JP2008011994A - Spots recurrence discrimination method - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a method for discriminating a recurrence possibility of spots by an image capturing the skin inside state of a spots portion after a phototherapy such as IPL (Intense Pulsed Light)/laser treatment or the blood flow volume of the spots portion before/after the phototherapy. <P>SOLUTION: The spots recurrence after the phototherapy of the spots portion is evaluated by the presence/absence of melanosome or the blood flow volume in the portion after the phototherapy of the spots portion. The presence/absence of the melanosome is evaluated by an image of the epidermal basal layer captured in an early stage after the therapy by a scanning type confocal microscope or a contact type digital video microscope, and the blood flow volume is evaluated by observing the blood flow volume in the skin of the spots portion after the therapy relative to that before the therapy using a device calculating the blood flow volume from the measurement of the amount of hemoglobins. <P>COPYRIGHT: (C)2008,JPO&INPIT

Description

  The present invention relates to a method for distinguishing recurrence of stains. More specifically, the present invention relates to an image of an epidermis basal layer in the skin of a spot site after light treatment imaged by a scanning confocal microscope or a contact digital video microscope, or before and after light treatment. The present invention relates to a method for discriminating the possibility of spot recurrence based on blood flow at the spot site.

  The present invention relates to a method for classifying a stain, and more specifically, using a scanning confocal microscope, an image of intracellular melanin in the skin of the stain site is acquired, and the obtained image is analyzed to analyze the stain site. The present invention relates to a method for classifying spots by analyzing and evaluating melanin status. The present invention also relates to a method for classifying stains by assessing melanin at the site of the stain, thereby sorting patients based on the stains classified for IPL / laser procedures.

In recent years, a confocal microscope has been used as a device for visualizing a skin tissue structure in order to non-invasively measure the structure of the internal tissue of the skin. (For example, see Patent Documents 1, 2, and 3.)
In the confocal microscope, it is possible to obtain a three-dimensional image by performing computer processing based on a two-dimensional image at a predetermined depth (depth) of the skin. For this reason, it has come to be used for research and application of the skin including the field of aesthetic medicine because it can visually detect the interface between the epidermis and dermis in the skin and the melanin present in the skin. It was. (For example, Non-Patent Document 1)
By the way, interest in health and beauty is increasing, and in particular, interest in the health and beauty of women's skin has become very high. Under such circumstances, in cosmetic skin / plastic surgery, etc., the opportunity to treat spots and freckles generated by ultraviolet rays has been greatly increased. For example, in the field of aesthetic medicine, treatment for eliminating spots is performed by phototherapy such as IPL or laser treatment.
JP 2003-57169 A JP 2003-52642 A JP 2003-57170 A Yamashita et al, Non-Invasive Visualization of Melanin and Melanocytes by Reflectance-Mode Confocal Microscopy, 2005, The Journal of Investigative Dermatology, Vol.124, pp235-240

  However, although the effect on the stain by IPL or laser treatment is at a high level, there is a possibility that the stain will recur from the same site after the treatment has been performed and the stain has disappeared. On the other hand, there have been few reports of detailed daily observations and instrument measurements at the spot site after surgery, and it was necessary to accumulate basic data for aftercare of the skin after surgery. Because of this current situation, doctors often do not know the extent of recurrence after surgery, and cannot be accurately predicted.

  Therefore, if the melanosomes including the melanin that causes the stains can be observed based on the state in the skin of the spot site after the IPL or laser treatment, and the melanocytes including the melanosomes can be observed and analyzed, the recurrence of the stains can be achieved. However, it has never existed to observe the skin of the spot site after IPL or laser treatment, and there is still no effective discrimination method for predicting the recurrence of the spot. It wasn't.

  Therefore, the present invention has been made in view of the above, and an image obtained by imaging an in-skin state of a spot site after phototherapy such as IPL / laser treatment or a blood flow rate of the spot site before and after the phototherapy is used to detect the stain. The purpose is to provide a method for identifying the possibility of recurrence.

  Therefore, in order to predict the recurrence of stains, the present inventors confirmed the presence of melanosomes including melanin existing in the skin corresponding to the stain sites, and the ability to produce melanosomes, that is, the activity of melanocytes By analyzing the degree, the present invention has been developed based on the idea that the recurrence of spots can be identified early after the treatment.

That is, the invention according to claim 1
The spot recurrence after phototherapy of the spot site can be achieved by a spot recurrence discrimination method characterized by evaluating the presence or absence of melanosomes or blood flow at the spot site after phototherapy for the spot site.

  According to the above invention, the recurrence of the spot after phototherapy of the spot site can be identified early by evaluating the presence or absence of melanosomes or blood flow in the spot site after phototherapy for the spot site, More effective measures can be taken.

  The invention according to claim 2 is that, in the invention according to claim 1, the evaluation based on the presence or absence of the melanosomes is evaluated by an image obtained by non-invasively imaging the intradermal epidermis basal layer of the spot site. Features.

