Mechanical Properties of Skin in Health and Disease evaluated by Viscoelasticity Skin Analyzer
AKIVA VEXLER*, IGOR POLYANSKY and RAPHAEL GORODETSKY
Laboratory of Radiobiology and Biotechnology, Sharett Institute of Oncology,
Hadassah University Hospital
P.O.Box 12000, Jerusalem 91120, Israel.
*current address: Laboratory of Radiobiology and Hyperthermia,
Department of Oncology, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel.
e-mail:
Abstract: The mechanical properties of the skin are known to be age, sex and race dependent and reflect different physiological skin conditions as well as skin disorders. Therefore, monitoring alteration in the mechanical properties of the skin may help to diagnose systemic diseases as well as local skin lesions. Reliable quantitative methods for the in-situ examination of skin viscoelasticity are scarce. We developed a dedicated viscoelasticity skin analyzer (VESA) that may be hooked into a sophisticated computerized system for maping skin viscoelasticity. The portable pocket size user-friendly device allows a fast and non-invasive measurement of the speed of shear wave propagation (SWP) in viscoelastic materials with highly reproducible results. The SWP parameter is correlated inversely with Young's modulus of elasticity. The directional nature of the measurement allows also the evaluation of skin anisotropy.
In healthy human subjects significant variations in skin stiffness and anisotropy were observed in 3 skin areas along the forearms, but the SWP was similar in all symmetric contra-lateral areas. Hydrating creams decreased the stiffness of the forearm skin for only ~3 h. The stiffness and anisotropy of the skin of the breasts in female volunteers (20-86 years) increased with age, but the SWP was similar in symmetric contra-lateral areas in the same individual.
The VESA device was also used to evaluate late radiation effects in the skin of breast cancer patients treated with different protocols of high dose radiation therapy. A current protocol of treatment in many breast cancer patients is based on the surgical removal of the tumor followed by adequate radiation therapy for the preservation of the affected breast. The major complications of this treatment are associated with late radiation damages to the skin, leading in extreme conditions to fibrosis, dermal atrophy, retraction, and susceptibility to necrosis. Breast cancer patients were examined by VESA 1-6 years after radiation therapy. Fractionated radiotherapy was given to the affected breast with a total dose ranging between 45-60 Gy in 1.8-2.5 Gy per fraction. The viscoelasticity and anisotropy of the skin of non-irradiated breasts were similar to the data recorded in breasts of healthy controls. The SWP in the skin of irradiated breasts was increased significantly with the elevation of dose per daily fraction and less by the total radiation dose given. These changes were more obvious along the horizontal direction of the breast contour. We found that the increase in dose of radiation per fraction had much more impact on the development of late skin effects than elevation in the total dose given.
Our results indicate that the VESA device may be very useful in experimental and clinical practice for quantitative evaluation of skin condition, with special reference to dermatology and plastic surgery. It may also have major application and market in other fields, especially in areas related to the cosmetics industry.
Key-Words: human skin viscoelasticity, speed of shear vawe propagation, age-place dependence, anisotropy, hydrating creams, radiation.
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1 Introduction
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The mechanical properties of the skin are known to be age, sex and race dependent and reflect different physiological skin conditions as well as skin disorders. Therefore, monitoring alteration in the mechanical properties of the skin may help to diagnose systemic diseases as well as local skin lesions [1,2]. Reliable quantitative methods for the in-situ examination of skin viscoelasticity are scarce. A number of techniques have so far been introduced in experimental and clinical medicine for quantitative in situ evaluation of the mechanical properties of skin [2-4]. These assays are based on different physical principles and they include indentometry, uni-axial tensiometry, torsion measurements, skin compliance to suction and measurements of speed of elastic shear wave propagation (SWP). The last assay is a most promising approach for the evaluation of the mechanical properties since SWP parameter correlated inversely with Young's modulus of elasticity [2,4-9]. Earlier prototypes of the device for the evaluation of skin viscoelasticity based on this principle were developed and tested on artificial materials and in the patients with chronic skin diseases such as psoriasis and mycosis fungoides [10-12] and with hypertrophic scars [13]. The increased SWP was recorded in all skin disorders tested, due to an increase of skin stiffness.
