JP4109133B2 - Fluorescence determination device - Google Patents

Description

[0001]
BACKGROUND OF THE INVENTION
The present invention relates to a fluorescence determination method and apparatus for determining a tissue property of a part to be measured based on fluorescence emitted from the part to be measured by irradiation with excitation light.
[0002]
[Prior art]
Conventionally, a fluorescence determination device that irradiates a measurement target part such as a living body with excitation light in a predetermined wavelength band and determines the tissue property of the measurement target part based on the fluorescence emitted from the measurement target part has been proposed. . Such a determination device includes a device that performs determination based on drug fluorescence emitted from a biological tissue that has previously absorbed a fluorescent diagnostic agent, and a determination based on autofluorescence that is emitted from the biological tissue without using the fluorescent diagnostic agent. There is a device that performs. In many cases, this type of fluorescence determination apparatus is configured to be incorporated in an endoscope inserted into a body cavity, a colposcope, a surgical microscope, or the like.
[0003]
In the initial autofluorescence determination apparatus, as shown in FIG. 8, the fluorescence intensity emitted from the diseased tissue is smaller than the fluorescence intensity emitted from the normal tissue. It was judged whether it was an organization. However, since the living body part has irregularities, the distance from the excitation light source to the measured part is not uniform, and the excitation light illuminance at the measured part of the living body is generally non-uniform. On the other hand, the intensity of fluorescence emitted from normal tissue is approximately proportional to the illuminance of excitation light, and the illuminance of excitation light decreases in inverse proportion to the square of the distance. As a result, strong fluorescence may be received from a lesion tissue that is closer than normal tissue that is far from the light source. If a determination based only on the fluorescence intensity is performed, the determination of the tissue property may be erroneous. obtain.
[0004]
In order to prevent such a misjudgment, a calculation value based on the ratio between the light intensity of the excitation light received by the site of the living tissue and the light intensity of the fluorescence emitted from the measurement target by receiving the excitation light, that is, There has been proposed a method for determining a tissue property of a part to be measured by obtaining a value reflecting a fluorescence yield, which is a value that is not affected by the distance and angle of irradiation with excitation light.
[0005]
However, when obtaining a value reflecting the above fluorescence yield, the excitation light in the ultraviolet to visible range is absorbed by various substances in the living body, so that even if the intensity distribution of the reflected excitation light is measured, The intensity distribution of the received excitation light is not correctly measured. Therefore, as one measure for obtaining a calculated value reflecting the fluorescence yield, the near-infrared light that receives uniform absorption compared to the ultraviolet to visible region is irradiated to the living tissue as the reference light, and the reflected near red is reflected. Using the light intensity of the external light as a substitute for the light intensity of the excitation light, obtain a fluorescence yield calculation value obtained by dividing the fluorescence intensity by the light intensity of the reflected near-infrared light, and based on this fluorescence yield calculation value An apparatus for determining tissue properties has been proposed. That is, by calculating the fluorescence yield calculation value, the fluorescence intensity term depending on the distance between the excitation light source and the fluorescence light receiving part and the measured part is canceled, and the calculation value reflecting only the difference in fluorescence yield A determination can be made based on
[0006]
On the other hand, as shown in FIG. 8, the development of a fluorescence determination apparatus that utilizes the fact that the spectrum shape of the fluorescence emitted from normal tissue and the spectrum shape of the fluorescence emitted from the diseased tissue are different has been underway. For example, an apparatus for determining tissue properties based on the ratio of the light intensity in the green wavelength band of fluorescent light to the light intensity in the red wavelength band has been proposed (see, for example, Patent Document 1). There has also been proposed an apparatus for determining the tissue properties by comparing the spectral shape of fluorescence acquired in advance from a normal tissue with the spectral shape of fluorescence acquired from a measurement target (see, for example, Patent Document 2).
[0007]
Furthermore, the present applicant has proposed an apparatus for determining a tissue property using a normalized fluorescence calculation value obtained by standardizing a light intensity in a narrow wavelength band acquired from a measured part with a light intensity in a wide wavelength band (for example, (See Patent Document 3). In this publication, a narrow-band fluorescence image in the vicinity of a wavelength band of 480 nm and a wide-band fluorescence image in the vicinity of 430 nm to 730 nm are taken, where the difference between the fluorescence intensity emitted from the normal tissue and the fluorescence intensity emitted from the diseased tissue is large. Then, a normalized fluorescence calculation value obtained by dividing the pixel value of the narrow-band fluorescence image by the pixel value of the broadband fluorescence image is obtained, and the tissue property is determined for each pixel based on the normalized fluorescence calculation value. A pseudo color image based on the tissue properties is displayed. That is, by obtaining the normalized fluorescence calculation value, the fluorescence intensity term depending on the distance between the excitation light source and the fluorescence light receiving part and the measured part is canceled, and the calculation value reflecting only the difference in the shape of the fluorescence spectrum is reflected. Based on this, tissue properties can be determined.
