The microcirculation of the skin is a complex dynamic system that plays a very important role in skin color, thermoregulation, skin metabolism and transdermal transit. Different states of the skin and topical topical drugs can induce significant changes in skin blood flow production. Monitoring skin microcirculation is an important reference for assessing the efficacy and safety of drugs and for understanding the underlying physiological mechanisms of the skin and the pathogenesis of skin diseases. Changes in skin blood flow can be reflected by visual changes in skin color, such as by visual assessment of erythema, or can be measured using instruments. However, the appearance of erythema may not be entirely dependent on the microcirculation of the skin; sometimes redness of the skin can be detected with the naked eye, but changes in blood flow rate are not always detected by blood flowmetry. Because of the high sensitivity of non-invasive, objective measurement techniques, they are of great value in measuring the microcirculation of the skin. Studies have shown that laser Doppler flowmetry is 3-4 times more sensitive than naked-eye measurements for objectively measuring changes in skin blood flow.
1. The significance of skin microcirculation measurement in dermatology clinical and cosmetic skin care
(1) Evaluation of the inflammatory response of the skin
Erythema can be caused whether the skin is irradiated with UV to determine the light protection index of skin care products, or due to the stimulation of external irritants, allergic reactions caused by topical medications or skin care products. The color (redness) of an area of the skin depends on the degree of blood flow in that area, and there is an indirect, non-constant relationship between skin blood flow and skin color. Therefore, measurement of skin blood flow can be more objective and sensitive than measurement of skin color to evaluate skin inflammation response, and the results of patch test are more reliable.
(2) Evaluation of the effect of topical drugs
Measurement of skin microcirculation is valuable for evaluating the acute effects caused by topical application of vasodilating drugs, and can also be used for drugs that require repeated application to cause vascular changes (e.g., retinoids). It is also suitable for evaluating the effects of anti-inflammatory products, such as glucocorticoids used in dermatology.
(3) Development of skin care products that regulate the color of the skin suit
The color of skin is mainly determined by melanin, hemoglobin and carotenoids. Oxyhemoglobin is bright red and hemoglobin is blue-red. Microcirculation transports hemoglobin to the skin. The speed of microcirculation increases the number of red blood cells passing through the skin per unit time, and the amount of hemoglobin increases, resulting in an increase in the red component of the skin and a reddish skin color.
Skin color essentially depends on the concentration of different pigments and their distribution in the various layers of the skin. Skin color is ultimately the result of the combined effect of several pigments, so simply measuring skin color does not determine the role played by the increased blood flow rate due to improved microcirculation, and must be evaluated by measuring the microcirculation of the skin.
(4) Evaluation of the effect of skin care products
Skin care products are often used to alleviate vasoconstriction caused by cold and excessive use of cleansing agents (e.g., frequent use of soap or surfactants). The vasodilating effect of these skin care products can be evaluated by measuring changes in the skin microcirculation.
(5) Significance of blood flow in different vascular plexuses
The differentiation of blood flow in different vascular plexuses also has clinical application. For example, usually eczema, psoriasis, acne and space weightlessness affect blood flow in superficial vascular plexuses and capillary pans, while deep circulation (deep dermal vascular plexuses, arteriovenous anastomoses) responds only to various regulatory reflexes that allow cardiovascular adaptation [33]. From a pharmacological point of view, after topical topical application, these drugs diffuse directly into the subpapillary vascular plexus and affect only the superficial microcirculation, but not the entire dermal blood circulation . In addition, the distribution of hemoglobin in different vascular plexuses (capillary pam, postcapillary plexus, deep vascular plexus and subdermal vascular plexus) has an effect on the color of the skin, such as bright red color of bright red nevus located in the superficial dermis, and purplish red color of angioma in deeper location, so the effect of blood flow on skin color is different in different locations.
2.Instruments for measuring skin microcirculation
There are many techniques that can be used to measure the skin microcirculation, the more commonly used are laser Doppler flowmetry, laser Doppler imaging, volumetric tracing method, capillary microscopy, etc. Others are fluorescence tracing, infrared thermography, heat conduction, isotope xenon washout technique, etc. can be used to observe the skin microcirculation blood flow. Among all these techniques, laser Doppler flowmetry is the most widely used, while isotope xenon washout is rarely used in skin studies.
(1) Laser Doppler flowmeter (LDF)
The laser beam emitted by the He-Ne laser tube is coupled to the measured tissue, which will produce light absorption and scattering, and the light reflected from the moving red blood cells in the tissue will have a frequency shift in frequency, the size of which is proportional to the speed of movement, and the intensity of the scattered light is proportional to the number of moving red blood cells. The blood perfusion voltage signal is proportional to the area of the laser beam irradiated to the skin surface, the depth of beam irradiation, and the number of blood vessels, blood flow velocity, and number of red blood cells in that volume. Therefore, the voltage level reflects the magnitude of blood perfusion flow per unit volume. the LDF system consists of a microcomputer, a laser measurement probe, and analysis software. During the measurement, the measuring probe is fixed to the measurement site with double-sided tape, and the probe emits laser light to the skin surface, and some of the light is reflected back by the skin tissue and the moving red blood cells, which is received by the receiving sensor on the probe surface, and the signal is processed by the software to obtain various information of microcirculatory blood flow.
The LDF can only measure the relative changes of the skin blood flow. It cannot be used to infer absolute values of blood flow unless a correction factor has been derived by comparison with other generally accepted measurement methods in the same part of the skin and under the same conditions. Because of the complexity of the skin microvascular system, it is now generally accepted that site-specific correction factors cannot be used for other parts of the body, and therefore some scholars have questioned some commercially available LDF instruments that measure absolute blood flow because the correction factors used by these instruments (based primarily on physical-optical models) are not always correct for different sites.