An advanced device based on the same principle, the Visco-Elasticity Skin Analyzer (VESA) was constructed in our Laboratory [14] and successfully used for follow-up of the effect of UVB phototherapy on graft-versus-host induced scleroderma in the patients after bone marrow transplantation [15]. The design, performance and the basic properties of the VESA device were described in our paper [16]. This manuscript presents the results of the evaluation of viscoelasticity and anisotropy in human intact and irradiated skin using VESA device.
2 Results
2.1 VESA device.
Portable clinical prototype of the VESA device consists of a small mechanical unit (probe) connected to an electronic control unit based on a microprocessor [16]. A hand-held probe of the device is made of 3 piezoelectric transducers of bi-morph structure on which plastic contact tips are loaded. The central transducer serves as a transmitter and the 2 others located equidistant on both sides are the receivers. The pressure of the probe on the surface examined is controlled to assure reproducible readings. The transmitter produces a tangential oscillatory deformation on the surface of the tissue (elastic shear surface waves in the acoustic frequency range of 4-6 kHz). The SWP is calculated by measuring the time-of-flight of the signal from the transmitter to the receivers and the results are displayed on a LCD screen (in m/sec). The VESA device allows one to measure the SWP in the range of 20 - 180 m/sec. This covers the range for the SWP in the skin of human beings and laboratory animals as well as in many artificial viscoelastic materials. The readings are highly reproducible with deviations not exceeding ± 2 - 4%. The VESA device is easy to operate and is user friendly.
2.2 Viscoelasticity of human forearm skin.
The viscoelasticity of intact forearm skin was examined in symmetric contra-lateral areas in healthy human subjects in both males and females with their informed consent. Bi-directional VESA measurements were performed on the volar surface of both forearms in 3 different locations (upper part - 3 cm below the cubital fossa, middle part - midway between the wrist and the cubital fossa and lower part - 3 cm above the wrist). In each location a square area of 4 points, located 2.0 cm apart, was examined. In each point the measurements were repeated 3 times and all values were averaged.
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Fig. 1. Correlation of the skin viscoelasticity of the right versus the left forearm in healthy volunteers.
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Measurements were performed in two directions, along to the longitudinal axis of the forearm (“vertical”) and perpendicularly to this axis (“horizontal”) for evaluation of both viscoelasticity and anisotropy. A high correlation was found for horizontal and vertical measurements in all symmetric contra-lateral areas of both forearms (Fig. 1). Therefore, for the comparison of the skin in 3 distinct areas examined the data for the same areas from both forearms were combined. The vertical SWP was similar in all tested areas of the forearm (Fig. 2).
Fig. 2. Skin viscoelasticity (averaged data) in upper, middle and lower parts of both forearms of healthy volunteers.
In contrast, the horizontal SWP decreased from the lower to the upper part of the forearm, indicating the reduced stiffness and increased anisotropy of the skin in the upper part relative to the lower part of the forearm.
Fig. 3. Effect of hydrating creams on skin viscoelasticity (relative to the SWP in untreated skin).
Possible changes in skin viscoelasticity following local application of a placebo and two hydrating (moisturizing) creams based on mineral oil (Ahava, Dead Sea Health Products, Mitzpe Shalem, Israel) were evaluated in volunteering women at different time intervals after cream application. Cream A is a basic hydrating cream “Ahava” and cream B is a hydrating cream “Advance” for normal-dry skin enriched with Dead Sea minerals. Each of the creams tested was applied for 15 min to the discrete forearm areas selected randomly. The non-absorbed cream was then removed with cotton pads. The effect of the cream tested was evaluated by normalizing the SWP recorded in the treated area at different time points to the SWP in the relevant untreated control area. Application of both hydrating creams for 15 min significantly reduced skin stiffness, as manifested by the lower SWP readings, while the placebo had no significant effect (Fig. 3). These changes were observed only along the long axis of the forearm and persisted for about 3 h.