[0008]
However, if determination is performed based on one type of parameter acquired from fluorescence as described above, sufficient determination accuracy may not be obtained. The present inventor has proposed a device for determining tissue properties based on a plurality of parameters acquired from fluorescence, focusing on the improvement of determination accuracy by determining tissue properties by combining a plurality of parameters. (For example, refer to Patent Document 4). In this publication, for example, by determining the tissue properties by combining the fluorescence intensity or the above-described fluorescence yield calculation value and the normalized fluorescence calculation value, it is shown that the determination accuracy between the normal tissue and the diseased tissue is improved. Has been.
[0009]
[Patent Document 1]
JP-A-6-54792.
[0010]
[Patent Document 2]
Japanese Patent Laid-Open No. 9-506027.
[0011]
[Patent Document 3]
Japanese Patent Laid-Open No. 10-225436.
[0012]
[Patent Document 4]
JP 2001-17379 A.
[0013]
[Problems to be solved by the invention]
On the other hand, there are cases where fluorescent mucus or residue adheres to the living tissue, and when the living tissue to which these adhere (hereinafter referred to as non-cleaned living tissue) is irradiated with excitation light, Fluorescence is also emitted from the mucus and residue. Fluorescence emitted from such unclean biological tissue is often different from fluorescence emitted from clean biological tissue in its light intensity and spectral shape. In conventional fluorescence determination, it is difficult to say “normal tissue” or It is often determined that it is difficult to say that it is a lesioned tissue. However, since the conventional fluorescence determination apparatus cannot determine that the measurement target is an unclean biological tissue, the measurement target determined as “difficult to say normal tissue” or “difficult to say lesion tissue” Is this determined because it is a non-clean biological tissue to which fluorescent mucus or residue adheres, or is a clean biological tissue, but it is difficult to say that it is a normal tissue or "lesioned tissue" Since it is an organization that is difficult to say, it is impossible to identify whether it is determined in this way, and the reliability of the determination result of the tissue property is lowered.
[0014]
In view of the above problems, an object of the present invention is to provide a fluorescence determination method and apparatus capable of improving the reliability of a tissue property determination result.
[0015]
[Means for Solving the Problems]
The fluorescence determination method according to the present invention is a fluorescence determination method for determining a tissue property of a measured portion based on fluorescence emitted from the measured portion by irradiation of excitation light.
Pre-store distribution information of a plurality of feature amounts acquired based on fluorescence information of fluorescence emitted from clean biological tissue irradiated with excitation light,
Fluorescence information of fluorescence emitted from the measured part by irradiation of excitation light is detected,
Acquiring a plurality of feature quantities based on the fluorescence information detected by the detection means;
On the basis of the plurality of feature amounts and the distribution information, it is determined that the measured portion is an unclean biological tissue.
[0016]
The fluorescence determination apparatus according to the present invention is a fluorescence determination apparatus that determines the tissue properties of a measurement target part based on the fluorescence emitted from the measurement target part by irradiation with excitation light.
Storage means for preliminarily storing distribution information of a plurality of feature amounts acquired based on fluorescence information of fluorescence emitted from clean biological tissue irradiated with excitation light;
Excitation light irradiating means for irradiating the portion to be measured with excitation light;
Detecting means for detecting fluorescence information of fluorescence emitted from the measurement target portion by irradiation of the excitation light;
Feature quantity acquisition means for acquiring a plurality of feature quantities based on the fluorescence information detected by the detection means;
A determination unit configured to determine that the measurement target is an unclean biological tissue based on the plurality of feature amounts acquired by the feature amount acquisition unit and the distribution information stored in the storage unit; It is characterized by that.
[0017]
Here, “clean biological tissue” means a tissue to which no mucus or residue that fluoresces is attached to the biological tissue. In addition, “non-cleaned biological tissue” means a tissue to which fluorescent mucus or residue is attached on the biological tissue.
[0018]
Specific examples of the plurality of feature amounts include fluorescence intensity, fluorescence spectrum shape, normalized fluorescence calculation value reflecting fluorescence spectrum shape, or fluorescence yield calculation value reflecting fluorescence fluorescence yield. It is done. The plurality of feature amounts may be a normalized fluorescence calculation value reflecting the fluorescence spectrum shape and a fluorescence yield calculation value reflecting the fluorescence yield of the fluorescence.
[0019]
The “standardized fluorescence calculation value” is a calculation value that reflects the spectrum shape of the fluorescence, and means a calculation value that reflects the ratio of the fluorescence intensity of the fluorescence in different wavelength bands acquired from the measurement target part. . As the different wavelength bands, for example, a narrow wavelength band near 480 nm and a narrow wavelength band near 630 nm can be selected.
[0020]
In addition, as the normalized fluorescence calculation value, the light intensity of a narrow band wavelength band (for example, a wavelength band of 430 nm to 530 nm) of fluorescence is expressed by the light intensity of a wide band wavelength band (for example, the entire wavelength band or a wavelength band of 430 nm to 730 nm). It may be divided.
