Possible mechanisms for an irregular vessel coagulation when long laser pulses are used in the treatment of port-wine stains.

The laser treatment of port-wine stains (PWS) has as a main aim the irreversible damage of ectatic vessels. Blood content of the subcutaneous venous plexus in PWS can be increased by a factor of seven or more, compared to that of the normal skin. The venous blood velocity ranges from 0.1-1 mm/s in capillaries to approximately 22 mm/s in larger vessels of about 300 microns in diameter. A PWS, selected for study, was irradiated with a multiline argon laser 488/515 nm wavelength, 1.5 W power, 200 ms pulse duration, 0.5 mm beam diameter and repetition frequency up to 5 Hz. Laser shots were placed adjacently in an area of 1 cm2. Using these parameters, in the case of dilated PWS vessels with an optical penetration depth and thermal diffusion length less than the diameter of the vessel, together with a transit time of blood across the irradiated spot less than the pulse duration, and estimating that during a pulsed laser emission of 200 ms, the blood has travelled a distance of 3-4 mm, there is a strong indication that hemodynamics during irradiation may influence the pattern of coagulation and agglutination. Thrombosis should occur in the case of small vessels and, in larger vessels, the coagulated blood will only partly fill the lumen. The structure developed in the vessel interior may also change continuously with time, as the coagulated material is progressively replaced by fibrotic tissue and the irregular agglutination pattern may be due to inhomogeneity in the absorbed optical energy.

Changes in optical properties of human whole blood in vitro due to slow heating.

Optical properties of human whole blood were investigated in vitro at 633 nm using a double integrating sphere set-up. The blood flow was maintained at a constant rate through a flow cell while continuously heating the blood at 0.2-1.1 degrees C/min from approximately 25 to 55 degrees C in a heat exchanger. A small, but rather abrupt decrease in the scattering asymmetry factor (g-factor) of 1.7 +/- 0.6% and a similar increase in the scattering coefficient of 2.9 +/- 0.6% were observed at approximately 45-46 degrees C yielding an increase in the reduced scattering coefficient of 40 +/- 10%. Furthermore, a continuous, manifest increase in the absorption coefficient was seen with increasing temperature, on average 80 +/- 70% from 25 to 50 degrees C. The effect of the heating on the blood cells was also studied under a white-light transmission microscope. A sudden change in the shape of the red blood cells, from discshaped to spherical, was observed at approximately the same temperature at which the distinct changes in g-factor and scattering coefficient were observed, i.e. at 45-46 degrees C. The results indicate that this shape transformation could explain the sudden change in scattering properties.

Optical absorption of blood depends on temperature during a 0.5 ms laser pulse at 586 nm.

Optical properties are important parameters in port wine stain laser treatment models. In this study we investigated whether changes in blood optical properties occur during a 0.5 ms laser pulse. Blood from three volunteers was irradiated in vitro with laser pulses (radiant exposure 2-12 J cm-2, wavelength 586 nm, pulse length 0.5 ms). Reflection and transmission coefficients, measured using double integrating spheres, decreased slightly during the first part of the pulse. At 2.9 J cm-2 radiant exposure, the reflectance increased, independent of total radiant exposure of the pulse. This was caused by blood coagulation. A second sudden increase in reflection and a significant increase in transmission occurred near 6.3 J cm-2 and was accompanied by a "popping" sound, indicating rapid expansion of bubbles due to blood vaporization. A multilayered model of blood was used to fit calculated transmission coefficient curves to the measurements and determine temperature-dependent optical blood absorption. Heat diffusion was shown to be of minor importance. A 2.5-fold increase in absorption for temperatures increasing from 20 to 100 degrees C, accurately describes transmission coefficients measured up to 2.9 J cm-2.

Wavelengths for port wine stain laser treatment: influence of vessel radius and skin anatomy.

