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Theoretical investigation on thermal responses of Port Wine Stain lesions to 585 nm, 595 nm and 1064 nm lasers BIN CHEN 1 , DONG LI 1 , WENJUAN WU 1 , GUO-XIANG WANG 1, 2 1 State Key Laboratory of Multiphase Flow in Power Engineering Xi’an Jiaotong University Xi’an, Shaanxi, 710049, China CHINA [email protected] http://chenbin.gr.xjtu.edu.cn 2 Department of mechanical engineering University of Akron Akron, Ohio 44325-3903, USA Abstract: - As a kind of congenital vascular malformations, Port Wine Stain (PWS) is composed of ectatic venular capillary blood vessels buried within healthy dermis. In clinic, Pulsed Dye Laser (PDL) in visible band (e.g. 585 or 595 nm) together with cryogen spray cooling has become the golden standard for treatment of PWS. However, due to the limited energy penetration depth of the PDL, deeply buried blood vessels are likely to survive from the laser irradiation and complete clearance of the lesion is rarely achieved. Nd:YAG laser in near infrared (1064nm) has great potential in the laser treatment of PWS due to its deeper penetration depth in tissue. In this study, the effect of wavelength in treating PWS lesions with various melanin concentrations in epidermis was theoretically investigated by a two-temperature model, in which two energy equations for blood and surrounding dermal tissue are constructed following the local thermal non-equilibrium theory of porous media. The results show that deeply buried blood vessels, which are likely to survive from PDL with wavelengths of 585 and 595 nm, can be coagulated by dual-wavelength laser combing 585 or 595 nm with 1064 nm laser. Furthermore, the dual-wavelength laser of 595 with 1064nm shows better treatment effect than dual-wavelength laser combing 585 and 1064 nm. Key-Words: - Port Wine Stain; Pulsed dye laser; Nd:YAG laser; two-temperature model; dual-wavelength laser 1 Introduction As congenital vascular malformations, Port Wine Stain (PWS) birthmarks occur in approximately 0.3% of newborn children [1]. PWS is composed of ectatic venular capillary blood vessels with diameters ranging from 30 to 300 µm buried within healthy dermal tissue [2], which may lead to increased cosmetic disfigurement and psychological distress, prompting patients and their families to seek effective treatments. Laser treatment of Port Wine Stains (Laser PWS) is based on the principle of selective photothermolysis developed by Anderson and Parrish [3]. According to the theory, PWS blood vessels can be selectively damaged by the thermal response due to their preferential absorption of laser energy with the specific wavelength. In comparison, normal skin tissues are minimally affected. However, absorption of laser energy by melanin in epidermis could result in unwanted thermal damage to skin surface (epidermis), which can be prevented by cryogen spray cooling (CSC) introduced by Nelson et al. [4]. Nowadays, Pulsed dye laser (PDL) with wavelength in visible brand of 585 nm or 595nm in conjunction with the CSC technique have become the golden standard for treating PWS. However, clinical studies indicate that complete blanching of the lesions is not commonly achieved (less than 20%). The possible reasons may be the limited light penetration depth in deeply-buried blood vessels [5]. Light in near-infrared wavelengths (e.g. Nd:YAG laser with 1064 nm) will be absorbed less by epidermal melanin and penetrate deeper into skin dermis than visible wavelengths [6]. Therefore, laser irradiation with near-infrared wavelengths may improve the therapeutic outcome of cutaneous hyper-vascular malformations with deeply-buried blood vessels. Some theoretical models have been developed to simulate laser treatment of PWS [5, 7-8]. Most models can be divided into two categories, the homogeneous model and the discrete blood-vessel model. The former refers to models in which the skin tissue with PWS is treated as a homogeneous Recent Advances in Environmental and Biological Engineering ISBN: 978-1-61804-259-0 106

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Page 1: Theoretical investigation on thermal responses of Port ......seek effective treatments. Laser treatment of Port Wine Stains (Laser PWS) is based on the principle of selective photothermolysis

Theoretical investigation on thermal responses of Port Wine Stain lesions to 585 nm, 595 nm and 1064 nm lasers

BIN CHEN1, DONG LI1, WENJUAN WU1, GUO-XIANG WANG1, 2

1State Key Laboratory of Multiphase Flow in Power Engineering Xi’an Jiaotong University

Xi’an, Shaanxi, 710049, China CHINA

[email protected] http://chenbin.gr.xjtu.edu.cn 2Department of mechanical engineering