[0021]
The “fluorescence yield” means the ratio of the light intensity of the excitation light irradiated to the part to be measured and the light intensity of the fluorescence emitted from the part to be measured by the irradiation of the excitation light. The “fluorescence yield calculation value” is, for example, as described above, by irradiating a living tissue with reference light and using the light intensity of the reflected reference light as a substitute for the light intensity of excitation light. This is a calculated value obtained by dividing the light intensity of the emitted fluorescence by the light intensity of the reflected reference light. As the reference light, near infrared light having a relatively uniform reflection characteristic can be used regardless of the tissue. Further, although the accuracy is slightly deteriorated, normal illumination light can be used as the reference light. If the variation in the distance between the distal end of the scope and the part to be measured can be kept small in the case of an excitation light emitting part, that is, an endoscope, the fluorescence intensity should be used as the fluorescence yield calculation value. You can also.
[0022]
Further, the clean living tissue is composed of a plurality of known property tissues,
If the storage unit stores in advance distribution information of a plurality of feature amounts for each known characteristic tissue, the determination unit includes the plurality of feature amounts acquired by the feature amount acquisition unit and the known property. Based on the distribution information of the feature amount for each tissue, the tissue property of the measured portion may be determined.
[0023]
In the fluorescence determination apparatus, the excitation light irradiation unit irradiates the observation part with the excitation light.
The detection means detects fluorescence information of fluorescence emitted from the observation unit as an image,
The feature amount acquisition means acquires a plurality of feature amounts for each pixel of the image based on the fluorescence information,
The determination unit determines, for each pixel, the measurement target corresponding to the pixel is an unclean biological tissue based on the plurality of feature amounts and the distribution information stored in the storage unit. Is what
A fluorescent diagnostic image generating means for generating a fluorescent diagnostic image based on a determination result by the determining means;
It may further comprise display means for displaying the fluorescence diagnostic image.
[0024]
When the ratio of the number of pixels determined to be an image of an unclean biological tissue to the number of pixels of a pixel unit composed of a predetermined number of pixels is equal to or greater than a predetermined value, the fluorescence diagnostic image generation means A display correction process may be performed on the pixel unit.
[0025]
The “display correction process” means a process that makes it possible to identify a pixel unit in which the ratio of the number of pixels is equal to or greater than a predetermined value from other pixel units, for example, assigning a special display color, or This is processing such as assigning colorlessness.
[0026]
In addition, the fluorescence diagnostic image generation unit may obtain reliability information according to a ratio of the number of pixels determined to be an image of unclean biological tissue to the number of pixels of a pixel unit including a predetermined number of pixels. It may be added to the unit.
[0027]
In addition, the said fluorescence determination apparatus can also be integrated in the fluorescence endoscope apparatus which has an endoscope insertion part inserted in a biological body.
[0028]
【The invention's effect】
The present inventor has advanced research on a determination method and a determination apparatus for determining tissue properties using a plurality of feature amounts acquired from the above-described fluorescence, and in the research process, a plurality of acquired from fluorescence emitted from clean biological tissue. The two-dimensional distribution of feature quantities (for example, the fluorescence yield calculation value and the normalized fluorescence calculation value) and the two-dimensional distribution of a plurality of feature quantities emitted from non-clean biological tissue have a considerably different distribution area. discovered.
[0029]
FIG. 1 shows fluorescence obtained from clean biological tissues such as many normal tissues, pre-cancerous tissues, and lesioned (cancerous) tissues, and unclean biological tissues to which mucus or residues are attached, and normalized fluorescence from each fluorescence. It is the schematic diagram which calculated the calculation value and the fluorescence yield calculation value, and produced two-dimensional distribution information linked | related with each structure | tissue. The distribution region of the normalized fluorescence calculation value and the fluorescence yield calculation value acquired from the fluorescence emitted from the unclean biological tissue from FIG. 1 indicates the normalized fluorescence calculation value and fluorescence acquired from the fluorescence emitted from the clean biological tissue. It can be seen that this is different from the distribution region of the yield calculation value.
[0030]
Therefore, the normalized fluorescence calculation value and the fluorescence yield calculation value acquired from the fluorescence emitted from the measured part are the distribution of the normalized fluorescence calculation value and the fluorescence yield calculation value acquired from the fluorescence emitted from the clean living tissue. If it does not correspond to the region, it can be determined that the measured part is an unclean biological tissue.
[0031]
That is, according to the fluorescence determination method and apparatus according to the present invention, for example, as shown in FIG. 1, a plurality of feature amounts acquired based on fluorescence fluorescence information emitted from a clean biological tissue irradiated with excitation light. Distribution information is stored in advance, a plurality of feature amounts are acquired based on fluorescence information of fluorescence emitted from the measurement target by irradiation with excitation light, and based on the plurality of feature amounts and the distribution information, Since it can be determined that the part to be measured is an unclean biological tissue, the reliability of the determination result of the tissue property can be improved.
[0032]
When the plurality of feature quantities are a normalized fluorescence calculation value reflecting the fluorescence spectrum shape and a fluorescence yield calculation value reflecting the fluorescence yield, the fluorescence spectrum shape and fluorescence yield Based on this, it can be determined that the part to be measured is an unclean biological tissue, so that the determination can be made with high accuracy.
