standard for cases in which the laser-beam diameter is larger than 3.5 mm when a “safety factor” of ten is used. A histopathological analysis of the skin damage is performed to determine the mechanisms of laser-induced damage in the skin.
We present a gentle mechanical method for the noninvasive transepidermal delivery of topically applied optical skin clearing agents. Optical skin clearing reduces light scattering in highly turbid skin with the aid of hyperosmotic chemicals such as glycerol, polyethylene glycol, and solutions of dextrose. Transepidermal delivery of such agents is believed to be most patient compliant and most likely to be used in a clinical environment. Optical skin clearing has the potential to expand the current limited use of laser light in medicine for diagnostic and therapeutic applications. Light scattering limits the penetration depth of collimated light into skin. In order to increase the diffusion of topically applied optical skin clearing agents into skin, we present a gentle mechanical delivery method involving glycerol and dextrose as optical skin clearing agents and fine 220-grit sandpaper to rub the clearing agent into the tissue. Gentle rubbing causes abrasion of the superficial skin layer including the stratum corneum, which otherwise prevents these optical skin clearing agents from freely diffusing into skin. Results indicate very fast optical skin clearing rates. In vivo hamster skin turned transparent within 2 min. The 1/e light penetration depth increased by 36±3.75% for dextrose and 43±8.24% for glycerol. Optical skin clearing was reversed using phosphate buffered saline solution. Skin viability was observed 70 h post-treatment and showed scabbing and erythema on a few percent of the total optically cleared skin surface.
With the advent of such systems as the airborne laser and advanced tactical laser, high-energy lasers that use 1315-nm wavelengths in the near-infrared band will soon present a new laser safety challenge to armed forces and civilian populations. Experiments in nonhuman primates using this wavelength have demonstrated a range of ocular injuries, including corneal, lenticular, and retinal lesions as a function of pulse duration. American National Standards Institute (ANSI) laser safety standards have traditionally been based on experimental data, and there is scant data for this wavelength. We are reporting minimum visible lesion (MVL) threshold measurements using a porcine skin model for two different pulse durations and spot sizes for this wavelength. We also compare our measurements to results from our model based on the heat transfer equation and rate process equation, together with actual temperature measurements on the skin surface using a high-speed infrared camera. Our MVL-ED50 thresholds for long pulses (350 µs) at 24-h postexposure are measured to be 99 and 83 Jcm–2 for spot sizes of 0.7 and 1.3 mm diam, respectively. Q-switched laser pulses of 50 ns have a lower threshold of 11 Jcm–2 for a 5-mm-diam top-hat laser pulse.
A series of experiments were conducted <i>in vivo</i> on female Yucatan mini-pigs to determine the ED<sub>50</sub> damage thresholds for 2000 nm continuous wave laser irradiation. These results provide new information for refinement of Maximum Permissible Exposure (MPE). The study employed Gaussian laser beam exposures with spot diameters (1/e<sup>2</sup>) of 4.83 mm, 9.65 mm and 14.65 mm and exposure durations of 0.25 s, 0.5 s, 1.0 s and 2.5 seconds as a function of laser power. The effect of each irradiation was evaluated within one minute after irradiation and the final determination was made at 48 hours post exposure. Probit analysis was conducted to estimate the dose for 50% probability of laser-induced damage (ED<sub>50</sub>) defined as persistent redness at the site of irradiation for the mini-pig skin after 48 hours. Histopathologic procedures were used to determine the mechanisms of the laser effects in the skin and map the extent and severity of the lesions. The thresholds study shows that consideration for lowering the current Maximum Permissible Exposure (MPE) limits should be explored as the laser beam diameter becomes larger than 3.5 mm. Based on the limited experimental data, the duration and size dependences of the ED<sub>50</sub> damage thresholds could be described by an empirical equation: (Equation available in manuscript.)