University of Akron Akron, Ohio 44325-3903, USA

Abstract: - As a kind of congenital vascular malformations, Port Wine Stain (PWS) is composed of ectatic venular capillary blood vessels buried within healthy dermis. In clinic, Pulsed Dye Laser (PDL) in visible band (e.g. 585 or 595 nm) together with cryogen spray cooling has become the golden standard for treatment of PWS. However, due to the limited energy penetration depth of the PDL, deeply buried blood vessels are likely to survive from the laser irradiation and complete clearance of the lesion is rarely achieved. Nd:YAG laser in near infrared (1064nm) has great potential in the laser treatment of PWS due to its deeper penetration depth in tissue. In this study, the effect of wavelength in treating PWS lesions with various melanin concentrations in epidermis was theoretically investigated by a two-temperature model, in which two energy equations for blood and surrounding dermal tissue are constructed following the local thermal non-equilibrium theory of porous media. The results show that deeply buried blood vessels, which are likely to survive from PDL with wavelengths of 585 and 595 nm, can be coagulated by dual-wavelength laser combing 585 or 595 nm with 1064 nm laser. Furthermore, the dual-wavelength laser of 595 with 1064nm shows better treatment effect than dual-wavelength laser combing 585 and 1064 nm. Key-Words: - Port Wine Stain; Pulsed dye laser; Nd:YAG laser; two-temperature model; dual-wavelength laser 1 Introduction As congenital vascular malformations, Port Wine Stain (PWS) birthmarks occur in approximately 0.3% of newborn children [1]. PWS is composed of ectatic venular capillary blood vessels with diameters ranging from 30 to 300 µm buried within healthy dermal tissue [2], which may lead to increased cosmetic disfigurement and psychological distress, prompting patients and their families to seek effective treatments. Laser treatment of Port Wine Stains (Laser PWS) is based on the principle of selective photothermolysis developed by Anderson and Parrish [3]. According to the theory, PWS blood vessels can be selectively damaged by the thermal response due to their preferential absorption of laser energy with the specific wavelength. In comparison, normal skin tissues are minimally affected. However, absorption of laser energy by melanin in epidermis could result in unwanted thermal damage to skin surface (epidermis), which can be prevented by cryogen spray cooling (CSC) introduced by Nelson et al. [4].

Nowadays, Pulsed dye laser (PDL) with wavelength in visible brand of 585 nm or 595nm in conjunction with the CSC technique have become the golden standard for treating PWS. However, clinical studies indicate that complete blanching of the lesions is not commonly achieved (less than 20%). The possible reasons may be the limited light penetration depth in deeply-buried blood vessels [5]. Light in near-infrared wavelengths (e.g. Nd:YAG laser with 1064 nm) will be absorbed less by epidermal melanin and penetrate deeper into skin dermis than visible wavelengths [6]. Therefore, laser irradiation with near-infrared wavelengths may improve the therapeutic outcome of cutaneous hyper-vascular malformations with deeply-buried blood vessels.

Some theoretical models have been developed to simulate laser treatment of PWS [5, 7-8]. Most models can be divided into two categories, the homogeneous model and the discrete blood-vessel model. The former refers to models in which the skin tissue with PWS is treated as a homogeneous

Recent Advances in Environmental and Biological Engineering

ISBN: 978-1-61804-259-0 106

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mixture of uniformly distributed blood vessel and surrounding dermal tissue with a given blood volumetric fraction. Since detailed anatomic structure of the blood was not taken into account [9], the homogeneous model is simple and computationally efficient. However, it fails to distinguish the temperature between the blood and the surrounding dermal tissue as they were assumed to be the same. For laser PWS, such a local thermodynamic equilibrium assumption makes the homogeneous model undesirable to simulate the selective photothermolysis.

In comparison, the discrete blood-vessel model treats PWS blood vessels as straight cylindrical tubes which are buried in dermis and parallel to the skin surface [7-8, 10-11]. In early discrete models, either single blood vessel [10] or blood vessel array regularly arranged within the dermis [11] were considered. Multiple blood vessels randomly arranged within the dermis have also been taken into consideration [12]. However, the tube-like arrangement departs a lot from the real distribution of the irregular blood vessels in PWS lesions, which may cause the inaccuracy of the discrete blood-vessel model for practical clinic applications.

In the authors’ previous work [13], a local thermodynamic non-equilibrium two-temperature model for simulating the thermal response of PWS to laser irradiation was developed. In the model, the skin containing PWS lesions was treated as a porous medium composed of a normal tissue matrix buried with highly-absorbing chromophores (blood confined within the vessels). Two energy equations, one for the blood and the other for the dermal tissue, were deduced based on the local thermal non-equilibrium theory of porous media. As an approximation, the geometric configuration of the blood vessels was represented by the volumetric fraction of the chromophores and a length scale, i.e., the average diameter of the blood vessels within a PWS. An approximate relation for the transient interfacial heat transfer coefficient was also proposed to quantify the heat conduction of the absorbed laser energy within blood to the surrounding dermal tissue. Furthermore, the validation of our two-temperature model was verified by the good agreement with those from the discrete-blood-vessel model [12] for same cases.

In this study, the two-temperature model is implemented to investigate the effect of wavelength in treating PWS lesions. The coagulation depth of typical PDL with 585 nm and 595 nm is compared with near-infrared Nd:YAG laser with 1064 nm for various melanin concentration in epidermis. Based on the investigation, the dual-wavelength laser

system combining 595 and 1064 nm is recommended for the treatment of PWS containing deeply-buried blood vessels, because its therapeutic result was proved to be better than the pulse dye lase (585 or 595 nm) alone and dual-wavelength laser combing 585 and 1064 nm.

2 Mathematical model 2.1 Basic assumptions In the two-temperature model, the skin tissue containing PWS is assumed to be a multi-layered skin geometry composed of a normal multi-layer skin matrix with the PWS blood vessels superposed on the matrix, see Fig. 1.

