Port Wine Stain Skin Research Articles

Hand‐held pulsed photothermal radiometry system to estimate epidermal temperature rise during laser therapy

During laser therapy of port wine stain (PWS) birthmarks in human skin, measurement of the epidermal temperature rise (DeltaT(epi)) is important to determine the maximal permissible light dose. In order to measure DeltaT(epi) on a specific PWS skin site, we developed an AC-coupled hand-held pulsed photothermal radiometry (PPTR) system, which overcomes the in vivo measurement limitations of bench-top systems. The developed hand-held PPTR system consists of an infrared (IR) lens, AC-coupled thermoelectrically cooled IR detector, laser hand-piece holder, and positioning aperture. The raw AC-coupled signal was integrated to obtain a higher signal-to-noise ratio (SNR). The experimental temperature difference (DeltaT) calibration was compared with theoretical computations. In vitro and in vivo measurements of DeltaT were performed with a tissue phantom as a function of radiant exposure and human subject as a function of melanin concentration, respectively. The integrated AC-coupled signal provided higher SNR as compared with the raw AC-coupled signal. The experimental DeltaT calibration resulted in good agreements with the theoretical results. The in vitro and in vivo results also presented good agreements with theory. A fiber-free, hand-held AC-coupled PPTR system is capable of accurate epidermis temperature rise (DeltaT(epi)) measurements of human skin during pulsed laser exposure.

Sturge-Weber Syndrome: Altered Blood Vessel Fibronectin Expression and Morphology

Sturge-Weber syndrome presents with vascular malformations of the brain, skin, and eye. Fibronectin has potent effects on angiogenesis, vessel remodeling, and vessel innervation density. To determine fibronectin expression in the blood vessels of Sturge-Weber syndrome brain and skin tissue and to quantify the density and circumference of Sturge-Weber syndrome blood vessels by type compared with controls, we performed in situ hybridization for fibronectin messenger ribonucleic acid (RNA) expression on six Sturge-Weber syndrome cortical brain samples, six epilepsy brain samples, skin from two port-wine stain skin lesions, and two normal skin samples from two subjects with Sturge-Weber syndrome. Fibronectin messenger RNA was expressed in blood vessels and endothelial cells in the parenchyma of both Sturge-Weber syndrome and control brain tissues and in skin samples. Fibronectin expression was significantly reduced by 23% in the Sturge-Weber syndrome meningeal vessels compared with the epilepsy controls (P < .01). Fibronectin expression was significantly increased by 19% in the Sturge-Weber syndrome parenchymal vessels compared with the epilepsy controls (P < .05). No difference was found in the expression of fibronectin in port-wine stain skin blood vessels. The density of leptomeningeal blood vessels in the Sturge-Weber syndrome brain tissue samples was 45% greater than in the epilepsy samples (P < .05). Blood vessel circumference was significantly decreased in the Sturge-Weber syndrome meningeal vessels compared with the controls (27%; P < .05). When blood vessels from different brain regions were compared, fibronectin expression was decreased in Sturge-Weber syndrome meningeal vessels and was increased in the parenchymal vessels. Altered blood vessel fibronectin expression in Sturge-Weber syndrome could contribute to abnormal vascular structure and function in this disorder.

Effects of hypobaric pressure on human skin: Feasibility study for port wine stain laser therapy (Part I)

Since the development of laser-induced photothermolysis for the therapy of port wine stain (PWS) birthmarks, clinical results have shown that dark purple lesions usually respond well to the first three to five treatments. However, for most PWS, complete blanching is never achieved, and the lesion stabilizes at a red-pink color. The aim of this feasibility study is to demonstrate that with the aid of a local vacuum applied to the lesion site prior to laser exposure, photocoagulation of the smaller PWS blood vessels may be successfully achieved. Suction cups were designed to fit onto the hand pieces of commercial laser devices used for PWS laser therapy. One subject with normal skin and another with PWS skin were recruited for this study. Laser pulses of various fluences were applied at atmospheric pressure or shortly after (5-15 seconds) hypobaric pressures (17-51 kPa) were placed as test sites on the forearm of both subjects. The laser-induced purpura at the test sites was documented over the course of 1 week on both subjects and the resulting PWS blanching was optically quantified by visible reflectance spectrometry 7 months after therapy. For the subject with normal skin, the laser fluence needed with hypobaric pressure (51 kPa) to induce similar purpura intensity to that observed with atmospheric pressure was approximately 35% lower. For PWS skin, all suction application times (5-15 seconds) and hypobaric pressures (17-51 kPa) resulted in more intense purpura and the PWS blanching 7 months after treatment was clinically significant for test sites treated with hypobaric pressures ranging from 17 to 34 kPa. The temporary and controlled dilation of the targeted blood vessels achieved with a local vacuum can significantly reduce the "small-vessel-limitation" in the treatment of PWS without increasing the risk of epidermal damage.

