Reconstructing in vivo reflectance spectrum of pigmented skin lesion by Monte Carlo simulation

Shuang Wanga,b,c, Qingli He*,a, Jianhua Zhaoa,b , Harvey Luib,c, Haishan Zengb,c

aDepartment of Physics, Northwest University, Xi’an, Shaanxi 710069, China

b Integrative Oncology Department, British Columbia Cancer Research Centre, Vancouver, BC, V5Z 1L3, Canada

c Laboratory for Advanced Medical Photonics, Photomedicine Institute, Department of Dermatology and Skin Science, University of British Columbia and Vancouver Coastal Health Research Institute,

Vancouver, BC, V5Z 4E8, Canada

Abstract In dermatology applications, diffuse reflectance spectroscopy has been extensively investigated as a promising tool for the noninvasive method to distinguish melanoma from benign pigmented skin lesion (nevus), which is concentrated with the skin chromophores like melanin and hemoglobin. We carried out a theoretical study to examine melanin distribution in human skin tissue and establish a practical optical model for further pigmented skin investigation. The theoretical simulation was using junctional nevus as an example. A multiple layer skin optical model was developed on established anatomy structures of skin, the published optical parameters of different skin layers, blood and melanin. Monte Carlo simulation was used to model the interaction between excitation light and skin tissue and rebuild the diffuse reflectance process from skin tissue. A testified methodology was adopted to determine melanin contents in human skin based on in vivo diffuse reflectance spectra. The rebuild diffuse reflectance spectra were investigated by adding melanin into different layers of the theoretical model. One of in vivo reflectance spectra from Junctional nevi and their surrounding normal skin was studied by compare the ratio between nevus and normal skin tissue in both the experimental and simulated diffuse reflectance spectra. The simulation result showed a good agreement with our clinical measurements, which indicated that our research method, including the spectral ratio method, skin optical model and modifying the melanin content in the model, could be applied in further theoretical simulation of pigmented skin lesions. Keywords: Monte Carlo simulation, Junctional Nevus, Reflectance Spectroscopy

1. INTRODUCTION In dermatology, diffuse reflectance spectroscopy has been extensively investigated by a need for noninvasive methods to distinguish skin cancer from benign lesions, especially for the pigmented skin cancer. The measured spectra could exhibit some entangled information regarding the scattering and absorption of light in tissue, and show molecule or pathology changes[1-4]. In order to understand detailed spectral properties, it is needed a theoretical model describing the diffuse reflectance in terms of light-tissue interaction[5] Even though there are several models describing diffuse reflectance spectra from biological tissue, most of which involve approximations to the radiative transport equation which incorporate potential inaccuracies and deviations in the final model[6, 7]. Monte Carlo simulation of light transport provides a numerically solution to light propagation in scattering biological tissues, which is an important tool for describing elastic-scattering spectroscopy from biological tissue[7, 8]. Based on radiative transfer theory, the microscopic properties could be described by three transport parameter: the absorption coefficient μa; the scattering coefficient μs; and the scattering coefficient g. In addition, the microscopic chromophore distribution inside the tissue determines the propagation of the in vivo diffuse reflectance signal. Therefore, a complete understanding of in vivo spectra must therefore consider all the above factors. As one of the most ubiquitous and biologically natural pigments, melanin has significant effects on the optical properties of normal and pigmented diseased skin[1, 9]. Melanin distribution and content in skin is an important factor for skin optical properties[1, 9-11]. Many groups devised optical models and algorithms for evaluation in vivo skin pigmentations by

Tenth International Conference on Photonics and Imaging in Biology and Medicine (PIBM 2011),edited by Qingming Luo, Lihong V. Wang, Valery V. Tuchin, Proc. of SPIE Vol. 8329, 83290Y

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investigate[1, 12, 13]. Also, our group has published a series of study to measure and study the reflectance spectra from pigmented skin lesions. Moreover, our previous experimental results demonstrate that skin fluorophore/chromophores distribution is not uniform, but has a layered structure indicating a layered skin model related the anatomical structure[14-16]. Thus, we intend to build a practical optical model of pigmented skin lesion based on published skin tissue optical properties and by adding different melanin factors into different location of the model. Monte Carlos simulation was employed to simulate photon propagation in optical model and calculate the diffuse reflectance of the model skin.

