KR102212622B1 - Measuring Method For Skin Regeneration - Google Patents

Abstract

The present invention relates to a method for measuring skin regeneration, in which the method for measuring skin regeneration according to an embodiment of the present invention includes an image measurement step of measuring an image of the surface of the skin or a cross section of the skin on which the wound is generated through optical coherence tomography. And an image extraction step of extracting a three-dimensional image or a two-dimensional image of the surface of the skin on which the wound is generated, and a wound using the measured image.

Description

How to measure skin regeneration {Measuring Method For Skin Regeneration}

The present invention relates to a method for measuring skin regeneration, and more particularly, to a method for measuring skin regeneration capable of accurately and accurately measuring skin regeneration through optical coherence tomography (OCT).

Skin regeneration is a complex process in which immunity, cell proliferation, and tissue reconstruction occur sequentially.

In order to observe the state of skin regeneration so far, a method of evaluating the proliferation rate at the cellular level or collecting and observing a part of skin tissue through a biopsy has been used. Specifically, as in Patent Document 1, a method of evaluating the proliferation rate at the cellular level using artificial skin or measuring skin regeneration efficacy through biopsy was used.

The method of evaluating the proliferation rate at the cellular level does not reflect the complex process of skin regeneration, and the method through biopsy has the disadvantage that it is difficult to apply to the living body.

Therefore, it is possible to measure the degree of skin regeneration by reflecting the complex process of skin regeneration, and there is a need for research on a method that can measure the degree of skin regeneration without damaging the individual itself.

KR 10-2013-0056957 A

Therefore, by applying to an artificial skin model, it is intended to provide a method for measuring different degrees of skin regeneration in various factors by measuring changes in wounds according to various variables such as the state of the skin tissue, the intensity of the laser, or the wavelength.

In addition, it is intended to provide a method for measuring skin regeneration that can perform objective evaluation by numerically quantifying skin regeneration conditions.

Further, it is intended to provide a method for measuring skin regeneration that can be applied to actual skin, so that it is applied without damaging the object itself and can visually image or quantify the skin regeneration state of the object.

The present invention is a method for measuring skin regeneration through analysis of a wound, through optical coherence tomography, an image measurement step of measuring an image of the skin surface or a cross section of the skin on which the wound is generated, and using the measured image, the It includes an image extraction step of extracting a three-dimensional or two-dimensional image of the surface of the skin on which the wound was created, or the wound.

The three-dimensional image or two-dimensional image of the wound may be measured through the optical coherence tomography, through one or more cross-sectional images of the skin on which the wound is generated, up to a predetermined depth.

The image of the surface of the skin on which the wound is generated may be measured through an image within a predetermined area of the surface of the skin on which the wound is generated.

The optical coherence tomography may be performed by 2D optical coherence tomography or 3D optical coherence tomography.

The image measuring step may be measured at predetermined time intervals to measure a degree of skin regeneration over time.

A wound quantification step of extracting one or more of a length, a cross-sectional area, and a volume of the wound through the 2D or 3D image of the wound may be further included.

The wound quantification step of extracting one or more values of the number of wounds, the width of the wound, and the location of the wound through the image of the skin surface on which the wound is generated may be further included.

The image of the wound according to one or more of the thickness and distribution of the keratin, the epidermis, and the dermis of the skin or the change of the wound image over time may be measured.

The wound may be a laser or chemical wound.

It is possible to measure a wound image according to the intensity or wavelength of the laser or a change in the wound image over time.

The laser is one selected from CO ₂ laser, argon (Ar) laser, YAG laser, Nd:YAG laser, Nd laser, Er:YAG laser, Ho:YAG laser, Ruby laser, diode laser, excimer laser, and multiple wavelength optical laser It can be more than that.

The skin may be artificial skin or biological skin.

The artificial skin may be an artificial skin including a dermal layer including collagen and fibroblasts, and keratinocytes proliferated and differentiated on the dermal layer.

