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Optical visualization of skin oxygen saturation for dermatological applications
Optik - International Journal for Light and Electron Optics 204 (2020) 163948
Contents lists available at ScienceDirect
Optik journal homepage: www.elsevier.com/locate/ijleo
Original research article
Optical visualization of skin oxygen saturation for dermatological applications
T
Audrey Huonga,*, Xavier Ngub a b
Faculty of Electric and Electronic Engineering, Universiti Tun Hussein Onn Malaysia, 86400, Johor, Malaysia Centre for Applied Electromagnetics, Universiti Tun Hussein Onn Malaysia, 86400, Johor, Malaysia
A R T IC LE I N F O
ABS TRA CT
Keywords: Antioxidant Cosmeceutical Optics Skin lesion Skin oxygen
The role of oxygen in skin care is well known for assisting in skin rejuvenation and repair. This work is an unprecedented scientific and clinical effort to understand changes in percent skin oxygen saturation level (StO2) with topical application of a range of oxygen therapeutic skin care products, and in a course of skin breakout, using a newly developed three-wavelength system in a trial involving a total of eight volunteers. This technology is able to provide measurable positive effects on facial StO2 of the recruited volunteers one week after the topical application of oxygen creams with mean (standard deviation, SD) relative change in StO2 of 5.8 (4.6) %. Meanwhile a case study using this system on an individual with untoward skin condition revealed a drastic change in the mapping of StO2 values from the formation of papule to pustule, and to its encrustation. This optical technology could be a significant breakthrough in the dermatology research by redefining pharma-cosmeceutical research design and process in the development of skin care products by evaluating the efficacy of these products in improving skin oxygen level. In the future, this system may have major applications in the translational research of human physiology and pharmacology.
1. Introduction The human skin, a complex integrity and ordered organization of cells, is considered as the largest organ in mammalian body; it functions as a protective barrier for the delicate organs inside from abrasive and harsh external environments. Skin disfigurement, also known as skin imperfection, comes in the form of vitiligo, age spots, scarring, skin diseases (such as acnes, eczema, psoriasis, rosacea, etc). These skin conditions particularly that on the facial region have negative impact on its bearer’s life. This problem is exacerbated by the media’s glamorization of flawless skin, which invariably portray skin imperfection in a negative light. It was reported in [1,2] that skin problem is likely to affect one’s psycho-social and emotional well-being, and this group of populations have high prevalence of depression and impaired self-esteem. The latter often unraveled through the selection of social activities and clothing practice, exhibiting social avoidance behavior, and affecting the person’s intimate relationship or behavior. The skin condition also subjected its bearer to public teasing and ridicule, including many reported struggling with limited career choice [3]. Appearance is so important to confidence that many have chosen to spend some time on their beauty and grooming regimes before starting their days. Whilst cosmetic camouflage is a most practiced non-surgical approach to conceal disfigurements hence providing both physical and psychosocial improvements [4], graphic editing tools such as Photoshop and photo editing apps are available to enhance a person’s appearance to achieve visual, but virtual, favorable results due to their competitive cost and wide
⁎
Corresponding author. E-mail address: [email protected] (A. Huong).
https://doi.org/10.1016/j.ijleo.2019.163948 Received 8 August 2019; Received in revised form 26 November 2019; Accepted 30 November 2019 0030-4026/ © 2020 Elsevier GmbH. All rights reserved.
Optik - International Journal for Light and Electron Optics 204 (2020) 163948
A. Huong and X. Ngu
accessibility. This ever increasing demand and societal perceptions of skin perfection leads to a booming in cosmetic and beauty industries. A report in year 2018 by market intelligence agency Mintel revealed £ 1.15 billion was spent by human population in the United Kingdom on the facial skincare in year 2017 alone [5]. This statistic is expected to rise to £ 1.36 billion in 2023. The related report also showed a tremendous increase in global cosmetic market (cosmetic, skin care and beauty products and services) with Mintel projected an increase in this market revenue from USD 46.2 billion in year 2015 to USD 61.2 billion in 2020 [6]. Recent years have witnessed predominance of cosmeceutical industry that comprehensively integrates the formulation of active ingredients in jar of creams for sustained improvement of the skin [7]. The role of oxygen in a wide range of skin care products is well known for assisting in skin rejuvenation and repair, to reverse signs of aging and hence to improve the general skin appearance. The efficacy of majority of these products was evaluated based on the questionnaires feedback obtained from the users recruited in its clinical trial, while others were via the conducted animal trials [8]. This is often a geographical limited trial depending on factors such as population’s genetic, climate, culture, environment, and other demographic factors, such as age, education level, health and skin condition, and socio-economic status. Facial oxygen therapy, which option is considered as expensive and inaccessible for many, is claimed able to boost the oxygen level in skin. There are, however, mixed responses to the efficacy of this technology, with many argued the observed temporarily plumped and youthful skins is due to the swollen effects as a result of the bombardment of the molecule particles on the skin cells. Different technologies have emerged in recent years in the efforts to provide an unbiased and scientific verification on the products’ claims by predicting skin age, pigmentation and moisture level [9]. To the best of the authors’ knowledge, no technology is available to date to predict facial skin oxygen level; the closest technology for single point skin tissue measurement is by using InSpectra StO2 monitor. This corresponding system requires the use of an adhesive tape for placement of its sensor during its operation, limiting their application to un-wounded and non-facial region. Still continuing research works have been carried out to develop and improve systems for