Port Wine Stain Blood Vessels Research Articles

In Vivo Assessment of Thermosensitive Liposomes for the Treatment of Port Wine Stains by Antifibrinolytic Site-Specific Pharmaco-Laser Therapy.

Antifibrinolytic site-specific pharmaco-laser therapy (SSPLT) is an experimental treatment modality for refractory port wine stains (PWS). Conceptually, antifibrinolytic drugs encapsulated in thermosensitive liposomes are delivered to thrombi that form in semi-photocoagulated PWS blood vessels after conventional laser treatment. Local release of antifibrinolytics is induced by mild hyperthermia, resulting in hyperthrombosis and complete occlusion of the target blood vessel (clinical endpoint). In this study, 20 thermosensitive liposomal formulations containing tranexamic acid (TA) were assayed for physicochemical properties, TA:lipid ratio, encapsulation efficiency, and endovesicular TA concentration. Two candidate formulations (DPPC:DSPE-PEG, DPPC:MPPC:DSPE-PEG) were selected based on optimal properties and analyzed for heat-induced TA release at body temperature (T), phase transition temperature (Tm), and at T > Tm. The effect of plasma on liposomal stability at 37 °C was determined, and the association of liposomes with platelets was examined by flow cytometry. The accumulation of PEGylated phosphocholine liposomes in laser-induced thrombi was investigated in a hamster dorsal skinfold model and intravital fluorescence microscopy. Both formulations did not release TA at 37 °C. Near-complete TA release was achieved at Tm within 2.0–2.5 min of heating, which was accelerated at T > Tm. Plasma exerted a stabilizing effect on both formulations. Liposomes showed mild association with platelets. Despite positive in vitro results, fluorescently labeled liposomes did not sufficiently accumulate in laser-induced thrombi in hamsters to warrant their use in antifibrinolytic SSPLT, which can be solved by coupling thrombus-targeting ligands to the liposomes.

The influence of morphological distribution of melanin on parameter selection in laser thermotherapy for vascular skin diseases.

Port wine stains (PWSs) are congenital vascular malformations that progressively darken and thicken with age. Currently, laser therapy is the most effective way in clinical management of PWS. It is known that skin pigmentation (melanin content) affects the radiant exposure that can be safely applied to treat PWS. However, the effect of melanin distribution in the epidermis on the maximum safe radiant exposure has not been studied previously. In this study, 10 different morphological distributions of melanin were proposed according to the formation and migration characteristics of melanin, and the two-scale heat transfer model was employed to investigate the influence of melanin distribution on the threshold radiant exposure of epidermis and blood vessels. The results show that melanin distributions do have a strong effect on laser parameter selection. When uniform melanin distribution is assumed, the threshold radiant exposure to damage a typical PWS blood vessel (50μm diameter) is 8.62J/cm2 lower than that to injure epidermis. The optimal pulse duration is 1-5ms for a typical PWS blood vessel of 50μm when melanin distribution is taken into consideration. PWS blood vessels covered by non-uniformly distributed melanin are more likely to have poor response to laser treatment.

Characterization of Laser-Resistant Port Wine Stain Blood Vessels Using In Vivo Reflectance Confocal Microscopy.