Fig. 1: Representative elementary volume (REV) for port

wine stains in a four-layer skin model

The multi-layer skin matrix is simplified as two parallel planar layers, which are the epidermal layer and the dermal layer without including any subcutaneous fat. Melanin in the epidermis is included by inserting a melanin-filled basal layer at the bottom of the epidermal layer. The melanin particles are assumed to be homogeneously distributed in the basal layer of the epidermis, simulating the situation of un-tanned skin [12]. As the thermal relaxation time of melanin particles (in nanoseconds) is much shorter than the pulse duration of the laser irradiation (in milliseconds) during treatment of PWS, a local thermodynamic equilibrium condition can be assumed within the epidermis during the process of laser treatment of PWS, i.e., both melanin and the epidermal tissues have the same temperature. The PWS blood vessels, on the other hand, are buried in the dermis below a small superficial portion of uninvolved dermis. They are assumed to be spread out and mixed with the dermal tissue, forming a PWS layer in the skin

PWS layer

Dermis without blood

Laser beam

z

r o

Epidermis Melanin-filled basal layer

REV with blood vessels superposed on the normal dermal tissue

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model. The PWS layer is treated as a porous medium with blood vessels buried within the matrix of normal dermal tissues. Due to selective absorption of the laser energy by the blood, the PWS layer is assumed to be at a local thermodynamic non-equilibrium condition, i.e., the blood within the vessels and the surrounding dermal tissue would have different temperatures. 2.2 Governing equations In the two-temperature model, blood perfusion and metabolic heat generation are not included in the energy equations because of the short pulse (1.5 ms) of the laser irradiation. The energy equations for each layer are given below:

Epidermis without melanin (0 < z < zepi/basal)

( )e ee e e e

p

T Qc k Tt t

ρ∂

= ∇ ∇ +∂

(1)

Basal layer with melanin (zepi/basal < z < z basal /der)

[ ] basalm m m e

basalbasalm m m e

p

( ) (1 )( )

( (1 ) )

Tc ct

Qk k Tt

ε ρ ε ρ

ε ε

∂+ − =

∇ + − ∇ +

(2)

Dermis without blood (zbasal /der < z < zder/PWS)

( )d dd d d d

p

T Qc k Tt t

ρ∂

= ∇ ∇ +∂

(3)

PWS layer (zder/PWS < z < zk)

( )bbb b b b b

b bb dbd bd

p

( )

Tc k Tt

Qh a T Tt

ε ρ ε

ε

∂= ∇ ∇

− − + (4)

( )ddb d d b d

b db dbd bd

p

(1 ) (1 )

(1 ) ( )

Tc k Tt

Qh a T Tt

ε ρ ε

ε

∂− = ∇ − ∇

∂−

+ − + (5)

where T represents the local temperature in the single phase medium and T represents the intrinsic volume-averaged temperature of the given phase in the mixture:

i

i ii

1

V

T T dVV

= ∫ (6)

where V is the volume and Vi is the volume of the phase i within the chosen representative element volume (see Fig. 1) and the subscript i represents melanin (m), epidermal tissue (e), blood (b), or dermal tissue (d), respectively. The thermal and the optical properties of the mixture can be obtained by the weighted average of each component. Q represents the energy deposition in skin by laser

irradiation during the pulse duration, which can be calculated by the Monte Carlo method developed in our previous publication [13]. The two volume fractions, εm and εb, in the two mixtures are defined within a given representative elementary volume (REV), VREV (see Fig. 1), in the melanin-filled basal layer and PWS layer respectively, by the following expressions:

m m REV, basal

b b REV, PWS

//

V VV V

ε

ε

=

= (7)

where VREV is: REV, basal m e

REV, PWS b d

V V V for the basal layerV V V for the PWS layer

= +

= + (8)

In Eqs. (4) and (5), hbd and abd are the heat transfer coefficient on the skin surface and the interfacial area per unit volume, respectively. Both of them have to be determined separately from supplemental models, i.e., a closure problem discussed in our previous publication [13]. The correlation of hbd during and after laser irradiation is presented below for εb = 6%:

p

p

* *bd

bd b

t

* *1/2b

1/2bd b

3.92141exp0.05132

2.69397exp0.00705

1.4250741ln 22

Nu t th d

k

t t

K

θ

θ

εε

∆−

∆= + − ≤ = +

>

− +

(9)

where db is the diameter of the blood vessels, Kbd = kb/kd is the ratio of the thermal conductivities of the blood to the dermal tissues. * 2

b b/t t dα= and * 2p b p b/t t dα= are the non-dimensional time and laser

pulse duration, respectively, with tp the dimensional laser pulse duration and αb the thermal diffusivity of

the blood. b d2

b b b/ 4T T

Q d kθ −

∆ = is the non-dimensional

temperature difference. The specific interfacial area abd can be simply written as below [13]:

bd b b4 /a dε= (10) On the skin surface (z=0), a convection heat

transfer condition is used to describe the cooling effect of CSC:

e c c0

e air air0

, )[ ( ,0, ) ]

during CSC

[ ( ,0, ) ]

after CSC or without cooling

z

z

Tk h r t T r t Tz

Tk h T r t Tz

=

=

∂− = − ∂

∂− = − ∂

(11)

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where Tc and Ta are the temperature of liquid cryogen on the skin surface and in the environment, respectively. hair is the constant convective heat transfer coefficient between the cold surface and air, while hc(r, t) is the convective heat transfer between the surface and the liquid cryogen on the surface during short-pulsed cryogen spray. The dynamic and temporal variation of hc(r, t) is determined from a general correlation developed recently by the authors [14].