According to the present invention, by applying to an artificial skin model, it is possible to provide a method capable of measuring different degrees of skin regeneration in various factors by measuring changes in wounds according to various variables such as the state of the skin tissue, the intensity of the laser, or the wavelength. I can.

In addition, it is possible to provide a method for measuring skin regeneration capable of performing objective evaluation by numerically quantifying the skin regeneration state.

Further, since it can be applied to actual skin, it is possible to provide a method of measuring skin regeneration that can visually image the skin regeneration state of the object by applying it without damaging the object itself.

1 is a photograph of a surface of a wound over time measured through an optical microscope ((a), (b)) and three-dimensional optical interference tomography ((c), (d)) according to an embodiment of the present invention. And the cross-section of the wound over time are measured through a tissue staining method (e) and a two-dimensional optical coherence tomography (f) according to an embodiment of the present invention.
2 is a cross-sectional photograph of a wound over time measured through optical coherence tomography according to an embodiment of the present invention.
3 are three-dimensional images of a wound over time derived using cross-sectional photographs of a wound over time according to the embodiment of FIG. 2.
4 is a graph showing a cross-sectional shape and length of a wound according to time of a wound measured according to the embodiment of FIG. 2.
5 is a graph showing the volume of wounds measured according to the example of FIG. 2 over time.
6 are skin surface images obtained by measuring a degree of skin regeneration over time for skin having a thick epidermis (a) and a thin epidermis (b) according to an embodiment of the present invention.
7 is a graph of a cross-sectional shape and length of a wound according to the intensity of a laser for skin having a thin epidermis (a, c) and a thick epidermis (b, d) according to an embodiment of the present invention. to be.
Figure 8 shows the volume change of the wound by measuring the intensity of the laser and the degree of skin regeneration over time for skin having a thick epidermis (a) and a thick epidermis (b) according to an embodiment of the present invention. This is a graph.

Hereinafter, a method for measuring skin regeneration according to various embodiments of the present invention will be described with reference to FIGS. 1 to 8.

According to an embodiment of the present invention, skin regeneration may be measured through wound analysis, and the method of measuring skin regeneration according to an embodiment includes an image of a skin surface or a cross section of a wound on which a wound is generated through optical coherence tomography. And an image extraction step of extracting a surface image of the skin on which the wound is generated, a 3D image or a 2D image of the wound using the measured image.

For the analysis of the wound, an image of the surface of the skin on which the wound is formed or a cross section of the skin may be measured. In addition, a three-dimensional image of a three-dimensional shape of the wound itself or a two-dimensional image of a cross-sectional view in various directions may be extracted using the image of the skin surface or cross section of the skin. In addition, it is possible to compare or analyze the degree of skin regeneration of how much or how much skin regeneration through the three-dimensional or two-dimensional image of the wound.

In addition, according to an embodiment of the present invention, the image measuring step may be measured at predetermined time intervals to measure a degree of skin regeneration over time. That is, it is possible to check the degree of skin regeneration through a two-dimensional or three-dimensional image of the wound over time.

According to an embodiment of the present invention, images of such wounds may be measured through optical coherence tomography. Optical coherence tomography is an optical imaging method in which an image of a sample is reconstructed using a time difference and an amount of light reflected according to a material or length of a tissue when a laser beam of a specific wavelength is transmitted through a sample.

Through this optical coherence tomography, the surface of the wound and the cross section up to a specific length of the wounded skin are scanned with a laser used for optical coherence tomography, and the image of the skin surface where the wound is created, the wound itself is 3D or 2 A dimensional image, or a 3D image and a 2D image can be simultaneously implemented.

According to an embodiment of the present invention, 2D optical coherence tomography or 3D optical coherence tomography may be used as optical coherence tomography, but the present invention is not limited thereto.

In addition, the method for measuring skin regeneration according to an embodiment of the present invention may measure regeneration of a wound by laser or chemical substances, but is not limited thereto.

In particular, in the case of laser-induced wounds, very small wounds are generated on the skin, so it is very difficult to visually check them and confirm the degree of regeneration. Therefore, the method for measuring skin regeneration according to an embodiment of the present invention can be used.