non-contact and non-invasively monitor skin tissue oxygen saturation (see [10] for discussions of some earlier works). Even though these systems have certain limitations in their operation (e.g. the need for calibration or bulkiness of the system), the algorithm and system used, and the contribution to the existing knowledge of skin oximetry are worth mentioning. In addition, some interesting works carried out by [11–13] showed the feasibility of using measurement of StO2 for indirect prediction of glucose level and human physiological information. This research aims to perform an unprecedented investigation on changes in facial StO2 level following the topical applications of oxygen therapeutic products and in a course of skin breakout using a developed handheld three-wavelength system. The development of this system for non-invasive measurement of StO2 level was presented in an earlier work [14]; the outputs of this system were also evaluated and compared with that given by other similar optical technologies. This system allows visualization of differences in StO2 level for tissues within field of view of the camera, and the results are presented in two-dimensional image (i.e. StO2 map). 2. Materials and methods 2.1. Subjects This study recruited ten Asian subjects aged between 20 and 25 years in a voluntary skin cream clinical trial, and an Asian woman aged 35 year old for the case study of facial skin disorder. The participants in the skin cream trial were chosen based on their skin condition and lifestyles; they were presented with no scar, birthmark or any forms of skin lesions, swelling, inflammation and infections (i.e. acnes, eczema and psoriasis) on their face region. Other inclusion criteria include facial skin color was in the range of II-IV according to the Fitzpatrick Scale. All volunteers were non-smokers and are of Malaysia origin; they declared no serious underlying illnesses (i.e. kidney or renal diseases, diabetes, heart diseases and anemia), and had similar diets, daily routines throughout the time of study. Pregnant or breastfeeding women or those who planned to conceive were excluded from this study. This non-profit, single blind trial was reviewed and approved by the Human Research Ethics Committee (HREC) of Universiti Tun Hussein Onn Malaysia (Ref no. UTHM/RMC.100-9/39(22)). This study was conducted according to the Helsinki’s declaration. 2.2. Study procedures The selected participants were briefed and received written information on the experimental procedures, and the ethics approval we obtained. They gave their signed informed consent prior to data collection on the day first measurement was taken. Under the skin cream trial, facial StO2 level measured from both the left and right cheek regions of these subjects prior to the commencement of the trial was used as baseline. Due to the time and budgetary limitations of this study, this research did not allow all subjects to receive the same products for every topical cream. Each volunteer was provided with a skin cream of volume 15 mL randomly selected through lot-drawing. Among the skin care products to be chosen were creams claimed to contain oxygen therapeutic formula (Product A–C) and ordinary skin care creams (Product D and E), which were used as the testing and control samples, respectively. The identity of these products was blinded to all subjects. These participants were instructed to patch-test the obtained product on areas behind their ears for two days consecutively to detect possible reactions to the supplied cream. The cream was topically applied by the volunteers themselves as instructed and was to be used together with their routine skin care products twice daily for three weeks if no adverse effects were experienced after the patch test. The follow-up was by weekly facial StO2 measurements after the application of the cream for a period of three weeks. The framework of this study is shown in Fig. 1. Each user was required to complete a set of questionnaires on their own perceptions of the supplied cream at the third week. There are four parameters to be evaluated; each parameter was assigned with score value 1–3 2
Optik - International Journal for Light and Electron Optics 204 (2020) 163948
A. Huong and X. Ngu
Fig. 1. Study scheme of skin cream trial.
indicating poor to excellent, respectively. Of the ten volunteers enrolled in this study, only seven remained at the end of the trial as shown in Fig. 2. This study also conducted an exploratory examination of StO2 level for acne affected skin of an individual who was not involved in the aforementioned trial shown in Fig. 2. The corresponding skin is located at the chin region of the subject, five measurements were recorded from the corresponding site for three days consecutively, from the formation of a sebum plug to the day skin encrustation was observed.
2.3. Optical imaging technology The schematic diagram of the developed skin oxygen monitor is shown in Fig. 3. A brief description of this system is provided in the following. This system used light emitting diodes (LEDs) of center wavelengths 532 nm, 560 nm and 650 nm selected based on the reports of [15] as its light sources. These LEDs were arranged in annular order surrounding a Complementary Metal Oxide Semiconductor (CMOS) (part no. CW-835) imager placed at the center of the system. Makeshift ring-shaped diffuser made of opaque sheet was placed in-front of the emitter ring to allow diffuse illumination of the examined skin site. Light reflected from the skin surface was received by the CMOS (focal number, f/# = 1) with an aperture diameter of 2.5 mm and exposure time of 0.25 s. The field of view of this imaging system is given by 15 mm × 20 mm and the produced image resolution is 640 × 480 pixels. Both light emitters and the imager were placed inside an enclosed compartment, and at a distance of approximately 30 mm from the skin surface. These LEDs of different wavelength were sequentially turned on at a sampling time of 3 s. Reflectance image at each wavelength was captured and quantized for processing by a microcontroller unit of analog-digital converter (ADC) resolution of 10 bits. The output was sent to a processing unit via Universal Serial Bus (USB 2.0) to predict for the most probable StO2 level. The entire data acquisition
Fig. 2. Consort diagram of skin cream trial and case study of skin inflammation. 3
Optik - International Journal for Light and Electron Optics 204 (2020) 163948
A. Huong and X. Ngu
Fig. 3. Schematic diagram of the topical system. (Image inset) An illustration of the use of the system in this study.