Use of erythema index imaging for systematic analysis of port wine stain skin response to laser therapy

Quantitative methods to assess port wine stain (PWS) skin response to laser therapy are needed to improve therapeutic outcome. In this study, PWS skin erythema was analyzed using erythema index difference (DeltaEI: erythema index difference between PWS and normal skin) images before and after treatment to investigate systematically subject-dependent response to laser therapy. Cross-polarized digital skin color images were acquired from 17 subjects with facial PWS and the associated DeltaEI images were computed. Qualitative and quantitative analyses of PWS skin erythema were performed with DeltaEI images, in which ranges of 40-6 and 5-0 represented PWS and normal skin, respectively. After laser therapy, we qualitatively observed a reduction in the DeltaEI values for all subjects. Regression fitting of DeltaEI values before and after PWS laser therapy was associated with strong positive linear correlation. The imaging modality and analysis method allowed systematic analysis of PWS skin erythema in response to laser therapy. PWS skin response was dependent on pretreatment DeltaEI values, suggesting that erythema can be utilized as an effective parameter to monitor PWS response to laser therapy.

Combined photodynamic and photothermal induced injury enhances damage to in vivo model blood vessels.

The degree of port wine stain (PWS) blanching following pulsed dye laser (PDL) therapy remains variable and unpredictable. Because of the limitations of current PDL therapy, alternative treatment approaches should be explored. The objective was to evaluate a novel methodology for selective vascular damage, combined photodynamic (PDT) and photothermal (PDL) treatment, using the in vivo chick chorioallantoic membrane (CAM) model. Thirty microliters of benzoporphyrin derivative monoacid ring A (BPD) solution was administered intraperitoneally into chick embryos at day 12 of development. Study groups were: (1) control (no BPD, no light); (2) BPD alone; (3) continuous wave irradiation (CW) alone (576 nm, 60 mW/cm2, 125 seconds); (4) CW + PDL; (5) BPD+PDL; (6) PDT (BPD+CW); (7) PDL alone (585 nm, 4 J/cm(2)); and (8) PDT+PDL (BPD + CW followed immediately by PDL). Vessels were videotaped prior to, and at 1 hour post-intervention and then assessed for damage based on the following scale: 0, no damage; 1, coagulation; 1.5, vasoconstriction; 2.0, coagulation+vasoconstriction; 2.5, angiostasis; 3.0, hemorrhage. Damage scores were weighted by vessel "order." PDT + PDL resulted in significantly (P < 0.01) more severe vascular damage than was observed in any other study group: 127% more than PDT, 47% more than PDL alone. PDT + PDL is a novel and promising approach for selective vascular damage and may offer a more effective method for treatment of PWS and other vascular skin lesions.

Characterization of port wine stain skin erythema and melanin content using cross-polarized diffuse reflectance imaging.

Objective methods to assess quantitatively port wine stain (PWS) blanching in response to laser therapy are needed to improve laser therapeutic outcome. Previous studies have attempted to assess objectively PWS color based on point measurement devices. To date, these approaches have typically been limited by a number of factors such as small test area and need for contact. To address these issues, a cross-polarized diffuse reflectance imaging system and color image analysis method has been developed to evaluate quantitatively erythema and melanin content in PWS skin. A cross-polarized diffuse reflectance system has been constructed to acquire high resolution digital images while minimizing artifacts such as glare, shadowing, and nonuniform illumination effects that can compromise image fidelity. Furthermore, an image analysis algorithm has also been developed to analyze normal and PWS skin in terms of CIEL*a*b* color space parameters. Using the algorithm, images of color space intensity, L*, and saturation, a*, indices have been calculated to extract quantitative metrics of melanin and erythema, respectively. Compared to the cross-polarized diffuse reflectance image, the a* index image enhanced the contrast in regions of high and low erythema and seems to have quasi correlation with the L* index image. In the presented PWS patient example, the relative a* index difference (Deltaa*) image showed less erythema in PWS skin after laser treatment when compared to pre-treatment values. Our cross-polarized imaging system and color image analysis method is a simple, noncontact technique that can indirectly provide quantitative measurement of erythema and melanin content in PWS skin.