In the case of the method for measuring skin regeneration according to an embodiment of the present invention, since it is possible to quantify and measure the cross-section and surface image of a fine-sized wound, it can be usefully used to measure the regeneration of a wound by a laser.

The lasers include CO ₂ laser, argon (Ar) laser, YAG laser, Nd:YAG laser, Nd laser, Er:YAG laser, Ho:YAG laser, ruby laser, diode laser, excimer laser, and complex wavelength light (IPL: At least one selected among Intensed Pulse Light) lasers may be used, but is not necessarily limited thereto, and various types of lasers used in the present technical field may be used for this.

For example, in the case of a CO ₂ laser, microscopic pores are created on the skin, and collagen regeneration and skin contraction may be induced by thermal damage accompanied by ablation and coagulation. It is used in various dermatological procedures such as pores, acne scars, fine wrinkles around the eyes, skin texture improvement, and skin elasticity improvement. Such a wound on the skin by the CO ₂ laser can be used to check the depth of the affected area, the degree of wound regeneration, and the like using the skin regeneration measurement method of the present invention.

According to an embodiment of the present invention, three-dimensional optical coherence tomography may be used to measure the regeneration of a wound created using a CO ₂ laser, and in this case, optical coherence tomography is performed with a laser having a wavelength of 800 nm. A two-dimensional image (cross-sectional image) or a three-dimensional image of a wound may be implemented by performing scanning in a predetermined area on the skin (for example, 1 cm x 1 cm) to a depth of 1 to 2 mm. It is not necessarily limited thereto, and may be performed in various ways depending on the type of laser and tissue characteristics of the skin.

Meanwhile, according to an embodiment of the present invention, the skin as a measurement target for measuring the degree of skin regeneration may be artificial skin or biological skin. More specifically, an artificial skin model can be used as a living skin mimic composed of the dermal layer and the epidermal layer, which has structural and functional similar characteristics to the actual skin, thus realizing the degree of wound creation and regeneration of the skin almost similar to the actual skin. have. Although not necessarily limited thereto, the artificial skin may include a dermal layer including collagen and fibroblasts, and an artificial skin including keratinocytes proliferated and differentiated on the dermal layer.

Accordingly, according to an embodiment of the present invention, it can be used experimentally by measuring the degree of skin regeneration on artificial skin, and it is applied directly to the living body to measure the degree of skin regeneration, thereby reflecting the complex action of skin regeneration. Can be analyzed.

Hereinafter, in order to measure the degree of skin regeneration, the degree of skin regeneration was measured and compared using the artificial skin described in Korean Patent Publication No. 10-2013-0056957 in the examples of FIGS. 1 to 8.

Specifically, with reference to FIG. 1, let's look at the image of a wound created on the skin in more detail. 1 is a photograph of a surface of a wound over time measured by an optical microscope ((a), (b)) and three-dimensional optical coherence tomography ((c), (d)) according to an embodiment of the present invention. And, the cross section of the wound over time is measured by the tissue staining method (e) and two-dimensional optical coherence tomography (f) according to an embodiment of the present invention.

In addition, FIG. 1 is a photograph showing a skin condition in which no wound was formed (comparative) and the skin condition measured immediately after the wound was created (0 hour), 6 hours, 12 hours, and 18 hours.

Columns (a) and (b) of FIG. 1 are photographs showing a surface image of a wounded skin measured using an optical microscope. And, (c) and (d) columns represent the surface image of the skin measured through 3D optical coherence tomography according to an embodiment of the present invention.

Figure 1 (e) column is a cross-sectional photograph of the skin measured by the tissue staining method, specifically the He staining method, and (f) the column is the skin image measured through two-dimensional optical coherence tomography according to an embodiment of the present invention. These are cross-sectional pictures.