Recent Monte Carlo computations in realistic port wine stain (PWS) models containing numerous uniformly distributed vessels suggest equal depth of vascular injury at wavelengths of 577 and 585 nm. This finding contradicts clinical experience and previous theory. From a skin model containing normal and PWS vessels in separate dermal layers, we estimate analytically the average volumetric heat production in the deepest targeted PWS vessel. The fluence rate distribution is approximated by Beer's law, which depends upon the tissue's effective attenuation coefficient, and includes a homogeneous fractional volumetric blood concentration corrected for finite-size blood vessels. The model predicts 585-587 nm wavelengths are optimal in adult PWSs containing at least one layer of small-radius blood vessels. In superficial PWSs, typically in young children with small-radius vessels, 577-580 nm wavelengths are optimal. Wavelength-independent results similar to those from Monte Carlo models are valid in single-layered PWSs of large-radius vessels. In conclusion, the volumetric heat production in the deepest targeted PWS blood vessel can be maximized on an individual patient basis. However, absorption of 585-587 nm wavelengths is sufficiently high in superficial lesions, so we hypothesize that these wavelengths may be considered adequate for the treatment of any PWS.

Modelling multiple laser pulses for port wine stain treatment.

Many port wine stains (PWS) are still resistant to pulsed dye laser treatment. However, anecdotal information suggests that multiple-pulse laser irradiation improves patient outcome. Our aims in this note are to explain the underlying mechanism and estimate the possible thermal effects of multiple pulses in vascular structures typical of PWS. Based on linear response theory, the linear combination of two thermal contributions is responsible for the total increase in temperature in laser irradiated blood vessels: direct light absorption by blood and direct bilateral thermal heat conduction from adjacent blood vessels. The latter contribution to the increase in temperature in the targeted vessel can be significant, particularly if some adjacent vessels are in close proximity, such as in cases of optical shielding of the targeted vessel, or if the vessels are relatively distant but many in number. We present evidence that multiple-pulse laser irradiation targets blood vessels that are optically shielded by other vessels. Therefore, it may be a means of enhancing PWS therapy for lesions that fail to respond to single-pulse dye laser treatment.

Modelling light distributions of homogeneous versus discrete absorbers in light irradiated turbid media.

Laser treatment of port wine stains has often been modelled assuming that blood is distributed homogeneously over the dermal volume, instead of enclosed within discrete vessels. The purpose of this paper is to analyse the consequences of this assumption. Due to strong light absorption by blood, fluence rate near the centre of the vessel is much lower than at the periphery. Red blood cells near the centre of the vessel therefore absorb less light than those at the periphery. Effectively, when distributed homogeneously over the dermis, fewer red blood cells would produce the same absorption as the actual number of red blood cells distributed in discrete vessels. We quantified this effect by defining a correction factor for the effective absorbing blood volume of a single vessel. For a dermis with multiple vessels, we used this factor to define an effective homogeneous blood concentration. This was used in Monte Carlo computations of the fluence rate in a homogeneous skin model, and compared with fluence rate distributions using discrete blood vessels with equal dermal blood concentration. For realistic values of skin parameters the homogeneous model with corrected blood concentration accurately represents fluence rates in the model with discrete blood vessels. In conclusion, the correction procedure simplifies the calculation of fluence rate distributions in turbid media with discrete absorbers. This will allow future Monte Carlo computations of, for example, colour perception and optimization of vascular damage by laser treatment of port wine stain models with realistic vessel anatomy.

Combining two excitation wavelengths for pulsed photothermal profiling of hypervascular lesions in human skin.

When pulsed photothermal radiometry (PPTR) is used for depth profiling of hypervascular lesions in human skin, melanin absorption also heats the most superficial skin layer (epidermis). Determination of lesion depth may be difficult when it lies close to the epidermal dermal junction, due to PPTR's limited spatial resolution. To overcome this problem, we have developed an approximation technique, which uses two excitation wavelengths (585 and 600 nm) to separate the vascular and epidermal components of the PPTR signal. This technique permits a noninvasive determination of lesion depth and epidermal thickness in vivo, even when the two layers are in close physical proximity to each other. Such information provides the physician with guidance in selecting the optimal parameters for laser therapy on an individual patient basis.

Non-invasive determination of port wine stain anatomy and physiology for optimal laser treatment strategies.