2. METHOD 2.1In vivo measurements

In vivo diffuse reflectance spectral system consists of a light source, a bifurcated fiber bundle, a skin probe and miniature CCD spectrometer[17]. It can be used to acquire both in vivo diffuse reflectance and fluorescence spectra. For the reflectance measurements, the light source is a quartz tungsten halogen lamp; for the fluorescence measurements, the light source is a filtered mercury arc lamp with an inline long pass filter in the collection path. The spectral measurement results of the normal skin and junctional nevus all come from our clinical measurements in the Skin Care Centre, Vancouver General Hospital. In this study, one case from the spectra database were chosen randomly and reconstructed by Monte Carlo simulation.

Fig. 1 The miniature fiber optic spectrometer system for in vivo skin autofluorescence and diffuse reflectance spectrum measurement. 2.2Theoretical modeling

Seven-layer optical model for normal skin We have previously published a systematic study on the modeling of light-tissue interaction of normal skin[14, 15]. Skin is a layered structure interspersed with various appendages, which we will ignore for the purposes of this discussion. A simplified seven-layer skin optical model for normal skin (Table 1)[14] was revised to determine the optical parameters of different skin layers in the pigmented model using published skin optical parameters by van Gemert et al[18]. Table 2 outlined seven-layer model by providing data for the thickness (d), refractive index (n), and the optical transport parameters (μa – absorption coefficient, μs – scattering coefficient, and g – scattering anisotropy) at 400 nm for each skin layer. Tissue optical parameters at 400 nm of the upper and deep blood plexus were calculated by the following matrix formula[14, 19-21]:

(1) where f1 and f2 are the percentages of individual component, superscripts 1 and 2 in the first matrix on the right side of the equation denote the optical properties of components 1 and 2, respectively. For example, the upper blood plexus took up 10% blood (f1 =0.1) and 90% dermal tissue (f2=0.9) in the optical tissue model. So the refractive index of the upper blood plexus was estimated as n=1.4×0.09+1.33×0.10=1.39. Tissue optical parameters at other wavelength were derived in a similar fashion.

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Table 1: A simplified Seven-layer Skin Model

Optical model for junctional nevus An optical model of junctional nevus, which is a mole found in the junction (border) between the skin epidermis and dermis layers, has been build based on published skin tissue optical properties and by adding melanin contents into different location of the skin model. We further modified the skin optical model into an eight-layer model, which has added a new layer (junctional layer, 10 μm thickness) into the model, which combines 5 μm epidermis layer and 5μm dermis for the purpose to model junctional nevus theoretically. Therefore, epidermis and dermis each contributes half of the optical parameters in this layer, respectively. We further modified the skin optical model into an eight-layer model (shown in Table 3).

Table 2: Eight-layer Skin optical model for Junctional Nevus Layer d(μm) n μ

s(cm-1) μ

a(cm-1) g

Air - 1.0 - - - Stratum corneum 10 1.45 2200 220 0.9

Epidermis 75 1.4 580 71 0.736 Junctional layer 10 1.4 6 40 0.736

Papillary dermis 95 1.4 800 9 0.736 Upper blood plexus 80 1.39 740 269.132 0.785

Reticular dermis 1500 1.4 800 9 0.736

Deep blood plexus 70 1.34 560 1049.528 0.931 Dermis 160 1.4 800 9 0.736

Subcutaneous fat - 1.46 - - -

3. RESULTS AND DISCUSSIONS Before the simulation, the melanin contents in normal skin and Junctional nevus of each case were calculated. An algorithm, which was developed and tested by Stamatas et al[22] for evaluating melanin content from in vivo reflectance spectrum, was adopted in this work to determine melanin factors based on our in vivo measurements. One case of Junctional nevi, measured in the Skin Care Centre, Vancouver General Hospital, Vancouver, Canada, have been chosen randomly from our clinical database. Figure 1 shows the measured spectrum of this case, where “J” denotes Junctional nevus and “N” denotes normal skin tissue. With this algorithm, we have calculated the melanin concentration in normal skin is Cm_normal=9.4%, and the melanin concentration in junctional nevus is Cm_lesion=21%.

Layer d(μm) n μs(cm-1) μ

a(cm-1) g

Air - 1.0 - - - Stratum corneum 10 1.45 2200 220 0.9

Epidermis 80 1.4 580 71 0.736 Papillary dermis 100 1.4 800 9 0.736

Upper blood plexus 80 1.39 740 269.132 0.785 Reticular dermis 1500 1.4 800 9 0.736

Deep blood plexus 70 1.34 560 1049.528 0.931 Dermis 160 1.4 800 9 0.736

Subcutaneous fat - 1.46 - - -

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Figure 1:In vivo reflectance spectrum of junctional nevus and its surrounding normal skin. “J” denotes junctional nvevus and “N” denotes normal skin tissue.