Increase of dermal blood volume fraction reduces the threshold for laser-induced purpura: implications for port wine stain laser treatment.

The average success rate in achieving total blanching of port wine stain (PWS) lesions treated with laser-induced selective photothermolysis is below 25%, even after multiple treatments. This is because smaller diameter (5-20 microm) PWS blood vessels are difficult to destroy with selective photothermolysis since the volumetric heat generated by absorption of laser light is insufficient to adequately heat the entire vessel wall. The aim of this study was to investigate a potential technique for more efficient photocoagulation of small diameter PWS blood vessels in PWS that respond poorly to selective photothermolysis. The blood volume fraction (BVF) in the upper dermis of the forearm of human volunteers was increased by placing an inflated blood pressure cuff on the upper arm. Applied pressures were in the range of 80-100 mm Hg for up to 5 minutes. The increased BVF was determined by matching reflectance spectra measured with that computed using a diffusion model. The impact of increased BVF on purpura formation induced by a 0.45 milliseconds pulsed dye laser (PDL) at 585 nm wavelength was investigated in normal and in PWS skin. In the presence of a 100 mm Hg pressure cuff, the BVF, as determined from the diffusion model, increased by a factor of 3 in the forearm and by 6 in the hand. Increasing BVF by a factor of 3 corresponds to an increase in blood vessel diameters by a factor of radical 3 approximately 1.7. BVF increased at 1-3 minutes after application of the pressure cuff, remained constant at 3-5 minutes, and returned to baseline values at 3 minutes after removal of the pressure cuff. Approximately 40% less radiant exposure was needed to induce the same amount of purpura after PDL irradiation when the blood pressure cuff was used. Applying an 80 mm Hg pressure cuff reduced the required radiant exposure for purpura formation by 30%. Heating of blood vessels was calculated as a function of vessel diameter and of radiant exposure (at 585 nm and at 0.5 and 1.5 milliseconds pulse duration). Enlarging the vessel lumen, for example, by obstructing venous return, can significantly reduce the "small-vessel-limitation" in PDL treatment of PWS. Dilation of PWS blood vessels enables a more efficient destruction of smaller vessels without increasing the probability of epidermal damage.

In vivo port-wine stain depth determination with a photoacoustic probe.

We have designed a photoacoustic probe for port-wine stain (PWS) depth measurements consisting of optical fibers for laser light delivery and a piezoelectric element for acoustic detection. We characterized the capabilities and limitations of the probe for profiling PWS skin. The probe induced and measured photoacoustic waves in acrylamide tissue phantoms and PWS skin in vivo. The optical properties of the phantoms were chosen to mimic those of PWS skin. We denoised acoustic waves using spline wavelet transforms, then deconvolved with the impulse response of the probe to yield initial subsurface pressure distributions in phantoms and PWS skin. Using the phantoms, we determined that the limit in resolving epidermal and PWS layers was less than 70 microm. In addition, we used the phantoms to determine that the maximum epidermal melanin concentration that allowed detection of PWS was between 13 and 20%. In vivo measurements of PWS skin with different epidermal melanin concentrations correlated with the phantoms. Thus the photoacoustic probe can be used to determine PWS depth for most patients receiving laser therapy.

Cryogen spray cooling efficiency: improvement of port wine stain laser therapy through multiple-intermittent cryogen spurts and laser pulses.

Cryogen spray cooling (CSC) is used to minimize the risk of epidermal damage during laser treatment of port wine stain (PWS) birthmarks. Unfortunately, CSC may not provide the necessary protection for patients with high concentrations of epidermal melanin. The objectives of this study are to: (1) provide a definition of cooling efficiency (eta) based on the amount of heat removed per unit area of skin for a given cooling time; (2) using this definition, establish the eta of previously reported spray nozzles; (3) identify the maximum benefit expected in PWS laser therapy based solely on improvement of eta; and (4) study the feasibility of using multiple-intermittent cryogen spurts and laser pulses to improve PWS laser therapy. A theoretical definition to quantify eta is introduced. Subsequently, finite difference heat diffusion and Monte Carlo light distribution models are used to study the spatial and temporal temperature distributions in PWS skin considering: (1) the current approach to PWS laser therapy consisting of a single cryogen spurt followed by a single pulsed dye laser exposure (SCS-SLP approach); and (2) multiple cryogen spurts and laser pulses (MCS-MLP approach). At the same time, an Arrhenius-type kinetic model is used to compute the epidermal and PWS thermal damages (Omega(E) and Omega(PWS), respectively) for a high epidermal melanin concentration (20%), corresponding to skin types V-VI. The eta corresponding to a wide range of heat transfer coefficients (h) is quantified. For reported CSC nozzle devices eta varies from 40 to 98%. Using the SCS-SLP approach, it is shown that even eta = 100% cannot prevent excessive Omega(E) for a skin types V-VI. In contrast, the MCS-MLP approach provides adequate epidermal protection while permitting PWS photocoagulation for the same skin types. The new proposed definition allows to compute the cooling efficiency of CSC nozzle devices. Computer models have been developed and used to show that the SCS-SLP approach will not provide adequate epidermal protection for darker skin patients (skin types V-VI), even for eta = 100%. In contrast, the MCS-MLP approach may be a viable solution to improve PWS laser therapy for darker skin patients.