[0033]
If the normalized fluorescence calculation value is obtained by dividing the light intensity of the narrow-band wavelength band of the fluorescence by the light intensity of the wide-band wavelength band, it is unlikely that division by zero is performed at the time of division. A normalized fluorescence calculation value appropriately reflecting the spectrum shape can be acquired.
[0034]
Further, the clean living tissue is composed of a plurality of known property tissues, the storage means stores in advance distribution information of a plurality of feature amounts for each known property tissue, and the determination means includes: If the tissue property of the measured part is to be determined based on the plurality of feature values acquired by the feature value acquisition means and the distribution information of the feature value for each known characteristic tissue, the measured part At the same time as determining that is a non-clean biological tissue, it is also possible to determine the tissue properties of the clean biological tissue.
[0035]
Further, the excitation light irradiating means irradiates the observation part with the excitation light, and the detection means detects fluorescence information emitted from the observation part as an image, and the fluorescent light is detected for each pixel of the image. A plurality of feature amounts are acquired based on the information, and the measurement target corresponding to the pixel is an unclean biological body based on the plurality of feature amounts for each pixel and the distribution information stored in the storage unit. If it is what determines the tissue, and further comprises a fluorescence diagnostic image generation means for generating a fluorescence diagnostic image based on the determination result and a display means for displaying the fluorescence diagnostic image, the determination result Can be displayed as an image, and the convenience of the fluorescence determination apparatus is improved.
[0036]
When the ratio of the number of pixels determined to be an image of an unclean biological tissue to the number of pixels of a pixel unit composed of a predetermined number of pixels is greater than or equal to a predetermined value, If the display correction processing is performed on the pixel unit, the ratio of the number of pixels of the pixel can be displayed in a display color or the like that allows the pixel unit to be distinguished from other pixel units with a predetermined value or more. Therefore, it is possible to easily identify an image region having a lot of non-clean biological tissue.
[0037]
The fluorescence diagnostic image generation means adds reliability information according to the ratio of the number of pixels determined to be an image of unclean biological tissue to the number of pixels of the pixel unit composed of a predetermined number of pixels to the pixel unit. If so, the reliability of the pixel unit can be displayed.
[0038]
DETAILED DESCRIPTION OF THE INVENTION
Hereinafter, embodiments of the present invention will be described in detail with reference to the drawings. First, with reference to FIGS. 2 to 5, a fluorescence endoscope apparatus as a first specific embodiment to which a fluorescence determination method and apparatus according to the present invention is applied will be described. FIG. 2 is a schematic configuration diagram of the fluorescence endoscope apparatus, FIGS. 3 and 4 are schematic diagrams of a mosaic filter and a switching filter mounted on the fluorescence endoscope apparatus, and FIG. 5 is a diagram of calculation value distribution information. It is explanatory drawing.
[0039]
This fluorescence endoscope apparatus is based on a normal image mode in which a normal image that is a normal color image is displayed, by irradiating excitation light to the measurement target unit 1 and based on fluorescence emitted from the observation unit 1. It operates by the fluorescence diagnostic image mode which displays the fluorescence diagnostic image which shows the determination result which determined the tissue property of each to-be-measured part 2 of a pseudo color. Switching between the two modes is performed by an input operation from the input device 601. In the observation unit 1, the region corresponding to each pixel of the CCD is the measurement unit 2, and the tissue properties are determined for each measurement unit 2. That is, a large number (the number of pixels of the CCD) of the measured parts 2 are gathered to form the observation part 1.
[0040]
In the normal image mode, a normal image by the reflected light of the observation unit 1 irradiated with frame sequential light (R light Lr, G light Lg, B light Lb) is obtained by the CCD image pickup device 101 provided at the distal end of the scope unit 10. A normal image that is captured and created by normal color signal processing is displayed on the monitor 70.
[0041]
In the fluorescence diagnostic image mode, a narrow-band fluorescence image and a broadband fluorescence image are picked up from the fluorescence emitted from the observation unit 1 irradiated with the excitation light Le using the CCD image pickup device 101 as the fluorescence detection means. An IR reflected image is captured from the IR reflected image Zs of the reflected light of the observation unit 1 irradiated with the reference light Ls, which is infrared light, using the CCD image pickup device 101, and the pixel value of the narrow-band fluorescent image is obtained from the broadband fluorescent image. A normalized fluorescence calculation value that is a value divided by the pixel value and a fluorescence yield calculation value that is a value obtained by dividing the pixel value of the broadband fluorescence image by the pixel value of the IR reflection image are calculated and stored in the storage unit 308 in advance. Using the calculated value distribution information, the fluorescence diagnostic image, which is a pseudo color image based on the determination result of the tissue property of each measured portion 2 in the observation unit 1, is displayed on the monitor 70. Details of the calculation value distribution information will be described later.