At the interface between the PWS layer and the dermal layer without blood (zder/PWS), a zero flux condition is used for bT and a continuum condition is used for dT :

der/PWS

der/PWSder/PWS

b

d

0z z

d

z zz z

Tz

TTz z −+

=

==

∂=

∂∂ = ∂ ∂

(12)

Adiabatic conditions are adopted for other three boundaries.

2.3 Arrhenius damage integral Damage processes can often be modelled as first-

order rate process (The Arrhenius rate process integral), for which two experimentally derived coefficients are sufficient. Thermal damage in this formulation is exponentially dependent on temperature while linearly dependent on the time of exposure. The Arrhenius integral can be expressed as below [15]:

0

( ) exp( )( )EA dt

RT

τ

ττ

−∆Ω = ∆∫ (13)

where ΔA is the frequency factor (1/second), ΔE is the activation energy (J/mol) and R is the universal gas constant (8.314 J/mol K). The values A =1.8 × 1051 1/s and ΔE = 327,000 J/mol are set for bulk skin, while A =7.6 × 1066 1/s and ΔE = 327,000 J/mol for blood [10]. Ω is calculated for a period of time until thermal damage accumulation is ceased.

The above mathematical equations constitute a multi-region, axial-symmetric transient heat conduction problem for pulsed heat generation, which can be numerically solved by a finite-volume method with a uniform grid. The validation of this model has been extensively verified in our previous publication [13]. 3 Results and Discussion The above mathematical equations are solved to investigate the effect of wavelength in the treatment

of port wine stains. 585 nm and 595nm in visible band, i.e., typical for modern pulsed dye lasers [2], and 1064nm (Nd:YAG) in near infrared band are selected. According to the clinic practice, the beam diameter of a flat hat-beam profile is set as 6 mm [12]. Based on our previous results [14], the pulse duration of 1.5 ms is used for all simulations. The thickness of each layer is 50 μm for the epidermal layer without melanin, 10 μm for the melanin-filled basal layer with a melanin volumetric fraction of 5%, 15% and 25% (corresponding to light, moderate and heavy pigmentation), 90 μm dermal layer without blood, and 850 μm PWS layer filled with 80μm blood vessels with volumetric fraction of 6% [12]. The initial skin temperature is assumed to be 33 oC, and the ambient temperature Ta is 25 oC. The convective heat transfer coefficient between the skin surface and air ha is set as 10 W/m2K [10]. The optical properties of the epidermis, melanin, dermis, and blood at three wavelengths can be found in our previous publications [13-14]. 3.1 Comparison between wavelength of 585 and 595 nm Fig. 2 shows the temperature distribution along tissue depth immediately after laser irradiation with wavelength of 585 and 595nm. The melanin concentration in epidermis is 5%, corresponding to light melanin concentration.

0 200 400 600 800 1000

40

80

120

160

200

240

BloodSurrounding tissue

585nm 595nm

T / o C

z / µm

Laser

Fig. 2 Temperature distribution along tissue depth

immediately after laser irradiation with wavelength of 585 and 595nm. The incident fluences are 3.1 and 8 J/cm2 for 585 and 595 nm lasers with pulse duration of 1.5 ms.

The melanin concentration in epidermis is 5%, corresponding to light pigmentation.

As the melanin concentration in epidermis is

low, high blood temperature can be achieved without damage the epidermis even the cryogen spray cooling is not used. Thus, different incident laser fluences of 3.1 and 8 J/cm2 are respectively

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used for 585 and 595 nm lasers to achieve the same maximum blood temperature of blood. As shown in the Fig. 3, the blood temperature attenuation after 595 nm laser irradiation along tissue depth is smaller than that of 585 nm laser irradiation. As a result, the corresponding thermal damage depth (600 μm) by 595 nm laser is much larger than that by 585 nm laser (400 μm).

x (cm)

z(c

m)

0 0.05 0.1 0.15 0.2 0.25 0.3

0

0.05

0.1

(a) 585 nm

x (cm)

z(c

m)

0 0.05 0.1 0.15 0.2 0.25 0.3

0

0.05

0.1

(b) 595 nm

Fig. 3 Thermal damage immediately after 585 and 595 nm laser irradiation. The incident fluences are 3.1 and 8

J/cm2 for 585 and 595 nm lasers with laser pulse duration of 1.5 ms. The melanin concentration in epidermis is 5%,

corresponding to light pigmentation.

We increase the melanin concentration in epidermis from 5% to 15%, corresponding to a moderate pigmentation. The temperature distribution along tissue depth immediately after laser irradiation with wavelength of 585 and 595nm is plotted in Fig. 4. Incident fluence of 3.1 J/cm2 is used for 585 nm laser, which is the threshold energy dose for epidermis damage. Higher incident fluence of 5.7 J/cm2 is used for 595 nm laser after 100 ms R134a cryogen spray cooling, which is also the threshold energy dose for epidermis damage obtained from our experimental work [16]. Here, cryogen spray cooling is not used during 585 nm laser irradiation, because the blood temperature is high enough without damage the epidermis due to high energy absorption of blood over epidermis for 585 nm laser. As illustrated from the figure, the maximum blood temperature after 585 nm laser irradiation is higher than that of 595 nm laser. On the other hand, the blood temperature attenuation after 595 nm laser irradiation along tissue depth is smaller than that of 585 nm laser irradiation. As a result, the corresponding thermal damage depth (450 μm) by 595 nm laser is slightly larger than that by 585 nm laser (400 μm) as shown in the Fig. 5.