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

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. 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. 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. Redness of PWS skin depends on both the concentration of dermal blood as well as on how it is distributed.

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

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

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

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

Estimation of internal skin temperatures in response to cryogen spray cooling: implications for laser therapy of port wine stains

In many port wine stain (PWS) patients, successful clearing is not achieved even after multiple laser treatments because of inadequate heat generation within the targeted blood vessels. Use of higher radiant exposures has been suggested to improve lesion clearing, but risk of epidermal injury due to nonspecific absorption by melanin increases. It has been demonstrated that cryogen spray cooling (CSC) can protect the epidermis from nonspecific thermal injury during laser treatment of PWS. Inasmuch as epidermal melanin concentration and blood vessel depth vary among patients, evaluation of internal skin temperatures in response to CSC is essential for further development and optimization of treatment parameters on an individual patient basis. We present internal temperature measurements in an epoxy resin phantom in response to CSC and use the results in conjunction with a mathematical model to predict the temperature distribution within human skin for various cooling parameters. Measurements on the epoxy resin phantom show that cryogen film temperature is well below the cryogen boiling point, but a poor thermal contact exists at the cryogen-phantom interface. Based on phantom measurements and model predictions, internal skin temperature reduction remains confined to the upper 400 /spl mu/m for spurt durations as long as 200 ms. At the end of a 100 ms spurt, our results show a 31/spl deg/C temperature reduction at the surface, 12/spl deg/C at a depth of 100 /spl mu/m, and 4/spl deg/C at a depth of 200 /spl mu/m in human skin. Analysis of estimated temperature distributions in response to CSC and temperature profiles obtained by pulsed photothermal radiometry indicates that a significant protective effect is achieved at the surface of laser irradiated PWS skin. Protection of the epidermal basal layer, however, poses a greater challenge when high radiant exposures are used.

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

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. 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. 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. 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.

Laser energy threshold for thermal vascular injury in a port-wine stain skin model

Monte Carlo simulation of laser energy deposition in a port-wine stain (PWS) skin model and numerical solution of the thermal diffusion equation have been used to calculate threshold energies for thermal injury of PWS blood vessels for different vessel sizes and laser pulse durations. It has been assumed that an average vessel temperature rise of 65 ‡C causes thermal injury to the blood vessel. The result is that for a certain combination of wavelength, pulse duration and incident energy density, only a limited range of blood vessel sizes can be injured optimally. Higher energy densities are required to injure smaller vessels with the same pulse duration, spot size and wavelength. This gives support to the mechanisms of selective photothermolysis suggested previously by Anderson and Parrish, although their model was based on the cooling behaviour of instantaneously heated vessels. The authors hypothesize that different laser parameter settings that match the individual PWS vessel anatomy during treatment will be used in the future, instead of many treatments with the same laser parameters. This could lead to less treatment sessions and to an improved predictability of clinical results.

Modeling the color perception of port wine stains and its relation to the depth of laser coagulated blood vessels.

To find the maximal depth of an ecstatic vessel in the dermis that contributes to the abnormal color of a port wine stain (PWS), "normal" and "laser treated PWS skin" are modeled, respectively, as a two-layer plane parallel geometry consisting of an epidermis and a dermis, and as a three-layer geometry consisting of an epidermis, a dermis without additional blood (the "treated" part of the stain, assumed identical to the "normal" dermis), and a layer of dermis containing 5% or 10% of blood per volume (the untreated part of the PWS). Spectral remittances were calculated for various wavelengths using the diffusion approximation to the transport equation for light propagation. These remittances were transformed into the CIE 1976 (L*a*b*)-color system. Color differences between "normal" and PWS skin as a function of the dermal depth of "injured" ecstatic blood vessels were calculated. The maximal depth where ecstatic blood vessels just contribute to the abnormal PWS color is predicted as 0.9 mm for a "normally" pigmented epidermis (60 microns thick) and a 5% or 10% blood per volume content. For a darker pigmented epidermis (60 microns thickness) and again at both 5% and 10% blood per volume content, this depth was found to be 0.8 mm.