[0042]
As shown in FIG. 2, the fluorescence endoscope apparatus according to the embodiment of the present invention includes a CCD imaging device 101 at the tip, and a scope unit 10 inserted into a site suspected to be a patient's lesion. A light source that emits surface-sequential light (R light Lr, G light Lg, and B light Lb) that is illumination light, a light source that emits excitation light Le for capturing a fluorescent image, and reference light Ls for capturing an IR reflected image Illumination unit 20 having an emitted light source, a fluorescence image processing unit that calculates a fluorescence calculation value from pixel values of a narrow-band fluorescence image and a broadband fluorescence image, and generates and outputs a fluorescence diagnostic image signal based on the fluorescence calculation value 30. Control of normal image signal generation and normal image processing unit 40 which converts the normal image signal and the fluorescence diagnostic image signal output from the fluorescence image processing unit 30 into a video signal and outputs the CCD image sensor 101. CCD drive Knit 50, controller 60 for controlling the operation of each unit, and a monitor 70 for displaying the input device 601 and the normal image or the fluorescence diagnostic image is connected to the controller 60. The illumination unit 20, the fluorescence image processing unit 30, the normal image processing unit 40, the CCD drive unit 50, and the controller 60 constitute a processor unit 80, and the scope unit 10 and the processor unit 80 and the processor unit 80 and the monitor 70 are respectively The connector is not shown in the figure and is connected so as to be freely separated.
[0043]
The scope unit 10 includes a light guide 102 and a CCD cable 103 extending to the tip. An illumination lens 104 and an objective lens 105 are provided at the distal ends of the light guide 102 and the CCD cable 103, that is, at the distal end of the scope unit 10. A CCD image pickup device 101 on which a mosaic filter 106 in which minute band filters are combined in a mosaic pattern is connected to the tip of the CCD cable 103 is connected. A prism 107 is attached to the CCD image pickup device 101. Yes. Further, an excitation light cut filter 108 for cutting light having a wavelength of 420 nm or less is attached between the prism 107 and the objective lens 105.
[0044]
The CCD image pickup device 101 is a frame transfer type CCD image pickup device including a light receiving portion that converts a picked-up optical image into signal charges and a storage portion that temporarily stores and transfers signal charges. The light guide 102 is a bundle of a light guide 102a for surface sequential light, a light guide 102b for excitation light, and a light guide 102c for reference light, and is integrated into a cable shape. Connected to.
[0045]
The cable 103 is a combination of a drive line 103a for transmitting a drive signal for the CCD image sensor 101 and an output line 103b for reading an image signal from the CCD image sensor 101. One end of the drive line 103a is connected to the CCD drive unit 50, and one end of the output line 103b is connected to the fluorescence image processing unit 30 and the normal image processing unit 40.
[0046]
As shown in FIG. 3, in the mosaic filter 106, a narrow band filter 106a that transmits light in a wavelength band of 430 nm to 530 nm and an all wavelength band filter 106b that transmits light in all wavelength bands are alternately combined, The filter has a one-to-one correspondence with the pixels of the CCD image sensor 101.
[0047]
The illumination unit 20 includes a white light source 201 that emits white light, a power source 202 for white light source, a switching filter 204 and a switching filter 204 for sequentially separating the white light into R light Lr, G light Lg, and B light Lb. Rotating filter rotating unit 205, GaN-based semiconductor laser 206 emitting excitation light Le with a wavelength of 410 nm for fluorescent image imaging, and semiconductor laser power source 207, reference emitting Ls reference light Ls, which is near infrared light for IR reflected image imaging The light source 209 includes a reference light source power source 210 electrically connected to the reference light source 209.
[0048]
As shown in FIG. 4, the switching filter 204 includes an R filter 204a that transmits R light Lr, a G filter 204b that transmits G light Lg, a B filter 204c that transmits B light Lb, and a mask unit 204d having a light shielding function. It consists of and. In the CCD imaging device 101, signal charges are transferred from the light receiving unit to the storage unit while the mask unit 204d is not irradiated with the surface sequential light (R light Lr, G light Lg, or B light Lb).
[0049]
The fluorescence image processing unit 30 is a signal processing circuit 301 that performs process processing of an image signal picked up by the CCD image pickup device 101 when the excitation light Le is irradiated, and digitizes the image signal output from the signal processing circuit 301 The A / D conversion circuit 302 that performs digitization of the image signal received by the pixel corresponding to the narrow band filter 106a of the mosaic filter 106 and the pixel corresponding to the full wavelength band filter 106b. Among the image signals captured by the CCD image sensor 101 when the reference light Ls is irradiated with the image memory 303 stored in a different storage area with the broadband fluorescent image composed of the image signal received at, the mosaic filter 106 A signal processing circuit 304 that performs process processing on an image signal received by a pixel corresponding to the all-wavelength band filter 106b, and outputs the image signal output from the signal processing circuit 304 A / D conversion circuit 305 for digitization, image memory 306 for storing an IR reflection image composed of digitized image signals, and pixel values of a narrow-band fluorescence image captured by adjacent pixels stored in the image memory 303 Of the IR reflection image obtained by imaging the normalized fluorescence calculation value obtained by dividing the pixel value by the pixel value of the broadband fluorescent image and the pixel value of the broadband fluorescence image stored in the image memory 303 with the corresponding pixel stored in the image memory 306 Calculated by a fluorescence calculation value calculation unit 307 that calculates a fluorescence yield calculation value divided by a value, a storage unit 308 that stores calculation value distribution information shown in FIG. 5, and a fluorescence calculation value calculation unit 307 for each pixel. The determination unit 309 that determines the tissue property using the normalized normalized fluorescence calculation value and the fluorescence yield calculation value and the calculation value distribution information stored in the storage unit 308, and a color is assigned based on the determination result Generate a fluorescent diagnostic image and And a fluorescence diagnostic image generation unit 310 to be output to the video signal processing circuit 405.