  According to the above invention, by evaluating the presence or absence of melanosomes with a noninvasive image of the intradermal epidermis basal layer of the spot site, it is possible to distinguish the recurrence of the spot at an early stage and to effectively deal with it.

The invention according to claim 3 is the invention according to claim 2, wherein the evaluation by the image is performed by using a scanning confocal microscope at an early stage after the light treatment for the stain.
Irradiating the skin with scanning laser light for intra-skin observation in a plane, and
Receiving reflected light reflected at a predetermined depth of the skin;
Obtaining a planar image of melanosomes present in the skin corresponding to the melanosomes in the skin at the predetermined depth based on the intensity of the reflected light; and
Removing noise from the planar image;
Setting a threshold for the image processed in the removing step;
Extracting a region with high luminance for the image processed in the threshold setting step;
An evaluation step by measuring a ratio of the extracted area to the total number of pixels of the image;
It is characterized by comprising.

  According to the above invention, by processing the image of the epidermis basal layer obtained by a scanning confocal microscope, it is possible to distinguish the recurrence of spots early after the operation, for example, after the scab is peeled off until about 20 days after the operation. For example, an optimal countermeasure can be taken, such as applying a whitening agent.

  The invention according to claim 4 is characterized in that, in the invention according to claim 3, the recurrence of the stain is evaluated at a ratio to the total number of pixels of the image in the extracted region.

  According to the above invention, it is possible to foresee the recurrence of spots depending on the ratio of the extracted area to the total number of pixels of the image, and early discrimination becomes possible, so that effective countermeasures can be taken.

  The invention according to claim 5 is the invention according to claim 2, characterized in that the evaluation by the image is made by a contact type digital video microscope.

  According to the above invention, by evaluating the image captured by the contact-type digital video microscope, it becomes possible to identify the recurrence of the spot early and to effectively deal with it.

  The invention according to claim 6 is the invention according to claim 1, wherein the evaluation based on the blood flow is measured by a device capable of calculating the blood flow by measuring the amount of hemoglobin, and before and after the phototherapy for the spot site. It is characterized by blood flow measured 2 to 3 weeks after treatment.

  According to the above invention, by measuring the blood flow measured by a device capable of calculating blood flow by measuring the amount of hemoglobin, and measuring the blood flow measured before or after phototherapy for the spot site and 2 to 3 weeks after the treatment, Early discrimination of recurrence is possible, and more appropriate measures can be taken.

  Further, the invention according to claim 7 is the invention according to claim 6, wherein when the measured blood flow rate at the spot portion increases with respect to the blood flow rate at the spot portion before the light treatment, Is characterized by recurrence.

  According to the above invention, when the measured blood flow at the spot site increases with respect to the blood flow at the spot site before the phototherapy, it is possible to foresee the recurrence of the spot, enabling early discrimination and more effective. Can cope with it.

  The invention according to claim 8 is the invention according to any one of claims 1 to 7, wherein the phototherapy is an IPL treatment or a laser treatment.

  According to the above-described invention, after the IPL treatment or the laser treatment based on an image obtained by a scanning confocal microscope or a contact digital video microscope or an evaluation of a blood flow measured by a device capable of calculating a blood flow by measuring a hemoglobin amount. Therefore, it is possible to determine early detection of the recurrence of the spot, and it is possible to perform an effective treatment (after care) for the spot site after the operation.

  According to the present invention, an image of the epidermis basal layer in the skin of the spot site after the IPL / laser treatment of the spot is taken with a scanning confocal microscope or a contact type digital video microscope, and the obtained image is analyzed. Recurrence of the stain can be predicted by the measured value obtained by obtaining the blood flow volume of the site by a device capable of calculating the blood flow volume by measuring the melanosome state of the spot site or the amount of hemoglobin. Thus, according to the present invention, it is possible to discriminate the recurrence of spots early, for example, in a period from about 20 days after the operation after the scab that appears by the operation is peeled off. More effective treatment such as application can be performed.

  Specific examples carried out according to the present invention will be described in more detail below, but the present invention is not limited to these examples. In addition, various aspects are possible about the detail, unless it deviates from the meaning and range of this invention.

  Before explaining the present invention, first, the action of the IPL / laser on the spot site will be explained. The IPL / laser is a light beam used for spot improvement treatment. IPL is an abbreviation for Intense Pulsed Light, which is light having a wide wavelength range used for blemishes and freckles improvement treatment. The laser uses light of one wavelength. These lights are generally used for blemishes and freckles improvement treatment in the field of aesthetic medicine and the like.