Port wine stain (PWS) is a congenital vascular malformation of the human skin. Laser is the treatment of choice for PWS. Laser-resistant PWS is one crucial factor accounting for inadequate treatment outcome, which needs to be fully characterized. This study aims to quantitatively characterize the morphology of laser-resistant PWS blood vessels in the upper papillary dermis using in vivo reflectance confocal microscopy (RCM). A total of 42 PWS subjects receiving laser treatment from August 2016 through July 2018 were enrolled into this study. Thirty-three subjects had facial PWS; nine had extremity PWS. All subject's PWS received multiplex 585/1,064 nm laser treatment. RCM images were taken before and after treatment. The density, diameter, blood flow, and depth of PWS blood vessels were analyzed. We found 44.4% PWS on the extremities (four out of nine subjects) were laser-resistant, which was significantly higher (P < 0.001) when compared with those PWS on the face (15.2%, 5 out of 33 subjects). The laser-resistant facial PWS blood vessels had significantly higher blood flow (1.35 ± 0.26 U vs. 0.89 ± 0.22 U, P < 0.001), larger blood vessel diameters (109.60 ± 18.24 µm vs. 84.36 ± 24.04 µm, P = 0.033) and were located deeper in the skin (106.01 ± 13.87 µm vs. 87.82 ± 12.57 µm, P < 0.001) in the skin when compared with laser-responsive PWS on the face. The average PWS blood vessel density (17.01 ± 4.63/mm2 vs. 16.61 ± 4.44/mm2 , P = 0.857) was not correlated to the laser resistance. Laser-resistant PWS blood vessels had significantly higher blood flow, larger diameters, and were located deeper in the skin. RCM can be a valuable tool for a prognostic evaluation on laser-resistant lesions before treatment, thereby providing guidance for tailored laser treatment protocols, which may improve the therapeutic outcome. The limitations for this study include relative small sample size and acquisitions of different blood vessels before and after 2 months of treatment. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.

Photothermal treatment of port-wine stains using erythrocyte-derived particles doped with indocyanine green: a theoretical study.

.Pulsed dye laser irradiation in the wavelength range of 585 to 600 nm is currently the gold standard for treatment of port-wine stains (PWSs). However, this treatment method is often ineffective for deeply seated blood vessels and in individuals with moderate to heavy pigmentation. Use of optical particles doped with the FDA-approved near-infrared (NIR) absorber, indocyanine green (ICG), can potentially provide an effective method to overcome these limitations. Herein, we theoretically investigate the effectiveness of particles derived from erythrocytes, which contain ICG, in mediating photothermal destruction of PWS blood vessels. We refer to these particles as NIR erythrocyte-derived transducers (NETs). Our theoretical model consists of a Monte Carlo algorithm to estimate the volumetric energy deposition, a finite elements approach to solve the heat diffusion equation, and a damage integral based on an Arrhenius relationship to quantify tissue damage. The model geometries include simulated PWS blood vessels as well as actual human PWS blood vessels plexus obtained by the optical coherence tomography. Our simulation results indicate that blood vessels containing micron- or nano-sized NETs and irradiated at 755 nm have higher levels of photothermal damage as compared to blood vessels without NETs irradiated at 585 nm. Blood vessels containing micron-sized NETs also showed higher photothermal damage than blood vessels containing nano-sized NETs. The theoretical model presented can be used in guiding the fabrication of NETs with patient-specific optical properties to allow for personalized treatment based on the depth and size of blood vessels as well as the pigmentation of the individual’s skin.

Membrane trafficking and exocytosis are upregulated in port wine stain blood vessels.

Port wine stain (PWS) is characterized as a progressive dilatation of immature venule-like vasculatures which result from differentiation-impaired endothelial cells. In this study, we aimed to identify the major biological pathways accounting for the pathogenesis of PWS. Sequential windowed acquisition of all theoretical fragment ion mass spectra (SWATH-MS) was used to identify differentially expressed proteins in PWS lesions, followed by confirmative studies with immunohistochemistry, immunoblot and transmission electron microscopy (TEM). 107 out of 299 identified proteins showed differential expressions in PWS lesions as compared to normal skin, mainly involving the functions of biosynthesis, membrane trafficking, cytoskeleton and cell adhesion/migration. The confirmative studies showed that expressions of membrane trafficking/exocytosis related proteins such as VAT1, IQGAP1, HSC70, clathrin, perlecan, spectrin α1 and GDIR1 were significantly increased in PWS blood vessels as compared to normal ones; while collagen subtypes 6A1 and 6A3 were decreased in PWS skin. Furthermore, TEM studies showed there is a significant upregulation of extracellular vesicle exocytosis from PWS blood vessels as compared to control. The biological process of membrane trafficking and exocytosis is enhanced in PWS blood vessels. Our results imply that the extracellular vesicles released by lesional endothelial cells may act as potential intercellular signaling mediators to contribute to the pathogenesis of PWS.