[0050]
Here, a method of creating the calculation value distribution information shown in FIG. 5 will be described. First, a clean normal tissue or a pre-clean cancer tissue that is a clean tissue that is a known tissue that has previously been clarified by other techniques and that does not have a mucus or residue that emits fluorescence on the tissue. Using the present fluorescence endoscope apparatus, the normalized fluorescence calculation value and the fluorescence yield calculation value are obtained for the clean lesion (cancer) tissue by the same operation as described above. A two-dimensional distribution graph associated with cancer tissue and lesion (cancer) tissue is created. Next, a normal area 7 associated with a normal tissue, a precancer area 6 associated with a precancerous tissue, and a lesion (cancer) area 5 associated with a lesion (cancer) tissue are defined on this graph. In the storage unit 308, the ranges of the normal area 7, the precancerous area 6, and the lesion (cancer) area 5 associated with each tissue property are stored as calculation distribution information.
[0051]
The normal image processing unit 40 is a signal processing circuit that performs process processing on the image signal received by the pixels corresponding to the full wavelength band filter 106b of the mosaic filter 106 when the R light Lr, G light Lg, or B light Lb is irradiated. 401, an A / D conversion circuit 402 for digitizing the image signal output from the signal processing circuit 401, and an image memory for storing the digitized image signal as an image (R image, G image, and B image) for each color 403, a normal image generation unit 404 that generates a normal image signal from an image of each color stored in the image memory; when displaying a normal image, the normal image signal output from the normal image generation unit 404 is converted into a video When the signal is converted into a signal and output, and the fluorescence diagnostic image is displayed, the video signal that is converted from the fluorescence diagnostic image signal output from the fluorescence diagnostic image generation unit 310 to a video signal and then output It has a sense circuit 405. The CCD drive unit 50 outputs an operation control signal for controlling the operation timing of the CCD image sensor 101. The controller 60 is connected to each part and controls the operation timing.
[0052]
The operation of the fluorescence endoscope apparatus according to the present invention will be described below. In the normal image mode, surface sequential light irradiation, normal image capturing, and normal image display are performed. In the fluorescence diagnostic image mode, excitation light Le or reference light Ls irradiation, fluorescent image capturing, or IR reflection is performed. Imaging of images is performed in a time-sharing manner, and a fluorescence diagnostic image is displayed.
[0053]
First, the operation in the normal image mode will be described. Prior to imaging, the observer inserts the scope unit 10 into the body cavity of the subject, and guides the distal end of the scope unit 10 to the vicinity of the observation unit 1.
[0054]
First, an operation when acquiring an R image will be described. Based on the signal from the controller 60, the white light source power source 202 is driven, and white light is emitted from the white light source 201. The white light is collected by the condenser lens 203 and passes through the switching filter 204. In the switching filter 204, an R filter 204a is arranged on the optical path based on a signal from the controller 60. For this reason, white light becomes R light Lr when passing through the switching filter 204. The R light Lr is incident on the light guide 102a, guided to the tip of the scope unit 10, and then irradiated to the observation unit 1 from the illumination lens 104.
[0055]
The reflected light of the R light Lr reflected by the observation unit 1 is collected by the condenser lens 105, reflected by the prism 107, and formed on the CCD image pickup device 101 as an R light reflected image Zr. Of the image signals output from the CCD image sensor 101, only the signals received by the pixels corresponding to the full-band filter 106b of the mosaic filter 106 are processed by the signal processing circuit 401 of the normal image processing unit 40. Are output as R image signals, and the remaining signals are discarded. The R image signal is converted into a digital signal by the A / D conversion circuit 402 and stored in the R image storage area of the image memory 403. Thereafter, the G image and the B image are acquired by the same operation, and stored in the G image storage area and the B image storage area of the image memory 403, respectively.
[0056]
When the R image, the G image, and the B image are stored in the image memory 403, a normal image signal is generated and output from the three color images in the normal image generation unit 404 in accordance with the display timing. The video signal processing circuit 405 converts the normal image signal into a video signal and outputs it to the monitor 70. A normal image that is a color image is displayed on the monitor 70.