2.3 Viscoelasticity of intact breast skin.
The viscoelasticity of the skin in symmetric contra-lateral areas of both breasts was evaluated
in a group of 20 healthy women, 20 - 86 years old with their informed consent. The patients were examined lying on their back without any manipulation of the breast position. The SWP was measured in a square matrix area of 9 points on the skin, 2.5 cm apart from each other. Measurements were repeated 3 times in each point in two directions, in parallel (“horizontal”) and perpendicularly (“vertical”) to the breast contour to characterize breast skin viscoelasticity and anisotropy. A high correlation (r=0.98) was recorded between the SWP readings in symmetric contra-lateral areas of skin on both breasts in each healthy individual for both horizontal and vertical measurements (Fig. 4a). The SWP measured in horizontal direction was significantly higher (62.0±2.2 m/sec) than those recorded in the vertical radial direction (36.6±1.4 m/sec) resulting in the high anisotropy of 1.73 (Fig. 4b). The breasts skin viscoelasticity was found to decrease with age (Fig. 5a) when this parameter was measured horizontally but not vertically resulting in the increase of skin anisotropy with age (Fig. 5b).
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Fig. 4. (a) Correlation of the skin viscoelasticity of the right versus the left breast in healthy volunteers as evaluated by the SWP. (b) Statistical analysis of the above data where upper and lower quartile (box), median value (horizontal line in box), and 10th and 90th percentile (whisker line) are presented.
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Fig. 5. Age dependence of breast skin viscoelasticity (a) and anisotropy (b) in healthy volunteer breasts.
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2.4 Viscoelasticity of irradiated breast skin.
The purpose of the current study was to evaluate objectively the severity of late changes in the skin viscoelasticity of breast cancer patients treated by different protocols of radiotherapy. The VESA measurements were performed on both irradiated and non-irradiated breasts in 110 patients, age range 32 - 80 years with their informed consent. The non-irradiated breast in the patients was used as an inner control. The effect of radiation was evaluated by the comparison of the averaged data recorded in the skin of the irradiated breast and the contra-lateral area of the non-irradiated breast. The SWP in the non-irradiated breast skin of the cancer patients was found to be almost the same as in the breast skin of healthy controls: 56.8±2.8 m/sec in the horizontal direction and 36.4±2.4 m/sec in the vertical direction. Also a significant skin anisotropy of 1.62 was recorded.
The patients treated with 1.8 Gy/fraction were divided into four subgroups according to the total dose delivered, ranging from 45 Gy to 50.4 Gy. Only in a few patients from each subgroup the SWP in the skin of the irradiated breast was elevated, indicating reduced skin viscoelasticity. The proportion of these patients increased with total dose given. The analysis of averaged data revealed a minor but still statistically significant radiation-induced increase of skin stiffness in irradiated breasts in all these subgroups relative to controls (Fig. 6a). Nevertheless, there was no significant dose dependent change in skin viscoelasticity in the irradiated breast between these subgroups. The elevation of the dose/fraction to 2.0 Gy resulted in a more obvious increase of the proportion of patients with altered skin viscoelasticity (Fig. 6b).
A more significant radiation-induced effect was recorded when the total dose of 50 Gy was given in higher dose/fraction of 2.5 Gy (Fig. 6b). In the 2 patients treated by a total dose of 60 Gy with the same dose/fraction of 2.5 Gy the SWP in the irradiated skin was extremely high, indicating increased skin stiffness (data not shown). In all the groups of patients the changes in skin viscoelasticity were recorded both along the breast contour (horizontally) and in the perpendicular direction (vertically). Therefore, skin anisotropy did not change considerably.
3 Conclusion
In conclusion, the viscoelasticity of the skin can be evaluated quantitatively using the non-invasive, portable and user-friendly VESA device. This assay may be applied for the evaluation of intact human skin and for the long-term follow-up of different skin diseases. VESA assay may also be used for the examination of skin of patients suffering from systemic diseases that are accompanied by dermatological disorders such as fibrosis, hyperkeratosis and edema. An objective evaluation of the efficiency of the treatments given for the alleviation of skin disorders may be a major application of this technique. Another possible field of application of the VESA device could be cosmetology, where it can be employed to provide fast and accurate quantitative measurements of the effect of a product on skin.
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Fig. 6. Dependence of the skin stiffness in irradiated breast on the total dose given with 1.8 Gy/fraction (a) and on the dose/fraction in total dose of 50 Gy (b).
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3. Elsner P. Skin Elasticity. Bioengineering of the skin: methods and instrumentation. CRC Press, 1995.