  FIG. 1 illustrates the action of the IPL / laser on the spot site. As can be seen from FIG. 1, the IPL / laser can specifically damage the pigmentation sites in the skin. When the IPL / laser is irradiated toward the pigmentation site in the skin which is the cause of the stain, melanin absorbs the light energy of the IPL / laser. After that, only keratinocytes rich in melanin die by heat, scabs appear and appear on the top of the skin. In this way, the IPL / laser treatment at the spot site is performed, and an example of the result is shown in FIG. In FIG. 2, a scab appears at the spot site after laser treatment, and it shows that the spot has been improved by peeling (about 20 days).

  Next, in practicing the present invention, a laser treatment method will be described below as a specific treatment method for treating a spot site.

  Laser treatment was performed on the face spot portion (five test subjects: Kuroko Nikko), and the daily change of the treatment site was observed. As a device used for treatment, a laser device (1B101 manufactured by Japan Infrared Industrial Co., Ltd.) equipped with a Q-switched ruby laser having a wavelength of about 680 nm was used. As a laser irradiation condition, irradiation was performed with an energy amount of 6 J and a 3 mm spot. One laser irradiation was performed on the above five female test subjects under the above laser irradiation conditions. After the disappearance of the stain due to the treatment, as a post-treatment treatment (aftercare), the subject is in charge of the antibacterial / antibacterial medicine designated by the doctor until immediately after the treatment until the scab (the brown scab occurs at the spot irradiated with the laser) is peeled off. An inflammatory drug (Linderon VG) was applied and coated with a bandage. After the scab peeled, a 5% hydroquinone-containing ointment was applied to treat the site where the stain disappeared.

  In this way, the spot site is improved. However, after the spot disappears completely after IPL or laser treatment, the spot may recur from the same site. This is Japanese Patent Application No. 2005-250174 filed by the present applicant, in which the melanosomes of the epidermal basal layer are removed together with the scab, but active melanocytes remain in the basal epidermis, and the remaining active melanocytes are There is a possibility that spots will recur, and it is necessary to apply laser and hydroquinone.

  Therefore, in the present invention, it is possible to effectively foresee the extent of spot recurrence after the operation, and in order to perform a more effective countermeasure after that, an image of the epidermis basal layer of the spot site or in the skin It is characterized by discriminating the recurrence of stains based on the blood flow volume.

  Explaining the discrimination method by the image of the epidermis basal layer of the spot site, analysis and evaluation of the image taken by the scanning confocal microscope or contact digital video microscope for the skin condition of the spot site before and after the laser treatment, and the evaluation Based on the analysis, the melanosome state of the epidermis basal layer in the skin is analyzed, and the recurrence of the stain is distinguished based on the analysis result.

  Observation of changes in the spot site due to laser treatment includes a confocal microscope (Vivascope1000, manufactured by Lucid) that can observe a horizontal section inside the skin, an ultraviolet photo for melanin observation, and a contact digital video microscope (hereinafter referred to as VMS). And: INT-200, manufactured by Integral). In the confocal microscope, a horizontal cross-sectional image of the epidermis basal layer was taken and partially compared with an image taken by VMS. In addition, skin images were taken using a digital camera (Coolpix 4500, manufactured by Nikon). In particular, measurement / photographing with a scanning confocal microscope was performed before laser treatment and after irradiation with laser (after scab removal) 12, 20, and 40 days. The method of the present invention by VMS will be described later.

  First, the method of the present invention using a scanning confocal microscope will be described below with reference to the drawings.

  FIG. 3 shows a schematic configuration of an optical inspection apparatus 1 applied to a skin two-dimensional image generation apparatus according to an embodiment of the present invention. FIG. 4 shows a drive system of the optical inspection apparatus 1. In the present invention, a scanning microscope is used as the optical inspection apparatus 1.

  In the figure, reference numeral 2 denotes a scanning microscope main body, and the confocal microscope main body 2 is provided with a light source 10. As will be described later in detail, the light source 10 irradiates the surface of the skin 4 of the measurement subject as a sample with laser light. The laser light emitted from the light source 10 passes through the half mirror 11 and travels to the optical scanning device 12. Here, the laser light emitted from the light source 10 provided in the confocal microscope main body 2 is a laser for observation in the skin specifically used in the confocal microscope, and for the treatment used for the light treatment of the stain described above. Different from laser. Actually, the intensity of the laser used as the light source 10 was 1.4 mW. A good image can be obtained by using a laser intensity in the range of 1.2 to 2.0 mW. Further, in this embodiment, the skin 4 is a spot site before the spot is treated, and is also a spot site where the scab is peeled off after the spot is treated.

  The optical scanning device 12 scans the laser beam from the light source 10 two-dimensionally in the XY direction in a predetermined measurement region of the skin 4 in accordance with a drive control command from the XY direction drive control device 13. As shown in FIG. 4, the optical scanning device 12 includes a polygon mirror 25, a polygon driver 26, a galvano mirror 27, a galvano driver 28, and the like.