[0057]
Next, the operation in the fluorescence diagnostic image mode will be described. The observer uses the input device 601 to select the fluorescence diagnostic image mode. First, based on a signal from the controller 60, the excitation light source power source 207 is driven, and excitation light Le having a wavelength of 410 nm is emitted from the GaN-based semiconductor laser 206. The excitation light Le passes through the lens 208, enters the light guide 102b, is guided to the distal end of the scope unit 10, and is irradiated from the illumination lens 104 to the observation unit 1.
[0058]
Fluorescence from the observation unit 1 generated by irradiating the excitation light Le is collected by the condenser lens 105, reflected by the prism 107, transmitted through the mosaic filter 106, and is reflected on the CCD image sensor 101. The image is formed as Zj. At this time, the reflected light of the excitation light Le is cut by the excitation light cut filter 108 and therefore does not enter the CCD image pickup device 101. In the CCD image pickup device 101, the fluorescent image Zj is received, photoelectrically converted, converted into an image signal corresponding to the intensity of light, and output.
[0059]
The signal output from the CCD image sensor 101 is processed in the signal processing circuit 301 of the fluorescence image processing unit 30, converted into a digital signal by the A / D conversion circuit 302, and transmitted through the narrowband filter 106a. The narrow-band fluorescence image and the broadband fluorescence image transmitted through the full-band filter 106b are divided and stored in the storage area of the image memory 303.
[0060]
Next, the operation when capturing the IR reflection image Zs of the reference light Ls will be described. Based on the signal from the controller 60, the reference light source power supply 210 is driven, and the reference light Ls which is near infrared light is emitted from the reference light source. The reference light Ls passes through the lens 211, enters the light guide 102c, is guided to the distal end of the scope unit, and then is irradiated from the illumination lens 104 to the observation unit 1.
[0061]
The reflected light of the reference light Ls reflected by the observation unit 1 is collected by the condenser lens 105, reflected by the prism 107, transmitted through the mosaic filter 106, and as an IR reflected image Zs on the CCD image sensor 101. Imaged. In the CCD image pickup device 101, the IR reflected image Zs is received, photoelectrically converted, converted into an image signal corresponding to the intensity of light, and output.
[0062]
The signal output from the CCD image pickup device 101 is processed by the signal processing circuit 304 of the fluorescence image processing unit 30 and only the signal received by the pixels corresponding to the all-band filter 106b is output after being processed. The digital signal is converted by the D conversion circuit 305 and stored in the image memory 306 as an IR reflected image.
[0063]
When the IR reflection image is stored in the image memory 306, the fluorescence calculation value calculation unit 307 divides the pixel value of the narrow-band fluorescence image stored in the image memory 303 by the pixel value of the broadband fluorescence image for each adjacent pixel. Then, the normalized fluorescence calculation value is calculated, and the pixel value of the broadband fluorescence image stored in the image memory 303 is divided by the pixel value of the IR reflection image captured by the corresponding pixel stored in the image memory 306 to obtain fluorescence. The yield calculation value is calculated.
[0064]
In the determination unit 309, the two-dimensional distribution point of the normalized fluorescence calculation value and the fluorescence yield calculation value of each measured unit 2 is calculated value distribution stored in the storage unit 308 as indicated by a point 2a in FIG. If it falls within the normal area 7 of information, it is determined that the measured part 2 corresponding to that pixel is a normal tissue, and if it falls within the precancerous area 6, as shown as point 2b, It is determined to be a precancerous tissue, and if it falls within the lesion (cancer) area 5 as indicated by a point 2c, it is determined to be a lesion (cancer) tissue. Further, when the two-dimensional distribution point of the normalized fluorescence calculation value and the fluorescence yield calculation value does not enter any of the normal area 7, the precancerous area 6 or the lesion (cancer) area 5, as indicated by the point 2d. In other words, it is determined that the measured part 2 corresponding to the pixel is an unclean biological tissue. The non-clean biological tissue is a region where mucous or residue that emits fluorescence adheres to the biological tissue.
[0065]
Based on these determination results, the fluorescence diagnostic image generation unit 310 first assigns green to pixels determined to be normal tissue, and assigns yellow to pixels determined to be precancerous tissue, Cancer) pixels that are determined to be tissue are assigned red, and pixels that are determined to be unclean biological tissue are assigned colorless.
[0066]
Next, for each pixel unit composed of a predetermined number of pixels, when the ratio of the number of pixels determined to be unclean biological tissue to the number of pixels of the pixel unit is equal to or greater than a predetermined value, All pixels are assigned colorlessness to generate a fluorescence diagnostic image signal.
[0067]
Further, the ratio (% display) of the number of pixels determined to be unclean biological tissue to the total number of pixels of the image is added to the fluorescence diagnosis image signal as reliability information, and the fluorescence diagnosis image signal and reliability The information is output to the video signal processing circuit 405. The video signal processing circuit 405 converts the fluorescent diagnostic image signal into a video signal, and the fluorescent diagnostic image is displayed on the monitor 70. The reliability information is also displayed in%. In this case, the image itself functions as the pixel unit of the invention.