and measurement process took approximately 10 s. The cartographic illustration of the predicted distribution of StO2 level (StO2 map) shown in Fig. 3 was via a standalone user interface. The processing of the recorded images was via MATLAB (version 2018a). All these components were arranged and inserted into a hollow-core structure as shown in the inset of Fig. 3. The prediction of StO2 is by using a wavelength dependent Modified Lambert Beer Model in [15], and is based on light attenuation (A), and molar extinction coefficient of oxyhemoglobin (εoxyHb) and deoxyhemoglobin (εdHb) of the employed three wavelengths. The feasibility of using this model and the choice of the wavelengths used here were studied using Monte Carlo method in [16] for possible integration of technology into functioning portable systems. The light attenuation value is calculated from the grayscale converted images and is given by the negative logarithm of the ratio of recorded light reflectance image from skin region, IS, to that from spectralon white reference panel, IW, at wavelength, λ, as followed:
A (λ ) = −20 log
IS (λ ) . IW (λ )
(1)
The percent StO2 is expressed as [15]:
St O2(p) =
A1 (λ2 εdHb3 − λ3 εdHb2) + A2 (λ3 εdHb1 − λ1 εdHb3) + A3 (λ1 εdHb2 − λ2 εdHb1 ) × 100 % A1 (λ3 Δε2 − λ2 Δε3) + A2 (λ1 Δε3 − λ3 Δε1) + A3 (λ2 Δε1 − λ1 Δε2 )
(2)
where Δε represents the difference between εoxyHb and εdHb, while the numerical subscript in Eq. (2) denotes index for λ, with 1 = 532 nm, 2 = 560 nm and 3 = 650 nm. Next the StO2 value in Eq. (2) was corrected in Eq. (3) following the discussions in [16] on the insufficiency of attenuation model:
St O2 = 1.85 St O2(p) − 43.4
(3)
The upper and lower threshold values of percent StO2 are chosen as 120 % and 0 %, which limits are based on the 95 % and 5 % of the StO2 distributions identified in this and in earlier work from this laboratory [14]. The flow of the StO2 prediction process for a selected skin region is shown in Fig. 4. 3. Results and analysis The StO2 map averaged from the right and left cheek regions of each individual predicted prior to the trial and on different trial week after the topical application of the supplied skin care product is shown in Table 1. The color bar shown at the bottom of the table indicates the magnitude of the percent StO2. The red colored regions in StO2 map correspond to higher StO2, while the blue ones correspond to lower values. Based on these results in Table 1, the percent relative change in StO2 map, Δd, for the whole imaged area for example that shown in Fig. 4 for each subject is calculated using Eq. (4) to reduce possible systematic error within the experiment. The mean and standard deviation (SD) of the calculated Δd are plotted in Fig. 5.
Δd =
Sn − Sb × 100 % Sb
(4)
where Sb and Sn denote StO2 map of baseline and nth trial week. Questionnaire survey conducted at the third week of the trial obtained positive feedbacks (satisfactory rating of 95 %) from all volunteers. Meanwhile changes in StO2 value during an episode of skin lesions in the case study of skin inflammation is presented in Table 2. Five measurements of StO2 for lesioned tissues were collected over duration of 3 days. Also shown in this table is the image of the skin condition (second column of the table) from the formation of papule (in measurement 1 and 2), to pustule (measurement 3), to its rupture (measurement 4) and encrustation (measurement 5). The location of the papule on skin image and its corresponding StO2 map is indicated by arrows. 4
Optik - International Journal for Light and Electron Optics 204 (2020) 163948
A. Huong and X. Ngu
Fig. 4. Flow diagram of image processing.
4. Discussion Based on the results shown in Table 1 and Fig. 5, it was shown that there is an overall marked increase in facial StO2 level for the group treated with oxygen products in the trial weeks as compared to that measured prior to the trial. The mean (SD) of Δd observed for volunteers I–V is given by 5.8 (4.6) % and 4.56 (5.9) %, respectively, for trial week 1 and 3. All the considered oxygen products contained active ingredients with antioxidant properties (e.g. enzymes/extracts containing vitamin A, C and E, hydroxyl acids (HA)), which superior role in slowing down oxidation process was well documented [7,17–19], henceforth reinforcing the possibility that StO2 is related indirectly to the oxidation process. The increase in this value is positively correlated with the treatment week. This is with the exception of subject II and IV, wherein the results in Fig. 5 showed a drop in Δd for both of these volunteers from mean (SD) Δd of 4.34 (6.4) % measured in the first week to −2.3 (9.68) % in the third trial week. Another interesting finding of this paper is the 5
Optik - International Journal for Light and Electron Optics 204 (2020) 163948
A. Huong and X. Ngu
Table 1 The StO2 map predicted for different volunteers in skin cream trial before (Baseline) and after 1 and 3 weeks study for the investigation (subject I–V) and control groups (subject VI-VII). Subjectproduct
Baseline
Trial week 1
Trial week 3
a
I
IIa
IIIb
IVc
Vc
VId
VIIe
a b c d e
Oxygen therapeutic product (Product A). Oxygen therapeutic product (Product B). Oxygen therapeutic product (Product C). Control product (Product D). Control product (Product E).