  The polygon mirror 25 driven by the polygon driver 26 scans laser light in the X direction. The galvanometer mirror 27 driven by the galvanometer driver 28 scans laser light in the Y direction. Therefore, the laser beam can be scanned on the skin 4 in the XY direction by the optical scanning device 12.

  The optical scanning device 12 is connected to an XY direction drive control device 13. This XY direction drive control device 13 has an XY direction control circuit 30 connected to a polygon driver 26 and a galvano driver 28 via I / Os 33 and 35. The X-Y direction control circuit 30 is connected to the computer 3 and controls the polygon driver 26 and the galvano driver 28 in accordance with commands from the computer 3 as will be described later. Thereby, the operations of the polygon mirror 25 and the galvanometer mirror 27 are controlled by the computer 3.

  As described above, the laser beam scanned in the XY directions by the optical scanning device 12 is irradiated to the skin 4 through the objective lens 14. The objective lens 14 is attached to a depth of focus adjustment device 15. In this embodiment, the magnification of the objective lens is 50 times. The focal depth adjusting device 15 moves the objective lens 14 in the optical axis direction (Z direction) in accordance with a control command of a Z direction drive control device 16 described later, thereby varying the focal depth.

  As shown in FIG. 4, the depth-of-focus adjustment device 15 includes a focus adjustment mechanism 31 and a focus depth adjustment driver 32. The focus adjustment mechanism 31 adjusts the focus position of the laser beam by the objective lens 14 by moving the position of the objective lens 14 in the Z direction. Therefore, by focusing the objective lens 14 on the inside of the skin 4, the tissue inside the skin 4 can be measured based on the reflected light.

  A depth-of-focus adjustment driver 32 that drives the focus adjustment mechanism 31 is connected to the Z-direction drive control device 16.

  The Z direction drive control device 16 has an XY direction control circuit 30 connected to a focal depth adjustment driver 32 via an I / O 36. The XY direction control circuit 30 is connected to the computer 3 and controls the depth-of-focus adjustment driver 32 in accordance with a command from the computer 3 as will be described later. Thereby, the operation of the focus adjustment mechanism 31 is controlled by the computer 3.

  On the other hand, the laser light applied to the skin 4 through the objective lens 14 is reflected at a predetermined depth in the skin 4 determined by the focal position of the objective lens 14. The reflected light passes through the objective lens 14 and returns to the optical scanning device 12, and further returns from the optical scanning device 12 to the half mirror 11.

  The half mirror 11 is a semi-transparent mirror, and is provided on the optical path between the light source 10 and the optical scanning device 12. The half mirror 11 is provided to guide the reflected light from the skin 4 traveling from the optical scanning device 12 toward the photodetector 20.

  The reflected light whose direction has been changed by the half mirror 11 is received by the photodetector 20 through the pinholes of the lens 18 and the pinhole plate 19. The lens 18 focuses reflected light toward the photodetector 20. The photodetector 20 has a light detection element that converts light obtained through the pinhole of the pinhole plate 19 into an electric signal corresponding to the light amount.

  The pinhole plate 19 has a pinhole having a predetermined diameter, and is disposed between the lens 18 and the photodetector 20. Further, the arrangement position is set so that the pinhole matches the focal position of the lens 18.

  The reflected light from the skin 4 that has entered the photodetector 20 is converted into an electrical signal by the photodetector and sent to the computer 21. The computer 21 generates a two-dimensional image by performing processing described later based on the transmitted electric signal, and displays it on the monitor 22.

  The computer main body 21 is also connected to the XY direction drive control device 13 and the Z direction drive control device 16 described above. The computer 21 comprehensively controls the XY direction drive control device 13 and the Z direction drive control device 16, thereby controlling the X-Y direction scanning of the laser light and the depth of focus by driving the objective lens 14. It is the structure which performs control.

  In the optical inspection apparatus 1 configured as described above, the focus microscope main body 2 forms a scanning confocal microscope. In this scanning confocal microscope, the laser light emitted from the light source 10 is irradiated by scanning the surface of the skin 4 in a dot-like manner, and the reflected light from the illuminated skin 4 is applied to the lens 18 and the pinhole plate 19. This is a microscope using a confocal effect in which light is condensed again into a spot shape by a pinhole and imaged on the light detector 20, and luminance information of the image is obtained by the light detector 20.

  In such a scanning confocal microscope, an image at a predetermined depth of the skin 4 in the range scanned with the laser light is obtained as a two-dimensional image in a focused state in the entire range by the above confocal action. Can do. This utilizes the fact that the luminance of the skin 4 (sample) obtained at the focal position is the maximum luminance.

  Specifically, the reflected light of the laser light is not reflected only at a predetermined depth of the skin 4, but is reflected within a predetermined thickness range centered on the predetermined depth. Therefore, the light reflected from the part other than the predetermined depth in the reflected light becomes noise. The scanning confocal microscope is configured to remove light reflected by a portion other than a predetermined depth, which becomes noise, using a pinhole plate 19. That is, the reflected light passing through the pinhole plate 19 is only light focused on a predetermined depth of the skin 4, and the image of the skin 4 finally obtained thereby becomes a two-dimensional image focused on the whole.