The treatment of port wine stains (PWSs) using a flashlamp-pumped pulsed dye laser is often performed using virtually identical irradiation parameters. Although encouraging clinical results have been reported, we propose that lasers will only reach their full potential provided treatment parameters match individual PWS anatomy and physiology. The purpose of this paper is to review the progress made on the technical development and clinical implementation of (i) infrared tomography (IRT), optical reflectance spectroscopy (ORS) and optical low-coherence reflectometry (OLCR) to obtain in vivo diagnostic data on individual PWS anatomy and physiology and (ii) models of light and heat propagation, predicting irreversible vascular injury in human skin, to select optimal laser wavelength, pulse duration, spot size and radiant exposure for complete PWS blanching in the fewest possible treatment sessions. Although non-invasive optical sensing techniques may provide significant diagnostic data, development of a realistic model will require a better understanding of relevant mechanisms for irreversible vascular injury.

Monoline argon laser (514 nm) treatment of benign pigmented lesions with long pulse lengths.

A dichroic filter was adjusted in order to make use of the green line of an argon laser for the treatment of pigmented lesions (actinic and senile lentigo, ephelis, café-au-lait marks and spilus nevus). Using a power of 1.5 W, a spot size of 0.5 mm and pulse lengths of 200 or 300 ms, satisfactory elimination of 620 pigmented cutaneous lesions was achieved. Although the pulse lengths used were much longer than the thermal relaxation time of the melanosomes, the histology after treatment showed little damage of adjacent structures. Good restoration of the epidermis and a return of normal pigmentation led to excellent cosmetic results, with few complications.

Simulation of color of port wine stain skin and its dependence on skin variables.

BACKGROUND AND OBJECTIVE: The understanding of why Port Wine Stain (PWS) skin is redder and darker as compared to normal skin has so far been based on qualitative analysis. This study aims at quantitatively analyzing the influence of skin anatomy variables on perceived skin color. STUDY DESIGN/MATERIALS AND METHODS: Reflectance spectra for visible light from normal and Port Wine Stain skin have been calculated using a Monte Carlo algorithm applied to a multi-layered skin model. Skin parameters that were varied are pigmentation, dermal scattering, dermal blood concentration, blood oxygenation, vessel diameter, and vessel depth. The CIE 1976 color system was used to interpret the resulting spectra as colors. RESULTS: A reduced dermal blood content results in a less red and lighter color. Distribution of a constant volume of blood in smaller vessels results in a redder and darker color. Skin with higher dermal scattering was calculated to be yellower and lighter and skin with increased epidermal pigmentation results in a yellower and darker color. CONCLUSIONS: Redness of PWS skin depends on both the concentration of dermal blood as well as on how it is distributed.

Modelling the assessment of port wine stain parameters from skin surface temperature following a diagnostic laser pulse.

BACKGROUND AND OBJECTIVE: Laser treatment of port wine stains (PWS) has become an established clinical modality over the past decade. However, in some cases full clearance of the PWS cannot be achieved. To improve the clinical results, it is necessary to match the laser treatment parameters to the PWS anatomy on an individual patient basis. Therefore, knowledge of the PWS structure is of great importance. The objective of this study is to describe a diagnostic method to assess the PWS blood vessels depth and diameter from the skin surface temperature-time course following a diagnostic laser pulse. STUDY DESIGN/MATERIALS AND METHODS: The Monte Carlo (MC) method was used to calculate the deposited laser energy into a port wine stain skin model following irradiation by a diagnostic laser pulse at 577 nm. The heat equation was solved numerically, using the deposited energy profile as the source term, yielding the temperature-time course at the skin surface. Subtraction of "bloodless" skin signal from that of the skin containing blood vessels gives us the net contribution of a heated dermal blood vessel to the skin surface temperature-time behaviour. RESULTS: The net blood vessel signal shows heat-diffusion behaviour and was found to be sensitive to the dermal blood vessel depth and diameter. The time delay for the peak signal temperature to occur depends quadratically on the blood vessel depth. The peak temperature relates linearly to the blood vessel diameter. The degree of epidermal melanin content can also be determined from the immediate temperature rise of the signal. CONCLUSION: The proposed method easily enables assessment of the blood vessel depth and diameter as well as the epidermal melanin content in a skin model. The method can be applied to a real PWS when using the adjacent normal skin as a reference.

Improving the results of facial dermal lesions elimination by laser.