Referring to columns (e) and (f) of FIG. 1, it can be seen that the artificial skin before laser irradiation is flat, but wounds are generated to the upper part of the dermis by the laser immediately after laser irradiation. In addition, 6 hours after irradiation, it can be observed that the wounds generated by the laser are reduced due to dermal contraction. After 12 hours of irradiation, almost all of the dermal wounds are recovered, and only the epidermal wounds are observed. And, it can be seen that 18 hours after irradiation, the cells of the epidermal layer migrate to the wound site and the regeneration of the epidermal layer proceeds.

Referring to FIG. 1, images of the surface of the skin on which the wound is formed are surface images having the same level of resolution as the optical microscope, even when optical coherence tomography is used when compared with images measured by an optical microscope or tissue staining method. Can be obtained.

In the case of measurement using an optical microscope, it is difficult to obtain a precise and complex image of the wound, and a sample must be taken to see the cross section of the wound, and in the case of tissue staining, a sample must be collected from the measurement object and undergo an additional staining process. According to an embodiment of, since optical coherence tomography is used, a complex image of a wound can be obtained from the skin surface directly from the measurement target without such a complicated process, that is, without taking a sample. In other words, it is possible to solve problems arising from the process of collecting a sample or harming a living body.

However, it is not necessarily limited thereto, and of course, it may be measured using artificial skin or a skin sample.

Meanwhile, referring to the column (f) of FIG. 1 and the example of FIG. 2, FIG. 2 is photographs showing cross-sectional images of skin measured over a predetermined area of a wound measured at a preset time interval.

In particular, it is possible to obtain a two-dimensional or three-dimensional image of a wound through such cross-sectional images of the skin.

More specifically, in the examples of FIGS. 2 and 3, respectively (a) is immediately after the wound is created, (b) is 6 hours later, (c) is 12 hours later, (d) is 18 hours and (f) is a photograph or graph showing the image of the wound after 24 hours.

3 is a graph showing a 3D image obtained through cross-sectional images measured through the embodiment of FIG. 2. FIG. 3 shows a 3D image of a wound derived through cross-sectional images measured at predetermined intervals of FIG. 2.

That is, referring to FIG. 2, by measuring cross-sectional images of the skin up to a preset depth of the skin at preset intervals within the wound area and collecting them, a three-dimensional three-dimensional image as in the embodiment of FIG. 3 can be obtained. .

That is, by collecting the images in the row (a) in FIG. 2 and obtaining the three-dimensional image of FIG. 3 (a), a three-dimensional image of the wound immediately after the wound is created can be obtained. And, in a similar way, a three-dimensional image after 6 hours (image (b) in Fig. 3), a three-dimensional image after 12 hours (image (c) in Fig. 3), and a three-dimensional image after 18 hours (image in Fig. 3) (d)) and after 24 hours, a three-dimensional image (image (e) in FIG. 3) can be obtained.

Two-dimensional images in various directions of the wound can be simultaneously acquired through such a three-dimensional image or by a layer similar to a method of obtaining a three-dimensional image.

Furthermore, in order to analyze the degree of skin regeneration as objective data, the degree of skin regeneration can be quantitatively analyzed by extracting one or more numerical data of the wound location, surface area, wound length, cross-sectional area, and volume from the skin.

For example, the location of the wound on the skin, the number of wounds, and the surface area of the wound can be measured through the skin surface image, and one or more of the wound length, cross-sectional area, and volume can be obtained as numerical data through a three-dimensional image. can do. This makes it possible to quantify the wound.

Accordingly, according to an embodiment of the present invention, a wound quantification step of extracting one or more values of length, cross-sectional area, and volume through a two-dimensional or three-dimensional image of the wound may be further included.

In addition, according to an embodiment of the present invention, a wound quantification step of extracting one or more of a location, number, and area of the wound surface may be further included through the image of the skin surface on which the wound is generated.

4 is a graph showing the depth (length) and cross-sectional shape of a wound over time in the example of FIG. 2. 5 is a graph showing the volume of a wound over time in the example of FIG. 2.

FIG. 4 is a diagram showing a two-dimensional or three-dimensional image obtained from the embodiment of FIG. 2 and extracting a cross-sectional shape of a wound over time and a length over time.