Coexistence of Eph receptor B1 and ephrin B2 in port-wine stain endothelial progenitor cells contributes to clinicopathological vasculature dilatation.

Port-wine stain (PWS) is a vascular malformation characterized by progressive dilatation of postcapillary venules, but the molecular pathogenesis remains obscure. To illustrate that PWS endothelial cells (ECs) present a unique molecular phenotype that leads to pathoanatomical PWS vasculatures. Immunohistochemistry and transmission electron microscopy were used to characterize the ultrastructure and molecular phenotypes of PWS blood vessels. Primary culture of human dermal microvascular endothelial cells and in vitro tube formation assay were used for confirmative functional studies. Multiple clinicopathological features of PWS blood vessels during the development and progression of the disease were shown. There were no normal arterioles and venules observed phenotypically and morphologically in PWS skin; arterioles and venules both showed differentiation impairments, resulting in a reduction of arteriole-like vasculatures and defects in capillary loop formation in PWS lesions. PWS ECs showed stemness properties with expression of endothelial progenitor cell markers CD133 and CD166 in non-nodular lesions. They also expressed dual venous/arterial identities, Eph receptor B1 (EphB1) and ephrin B2 (EfnB2). Co-expression of EphB1 and EfnB2 in normal human dermal microvascular ECs led to the formation of PWS-like vasculatures in vitro, for example larger-diameter and thick-walled capillaries. PWS ECs are differentiation-impaired, late-stage endothelial progenitor cells with a specific phenotype of CD133+ /CD166+ /EphB1+ /EfnB2+ , which form immature venule-like pathoanatomical vasculatures. The disruption of normal EC-EC interactions by coexistence of EphB1 and EfnB2 contributes to progressive dilatation of PWS vasculatures.

A novel approach to port-wine stains.

ORIGINAL ARTICLE, p 669 Port‐wine stains (PWSs) are capillary vascular malformations that occur in 3 per 1000 live births. Selective photothermolysis of PWS blood vessels with the pulsed‐dye laser (PDL) is considered the gold standard of treatment. PDL is very effective at PWS clearance, with a low incidence of side‐effects.1 However, multiple treatments are required in part due to the body's normal wound healing response, which results in revascularization and regeneration of PWS blood vessels following laser exposure.2 PDL‐induced angiogenesis makes it very difficult to achieve complete clearance of PWSs. This has prompted investigation into combination therapy with antiangiogenic agents after laser irradiation to modulate the neovascularization skin response to laser damage and enhance the effects of laser therapy. Rapamycin, a specific inhibitor of mammalian target of rapamycin (mTOR), was initially investigated as a potential adjuvant therapy after laser irradiation. Rapamycin is thought to have antiangiogenic properties through downregulation of hypoxia‐inducible factor (HIF)‐1α, which leads to a decrease in vascular endothelial growth factor (VEGF) production and reduction in the stimulation of VEGF by vascular endothelial cells.3 4 Both systemic and topical formulations of rapamycin have shown promising inhibition of neovascularization in the skin after laser treatment.5 6 Topical formulations are preferable in order to obviate systemic side‐effects, assuming that an appropriate depth of penetration is achievable. Initial studies with rapamycin have led to the investigation of other antiangiogenic agents such as imiquimod, which activates toll‐like receptor 7 leading to activation of antiangiogenic cytokines and reduction of angiogenic stimulators.7

Sustained activation of c-Jun N-terminal and extracellular signal-regulated kinases in port-wine stain blood vessels