inconsistency in the pattern of Δd in individuals (subject I and II, and subject IV and V) using the same product; the results in Fig. 5 revealed the opposite magnitude direction in Δd for these subjects. Since all subjects responded positively in the questionnaire survey with satisfactory rating of 95 %, these observations could be best interpreted as the diversity of one’s natural antioxidant reservoir, hence affecting biological cells response towards the topical antioxidation treatment. The similar finding was reported in [18,20,21] and was attributed to factors such as hormonal change, stress level, environment condition, and the activity, amount of rest and fatrich food these individuals were taking in days leading to the experiment. Of the results shown in Fig. 5, subject IV shows the largest variation in the calculated relative StO2 change for both trial weeks, further inspection into the data of this subject confirmed the present of one outlier value recorded during baseline. Removing this outlier brings the SD values down to around 5–6 %, while not much difference was observed in the respective mean values from Fig. 5. Interestingly, even though the drop in percent StO2 level was noticeable in the control group, with the mean (SD) Δd calculated as −11.95 (2) % and −7.94 (2.4) %, respectively, for trial week 1 and 3, following the use of non-oxygen boosting skin care products, the recruits did not report adverse skin reactions both during and after the trial completion. It must be mentioned that the ingredients stated in the formula of these control products have not had previous reports on their pro-oxidation effects. Thus the positive feeling experienced by the respondents in this group may suggest the effects of other active ingredients in the supplied cream (such as minerals with anti-inflammation, moisture, pH stabilizer and antibacterial properties). Even though the employed three-wavelength technology has not been able to quantitatively identify the skin condition where 6
Optik - International Journal for Light and Electron Optics 204 (2020) 163948
A. Huong and X. Ngu
Fig. 5. Mean and standard deviation (SD) of percent relative change in the StO2 map, Δd, of the recruits (represented by symbol subject I-VII) in first (w1) and third week (w3) of the trial. A black dotted line is drawn at zero relative change for reference. Table 2 Changes in facial StO2 level with progression of skin lesion. Measurement
Skin image
StO2 map
1
2
3
4
5
7
Optik - International Journal for Light and Electron Optics 204 (2020) 163948
A. Huong and X. Ngu
oxidation and antioxidation processes are in its optimal balance, and whence the skin health is at its optimum, the qualitative feedbacks from the respondent was taken here as empirical validation of their skin health; and the survey results showed an overall good rating of 95 % (or 2.85 of 3). On this note, the results in Table 1 may suggest the variation in optimum oxygen absorption capacity of cells among individuals, where the highest possible StO2 value (red colored regions) might not necessary indicate the optimum skin condition. In addition, this work observed a shorter time (i.e. 1 weeks) for the topical cream to take effect as compared to the duration of 1–3 months reported in [22]. Unlike the minute changes in StO2 shown in Table 1 for volunteers with no untoward skin conditions, Table 2 showed pronounced changes in the pattern of StO2 map for the inflamed skin. Pores clogged with oily substances (i.e. sebum) facilitate bacterial growth under the skin; this growth is stimulated in the presence of oxygen deprivation condition [23]. This is evidence in the StO2 maps shown in Table 2, which showed a comparative lower StO2 range (encircled by black line in measurement 1) of 30–40 % at the skin proximal to the papule; this condition promotes build-up of bacteria, resulting in pus filled lesion in measurement 2. The lesion further aggravated into pustule in measurement 3, where there is visible inflammation of the skin; at the same time there is a progressive increase in StO2 of approximately 90–110 % around the pustule (indicated by black dashed line in measurement 3) leading to its rupture in measurement 4. This sequential event is due to the body autoimmune system as a defense towards the bacteria inflammation. It is interesting to note on the uniformly high percent StO2 level of 80–95 % in measurement 4, although the magnitude has descended as compared to its preceding episodes, in regions around the affected skin. This relatively high StO2 level around the open wound helps to reduce swelling, accelerates the growth of new blood vessels (angiogenesis) that is essential in wound healing, and prepares the body with necessary energy component to fight and prevent infection. The encrustation of the pustule shown in the final measurement revealed a significant drop in the skin StO2 level to 65–80 % range, which was shown to return to that similar to the surrounding unaffected skin. These changes in StO2 with acute wound healing process agreed remarkably well with the previous studies using comparatively complex technologies presented in [24–26]. Even though the study on long term effects and performance of each antioxidant components are not being able to carry out in this time-limited trial, the overall increase in the skin StO2 for subjects in the investigation group suggests the likelihood of oxygen therapeutics functionality of the considered products within the considered duration. It is recognized that the performance of skin care products should be explored extensively using quantitative tools so that their effectiveness for the claimed applications could be confirmed before reaching the markets. Hence, the system used herein could be of the interest of scientists from cosmeceutical industry in the evaluation of products for treatment of skin disorders and problems, and on the claimed benefits. 5. Conclusion This research presented the use of optical technology as a promising tool to reveal StO2 level, with the aim to supplement the use of globally accepted qualitative survey techniques in cosmeceutical industry, in the evaluation of efficacy of the marketed skin care products for the claimed benefits. This study has seen remarkable increase in StO2 level in the group of subjects using different types of considered oxygen therapy creams after the first week of topical application. The opposite trend was observed in the control group. The detected sequential change in StO2 with different episodes of skin outbreak further supported the feasibility of using this technology in the cosmeceutical research and development. In addition, this technology may also be beneficial in the research of glucose metabolism and in studies of human physiological responses. Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Acknowledgements The authors are grateful to Ministry of Education Malaysia (K038 and 1581) and Universiti Tun Hussein Onn Malaysia for financially supporting this work. Special thanks must go to Tsen Vui Hin and Ong Pek Ek for their help during system development phase, and Sheena Philimon for her help in clinical selection of subjects. Last but certainly not least, thanks must go to all individuals involved in the study. References [1] F.E. Fox, N. Rumsey, M. Morris, Ur skin is the thing that everyone sees and you cant change it!- exploring the appearance-related concerns of young people with psoriasis, Dev. Neurorehabil. 10 (2007) 133–141. [2] D.L. Harris, A.T. Carr, Prevalence of concern about physical appearance in the general population, Br. J. Plast. Surg. 54 (2001) 223–226. [3] P. Magin, J. Adams, G. Heading, D. Pond, W. Smith, Experiences of appearance-related teasing and bullying in skin diseases and their psychological sequele: results of a qualitative study, Scand. J. Caring Sci. 22 (2008) 430–436. [4] R. Kornhaber, D. Visentin, D.K. Thapa, S. West, A. Mckittrick, J. Haik, M. Cleary, Cosmetic camouflage improves quality of life among patients with skin disfigurement: a systematic review, Body Image 27 (2018) 98–108. [5] Britain’s Women Spend a Beautiful £ 1.15 Billion on Facial Skincare, Mintel Press, 2018 Retrieved April 20, 2019, from https://www.mintel.com/press-centre/ beauty-and-personal-care/britains-women-spend-a-beautiful-1-15-billion-on-facial-skincare. [6] 7 In 10 US Female Beauty Consumers Say its Important to Look their Best When Leaving the House, Mintel Press, 2016 Retrieved April 20, 2019, from https:// www.mintel.com/press-centre/beauty-and-personal-care/7-in-10-us-female-beauty-consumers-say-its-important-to-look-their-best-when-leaving-the-house.