The Monte Carlo code from Wang and Jacques[23] was used directly, without any modifications to calculate the diffuse reflectance to reconstruct the diffuse reflectance spectra of normal skin and Junctional nevus) with various skin optical model (melanin in epidermis only, melanin in Junctional layer only, and melanin in both epidermis and Junctional layer). In the simulation, 100,000,000 photons were launched for each wavelength point. The reflectance spectra ranging from 400 nm to 700 nm were calculated using a 20 nm interval, and hence a total of 16 data points were generated to form each reflectance spectrum curve. Figure 2 shows the rebuilt reflectance spectra. In the figure, “N” denotes “normal skin”; “J” denotes “Junctional nevus”; “J/N” denotes the spectral intensity ratio between Junctional nevus and normal skin; “in vivo J/N” denotes the spectral ratio of clinical results; and “MC_J/N” denotes the spectral ratio of reconstructed diffuse reflectance spectra. Fig. 2a and 2b are the calculated diffuse reflectance spectra by MC simulation with melanin distribution in the epidermis layer and the corresponding spectral ratio of the in vivo experimental results and MC rebuilt results. Fig. 3a and 3b are the rebuilt reflectance spectrum with the model that half of melanin is concentrated in the epidermis layer and the other half is distributed in the junctional layer and their corresponding spectral ratio curves of the in vivo experimental results and MC rebuilt results.

(a) (b)

Figure 2: (a) the calculated diffuse reflectance spectra by MC simulation with melanin distribution in the epidermis layer;(b) the corresponding spectral ratio of the in vivo experimental results and MC rebuilt results.

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(a) (b)

Figure 3: (a) the rebuilt reflectance spectrum with the model that melanin distribute in both epidermis and Junctional layers; (b) the corresponding spectral ratio of the in vivo experimental results and MC rebuilt results.

Analysis of Figs. 2 & 3 suggests that the MC calculated reflectance spectra are very similar to the experimental reflectance spectra with some characteristics. Normal skin area has higher reflectance intensity than Junctional nevus, because there is less melanin absorption in the superficial layer of normal skin tissue than Junctional nevus skin. The general intensity trend and spectral shape of the reflectance ratio curves by MC simulation was determined by melanin distribution. If assuming melanin only distributed in the Junctional layer, the reflectance spectral ratios were not in good agreement with those of in vivo measurement as shown in Fig. 2a and Fig. 2b. However, if assuming melanin is distributed in both the epidermis layer and the Junctional layer, the MC simulated reflectance spectral ratios were in perfect agreement with those of the experimental results as shown in Fig. 3a and Fig. 3b. The simulation results showed that reflectance spectra calculated by MC simulation were in good agreement with the experimental results. Similar reconstructed spectra are observed when we suppose that the tissue were pigmented in the same pattern. Because hemoglobin absorption and different melanin factors were added into the model, the simulated reflectance intensity slightly varied. However, we can achieve a good agreement with clinical results when we add melanin factors into both the epidermis and the Junctional layer, shown in Fig. 3aand Fig. 3b. We attribute this to the histology nature of Junctional nevus, where melanocytic nevus cells are proliferated into the dermoepidermal junction[24].

4. CONCLUSIONS: In summary, we designed an eight-layer skin model to incorporate melanin distribution in pigmented skin lesions. The effect of skin melanin content and distribution on skin diffuse reflectance spectra was studied by tissue optical model and MC simulation. The reconstructed reflectance spectra, which were randomly picked from our database, were calculated by MC simulation and showed in agreement with the experimental data with melanin distributed in both the epidermis layer and Junctional layer. From this study, we found out that Junctional nevus could be modeled for studying the effect of skin melanin content and distribution on skin spectroscopy properties. Based on the adopted methodology, the content of melanin in pigmented skin lesion could be determined by the in vivo diffuse reflectance spectra. Moreover, combining the skin optical model with MC simulation, the reflectance and other spectroscopic properties of pigmented skin tissue could be simulated and predicted. The research methods, including the spectral ratio method, the method of adding and modifying the melanin content in skin optical model, and MC simulation could be applied in other theoretical simulation of pigmented skin lesions.

5. ACKNOWLEDGEMENT: This work is partially supported by the Nature Science Fund of Shaanxi Province (No. 2010JK868), The Canadian Institute of Health Research, the Canadian Cancer Society, and the Canadian Dermatology Foundation.

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