  Next, various measurement processes for the skin 4 using the optical inspection apparatus 1 configured as described above will be described. First, a two-dimensional image generation process for generating a two-dimensional image of the skin 4 using the optical inspection apparatus 1 will be described.

  FIG. 5 is a flowchart showing a two-dimensional image generation process of the skin 4. When the process shown in the figure is activated, the activation process is first performed. Specifically, in step 10 (step is abbreviated as S in the figure), the focal depth D (μm) is set to α (initial value) (D = α), and step 11 will be described later. A count value N indicating the number of two-dimensional images generated is set to “1” (N = 1). Although not shown in the flowchart, in the startup process, a startup process of the computer 3 and the light source 10 (laser light source) is also performed.

  In the subsequent step 12, a process for setting the depth of focus D is performed. In this optical scanning device 12, the computer 3 transmits a control signal to the Z-direction control circuit 33 of the Z-direction drive control device 16 so that the focal depth becomes the focal depth D that is the initial value set in Step 10.

  The Z-direction control circuit 33 drives and controls the focal depth adjustment driver 32 of the focal depth adjustment device 15 so that the focal seismic intensity of the objective lens 14 becomes D. Accordingly, the objective lens 14 is driven in the Z direction by the focus adjustment mechanism 31 so that the depth of focus becomes D. When acquiring a three-dimensional image, the measurement of the sample 4 is performed sequentially from the skin surface toward the deep layer, but in this embodiment, since a two-dimensional image is acquired, the focal depth D as an initial value is a spot region. It is set in accordance with the epidermal basal layer so as to obtain an optimum depth in the skin 4 (sample) in which the melanosomes are accumulated.

  Here, referring to FIG. 6, a cross-sectional view showing the structure of the skin 4 is shown. As shown in the figure, the skin 4 is roughly divided into an epidermis and a dermis. The epidermis is classified from the upper part into the skin surface (indicated by arrow A in the figure), the spiny layer (indicated by arrow B in the figure), and the basal layer (indicated by arrow C in the figure). The dermis (indicated by an arrow E in the figure) exists below the epidermis. In addition, it is known that melanosomes including melanin causing stains and melanocytes containing these melanosomes are scattered in the vicinity of the epidermis basal layer. Therefore, it is important for the research of the stain regarding the recurrence of the stain to correspond the focal depth D to the vicinity of the epidermis basal layer. Moreover, since the depth to the vicinity of the epidermis basal layer varies depending on the physical characteristics of the subject, the depth of focus is preferably adjusted as appropriate according to the subject.

  When the depth of focus D is set as described above, in the subsequent step 13, laser light is emitted from the light source 10 and processing for scanning this laser light is performed. Specifically, as described above, the laser light emitted from the light source 10 and passed through the half mirror 11 is scanned in the X direction by the polygon mirror 25 provided in the optical scanning device 12, and in the Y direction by the galvano mirror 27. Scanned. Thereby, the laser beam scans the skin 4 two-dimensionally in the XY direction.

  The scanning speed of the laser light is controlled by the computer 3 so as to be an optimum speed for image generation to be described later via the XY direction control circuit 30, the polygon driver 26, the galvano driver 28, and the like.

  In the following step 14, the brightness of the reflected light is detected. That is, the laser light irradiated on the skin 4 is reflected on the skin 4. The reflected light from the skin 4 returns to the two-dimensional scanning mechanism 12 through the objective lens 14, and passes from the two-dimensional scanning mechanism 12 to the photodetector 20 through the half mirror 11, the lens 18, and the pinhole plate 19. Incident light is photoelectrically converted by the photodetector 20 and transmitted to the computer 3 as an electrical signal.

  At this time, as described above, in the scanning confocal microscope, the laser light emitted from the light source 10 irradiates the surface of the skin 4 in a dot-like manner and irradiates the reflected light from the illuminated skin 4 with the lens 18. In addition, the light is condensed again in a spot shape by the pinhole of the pinhole plate 19 and imaged on the light detector 20, and the light intensity information of the image formation is obtained by the light detector 20. Yes. Since the luminance of the skin 4 (sample) obtained at the focal position is the maximum luminance, the dynamic range of the electrical signal that is photoelectrically converted and output from the photodetector 20 can be improved.

  In the subsequent step 15, a two-dimensional image generation process is performed based on the luminance signal of the reflected light obtained in step 14. As described above, the laser light emitted from the light source 10 is scanned as spot light, and the reflected light is detected by the photodetector 20, but the computer 3 synchronizes with the scanning of the laser light by the optical scanning device 12. The detection signal from the photodetector 20 is captured. As a result, the computer 3 can generate a two-dimensional image in the scanned range of the laser light based on the detection signal transmitted from the photodetector 20.