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Contents lists available at ScienceDirect
Optik journal homepage: www.elsevier.com/locate/ijleo
Original research article
Optical visualization of skin oxygen saturation for dermatological applications
T
Audrey Huonga,*, Xavier Ngub a b
Faculty of Electric and Electronic Engineering, Universiti Tun Hussein Onn Malaysia, 86400, Johor, Malaysia Centre for Applied Electromagnetics, Universiti Tun Hussein Onn Malaysia, 86400, Johor, Malaysia
A R T IC LE I N F O
ABS TRA CT
Keywords: Antioxidant Cosmeceutical Optics Skin lesion Skin oxygen
The role of oxygen in skin care is well known for assisting in skin rejuvenation and repair. This work is an unprecedented scientific and clinical effort to understand changes in percent skin oxygen saturation level (StO2) with topical application of a range of oxygen therapeutic skin care products, and in a course of skin breakout, using a newly developed three-wavelength system in a trial involving a total of eight volunteers. This technology is able to provide measurable positive effects on facial StO2 of the recruited volunteers one week after the topical application of oxygen creams with mean (standard deviation, SD) relative change in StO2 of 5.8 (4.6) %. Meanwhile a case study using this system on an individual with untoward skin condition revealed a drastic change in the mapping of StO2 values from the formation of papule to pustule, and to its encrustation. This optical technology could be a significant breakthrough in the dermatology research by redefining pharma-cosmeceutical research design and process in the development of skin care products by evaluating the efficacy of these products in improving skin oxygen level. In the future, this system may have major applications in the translational research of human physiology and pharmacology.
1. Introduction The human skin, a complex integrity and ordered organization of cells, is considered as the largest organ in mammalian body; it functions as a protective barrier for the delicate organs inside from abrasive and harsh external environments. Skin disfigurement, also known as skin imperfection, comes in the form of vitiligo, age spots, scarring, skin diseases (such as acnes, eczema, psoriasis, rosacea, etc). These skin conditions particularly that on the facial region have negative impact on its bearer’s life. This problem is exacerbated by the media’s glamorization of flawless skin, which invariably portray skin imperfection in a negative light. It was reported in [1,2] that skin problem is likely to affect one’s psycho-social and emotional well-being, and this group of populations have high prevalence of depression and impaired self-esteem. The latter often unraveled through the selection of social activities and clothing practice, exhibiting social avoidance behavior, and affecting the person’s intimate relationship or behavior. The skin condition also subjected its bearer to public teasing and ridicule, including many reported struggling with limited career choice [3]. Appearance is so important to confidence that many have chosen to spend some time on their beauty and grooming regimes before starting their days. Whilst cosmetic camouflage is a most practiced non-surgical approach to conceal disfigurements hence providing both physical and psychosocial improvements [4], graphic editing tools such as Photoshop and photo editing apps are available to enhance a person’s appearance to achieve visual, but virtual, favorable results due to their competitive cost and wide
⁎
Corresponding author. E-mail address: [email protected] (A. Huong).
https://doi.org/10.1016/j.ijleo.2019.163948 Received 8 August 2019; Received in revised form 26 November 2019; Accepted 30 November 2019 0030-4026/ © 2020 Elsevier GmbH. All rights reserved.
Optik - International Journal for Light and Electron Optics 204 (2020) 163948
A. Huong and X. Ngu
accessibility. This ever increasing demand and societal perceptions of skin perfection leads to a booming in cosmetic and beauty industries. A report in year 2018 by market intelligence agency Mintel revealed £ 1.15 billion was spent by human population in the United Kingdom on the facial skincare in year 2017 alone [5]. This statistic is expected to rise to £ 1.36 billion in 2023. The related report also showed a tremendous increase in global cosmetic market (cosmetic, skin care and beauty products and services) with Mintel projected an increase in this market revenue from USD 46.2 billion in year 2015 to USD 61.2 billion in 2020 [6]. Recent years have witnessed predominance of cosmeceutical industry that comprehensively integrates the formulation of active ingredients in jar of creams for sustained improvement of the skin [7]. The role of oxygen in a wide range of skin care products is well known for assisting in skin rejuvenation and repair, to reverse signs of aging and hence to improve the general skin appearance. The efficacy of majority of these products was evaluated based on the questionnaires feedback obtained from the users recruited in its clinical trial, while others were via the conducted animal trials [8]. This is often a geographical limited trial depending on factors such as population’s genetic, climate, culture, environment, and other demographic factors, such as age, education level, health and skin condition, and socio-economic status. Facial oxygen therapy, which option is considered as expensive and inaccessible for many, is claimed able to boost the oxygen level in skin. There are, however, mixed responses to the efficacy of this technology, with many argued the observed temporarily plumped and youthful skins is due to the swollen effects as a result of the bombardment of the molecule particles on the skin cells. Different technologies have emerged in recent years in the efforts to provide an unbiased and scientific verification on the products’ claims by predicting skin age, pigmentation and moisture level [9]. To the best of the authors’ knowledge, no technology is available to date to predict facial skin oxygen level; the closest technology for single point skin tissue measurement is by using InSpectra StO2 monitor. This corresponding system requires the use of an adhesive tape for placement of its sensor during its operation, limiting their application to un-wounded and non-facial region. Still continuing research works have been carried out to develop and improve systems for non-contact and non-invasively monitor skin tissue oxygen saturation (see [10] for