Argon laser therapy of superficial pigmented lesions in both young and old people is associated with a risk of complications including delayed wound closure and hypo/hypertrophic scarring. Problems may also occur after treatment of lesions located on the eyelid. To minimize the risk of these problems coagulation of deep tissue should be avoided. We discuss a technique using mercurochrome, a red-colored compound that absorbs the blue and green lines of the argon laser, as a barrier for the irradiated light that eliminates these complications and we provide probable reasons for this technique's effectiveness.

Er:YAG laser skin resurfacing using repetitive long-pulse exposure and cryogen spray cooling: I. Histological study.

BACKGROUND AND OBJECTIVE: To evaluate histologically the characteristics of repetitive Er:YAG laser exposure of skin in combination with cryogen spray cooling (CSC), and its potential as a method of laser skin resurfacing. STUDY DESIGN/MATERIALS AND METHODS: Rat skin was irradiated in vivo with sequences of 10 Er:YAG laser pulses (repetition rate 20 Hz, pulse duration 150 or 550 micros, single-pulse fluence 1.3-5.2 J/cm(2)). In some examples, CSC was applied to reduce epidermal injury. Histologic evaluation was performed 1 hour, 1 day, 5 days, and 4 weeks post-irradiation. RESULTS: A sequence of ten 550-micros pulses with fluences around 2 J/cm(2) resulted in acute dermal collagen coagulation to a depth of approximately 250 microm, without complete epidermal ablation. CSC improved epidermal preservation, but also diminished the coagulation depth. Four weeks after irradiation, neo-collagen formation was observed to depths in excess of 100 microm. CONCLUSIONS: Dermal collagen coagulation and neo-collagen formation to depths similar to those observed after CO(2) laser resurfacing can be achieved without complete ablation of the epidermis by rapidly stacking long Er:YAG laser pulses. Application of CSC does not offer significant epidermal protection for a given dermal coagulation depth.

Er:YAG laser skin resurfacing using repetitive long-pulse exposure and cryogen spray cooling: II. Theoretical analysis.

BACKGROUND AND OBJECTIVE: To analyze the effects of laser pulse duration and cryogen spray cooling (CSC) on epidermal damage and depth of collagen coagulation in skin resurfacing with repetitive Er:YAG laser irradiation. STUDY DESIGN/MATERIALS AND METHODS: Evolution of temperature field in skin is calculated using a simple one-dimensional model of sub-ablative pulsed laser exposure and CSC. The model is solved numerically for laser pulse durations of 150 and 600 microsec, and 6 msec cryogen spurts delivered just prior to ("pre-cooling"), or during and after ("post-cooling") the 600 microsec laser pulse. RESULTS: The model indicates a minimal influence of pulse duration on the extent of thermal effect in dermis, but less epidermal damage with 600 microsec pulses as compared to 150 microsec at the same pulse fluence. Application of pre- or post-cooling reduces the peak surface temperature after laser exposure and accelerates its relaxation toward the base temperature to a different degree. However, the temperature profile in skin after 50 msec is in either example very similar to that after a lower-energy laser pulse without CSC. CONCLUSIONS: When applied in combination with repetitive Er:YAG laser exposure, CSC strongly affects the amount of heat available for dermal coagulation. As a result, CSC may not provide spatially selective epidermal protection in Er:YAG laser skin resurfacing.

Modeling the effect of wavelength on the pulsed dye laser treatment of port wine stains.

To determine the influence of wavelength on the depth of vascular injury in port wine stains following pulsed dye laser treatment, we calculated fluence rates at wavelengths varying from 415 to 590 nm in a two-layer Monte Carlo model representing the epidermis and the dermis. Calculations were made for four different volumetric fractions of blood in the dermis: 0%, 1%, 5%, and 10%. The depth of the selective vascular injury was determined to be the depth at which the rate of temperature rise at some point within the vessel just equals that at the epidermal-dermal junction. This was maximal between 577 and 590 nm with the maximum shifted toward 590 nm for a greater dermal blood content and for larger vessels. The effect of greater epidermal pigmentation was not only to reduce the depth of vascular injury but to shift slightly the wavelength of the maximum vascular injury to a shorter wavelength.

Light distributions in a port wine stain model containing multiple cylindrical and curved blood vessels.