Port-wine stain (PWS) is a congenital, progressive vascular malformation but the pathogenesis remains incompletely understood. We sought to investigate the activation status of various kinases, including extracellular signal-regulated kinase, c-Jun N-terminal kinase, AKT, phosphatidylinositol 3-kinase, P70 ribosomal S6 kinase, and phosphoinositide phospholipase C γ subunit, in PWS biopsy tissues. Immunohistochemistry was performed on 19 skin biopsy samples from 11 patients with PWS. c-Jun N-terminal kinase, extracellular signal-regulated kinase, and P70 ribosomal S6 kinase in pediatric and adult PWS blood vessels were consecutively activated. Activation of AKT and phosphatidylinositol 3-kinase was found in many adult hypertrophic PWS blood vessels but not in infants. Phosphoinositide phospholipase C γ subunit showed strong activation in nodular PWS blood vessels. Infantile PWS sample size was small. Our data suggest a subsequent activation profile of various kinases during different stages of PWS: (1) c-Jun N-terminal and extracellular signal-regulated kinases are firstly and consecutively activated in all PWS tissues, which may contribute to both the pathogenesis and progressive development of PWS; (2) AKT and phosphatidylinositol 3-kinase are subsequently activated, and are involved in the hypertrophic development of PWS blood vessels; and (3) phosphoinositide phospholipase C γ subunit is activated in themost advanced stage of PWS and may participate in nodular formation.

A new Monte Carlo program for simulating light transport through Port Wine Stain skin

A new Monte Carlo program is presented for simulating light transport through clinically normal skin and skin containing Port Wine Stain (PWS) vessels. The program consists of an eight-layer mathematical skin model constructed from optical coefficients described previously. A simulation including diffuse illumination at the surface and subsequent light transport through the model is carried out using a radiative transfer theory ray-tracing technique. Total reflectance values over 39 wavelengths are scored by the addition of simulated light returning to the surface within a specified region and surface reflections (calculated using Fresnel's equations). These reflectance values are compared to measurements from individual participants, and characteristics of the model are adjusted until adequate agreement is produced between simulated and measured skin reflectance curves. The absorption and scattering coefficients of the epidermis are adjusted through changes in the simulated concentrations and mean diameters of epidermal melanosomes to reproduce non-lesional skin colour. Pseudo-cylindrical horizontal vessels are added to the skin model, and their simulated mean depths, diameters and number densities are adjusted to reproduce measured PWS skin colour. Accurate reproductions of colour measurement data are produced by the program, resulting in realistic predictions of melanin and PWS blood vessel parameters. Using a modest personal computer, the simulation currently requires an average of five and a half days to complete.

Three-dimensional Monte Carlo model of pulsed-laser treatment of cutaneous vascular lesions

We present a three-dimensional Monte Carlo model of optical transport in skin with a novel approach to treatment of side boundaries of the volume of interest. This represents an effective way to overcome the inherent limitations of "escape" and "mirror" boundary conditions and enables high-resolution modeling of skin inclusions with complex geometries and arbitrary irradiation patterns. The optical model correctly reproduces measured values of diffuse reflectance for normal skin. When coupled with a sophisticated model of thermal transport and tissue coagulation kinetics, it also reproduces realistic values of radiant exposure thresholds for epidermal injury and for photocoagulation of port wine stain blood vessels in various skin phototypes, with or without application of cryogen spray cooling.

Numerical optimization of sequential cryogen spray cooling and laser irradiation for improved therapy of port wine stain