0 200 400 600 800 1000

0

40

80

120

160

200

240

T / o C

z / µm

585nm 595nm

LaserSurrounding tissueBlood

Fig. 4 Temperature distribution along tissue depth

immediately after laser irradiation with wavelength of 585 and 595nm. The incident fluences are 3.1 and 5.7 J/cm2 for 585 and 595 nm lasers with pulse duration of 1.5 ms. The melanin concentration in epidermis is 15%,

corresponding to moderate pigmentation.

x (cm)

z(c

m)

0 0.05 0.1 0.15 0.2 0.25 0.3

0

0.05

0.1

(a) 585 nm

x (cm)

z(c

m)

0 0.05 0.1 0.15 0.2 0.25 0.3

0

0.05

0.1

(b) 595 nm

Fig. 5 Thermal damage immediately after 585 and 595 nm laser irradiation. The incident fluences are 3.1 and 5.7 J/cm2 for 585 and 595 nm lasers with pulse durations of 1.5 ms. The melanin concentration in epidermis is 15%,

corresponding to moderate pigmentation.

We further increase the melanin concentration in epidermis from 15% to 25%, corresponding to a heavy pigmentation. Fig. 6 shows the temperature distribution along tissue depth immediately after laser irradiation with wavelength of 585 and 595nm without cryogen spray cooling. The laser incident fluences are 1.4 J/cm2 which are the thresholds for the thermal damage in epidermis for both wavelengths. As we can see from the figure, the temperatures in epidermis are almost the same after 585 and 595 nm laser irradiations, due to their similar energy absorption by melanin. In dermis, blood has much higher absorption to 585 nm laser (191 cm-1) than the 595 nm laser (40 cm-1). Therefore, as displayed in the figure, the maximum temperature of heavy pigmented epidermis is lower than that of blood after 585 nm laser irradiation,

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while higher than that of blood after 595 nm laser irradiation. Compared with 595 nm laser irradiation, a much stronger attenuation of blood temperature is observed after 585 nm laser irradiation. The corresponding thermal damages in skin tissue after two laser irradiations are illustrated in Fig. 7. It can be found that, there is no thermal damage in skin tissue after both laser irradiations due to a low incident energy dose.

0 200 400 600 800 1000

40

60

80

100

120

T / o C

z / µm

585nm 595nm

LaserSurrounding tissueBlood

Fig. 6 Temperature distribution along tissue depth

immediately after laser irradiation with wavelength of 585 and 595nm without cryogen spray cooling. The

incident fluence is 1.4 J/cm2 and the pulse durations is1.5 ms for two lasers. The melanin concentration in

epidermis is 25%, corresponding to heavy pigmentation.

x (cm)

z(c

m)

0 0.05 0.1 0.15 0.2 0.25 0.3

0

0.05

0.1

(a) 585 nm

x (cm)

z(c

m)

0 0.05 0.1 0.15 0.2 0.25 0.3

0

0.05

0.1

(b) 595 nm

Fig. 7 Thermal damage immediately after 585 and 595 nm laser irradiation. The incident fluences is 1.4 J/cm2

and the pulse duration is 1.5 ms for two lasers. The melanin concentration in epidermis is 25%,

corresponding to heavy pigmentation.

Keeping the melanin concentration unchanged, we can increase the threshold of laser incident fluences for epidermis injury from 1.4 to 2.3 J/cm2 for both wavelengths by using cryogen spray cooling with R134a. Fig. 8 plots the temperature distribution along tissue depth immediately after laser irradiation with wavelength of 585 and 595nm

after 100 ms R134a cryogen spray cooling. As illustrated in the figure, the temperature profiles in heavy pigmented epidermis for both wavelengths are almost the same. Furthermore, due to higher incident energy, the blood temperatures for both lasers are higher than the case without cryogen spray cooling as shown in Fig. 6. The corresponding thermal damages in skin tissue after two lasers irradiations are plotted in Fig. 9. As the laser incident energy increases from 1.4 to 2.3 J/cm2 benefited from cryogen spray cooling, partial thermal damage in dermis extended to a depth of about 350μm is observed after 585 nm laser irradiation. However, on the other hand, no thermal damage is observed in skin tissue after 595 nm laser irradiation due to a relative low blood temperature as shown in Fig. 9.

0 200 400 600 800 1000

0

40

80

120

160

T / o C

z / µm

585nm 595nm

LaserSurrounding tissueBlood

Fig. 8 Temperature distribution along tissue depth

immediately after laser irradiation with wavelength of 585 and 595nm after 100 ms cryogen spray cooling. The

incident fluence is 2.3 J/cm2 and the pulse durations is 1.5 ms for two lasers. The melanin concentration in

epidermis is 25%, corresponding to heavy pigmentation.

x (cm)

z(c

m)

0 0.05 0.1 0.15 0.2 0.25 0.3

0

0.05

0.1

(a) 585 nm

x (cm)

z(c

m)

0 0.05 0.1 0.15 0.2 0.25 0.3

0

0.05

0.1

(b) 595 nm

Fig. 9 Thermal damage immediately after 585 and 595 nm laser irradiation. The incident fluence is 2.3 J/cm2 and the pulse duration is 1.5 ms for two lasers. The melanin

concentration in epidermis is 25%, corresponding to heavy pigmentation.