BACKGROUND AND OBJECTIVES: Knowledge of the light distribution in skin tissue is important for the understanding, prediction, and improvement of the clinical results in laser treatment of port wine stains (PWS). The objective of this study is to improve modelling of PWS treated by laser using an improved and more realistic PWS model. STUDY DESIGN/MATERIALS AND METHODS: Light distributions are calculated by the Monte Carlo method for various PWS blood vessel configurations, such as single and multiple vessels oriented horizontally, curved vessels, and "vertically" oriented vessels. Various vessel sizes and wavelengths are used. RESULTS: Our modelling confirms the concept of selective photothermolysis; 577nm laser light gives maximal deposited energy at the top side of the blood vessels closest to the skin surface and 585nm gives a more uniform energy distribution in the vessel. In the distribution of deposited energy multiple vessels mutually influence each other, because of "shadowing" of diffuse light. CONCLUSION: Modelling PWS laser treatments with multiple vessels confirms the need for successive treatments of vessels layer by layer. The use of different wavelengths affects the local deposited energy profiles in the blood vessels. It predicts that the significance of 585nm laser light lies in the uniform energy distribution in the vessels rather than in gain in energy deposition with depth. The calculated light distributions provide a more realistic input for modelling thermal damage effects in PWS laser treatment and modelling of the epidermal response in thermal imaging of the PWS blood vessel structure.

Optimal cryogen spray cooling parameters for pulsed laser treatment of port wine stains.

BACKGROUND AND OBJECTIVE: In dermatologic laser therapy, cryogen spray cooling (CSC) is a means to protect the epidermis while leaving dermal structures susceptible to thermal damage. The purpose of this study was to determine optimal spurt duration, tau(s), and optimal delay, tau(d), between the cryogen spurt and laser pulse when using CSC in treatment of port wine stain birthmarks. STUDY DESIGN/MATERIALS AND METHODS: A finite difference method is used to compute temperature distributions in human skin in response to CSC. Optimal tau(s) and tau(d) are determined by maximizing the temperature difference between a modeled basal layer and an imaginary target chromophore. RESULTS: The model predicts an optimal tau(s) of 170-300 msec and approximately 400 msec for shallow (150 microm) and deeper (400 microm) targets, respectively. Spraying for longer than the optimal tau(s) does not critically impair cooling selectivity. For a spurt duration of 100 msec, optimal delays are 5-10 msec and 25-70 msec for a shallow and deep basal layer, respectively. CONCLUSION: In the absence of knowledge about the lesion anatomy, using a tau(s) of 100-200 msec and no delay is a good compromise. A delay is justified only when basal layer and target chromophore are relatively deep and the optimal spurt duration cannot be applied, e.g., to avoid frostbite.

Laser pulse impact on rat mesenteric blood vessels in relation to laser treatment of port wine stain.

BACKGROUND AND OBJECTIVE: To study the impact of laser pulses on animal microvasculature as a model for laser treatment of port wine stains. STUDY DESIGN/MATERIALS AND METHODS: Rat mesenteric blood vessels were irradiated with a laser pulse (585 nm, 0.2-0.6 ms pulse duration, 0.5-30 J/cm(2) radiant exposure). Video microscopy was used to assess vessel dilation, formation of intravascular thrombi, bubble formation, and vessel rupture. Changes in reflection during a laser pulse were measured by simultaneously recording the temporal behavior of the incident and reflected signals. RESULTS: A threshold radiant exposure of approximately 3 J/cm(2) was found for changes in optical properties of blood in vivo, confirming previous in vitro results. Often, laser exposure induced a significant increase in vessel diameter, up to three times the initial diameter for venules and four times for arterioles, within 200 ms after laser exposure. Arterioles were more likely to dilate than venules. Sometimes, immediately after the pulse, round structures, interpreted as being gas bubbles, were seen within the vessel lumen. CONCLUSIONS: A variety of phenomena can occur when blood vessels of sizes comparable to those in port wine stains are irradiated with laser pulses as used in port wine stain treatment. Thrombus formation and vessel rupture have been described before from histological sections of laser-irradiated port wine stains. However, vessel dilation and formation of non-transient gas bubbles as found in this study have not been described before.