Despite application of cryogen spray (CS) precooling, customary treatment of port wine stain (PWS) birthmarks with a single laser pulse does not result in complete lesion blanching for a majority of patients. One obvious reason is nonselective absorption by epidermal melanin, which limits the maximal safe radiant exposure. Another possible reason for treatment failure is screening of laser light within large PWS vessels, which prevents uniform heating of the entire vessel lumen. Our aim is to identify the parameters of sequential CS cooling and laser irradiation that will allow optimal photocoagulation of various PWS blood vessels with minimal risk of epidermal thermal damage. Light and heat transport in laser treatment of PWS are simulated using a custom 3D Monte Carlo model and 2D finite element method, respectively. Protein denaturation in blood and skin are calculated using the Arrhenius kinetic model with tissue-specific coefficients. Simulated PWS vessels with diameters of 30-150 µm are located at depths of 200-600 µm, and shading by nearby vessels is accounted for according to PWS histology data from the literature. For moderately pigmented and dark skin phototypes, PWS blood vessel coagulation and epidermal thermal damage are assessed for various parameters of sequential CS cooling and 532-nm laser irradiation, i.e. the number of pulses in a sequence (1-5), repetition rate (7-30 Hz), and radiant exposure. Simulations of PWS treatment in darker skin phototypes indicate specific cooling/irradiation sequences that provide significantly higher efficacy and safety as compared to the customary single-pulse approach across a wide range of PWS blood vessel diameters and depths. The optimal sequences involve three to five laser pulses at repetition rates of 10-15 Hz. Application of the identified cooling/irradiation sequences may offer improved therapeutic outcome for patients with resistant PWS, especially in darker skin phototypes.

Confocal Microscopy Study of Neurovascular Distribution in Facial Port Wine Stains (Capillary Malformation)

Background/Purpose Vascular ectasia observed in port wine stain (PWS) birthmarks might be secondary to localized reduction of neural innervation and associated loss of autonomic stimulation. Our objective was to investigate this theory and evaluate nerve density, blood vessel density, and average blood vessel size in untreated and pulsed dye laser with cryogen spray cooling (PDL-CSC) treated PWS skin. Methods Biopsy skin specimens were taken from 14 adults with a PWS, categorized by: uninvolved skin; untreated PWS skin; PWS skin with a history of good blanching, and PWS skin with a history of poor blanching both in response to PDL treatment. Seven specimens of normal, unaffected skin were used as the experimental control group. Indirect immunohistochemistry was performed on all specimens followed by confocal microscopy imaging with computer analysis to determine nerve density, blood vessel density, and average blood vessel size. Results Nerve density was significantly decreased in all PWS sites as compared to uninvolved skin ( p < 0.01). Average blood vessel diameter was larger in untreated as compared to treated PWS sites and varied between different sites within a single PWS. Conclusion Nerve density was decreased in all evaluated PWS sites, and this may be a factor in lesion pathogenesis. PWS blood vessel size correlated with the PDL blanching response and may prove to be a useful prognostic indicator of therapeutic outcome.

Laser surgery of port wine stains using local vacuum pressure: Changes in skin morphology and optical properties (Part I)

In a recent case study, the use of a suction device to aid in port wine stain (PWS) laser treatments showed favorable results. It is our objective to further understand the mechanisms of vacuum-assisted laser therapy by analyzing the mechanical and optical changes of the skin and musculoskeletal tissues during the application of mild vacuum pressure from a suction cup. A mathematical model of tissue deformation was used to determine the changes in tissue morphology that affect the underlying laser-tissue interactions, such as epidermal stretching and thinning, blood vessel dilation, and change in blood vessel depth. Video imaging experiments were used to verify the bulk tissue deformation and skin surface stretching computed by the mathematical model. Additionally, visible reflectance spectroscopy was used to determine the changes in the optical characteristics of tissue, including blood vessel dilation and epidermal absorption coefficient. At a vacuum pressure of 50 kP(a), the epidermis at the center of the suction cup was measured to stretch 4% and was calculated to be thinned approximately 6%. Blood vessels embedded in the dermis were measured to dilate up to two times their original size. However, these vessels were calculated to be displaced toward the skin surface by a very small amount, approximately 1-3 microm. The absorption coefficient of the epidermis was also measured to be reduced significantly by approximately 25% at a wavelength of 585 nm. Mild vacuum pressure applied to the skin surface causes considerable changes in the morphology and optical properties of the tissue. These changes may be used for more efficient photothermolysis of small PWS blood vessels.