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Based on above results, it can be concluded that the therapeutic effects of PWS by 585 and 595 nm lasers are highly related to the melanin concentration in epidermis. In the light pigmented skin with low melanin concentration in epidermis, 595 nm laser has better clinic effect than 585 nm laser due to the larger light penetration depth in skin tissue. With a moderate melanin concentration, two lasers have similar treatment effects. In the heavy pigmented skin with high melanin concentration in epidermis, as we can see from the results of Figs. 6-9, the treatment effect of port wine stain by 585 nm lasers seems better than that by 595 nm lasers due to higher blood absorption. By using cryogen spray cooling, the threshold incident fluence can be slightly improved. Nevertheless, it is still insufficient to damage the deeply buried malformed blood vessels. In the next sections, we will further investigate the feasibility of using near infrared Nd:YAG laser with 1064 nm wavelength to improve the therapeutic in treating deeply buried PWS blood vessels.

3.2 Comparison between pulsed dye laser (585 and 595 nm) and Nd:YAG laser (1064 nm) In this section, we compare the treatment effect of port wine stains in heavy pigmented skin between pulsed dye laser (585 and 595 nm) and Nd:YAG laser (1064 nm). Fig. 10 shows the temperature distribution along tissue depth immediately after laser irradiation with wavelength of 585, 595 and 1064 nm without cryogen spray cooling. The melanin concentration in epidermis is 25%, corresponding to a heavy pigmentation. Due to the high melanin concentration, the maximum temperature in epidermis and possible thermal damage of epidermis should be considered. Therefore, same incident laser fluences of 3.1 J/cm2 are used for 585 and 595 nm. For 1064 nm laser, 50 J/cm2 is selected to achieve the same maximum temperature as PDL laser irradiation. As displayed in the figure, the temperatures in heavy pigmented epidermis for 585 and 595 nm lasers are almost the same with same incident energy dose. Furthermore, the blood temperatures after 585 and 595 nm laser irradiations are higher than that in Fig. 6 (1.4 J/cm2) due to higher incident energy. In epidermis, the temperature after the 585 and 595 nm lasers irradiation is much higher than that after 1064 nm laser irradiation due to the low absorption to 1064 nm laser by melanin.

In bloody dermis, on the other hand, 585 nm laser has high absorption in blood. The blood

0 200 400 600 800 1000

40

80

120

160

200

240

T / o C

z / µm

585nm 595nm 1064nm

Surrounding tissue LaserBlood

(a) 50 J/cm2 Nd:YAG laser

0 200 400 600 800 1000

40

80

120

160

200

240

T / o C

z / µm

585nm 595nm 1064nm

Surrounding tissue LaserBlood

(b) 8 J/cm2 Nd:YAG laser

Fig. 10 Temperature distribution along tissue depth immediately after laser irradiation with wavelength of

585 nm, 595nm and 1064 nm. The laser incident fluences are 3.1 J/cm2 for 585 and 595 nm, while 50 J/cm2 (a) and 8 J/cm2 (b) for 1064 nm laser. The pulse durations of 1.5 ms is used for three lasers. The melanin concentration in

epidermis is 25%, corresponding to heavy pigmented skin.

temperature is high and decayed fast along the tissue depth. The maximum blood temperature after 595 nm laser irradiation is much lower and the temperature attenuation is smaller than that of 585 nm because the blood absorption to 595 nm laser is much less than that of 585 nm. 1064 nm laser has a low absorption in blood, thus higher incident laser fluence is needed to achieve same blood temperature as pulse dye laser (585 and 595 nm laser) did. As illustrated in the figure, after 1064nm laser irradiation, the blood temperature attenuated slowly. However, the temperature of normal dermal tissue after 1064 nm laser irradiation is much higher than that irradiated by pulsed dye laser (585 and 595 nm) due to the high incident dose. A high dermal temperature may cause uncomfortable or even the thermal damage to the normal tissue, which should be avoided.

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Decreasing the incident energy dose to 8J/cm2, the dermal temperature after 1064 nm laser irradiation will decrease to the same as irradiated after 585 nm laser, as shown in Fig. 10b. At the same time, however, the blood temperature gets pretty low as the incident energy dose for Nd:YAG laser greatly decreased.

Therefore, when the 1064 nm laser was used alone to treat port wine stain, the light absorption by the normal dermal tissue should be considered in clinic and energy dose should be carefully controlled to avoid potential thermal injury to normal dermal tissue. However, low energy dose may not be sufficient enough to induce thermal injury to the malformed blood vessels as shown in Fig. 10. It may be a good option to use the 1064 nm laser to work combined with pulsed dye laser (585 or 595 nm) as a dual wavelength in clinic practice.

3.3 Comparison between PDL (585 and 595 nm) alone and dual wavelength laser (Nd:YAG laser combined with PDL) The comparison of the temperature attenuation along tissue depth immediately after laser irradiation between 585 nm laser alone with dual-wavelength of 585 and 1064 nm is shown in Fig. 11. The incident energy dose of 2.3 J/cm2 and pulse duration of 1.5 ms are used for 585nm laser alone.