discussions of some earlier works). Even though these systems have certain limitations in their operation (e.g. the need for calibration or bulkiness of the system), the algorithm and system used, and the contribution to the existing knowledge of skin oximetry are worth mentioning. In addition, some interesting works carried out by [11–13] showed the feasibility of using measurement of StO2 for indirect prediction of glucose level and human physiological information. This research aims to perform an unprecedented investigation on changes in facial StO2 level following the topical applications of oxygen therapeutic products and in a course of skin breakout using a developed handheld three-wavelength system. The development of this system for non-invasive measurement of StO2 level was presented in an earlier work [14]; the outputs of this system were also evaluated and compared with that given by other similar optical technologies. This system allows visualization of differences in StO2 level for tissues within field of view of the camera, and the results are presented in two-dimensional image (i.e. StO2 map). 2. Materials and methods 2.1. Subjects This study recruited ten Asian subjects aged between 20 and 25 years in a voluntary skin cream clinical trial, and an Asian woman aged 35 year old for the case study of facial skin disorder. The participants in the skin cream trial were chosen based on their skin condition and lifestyles; they were presented with no scar, birthmark or any forms of skin lesions, swelling, inflammation and infections (i.e. acnes, eczema and psoriasis) on their face region. Other inclusion criteria include facial skin color was in the range of II-IV according to the Fitzpatrick Scale. All volunteers were non-smokers and are of Malaysia origin; they declared no serious underlying illnesses (i.e. kidney or renal diseases, diabetes, heart diseases and anemia), and had similar diets, daily routines throughout the time of study. Pregnant or breastfeeding women or those who planned to conceive were excluded from this study. This non-profit, single blind trial was reviewed and approved by the Human Research Ethics Committee (HREC) of Universiti Tun Hussein Onn Malaysia (Ref no. UTHM/RMC.100-9/39(22)). This study was conducted according to the Helsinki’s declaration. 2.2. Study procedures The selected participants were briefed and received written information on the experimental procedures, and the ethics approval we obtained. They gave their signed informed consent prior to data collection on the day first measurement was taken. Under the skin cream trial, facial StO2 level measured from both the left and right cheek regions of these subjects prior to the commencement of the trial was used as baseline. Due to the time and budgetary limitations of this study, this research did not allow all subjects to receive the same products for every topical cream. Each volunteer was provided with a skin cream of volume 15 mL randomly selected through lot-drawing. Among the skin care products to be chosen were creams claimed to contain oxygen therapeutic formula (Product A–C) and ordinary skin care creams (Product D and E), which were used as the testing and control samples, respectively. The identity of these products was blinded to all subjects. These participants were instructed to patch-test the obtained product on areas behind their ears for two days consecutively to detect possible reactions to the supplied cream. The cream was topically applied by the volunteers themselves as instructed and was to be used together with their routine skin care products twice daily for three weeks if no adverse effects were experienced after the patch test. The follow-up was by weekly facial StO2 measurements after the application of the cream for a period of three weeks. The framework of this study is shown in Fig. 1. Each user was required to complete a set of questionnaires on their own perceptions of the supplied cream at the third week. There are four parameters to be evaluated; each parameter was assigned with score value 1–3 2
Optik - International Journal for Light and Electron Optics 204 (2020) 163948
A. Huong and X. Ngu
Fig. 1. Study scheme of skin cream trial.
indicating poor to excellent, respectively. Of the ten volunteers enrolled in this study, only seven remained at the end of the trial as shown in Fig. 2. This study also conducted an exploratory examination of StO2 level for acne affected skin of an individual who was not involved in the aforementioned trial shown in Fig. 2. The corresponding skin is located at the chin region of the subject, five measurements were recorded from the corresponding site for three days consecutively, from the formation of a sebum plug to the day skin encrustation was observed.
2.3. Optical imaging technology The schematic diagram of the developed skin oxygen monitor is shown in Fig. 3. A brief description of this system is provided in the following. This system used light emitting diodes (LEDs) of center wavelengths 532 nm, 560 nm and 650 nm selected based on the reports of [15] as its light sources. These LEDs were arranged in annular order surrounding a Complementary Metal Oxide Semiconductor (CMOS) (part no. CW-835) imager placed at the center of the system. Makeshift ring-shaped diffuser made of opaque sheet was placed in-front of the emitter ring to allow diffuse illumination of the examined skin site. Light reflected from the skin surface was received by the CMOS (focal number, f/# = 1) with an aperture diameter of 2.5 mm and exposure time of 0.25 s. The field of view of this imaging system is given by 15 mm × 20 mm and the produced image resolution is 640 × 480 pixels. Both light emitters and the imager were placed inside an enclosed compartment, and at a distance of approximately 30 mm from the skin surface. These LEDs of different wavelength were sequentially turned on at a sampling time of 3 s. Reflectance image at each wavelength was captured and quantized for processing by a microcontroller unit of analog-digital converter (ADC) resolution of 10 bits. The output was sent to a processing unit via Universal Serial Bus (USB 2.0) to predict for the most probable StO2 level. The entire data acquisition
Fig. 2. Consort diagram of skin cream trial and case study of skin inflammation. 3
Optik - International Journal for Light and Electron Optics 204 (2020) 163948
A. Huong and X. Ngu
Fig. 3. Schematic diagram of the topical system. (Image inset) An illustration of the use of the system in this study.