The two-dimensional image generated in step 15 is stored in a storage device (not shown) provided in the computer 3 in step 16. FIG. 8 shows, on the right side, a two-dimensional image of the epidermal basal layer corresponding to each spot site on the five panels obtained by the above-described method of the optical inspection apparatus 1 (scanning confocal microscope). An image of the skin surface corresponding to each spot site taken is shown on the left side.
As can be seen from FIG. 8, a large amount of melanin is present in the basal layer of the epidermis at the spot site before treatment. Compared with panels 1 to 3 and panels 4 and 5 with reference to the scanning microscope image on the 12th day after the operation, the stain sites of panels 4 and 5 where the post-treatment spots reappeared have high activity. It can be seen that many melanocytes are present early after the treatment. The melanosomes are transferred to the upper skin layer by laser treatment, so that the scab that contains melanin differs depending on the state or the number of days until detachment depending on humans. In the case of recurrence, it can be seen that melanocytes with high ability to produce melanosomes already exist immediately after the scab is removed. In the present specification, the term “early after treatment” means a period of about 20 days after the treatment after the scab appeared by the laser treatment is peeled off. Further, from panels 4 and 5, it can be confirmed that melanosomes are scattered in the epidermal basal layer of the spot site on the 40th day after the treatment. In addition, the schematic in the cross section of the skin of a spot part is shown in FIG. 9 about the change after a treatment.

  Next, a method for evaluating a spot site by analyzing a two-dimensional image acquired as shown in FIG. 8 will be described.

  FIG. 7 is a flowchart showing a melanosome evaluation process for a spot site. Each step described in the flowchart of FIG. 7 is a two-dimensional image (right side of FIG. 8) of the epidermal basal layer of each spot site acquired by aiming at the spot site indicated by panels 1 to 5 shown on the left side of FIG. The method of distinguishing the recurrence of the stain by analyzing the analysis process and detecting the melanosome state, that is, the active state of the melanocyte, will be described with reference to FIG.

  FIG. 10 shows an analysis image obtained by performing analysis processing along each step of the flowchart of FIG. 7 based on the image of the epidermis basal layer in the skin of the spot site obtained from each panel shown in FIG. 8 and the result. .

  In step 17, filtering processing for removing noise (threshold setting) from the obtained two-dimensional image is performed. This process can remove noise that is undesirable for the analysis process from the original image, and the subsequent image analysis process makes it easier to extract highly active melanocytes that are in a state of newly producing melanosomes. . In the skin immediately after scab detachment, there are almost no melanosomes present in epidermal basal cells, and many of them are limited to melanosomes newly produced in melanocytes. For this reason, the reflection image (derived from melanosomes) of the epidermal basal layer obtained from the scanning confocal microscope immediately after the scab is peeled off can be an index for evaluating the activity of melanocytes.

  That is, the noise removal processing of the image means that the threshold value is appropriately set according to the obtained image.

  In the case of the present embodiment, a high luminance region was extracted by setting 128 gradations as a threshold for the reflection image (256 gradation images) of the epidermal base layer obtained from the scanning confocal microscope. The result is shown in image (2) in FIG. In this way, it is possible to extract highly active melanocytes that are in a state of newly producing melanosomes.

  Furthermore, the step for analyzing the extracted highly active melanocyte and distinguishing the recurrence of the spot at the spot after laser treatment will be described. In the subsequent step 18, the ratio of the extracted region (number of pixels) to the total number of pixels (number of pixels) in the melanocyte pattern extracted by the above processing, that is, the area ratio of melanocytes is measured. When each numerical value is shown for each panel, the panel 1 has an area ratio of 0.03%, the panel 2 has an area ratio of 0.33%, and the panel 3 has an area ratio of 0.60%. In panel 4, the area ratio was 1.26%, and in panel 5, the area ratio was 2.85%. As can be seen from FIG. 10, it can be seen that panels 1 to 3 in which the spots did not recur and panels 4 and 5 in which the spots recurd differ in the area ratio of melanocytes on the 12th day after the treatment. That is, when the threshold value is set to 128 gradations, it is clear that if the extracted area is 1% or more, the stain is highly likely to recur on the 40th day. As described above, it is difficult to distinguish the recurrence of the spot on the skin after the operation, but from the results of panels 4 and 5 where the spot reappeared, melanosomes in the epidermis basal layer in the skin at the spot were newly added. It was confirmed that the active state of the produced melanocytes was active, and the spots recurred based on the degree of melanocyte activity. Therefore, it is possible to effectively foresee and evaluate the recurrence of the spot site after surgery based on the area ratio of the melanocyte on the image obtained by imaging this state. Can be identified.