0 200 400 600 800 1000

0

40

80

120

160

T / o C

z / µm

585nm 585nm+1064nm

Surrounding tissue LaserBlood

Fig. 11 The comparison of the temperature attenuation along tissue depth immediately after laser irradiation between 585 nm laser alone with dual wavelengths of

585 and 1064 nm. The melanin concentration in epidermis is 25%, corresponding to heavy pigmentation.

As for the dual-wavelength laser, two laser

pulses irradiated on the skin surface sequentially: 585nm laser with energy doses of 2.3 J/cm2 and pulse duration of 1.5 ms first, and 1064 nm laser with energy dose of 10 J/cm2 and pulse duration of 1.5 ms subsequently. As displayed in the figure, the temperature of normal dermal tissue is not

dramatically increased due to the low energy dose of 1064nm laser. On the other hand, the temperature attenuation is greatly decreased with 1064 nm laser. In other words, the energy deposition depth is increased by dual wavelength laser. Furthermore, the depth of thermal damage can be increased from 350 to 750μm by using dual wavelength, compared to 585 nm laser alone as illustrated in Fig. 12.

x (cm)

z(c

m)

0 0.05 0.1 0.15 0.2 0.25 0.3

0

0.05

0.1

(a) 585 nm

x (cm)

z(c

m)

0 0.05 0.1 0.15 0.2 0.25 0.3

0

0.05

0.1

(b) 585 nm+1064 nm

Fig. 12 Thermal damage immediately after 585 nm alone and dual wavelengths of 585 and 1064 nm laser

irradiation. The melanin concentration in epidermis is 25%, corresponding to heavy pigmentation.

The comparison of the temperature attenuation

along tissue depth immediately after laser irradiation between 595 nm laser alone with dual wavelengths of 595 and 1064 nm is shown in Fig. 13. The incident energy dose of 2.3 J/cm2 and pulse duration of 1.5 ms are used for 595 nm laser alone. As for the dual-wavelength laser, two laser pulses with wavelength of 595 nm and 1064 nm irradiated on the skin surface sequentially: 595nm laser with energy doses of 2.3 J/cm2 and pulse duration of 1.5 ms first, and 1064 nm laser with energy dose of 20 J/cm2 and pulse duration of 1.5 ms subsequently. Higher energy dose of 1064nm laser is used here because the absorption of blood to 595 nm laser is much less than that of 585 nm laser. As illustrated in the figure, the temperature of normal dermal tissue is not dramatically increased. On the other hand, using of 1064 nm laser, the temperature attenuation is greatly decreased. In other words, the energy deposition depth is increased by dual wavelength laser. Moreover, the depth of thermal damage cover the entire the skin tissue by using this dual wavelength, compared to no thermal injury by using 595 nm laser alone as shown in Fig. 14.

Dual wavelength laser system combing pulse dye laser of 585 or 595 nm with near infrared laser with 1064 nm may be a promising treatment strategy for the clearance of deep buried PWS blood vessels, which cannot be achieved by pulsed dye laser alone,

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because 1064 nm laser has a deeper energy penetration depth in bloody dermis than 585 or 595 nm laser. Furthermore, 595 nm laser has a deeper light penetration depth than the 585 nm laser in skin tissue containing PWS due to its lower blood absorption [2]. Therefore, as we predicted, larger coagulation depth of PWS blood vessels can be achieved by dual-wavelength laser of 595 with 1064nm compared to that of 585 with 1064 nm.

0 200 400 600 800 1000

0

40

80

120

T / o C

z / µm

595nm 595nm+1064nm

Surrounding tissue LaserBlood

Fig. 13 The comparison of the temperature attenuation along tissue depth immediately after laser irradiation between 595 nm laser alone with dual wavelengths of

595 and 1064 nm. The melanin concentration in epidermis is 25%, corresponding to heavy pigmentation.

x (cm)

z(c

m)

0 0.05 0.1 0.15 0.2 0.25 0.3

0

0.05

0.1

(a) 595 nm

x (cm)

z(c

m)

0 0.05 0.1 0.15 0.2 0.25 0.3

0

0.05

0.1

(b) 595 nm+1064nm

Fig. 14 Thermal damage immediately after 595 nm laser alone and dual wavelengths of 595 and 1064 nm laser irradiation. The melanin concentration in epidermis is

25%, corresponding to heavy pigmentation

4 Conclusion In this work, a two-temperature model is implemented to investigate the effect of wavelength in treating port wine stain lesions. In this model, the complex structure of skin with PWS is treated as a porous medium composed of a tissue matrix buried with the blood in the dermis. Following the local thermal non-equilibrium assumption of porous

media, two energy equations are deduced for the blood and other non-absorbing tissues, separately. The light distribution within the two-phase PWS layer is simulated by multi-layered Monte-Carlo method, while the corresponding thermal damage in the skin tissue is modelled by the Arrhenius integral. Typical PDL (585 and 595 nm) and near-infrared Nd:YAG laser (1064 nm) are compared for the coagulation depths in tissue with various melanin concentrations in epidermis.

The simulation results show that the therapeutic results of PWS by 585 and 595 nm lasers is highly related to the melanin concentration in epidermis. In the light pigmented skin with low melanin concentration in epidermis, 595 nm laser has better clinic result than 585 nm laser due to its larger light penetration depth in skin tissue. For a moderate melanin concentration, two lasers have similar treatment effect. In the heavy pigmented skin with high melanin concentration in epidermis, 585 nm laser seems better than that by 595 nm laser. However, the thermal damage to the deeply buried malformed blood vessels cannot be achieved by pulsed dye lasers in highly pigmented skin even the cryogen R134a spray cooling is used.