Improvement of port wine stain laser therapy by skin preheating prior to cryogen spray cooling: A numerical simulation

Although cryogen spray cooling (CSC) in conjunction with laser therapy has become the clinical standard for treatment of port wine stain (PWS) birthmarks, the current approach does not produce complete lesion blanching in the vast majority of patients. The objectives of this study are to: (1) experimentally determine the dynamic CSC heat flux when a skin phantom is preheated, and (2) numerically study the feasibility of using skin preheating prior to CSC to improve PWS laser therapeutic outcome. A fast-response thin-foil thermocouple was used to measure the surface temperature and thus heat flux of an epoxy skin phantom during CSC. Using the heat flux as a boundary condition, PWS laser therapy was simulated with finite element heat diffusion and Monte Carlo light distribution models. Epidermal and PWS blood vessel thermal damage were calculated with an Arrhenius-type kinetic model. Experimental results show that the skin phantom surface can be cooled to a similar minimum temperature regardless of the initial temperature. Numerical simulation indicates that upon laser irradiation, the epidermal temperature increase is virtually unaffected by preheating, while higher PWS blood vessel temperatures can be achieved. Based on the damage criterion we assumed, the depth and maximum diameter of PWS vessels that can be destroyed irreversibly with skin preheating are greater than those without. Skin preheating prior to CSC can maintain epidermal cooling while increasing PWS blood vessel temperature before laser irradiation. Numerical models have been developed to show that patients may benefit from the skin preheating approach, depending on PWS vessel diameter and depth.

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.

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.

Correlations between light penetration into skin and the therapeutic outcome following laser therapy of port-wine stains.

For several years the flashlamp-pumped pulsed dye laser (FPDL) has been the favoured method for the treatment of port-wine stains (PWS). The therapeutic outcome of FPDL laser therapy depends on the anatomical location of the PWS and is mainly attributed to morphological parameters such as size and depth of the PWS blood vessels. The aim of this study was to show a correlation between the therapeutic outcome following FPDL therapy and the optical properties of the skin overlying the PWS vessels. For this purpose the therapeutic outcome following FPDL treatment (585 nm; 0.45 ms) of 884 PWS situated on different body sites was evaluated by judging the grade of fading of PWS colour. On the other hand the light penetration into 123 skin samples (thickness 0.10-1.35 mm) was determined between 450 nm and 1030 nm and compared with the PWS laser therapy outcome for equal locations by statistical analysis. PWS on the neck, trunk, arms or legs yielded a higher mean grade of fading as compared to PWS on the head. Within the face, a wide range of fading was evident. The light penetration into skin increased linearly with increasing wavelength and location-dependent differences were found. The attenuation coefficient was 22.8+/-5.3 mm(-1) at 585 nm. No significant or strong correlation was observed between the therapeutic outcome of PWS laser therapy and the light penetration into skin. However, a correlation was obvious by plotting the respective profile plots. Therefore, among other effects, in particular morphological parameters of PWS vessels, the optical properties of the skin contribute to a small extent to the clinical outcome of PWS laser therapy.

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 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.

Infra-red tomography of port-wine-stain blood vessels in human skin

Specifying the distribution of laser energy within a tissue is the first step towards understanding and capitalizing on a variety of laser-tissue interactions. Whether photothermal, photochemical or photomechanical in nature, laser-tissue interactions begin with the absorption of photon energy. The spatial distribution of photon absorption specifies the required laser exposure to be delivered and the extent of subsequent therapeutic action. Using infra-red tomography (IRT), the broad, long-term objective of this research is the development of a tomographic reconstruction algorithm as a means to determine: (1) the depths and physical dimensions of discrete subsurface port-wine-stain (PWS) blood vessels in human skin; and (2) the initial space-dependent temperature increase in PWS blood vessels immediately following pulsed laser exposure. In this report, preliminary studies are described which demonstrate the potential application of IRT in the clinical management of PWS patients.