  Therefore, the present invention uses a scanning confocal microscope to acquire an image of the epidermal basal layer in the skin at the spot site, and to analyze and evaluate the melanocyte activity state by analyzing and processing the obtained image. Can be identified. Thus, by evaluating recurrence at an early stage after laser treatment of a spot site, an effective treatment such as a whitening agent for the spot site can be applied.

  Next, the method of the present invention using VMS will be described below with reference to the drawings.

  With the contact video microscope that can non-invasively observe the state of the dermal base layer in the skin of the above-mentioned three female subjects (panels 1, 2 and 4 above), the scab before and after the laser treatment Immediately after peeling and every other week after peeling, it was carried out for two months. Note that the observation objects are melanosomes that are brown-colored and observed in a granular form on VMS, melanocytes that newly produce melanosomes, and capillaries that can confirm the flow of red blood cells. In the three panels, after laser treatment, panels 1 and 2 are subjects whose spots have been improved, and panel 4 is a subject whose spots have recurred.

  The observation method using the VMS will be described below.

  VMS was brought into contact with the spot site at a magnification of about 650 times, and images were adjusted and adjusted so that the melanin and blood vessels in the skin were in focus. The focus adjustment method is the same as that of a normal microscope, that is, a microscope operation method, and a detailed adjustment method will not be described here. In this example, INT-200 (manufactured by Integral) was used as the VMS, but the VMS is not limited to this as long as it can image the state in the skin non-invasively.

  When contacting the VMS with a spot site, apply water or oil to the skin surface to prevent reflected light and morphological noise on the skin surface. The lens part is brought into contact with the skin. In order to obtain a clear and clear image of VMS, it is desirable that the water or oil used is close to the refractive index of the stratum corneum of the skin. In this example, baby oil (manufactured by Johnson & Johnson) was used. . In addition, if it is a thing close | similar to the refractive index of the horny layer of skin, it can be used without being limited to water or oil. FIG. 11 shows images taken by the VMS of panels 1, 2 and 4. FIG. 12 shows an image captured using the VMS of the panel 4 in which the stain recurs.

  As a result, even when an image captured by VMS was confirmed, as can be seen from the panel 4 where the stain recurred, it was confirmed that melanocytes were activated in the vicinity of the skin epidermis basal layer at the spot site. Therefore, as a result of observing the progress of the spot site after phototherapy, it was confirmed that the recurrence of the spot at the spot site can also be identified by an image of the epidermis basal layer imaged by VMS. can do. In this way, it is possible to foresee the recurrence of a spot from an image simply captured using VMS, but the captured image is subjected to general-purpose image processing (for example, processing by extracting color shading on the image), and processing It is also possible to make a discrimination based on a luminance value obtained by further analyzing the digitized image and digitizing it.

  Next, the method of the present invention by observing the blood flow state in the skin at the spot site will be described below.

  For the panel of 4 female subjects described above (panels 1, 2, 4 and 5 above), the skin of the spot site for 2 months, immediately after the scab was peeled off after laser treatment and every other week after peeling The internal blood flow state was observed. As described above, the four female subjects improved with the panels 1 and 2 without any recurrence after laser treatment, but the stains reappeared on the panels 4 and 5.

  The instrument used for observing the blood flow state in the skin at the spot site was a measuring instrument capable of quantifying the amount of hemoglobin. In this example, measurement was performed using Mexameter MX16 (manufactured by Courage + Khazaka), and the blood flow state was measured and evaluated using the Erythema Index (value obtained by quantifying erythema derived from hemoglobin) as an index. That is, it was evaluated whether or not the blood flow at the spot site after laser treatment was increased compared with the blood flow at the spot site before laser treatment.

  As a specific method of this example, the measurement was performed by a known method described in Japanese Patent Application No. 11-299743 using Mexameter MX16. The device to be used is not limited to the Mexameter MX16, and any device that can calculate the blood flow volume by measuring the hemoglobin amount may be used. For example, a blood flow meter using the laser Doppler method: PeriFlux system (manufactured by Eurotech Japan), PeriScanPIM II (manufactured by PERIMED), etc. Also, taking a picture of the whole face, analyzing the spectral curve in the visible region A skin image analyzer (Shiseido Co., Ltd.) or a spectrocolorimeter (CM-2000: manufactured by Minolta Co., Ltd.), which employs a method for calculating the amount of hemoglobin from the sample, can be used.

  Below, the measurement result of the erythema degree by Mexameter MX16 is shown.

  Table 1 shows the numerical value of the raw data of the spot site measured by the Mexameter MX16, and Table 2 shows the change rate of the blood flow after the operation when the pre-laser operation is set to 100 based on the value of Table 1. .

From Table 2, in the panels 4 and 5 where the stain recurred, it was confirmed that the blood flow increased in the measurement for 2 to 3 weeks after the operation compared to before the operation. It can be determined that recurrence is likely to occur when an increase in blood flow of 2% or more is observed. Moreover, it turns out that the tendency higher than the value of the blood flow rate before a treatment is seen also after six to 14 weeks after that.