and measurement process took approximately 10 s. The cartographic illustration of the predicted distribution of StO2 level (StO2 map) shown in Fig. 3 was via a standalone user interface. The processing of the recorded images was via MATLAB (version 2018a). All these components were arranged and inserted into a hollow-core structure as shown in the inset of Fig. 3. The prediction of StO2 is by using a wavelength dependent Modified Lambert Beer Model in [15], and is based on light attenuation (A), and molar extinction coefficient of oxyhemoglobin (εoxyHb) and deoxyhemoglobin (εdHb) of the employed three wavelengths. The feasibility of using this model and the choice of the wavelengths used here were studied using Monte Carlo method in [16] for possible integration of technology into functioning portable systems. The light attenuation value is calculated from the grayscale converted images and is given by the negative logarithm of the ratio of recorded light reflectance image from skin region, IS, to that from spectralon white reference panel, IW, at wavelength, λ, as followed:
A (λ ) = −20 log
IS (λ ) . IW (λ )
(1)
The percent StO2 is expressed as [15]:
St O2(p) =
A1 (λ2 εdHb3 − λ3 εdHb2) + A2 (λ3 εdHb1 − λ1 εdHb3) + A3 (λ1 εdHb2 − λ2 εdHb1 ) × 100 % A1 (λ3 Δε2 − λ2 Δε3) + A2 (λ1 Δε3 − λ3 Δε1) + A3 (λ2 Δε1 − λ1 Δε2 )
(2)
where Δε represents the difference between εoxyHb and εdHb, while the numerical subscript in Eq. (2) denotes index for λ, with 1 = 532 nm, 2 = 560 nm and 3 = 650 nm. Next the StO2 value in Eq. (2) was corrected in Eq. (3) following the discussions in [16] on the insufficiency of attenuation model:
St O2 = 1.85 St O2(p) − 43.4
(3)
The upper and lower threshold values of percent StO2 are chosen as 120 % and 0 %, which limits are based on the 95 % and 5 % of the StO2 distributions identified in this and in earlier work from this laboratory [14]. The flow of the StO2 prediction process for a selected skin region is shown in Fig. 4. 3. Results and analysis The StO2 map averaged from the right and left cheek regions of each individual predicted prior to the trial and on different trial week after the topical application of the supplied skin care product is shown in Table 1. The color bar shown at the bottom of the table indicates the magnitude of the percent StO2. The red colored regions in StO2 map correspond to higher StO2, while the blue ones correspond to lower values. Based on these results in Table 1, the percent relative change in StO2 map, Δd, for the whole imaged area for example that shown in Fig. 4 for each subject is calculated using Eq. (4) to reduce possible systematic error within the experiment. The mean and standard deviation (SD) of the calculated Δd are plotted in Fig. 5.
Δd =
Sn − Sb × 100 % Sb
(4)
where Sb and Sn denote StO2 map of baseline and nth trial week. Questionnaire survey conducted at the third week of the trial obtained positive feedbacks (satisfactory rating of 95 %) from all volunteers. Meanwhile changes in StO2 value during an episode of skin lesions in the case study of skin inflammation is presented in Table 2. Five measurements of StO2 for lesioned tissues were collected over duration of 3 days. Also shown in this table is the image of the skin condition (second column of the table) from the formation of papule (in measurement 1 and 2), to pustule (measurement 3), to its rupture (measurement 4) and encrustation (measurement 5). The location of the papule on skin image and its corresponding StO2 map is indicated by arrows. 4
Optik - International Journal for Light and Electron Optics 204 (2020) 163948
A. Huong and X. Ngu
Fig. 4. Flow diagram of image processing.
4. Discussion Based on the results shown in Table 1 and Fig. 5, it was shown that there is an overall marked increase in facial StO2 level for the group treated with oxygen products in the trial weeks as compared to that measured prior to the trial. The mean (SD) of Δd observed for volunteers I–V is given by 5.8 (4.6) % and 4.56 (5.9) %, respectively, for trial week 1 and 3. All the considered oxygen products contained active ingredients with antioxidant properties (e.g. enzymes/extracts containing vitamin A, C and E, hydroxyl acids (HA)), which superior role in slowing down oxidation process was well documented [7,17–19], henceforth reinforcing the possibility that StO2 is related indirectly to the oxidation process. The increase in this value is positively correlated with the treatment week. This is with the exception of subject II and IV, wherein the results in Fig. 5 showed a drop in Δd for both of these volunteers from mean (SD) Δd of 4.34 (6.4) % measured in the first week to −2.3 (9.68) % in the third trial week. Another interesting finding of this paper is the 5
Optik - International Journal for Light and Electron Optics 204 (2020) 163948
A. Huong and X. Ngu
Table 1 The StO2 map predicted for different volunteers in skin cream trial before (Baseline) and after 1 and 3 weeks study for the investigation (subject I–V) and control groups (subject VI-VII). Subjectproduct
Baseline
Trial week 1
Trial week 3
a
I
IIa
IIIb
IVc
Vc
VId
VIIe
a b c d e
Oxygen therapeutic product (Product A). Oxygen therapeutic product (Product B). Oxygen therapeutic product (Product C). Control product (Product D). Control product (Product E).