Treating port wine stains with 1064 nm laser alone, the energy dose should be carefully controlled to avoid potential thermal injury to normal dermal tissue. Working together with pulsed dye laser of 585 nm and 595 nm laser, the dual-wavelength laser system combining 585 or 595 nm with 1064 nm has better clinic result than pulsed dye laser or Nd:YAG laser used alone to treat resistant PWS blood vessels deeply buried. Furthermore, the dual-wavelength laser of 595 with 1064nm shows deeper energy deposition depth, causing better treatment effect in treating PWS with deeply-buried blood vessels than dual-wavelength laser combing 585 and 1064 nm. Acknowledgments The work is supported by Joint Research Fund for National Natural Science Foundation of China (51336006, 51228602), the International Science & Technology Cooperation Plan of Shaanxi Province (No. 2013KW30-05) and the Fundamental Research Funds for the Central University. References: [1] J.C. Alper, L.B. Holmes, The incidence and

significance of birthmarks in a cohort of 4,641 newborns, Pediatric dermatology, Vol.1, 1983, 58-68.

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[2] K.M. Kelly, B. Choi, S. McFarlane, A, Motosue, B. Jung, M.H. Khan, J.C. Ramirez-San-Juan, J.S. Nelson, Description and analysis of treatments for port-wine stain birthmarks, Arch. Facial Plast. Surg. Vol. 7, 2005, 287-294.

[3] R.R. Anderson, J.A. Parrish, Microvasculature can be selectively damaged using dye laser: a basic theory and experimental evidence in human skin, Lasers Surg. Med., Vol. 1, 1981, 263-276.

[4] J.S. Nelson, T.E. Milner, B. Anvari, et al., Dynamic epidermal cooling in conjunction with laser-induced photothermolysis of port wine stain blood vessels, Lasers Surg. Med., Vol. 19, 1996, 224-229.

[5] T. Dai, B.M. Pikkula, L.H. Wang, B. Anvari, Comparison of human skin opto-thermal response to near-infrared and visible laser irradiations: a theoretical investigation, Phys. Med. Biol., Vol. 49, 2004, 4861-4877.

[6] M.U. Yang, A.N. Yaroslavsky, W.A. Farinelli, T.J. Flotte, F. Rius-Diaz, S.S. Tsao and R.R. Anderson, Long-pulsed neodymium: yttrium-aluminum-garnet laser treatment for port-wine stains, J Am Acad Dermatol, Vol. 52, 2005, 480-490.

[7] G. Shafirstein, L.M. Buckmiller, M. Waner, W. Bäumler, Mathematical modeling of selective photothermolysis to aid the treatment of vascular malformations and hemangioma with pulsed dye laser, Lasers Med. Sci., Vol. 22, 2007, 111-118.

[8] W. Bäumle, A. Vogl, M. Landthaler, M Waner, G. Shafirstein, Port wine stain laser therapy and the computer-assisted modeling of vessel coagulation using the finite elements method. Medical Laser Application, Vol. 20, 2005, 247-254.

[9] G. Aguilar, S.H. Diaz, E.J. Lavernia, J.S. Nelson, Cryogen spray cooling efficiency: improvement of port wine stain laser therapy through multiple-intermittent cryogen spurts and laser pulses, Lasers Surg. Med., 31, 2002, 27-35.

[10] W.C. Jia, B. Choi, W. Franco, J. Lotfi, B. Majaron, G. Aguilar, J.S. Nelson, Treatment of cutaneous vascular lesions using multiple-intermittent cryogen spurts and two-wavelength laser pulses: numerical and animal studies, Lasers Surg. Med., Vol. 39, 2007, 494-503.

[11] G.W. Lucassen, W. Verkruysse, M. Keijzer, M.J.C. van Gemer, Light distribution in a port wine stain model containing multiple

cylindrical and curved blood vessels, Lasers Surg. Med., Vol. 18, 1996, 345-357.

[12] J.W. Tunnell, L.V. Wang, B. Anvari, Optimum pulse duration and radiant exposure for vascular laser therapy of dark port wine skin: A theoretical study, Appl. Opt., Vol. 42, 2003, 1367-1378.

[13] D. Li, G.X. Wang, Y.L. He, K.M. Kelly, W.J. Wu, Y.X. Wang and Z.X. Ying, A two temperature model for selective photo-thermolysis laser treatment of port wine stains, Applied Thermal Engineering., Vol. 59, 2013, 41-51.

[14] D. Li, Y.L. He, G.X. Wang, Y.X. Wang and Z.X. Ying, A new model of selective photothermolysis to aid laser treatment of port wine stains, Chinese Science Bulletin, Vol. 58, 2013, 416-426.

[15] B. Chen, S.L. Thomsen, R.J. Thomas, J Oliver, A.J. Welch, Histological and modeling study of skin thermal injury to 2.0 μm laser irradiation, Lasers Surg. Med., Vol. 40, 2008, 358-370.

[16] D. Li, D. Farshidi, G.X. Wang, Y.L. He, K.M. Kelly, W.J. Wu, Z.X Ying and B. Chen. A comparison of microvascular responses to visible and near-infrared lasers, Lasers in Surgery and Medicine., Vol. 46, 2014, 479-487.

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