  As a result, if the Erythema Index shows a higher value than before the operation even after about one month after the operation, it can be determined that there is a possibility of the regeneration of the stain. Therefore, the present invention can not only distinguish the possibility of spot recurrence using a scanning confocal microscope and VMS, but also by observing blood flow in the skin at the spot site before and after treatment. The recurrence can be differentiated.

  Therefore, the present invention can distinguish the possibility of spot recurrence after phototherapy using a scanning confocal microscope, VMS, or a device capable of calculating blood flow from measurement of hemoglobin amount. It is possible to effectively deal with the spot site at an early stage.

  The preferred embodiments of the present invention have been described in detail above, but the present invention is not limited to such specific embodiments, and various modifications and changes can be made within the scope of the gist of the present invention described in the claims. It can be changed.

It is a figure which shows the effect | action of IPL / laser to a spot site | part. It is a figure which shows an example of the improvement of the spot site | part after laser treatment. It is a whole block diagram of the optical inspection apparatus used for this invention. It is a block diagram which shows the drive system of an optical inspection apparatus. It is a flowchart which shows the two-dimensional image generation process implemented using an optical inspection apparatus. It is a figure for demonstrating the structure of skin. It is a flowchart which performs the melanosome evaluation process of a spot site | part. It is a figure which shows the skin internal change of the spot site | part before and behind laser treatment, The two-dimensional image of the epidermis basal layer corresponding to each spot site | part of five panels imaged with the scanning confocal microscope is shown on the right side, and a digital camera It is a figure which shows the image of the skin surface corresponding to each spot site | part imaged on the left side. It is a figure which shows the schematic in the cross section of the skin of a spot part about the change after laser treatment. It is a figure which shows the analysis image and analysis result which were analyzed according to each step of the flowchart of FIG. 7 based on the image of the epidermis basal layer in the skin of the spot site | part obtained from each panel shown in FIG. It is a figure which shows the image which imaged the progress before and after phototherapy of a spot site | part with VMS of the panels 1, 2, and 4. FIG. It is a figure which shows the image imaged using VMS of the stain part of the panel 4 which the stain recurred.

Explanation of symbols

DESCRIPTION OF SYMBOLS 1 Optical inspection apparatus 2 Operation type | mold microscope main body 3 Computer 4 Sample (skin)
DESCRIPTION OF SYMBOLS 10 Light source 12 Optical scanning device 13 XY direction drive control device 14 Objective lens 15 Depth of focus adjustment device 16 Z direction drive control device 18 Lens 19 Pinhole board 20 Photo detector 21 Computer main body 22 Monitor 25 Polygon mirror 26 Polygon driver 27 Galvano mirror 28 Galvano driver 30 XY direction control device 31 Focus adjustment mechanism 32 Focus adjustment mechanism driver 33 Z direction control device

Claims (8)

  A method for distinguishing a recurrence of a stain, characterized by evaluating the recurrence of a stain after phototherapy of the stain site based on the presence or absence of melanosomes in the stain site after the phototherapy for the stain site or a blood flow volume.   The method according to claim 1, wherein the evaluation based on the presence or absence of the melanosomes is evaluated by an image obtained by noninvasively imaging the intradermal epidermis basal layer of the spot site. The evaluation by the image is performed by using a scanning confocal microscope at an early stage after phototherapy for a stain.
Irradiating the skin with scanning laser light for intra-skin observation in a plane, and
Receiving reflected light reflected at a predetermined depth of the skin;
Obtaining a planar image of melanosomes present in the skin corresponding to the melanosomes in the skin at the predetermined depth based on the intensity of the reflected light; and
Removing noise from the planar image;
Setting a threshold for the image processed in the removing step;
Extracting a region with high luminance for the image processed in the threshold setting step;
An evaluation step by measuring a ratio of the extracted area to the total number of pixels of the image;
The method for distinguishing recurrence of spots according to claim 2, comprising:   The spot recurrence discrimination method according to claim 3, wherein the spot recurrence is evaluated based on a ratio of the extracted area to the total number of pixels of the image.   The method according to claim 2, wherein the evaluation by the image is performed by a contact type digital video microscope.   The evaluation based on the blood flow rate is measured by a device capable of calculating the blood flow rate by measuring the amount of hemoglobin, and is based on the blood flow rate measured before phototherapy for the spot site and 2 to 3 weeks after the treatment. Item 2. A method for distinguishing recurrence of spots according to Item 1.   The spot recurrence discrimination method according to claim 6, wherein the spot recurrence occurs when the measured blood flow volume at the spot area increases with respect to the blood flow volume at the spot area before the phototherapy. .   The method for distinguishing spot recurrence according to any one of claims 1 to 7, wherein the phototherapy is IPL treatment or laser treatment.