Referring to the embodiment of FIG. 4, it can be seen that the cross-sectional area of the wound is the largest immediately after the wound is created, and the cross-sectional area of the wound gradually decreases over time, and thus has the smallest cross-sectional area after 24 hours.

In addition, it can be seen that the length of the wound gradually decreases to 1967, 1252, 840, 189, and 114 (pixels), respectively, after 6 hours, 12 hours, 18 hours, and 24 hours elapsed immediately after the wound was created. .

The graph of FIG. 5 shows a change in volume of a wound over time by acquiring a two-dimensional or three-dimensional image from the embodiment of FIG. 2.

Immediately after the wound was created, when 6 hours, 12 hours, 18 hours and 24 hours elapsed, the volume gradually decreased, and especially when 18 hours were cured, only a very small volume of wounds remained compared to the first wound. I can.

In the conventional case, since the observer observes the degree of wound or skin regeneration only through subjective observation, there is a tendency to depend on the experience or ability of the observer. However, according to various embodiments of the present invention, not only observing the wound as an image, but also expressing the length (depth), volume, and area of the wound as numerical values enables quantitative comparison of wounds, so that more precise and accurate observation This becomes possible. Repeatability, reproducibility and precision increase in the skin regeneration measurement method.

In addition, according to an embodiment of the present invention, by measuring the degree of skin regeneration according to the tissue characteristics of the skin, skin regeneration may be analyzed by reflecting a complex mechanism involved in skin regeneration.

More specifically, each skin has various tissue characteristics. That is, it may have different characteristics in one or more of the thickness and distribution of keratin, epidermis, and dermis of the skin.

Therefore, by measuring the degree of skin regeneration by changing the tissue characteristics as described above, it is possible to more accurately analyze and confirm the factors affecting skin regeneration and their influence.

In addition, according to an embodiment of the present invention, by controlling the wavelength and intensity of a laser that causes a wound, it is possible to check the size of the wound and the degree of skin regeneration according to the characteristics of the laser.

Specifically, FIG. 6 is a graph comparing the degree of skin regeneration according to the thickness of the epidermis of the skin according to an embodiment of the present invention.

Figure 6 (a) columns are pictures showing the degree of skin regeneration over time of skin having a thick epidermis (about 100 μm thick), and (b) the column is a thin epidermis (approximately 5 μm thick) These are pictures showing the degree of skin regeneration over time of the skin with.

Referring to FIG. 6, it can be seen that the size of the wound is somewhat larger when the thickness of the epidermis is thin (column (b)). Also, if you compare the size of the wound on the surface of the skin, you can compare it more clearly.

7 is a graph showing the cross-sectional shape and depth (length) of a wound measured by varying the thickness of the skin and the intensity of the laser according to an embodiment of the present invention.

7A and 7B show cross-sections of a wound against a laser of 40 mJ intensity for skin tissue having a thin epidermis (approximately 5 μm thick) and a thick epidermis (approximately 100 μm thick). It is a graph showing the depth, and (c) and (d) are wounds with a laser of 120 mJ intensity for skin tissue having a thin epidermis (approximately 5 μm thick) and a thick epidermis (approximately 100 μm thick). It is a graph showing the cross section and its depth.

Referring to FIG. 7, the depth of the wound increases as the intensity of the laser increases, but the depth of the wound increases by about 1.78 times when the skin thickness is thick as the intensity of the laser increases. It was increased by 1.97 times, and it can be seen that a deeper wound is generated as the intensity of the laser increases than when the skin thickness is thin.

In addition, FIG. 8 shows the volume of wounds different from the laser intensity in the skin (a) having a thick epidermis (about 100 μm thick) and the skin (b) having a thin epidermis (about 5 μm thick), This is a graph showing the volume change of the wound over time.

Referring to (a) and (b) of Fig. 8, the time when the volume value of the wound falls below 10000 for a laser of 120 mJ takes about 14 hours for thick skin and 24 hours or more for thin skin, If you have a thin epidermis, it can be seen that it takes more time for the skin to recover.