Comparative Histochemistry of Port-Wine Stains After Copper Vapor Laser (578 nm) and Argon Laser Treatment

The present study compared the histologic changes occurring 15 min after copper vapor laser (CVL; operating at 578 nm) and argon laser (488/514 nm) treatment of port-wine stains (PWS) over a range of energy densities (8-32 J/cm2) with corresponding pulse widths of 50-200 ms. Frozen tissue sections were stained with nitroblue tetrazolium chloride (NBTC). This histochemical method permits an accurate color differentiation between blue-stained viable and unstained thermally damaged cells. At 8, 10, and 12 J/cm2 the argon-laser injury was confined to epidermal cell layers; none to superficial dermal effects were found. Fluences of at least 15 J/cm2 produced a diffuse NBTC-negative coagulation necrosis. Exposure of PWS skin to 8-12 J/cm2 at 578 nm did not alter the integrity of epidermal cells. In the dermis, damage was confined to blood vessels and surrounding collagen, showing a clear demarcation from adjacent viable structures. The maximum penetration depth achieved with these vessel selective energy densities was 0.44 mm. At 15 J/cm2, besides vascular injury, damage to the basal cell layer also occurred. At fluences of 17-20 J/cm2 a diffuse necrosis similar to that induced by the argon laser was found. Vessel selectivity of the 578 nm wave band was achieved with pulse widths from 50-74 ms, exceeding the estimated "ideal" exposure time (0.1-10.0 ms) for a vascular selective laser effect. The NBTC method allowed identification of subtle laser-induced tissue changes providing accurate quantitative data relating to the extent of vascular injury.

Tunable Dye Laserによる単純性血管腫の治療

For port-wine stains (PWS), argon laser treatment is now generally accepted as the treatment of choice, but hypertrophic scarring remains a serious side-effect.The tunable dye laser ( 577 nm ) has been shown to cause selective vascular destruction in PWS skin. We have treated ninety patients of PWS using a tunable dye laser (577nm, 500μs ec) without any evidence of hypertrophic scarring. This treatment requiered no anesthesia or wound care. It did not requier a special surgicar art. The laser beam was magnified to a 5mm-diameter spot size on the skin.It appeared that tunable dye laser was very useful in the treatment of PWS.

Tunable dye laser (577 nm) treatment of port wine stains.

Despite steady improvement in the laser treatment of port wine stains (PWS), hypertrophic scarring remains a serious side-effect in approximately 10% of patients. The tunable dye laser (577 nm) has been shown to cause selective vascular destruction in normal and PWS skin. We have treated ten patients using a tunable dye laser (577 nm, 300 mu sec) resulting in clearing of the PWS without any evidence of hypertrophic scarring. Treatment requires no anesthesia or wound care, and there were no postoperative infections.

色素レーザー装置による照射後の鶏冠および単純血管しゅの組織変化

レーザー照射による単純血管腫の治療は, 選択的に血管だけを破壊することができず, 照射後の再発と皮膚表面の瘢痕の問題があるため, いまだ本治療だけで血管腫を完治させるまでにはいたつていない。そこでわれわれは従来使われてきたアルゴンレーザー装置のかわりに色素レーザー装置を用いて鶏の鶏冠および単純血管腫への照射を行い, 経時的に組織変化を観察した。色素レーザー装置は励起する色素の種類を変えることにより任意の波長を発振することができ, 0.7μsというきわめて短い時間のパルス発振方式である。そこで装置の発振波長を色素ローダミン575を用いることにより, 赤血球の最大吸収波長である575nmに同調させ鶏冠および単純血管腫への照射を行つてみた。組織学的には鶏冠の場合, 表在性の豊富な血管組織にレーザー光がほとんど吸収されるため均一な同部位の凝固変動が見られたが, 単純血管腫への照射では出力を変えることにより, 血管周囲の正常組織の変性を最小限にとどめて血管のみの選択的破壊変性が起るのが観察された。