Of course, if the zero correction (mechanical and electronic) is performed correctly throughout the experiment and the instrument parameters (gain, bandwidth, interference rejection, etc.) are set constant, the measurements obtained can be compared between subjects and between sites on the same subject. The most commonly used study in practice is the measurement of acute blood flow changes after a short-term intervention (physiological or pharmacological). In this case, one is interested in the change in blood flow velocity relative to basal values. And the results are likely to be more reliable when using the subjects’ own controls. Many companies offer software to record these short-term changes, and the latest instruments are capable of displaying trends in changes and calculating absolute and percent changes compared to basal values using built-in digital acquisition devices and large LCD screens.
(2) Laser Doppler perfusion imager (LDI)
In order to overcome the effects of direct contact measurement and spatial variations on the measurement results, non-contact, horizontal scanning laser devices have been developed in recent years. These devices are based on the same principles as laser Doppler, but do not require direct contact with the skin to collect data. It is capable of non-contact continuous measurement of tissue blood perfusion in an area and produces color-coded images of the distribution of tissue perfusion.
(3) Volume tracing method (PGG)
An optical volumetric tracing map is obtained by measuring the autoregulatory pulsations generated by the intensity of reflected light from human skin in response to changes in microcirculation. When a light beam from a light source hits the skin of a part of the body, some of the light is directed through the skin to the capillaries, and this part of the light directed to the capillaries is scattered by the blood flowing in the capillaries. This scattered light is then collected by a lens and delivered to a photosensitive sensor, which converts the light signal into an electrical signal. The magnitude of the electrical signal is determined by the total blood flow present in a given area, and the higher the hemoglobin content, the higher the total amount of light absorbed. Therefore PPG is sensitive to changes in blood flow. The effect of the red blood cell velocity causes a change in its direction of motion and thus a change in the optical transmission, which may eventually affect the results.
Compared to the LDF, this electronic device is simple and inexpensive. This is because the signal output is only proportional to the intensity of the collected light. Many of the basic principles of DPF are also applicable to PPG, which measure reflected light. ppg is used for monitoring related to various skin microcirculation such as reactive congestion after local compression, exercise and topical topical medications and skin care products.
(4) Capillary microscopy method
Before measurement, a drop of oil is placed on the skin surface to reduce the reflection of light from the skin surface, and then, the capillaries to be measured are placed under a microscope for magnification (10 to 100 times) and observation. Capillaroscopy can only measure the density and morphology of the capillaries being examined, the caliber of the vessels and the rate of red blood cells. With aging, the density of capillary pannus decreases and the vessel morphology becomes more irregular. These changes can be quantified by image analysis and compared in digital form. Various software packages are often used to measure capillary diameters and average erythrocyte transit rates [].
(5) Temperature recording method
The temperature of the skin is closely related to its blood flow and perfusion. Therefore, measurement of skin surface temperature can also be used as an indirect method to assess skin blood circulation.
The temperature recording method is to measure and record the temperature change on the skin surface, and there are two methods: contact and non-contact. Contact measurement is to place a measurement probe made of liquid crystal on the skin surface and read the temperature of the skin directly. Non-contact measurement is also called infrared temperature measurement, according to the principle of infrared temperature measurement, the infrared radiation energy emitted by the object and the surface temperature of the object there is a certain functional relationship, infrared thermometer to receive the infrared radiation energy emitted by the skin suit, through the internal conversion of the instrument, calculation, you can display the skin surface temperature. It is based on the thermal radiation emitted from the skin – infrared light to change the state of the probe, the wavelength of thermal radiation in the range of the wavelength than the visible light. The functional state of the skin changes, surface water content changes, topical drugs or cosmetics can change the radiation characteristics of the skin, thus changing the temperature of the skin surface.
3.The error control in LDF measurement
(1) Probe position instability
For clinicians, interference from probe sliding is the most common problem in LDF using optical fiber probes. The lack of correlation between blood flow signal changes and actual physiological changes is usually caused by the movement of the optical fiber connected to the probe, a condition that is more likely to occur when the subject is not compliant or when the observation time is long. The use of thinner and more easily bendable optical fibers that emphasize the specificity of the collected vessels has reduced but not yet eradicated this problem.
(2) Pressure of the probe
Studies have shown that a very small pressure (<15 mm Hg) on the skin surface can significantly reduce blood flow to the skin. Using lighter weight probes, easily bendable leads and securing the probe to the skin with double-sided tape rather than using duct tape can help reduce pressure variations... Place the probe gently to avoid movement of the probe's optical fibers, and when no integrated probe is available, perform at least three tests and take the average.
(3) Subject factors
As far as possible, all subjects should be controlled under the same conditions. Unless specifically limited, all subjects should be in the same position, with the test point at the same level as the heart, preferably in the prone position. Subjects are in a quiet state and are not under the influence of vasodilators (e.g., alcohol, nicotine, spicy foods, drugs, etc.). The subject is kept quiet and the test area is exposed for at least 30 minutes prior to the measurement.
(4) Measurement environment
The temperature and humidity in the measurement environment should be kept constant to avoid direct sunlight, air convection and effects on temperature. The measurement environment should be quiet so as not to cause mood swings in the subject, which could affect blood flow.
(5) Validation of the instrument
The test conditions and measurement devices vary with each operation. Therefore, the instrumentation used should be validated. Recently published operating guidelines suggest that reactive congestion is helpful as a standard procedure for validating the measurement instrument. After compressing the artery for 3 minutes the flow signal drops to a very low level, after releasing the artery the flow rises to 150-500% of the quiet value and drops to the quiet value after a few minutes.