In addition, for 80 mJ, it was confirmed that the time when the volume value of the wound falls below 10000 is approximately 3 hours after the lapse of thick skin and about 12 hours after the lapse of thin skin. That is, in the case of a laser with an intensity of 80mJ, it can be seen that it takes about 4 times longer to recover when a thin skin is formed.

And, for 40 mJ, the time when the wound volume value approaches zero is about 24 hours for thick epidermis, but about 18 hours for thin epidermis. Rather, when the laser intensity is low, recovery is difficult when thin epidermis is present. You can see that it is faster.

That is, rather than analyzing only the skin surface, it is possible to more accurately analyze the creation and regeneration of the wound through the analysis of a two-dimensional or three-dimensional image of the wound.

In addition, according to various embodiments of the present invention, it is possible to check the depth, volume, and cross-sectional area of the wound of the skin generated by complex factors such as the tissue characteristics of the skin and the intensity of the laser, and the degree of regeneration thereof can be compared and analyzed. I can. Accordingly, it is possible to provide a method for measuring skin regeneration capable of quantitatively and precisely analyzing the regeneration action caused by complex factors of the skin.

Claims (13)

As a method of measuring skin regeneration through wound analysis,
A wound image measurement step of measuring an image of a skin surface or a cross section of the skin on which the wound is generated through optical coherence tomography; And
An image extraction step of extracting a surface image of the skin on which the wound was generated, a three-dimensional image or a two-dimensional image of the wound, using the measured image,
The wound includes a laser wound,
The image of the wound is extracted over time by changing the characteristics of the laser or the thickness of the skin surface,
A method for measuring skin regeneration, comprising measuring a change in the characteristics of the laser or the wound image in the thickness of the skin surface over time.
The method of claim 1,
The three-dimensional image or two-dimensional image of the wound, through the optical interference tomography, the skin regeneration measurement method characterized in that it is measured through one or more cross-sectional images up to a predetermined depth from the skin where the wound is created.
The method of claim 1,
The skin regeneration measurement method, characterized in that the image of the surface of the skin on which the wound is generated is measured through an image within a predetermined area of the skin surface on which the wound is generated.
The method of claim 1,
The method of measuring skin regeneration, characterized in that 2D optical coherence tomography or 3D optical coherence tomography is used for the optical coherence tomography.
The method of claim 1,
In the step of measuring the image, the skin regeneration measuring method is measured at predetermined time intervals to measure a degree of skin regeneration over time.
The method of claim 1,
The method of measuring skin regeneration, further comprising the step of quantifying a wound of extracting one or more of a length, a cross-sectional area, and a volume of the wound through the 2D or 3D image of the wound.
The method of claim 1,
The method of measuring skin regeneration, further comprising the step of quantifying a wound of extracting one or more of the number of wounds, the area of the wound, and the location of the wound through the image of the skin surface where the wound is generated.
The method of claim 1,
A method of measuring skin regeneration, characterized in that measuring a change in time of the wound image or the wound image according to one or more of the thickness and distribution of the keratin, epidermis, and dermis of the skin.
The method of claim 1,
The method of measuring skin regeneration, wherein the wound further comprises a wound caused by a chemical substance.
The method of claim 9,
The laser characteristic is the skin regeneration measurement method, characterized in that the intensity or wavelength of the laser.
The method of claim 9,
The laser is one selected from CO ₂ laser, argon (Ar) laser, YAG laser, Nd:YAG laser, Nd laser, Er:YAG laser, Ho:YAG laser, Ruby laser, diode laser, excimer laser, and multiple wavelength optical laser Skin regeneration measurement method, characterized in that the above.
The method of claim 1,
The skin regeneration measurement method, characterized in that the skin is artificial or living skin.
The method of claim 12,
The artificial skin is a skin regeneration measurement method, characterized in that the dermal layer comprising collagen and fibroblasts and artificial skin comprising keratinocytes proliferated and differentiated on the dermal layer.

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