inconsistency in the pattern of Δd in individuals (subject I and II, and subject IV and V) using the same product; the results in Fig. 5 revealed the opposite magnitude direction in Δd for these subjects. Since all subjects responded positively in the questionnaire survey with satisfactory rating of 95 %, these observations could be best interpreted as the diversity of one’s natural antioxidant reservoir, hence affecting biological cells response towards the topical antioxidation treatment. The similar finding was reported in [18,20,21] and was attributed to factors such as hormonal change, stress level, environment condition, and the activity, amount of rest and fatrich food these individuals were taking in days leading to the experiment. Of the results shown in Fig. 5, subject IV shows the largest variation in the calculated relative StO2 change for both trial weeks, further inspection into the data of this subject confirmed the present of one outlier value recorded during baseline. Removing this outlier brings the SD values down to around 5–6 %, while not much difference was observed in the respective mean values from Fig. 5. Interestingly, even though the drop in percent StO2 level was noticeable in the control group, with the mean (SD) Δd calculated as −11.95 (2) % and −7.94 (2.4) %, respectively, for trial week 1 and 3, following the use of non-oxygen boosting skin care products, the recruits did not report adverse skin reactions both during and after the trial completion. It must be mentioned that the ingredients stated in the formula of these control products have not had previous reports on their pro-oxidation effects. Thus the positive feeling experienced by the respondents in this group may suggest the effects of other active ingredients in the supplied cream (such as minerals with anti-inflammation, moisture, pH stabilizer and antibacterial properties). Even though the employed three-wavelength technology has not been able to quantitatively identify the skin condition where 6
Optik - International Journal for Light and Electron Optics 204 (2020) 163948
A. Huong and X. Ngu
Fig. 5. Mean and standard deviation (SD) of percent relative change in the StO2 map, Δd, of the recruits (represented by symbol subject I-VII) in first (w1) and third week (w3) of the trial. A black dotted line is drawn at zero relative change for reference. Table 2 Changes in facial StO2 level with progression of skin lesion. Measurement
Skin image
StO2 map
1
2
3
4
5
7
Optik - International Journal for Light and Electron Optics 204 (2020) 163948
A. Huong and X. Ngu
oxidation and antioxidation processes are in its optimal balance, and whence the skin health is at its optimum, the qualitative feedbacks from the respondent was taken here as empirical validation of their skin health; and the survey results showed an overall good rating of 95 % (or 2.85 of 3). On this note, the results in Table 1 may suggest the variation in optimum oxygen absorption capacity of cells among individuals, where the highest possible StO2 value (red colored regions) might not necessary indicate the optimum skin condition. In addition, this work observed a shorter time (i.e. 1 weeks) for the topical cream to take effect as compared to the duration of 1–3 months reported in [22]. Unlike the minute changes in StO2 shown in Table 1 for volunteers with no untoward skin conditions, Table 2 showed pronounced changes in the pattern of StO2 map for the inflamed skin. Pores clogged with oily substances (i.e. sebum) facilitate bacterial growth under the skin; this growth is stimulated in the presence of oxygen deprivation condition [23]. This is evidence in the StO2 maps shown in Table 2, which showed a comparative lower StO2 range (encircled by black line in measurement 1) of 30–40 % at the skin proximal to the papule; this condition promotes build-up of bacteria, resulting in pus filled lesion in measurement 2. The lesion further aggravated into pustule in measurement 3, where there is visible inflammation of the skin; at the same time there is a progressive increase in StO2 of approximately 90–110 % around the pustule (indicated by black dashed line in measurement 3) leading to its rupture in measurement 4. This sequential event is due to the body autoimmune system as a defense towards the bacteria inflammation. It is interesting to note on the uniformly high percent StO2 level of 80–95 % in measurement 4, although the magnitude has descended as compared to its preceding episodes, in regions around the affected skin. This relatively high StO2 level around the open wound helps to reduce swelling, accelerates the growth of new blood vessels (angiogenesis) that is essential in wound healing, and prepares the body with necessary energy component to fight and prevent infection. The encrustation of the pustule shown in the final measurement revealed a significant drop in the skin StO2 level to 65–80 % range, which was shown to return to that similar to the surrounding unaffected skin. These changes in StO2 with acute wound healing process agreed remarkably well with the previous studies using comparatively complex technologies presented in [24–26]. Even though the study on long term effects and performance of each antioxidant components are not being able to carry out in this time-limited trial, the overall increase in the skin StO2 for subjects in the investigation group suggests the likelihood of oxygen therapeutics functionality of the considered products within the considered duration. It is recognized that the performance of skin care products should be explored extensively using quantitative tools so that their effectiveness for the claimed applications could be confirmed before reaching the markets. Hence, the system used herein could be of the interest of scientists from cosmeceutical industry in the evaluation of products for treatment of skin disorders and problems, and on the claimed benefits. 5. Conclusion This research presented the use of optical technology as a promising tool to reveal StO2 level, with the aim to supplement the use of globally accepted qualitative survey techniques in cosmeceutical industry, in the evaluation of efficacy of the marketed skin care products for the claimed benefits. This study has seen remarkable increase in StO2 level in the group of subjects using different types of considered oxygen therapy creams after the first week of topical application. The opposite trend was observed in the control group. The detected sequential change in StO2 with different episodes of skin outbreak further supported the feasibility of using this technology in the cosmeceutical research and development. In addition, this technology may also be beneficial in the research of glucose metabolism and in studies of human physiological responses. Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Acknowledgements The authors are grateful to Ministry of Education Malaysia (K038 and 1581) and Universiti Tun Hussein Onn Malaysia for financially supporting this work. Special thanks must go to Tsen Vui Hin and Ong Pek Ek for their help during system development phase, and Sheena Philimon for her help in clinical selection of subjects. Last but certainly not least, thanks must go to all individuals involved in the study. References [1] F.E. Fox, N. Rumsey, M. Morris, Ur skin is the thing that everyone sees and you cant change it!- exploring the appearance-related concerns of young people with psoriasis, Dev. Neurorehabil. 10 (2007) 133–141. [2] D.L. Harris, A.T. Carr, Prevalence of concern about physical appearance in the general population, Br. J. Plast. Surg. 54 (2001) 223–226. 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