[0068]
As is clear from the above description, in the fluorescence endoscope apparatus according to the present embodiment, the two-dimensional distribution point of the normalized fluorescence calculation value and the fluorescence yield calculation value acquired from the fluorescence emitted from the observation unit 1 In addition, since it is possible to determine that the part to be measured is an unclean biological tissue based on the calculation value distribution information stored in advance in the storage unit 308, the reliability of the determination result of the tissue property can be improved. Can do. It is also possible to simultaneously determine whether the tissue properties of the clean biological tissue are normal tissue, pre-cancerous tissue, or lesion (cancer) tissue.
[0069]
Furthermore, since the fluorescence diagnostic image reflecting the determination result is displayed on the monitor 70, the diagnostician can easily know the determination result. In addition, since the display area corresponding to the pixel unit in which the ratio of the number of pixels determined to be unclean biological tissue is equal to or greater than a predetermined value is displayed in colorless, the diagnostician has a display area with many unclean biological tissues. Can be easily identified. In addition, since the ratio of the number of pixels determined to be unclean biological tissue to the total number of pixels in the fluorescent diagnostic image is displayed as a percentage on the fluorescent diagnostic image, the diagnostician increases the reliability of the image. I can know.
[0070]
In addition, since the above determination is performed based on the normalized fluorescence calculation value that appropriately reflects the spectrum shape of the fluorescence emitted from the measurement target 2 and the fluorescence yield calculation value that reflects the fluorescence yield of the fluorescence, The determination can be performed with higher accuracy. Also, as the normalized fluorescence calculation value, a value obtained by dividing the light intensity in the narrow-band wavelength band of fluorescence by the light intensity in the wide-band wavelength band is used. A normalized fluorescence calculation value that appropriately reflects the spectrum shape of the fluorescence emitted from the measurement target 2 can be used.
[0071]
Next, a second embodiment of the present invention will be described with reference to FIGS.
[0072]
Since the schematic configuration of the fluorescence endoscope apparatus according to the second embodiment is substantially the same as that of the fluorescence endoscope apparatus according to the first embodiment shown in FIG. 2, only the numbers are shown in FIG. FIG. 6 is a schematic diagram of calculation value distribution information used in the present embodiment.
[0073]
In the fluorescence endoscope apparatus in the present embodiment, instead of the fluorescence image processing unit 30, a signal processing circuit 301, an A / D conversion circuit 302, an image memory 303, a signal processing circuit 304, an A / D conversion circuit 305, An image memory 306, a fluorescence calculation value calculation unit 307, a storage unit 318 that stores calculation value distribution information shown in FIG. 6, and a normalized fluorescence calculation value calculated by the fluorescence calculation value calculation unit 307 for each pixel. The determination unit 319 for determining the tissue properties using the calculated fluorescence yield value and the calculated value distribution information stored in the storage unit 318, and the fluorescent diagnostic image generation unit 310 for generating a fluorescent diagnostic image based on the determination result A fluorescence image processing unit 31 is provided.
[0074]
Here, a method of creating the calculation value distribution information shown in FIG. 6 will be described. First, normal tissue, pre-cancerous tissue, lesion that is a known tissue whose tissue properties have been clarified in advance by other methods, and is a clean biological tissue to which no mucus or residue that emits fluorescence is attached. (Cancer) Normal fluorescence calculation value and fluorescence yield calculation value are obtained by using this fluorescence endoscope device for tissue and unclean biological tissue to which mucus or residue adheres. A two-dimensional distribution graph associated with tissue, precancerous tissue, lesion (cancer) tissue, and unclean biological tissue is created. Next, the threshold value S1 of the normalized fluorescence calculation value and the threshold value S2 of the fluorescence yield calculation value that can define the area of the unclean biological tissue are set from this graph. Furthermore, a normal area 7 ′ associated with a normal tissue, a precancer area 6 ′ associated with a precancerous tissue, and a lesion (cancer) area 5 ′ associated with a lesion (cancer) tissue are defined. In the storage unit 318, the threshold value S1 of the normalized fluorescence calculation value and the threshold value S2 of the fluorescence yield calculation value, and the normal area 7 ′, pre-cancer area 6 ′, and lesion (cancer) area 5 ′ associated with each tissue property are stored. The range is stored as calculation distribution information.
[0075]
The determination unit 319 determines for each pixel whether or not the two-dimensional distribution point of the normalized fluorescence calculation value and the fluorescence yield calculation value falls within the range defined by the threshold value S1 and the threshold value S2. . Specifically, if the normalized fluorescence calculation value is equal to or less than the threshold value S1 and the fluorescence yield calculation value is equal to or more than the threshold value S2, it is determined that the measured part 2 corresponding to the pixel is an unclean biological tissue. To do. If the two-dimensional distribution point falls within the normal area 7 ′ shown in FIG. 6, it is determined that the measured part 2 corresponding to the pixel is a normal tissue and falls within the precancerous area 6 ′. For example, it is determined to be a precancerous tissue, and if it falls within the lesion (cancer) area 5 ′, it is determined to be a lesion (cancer) tissue.
[0076]
Based on these determination results, the fluorescent diagnostic image generation unit 310 generates a fluorescent diagnostic image signal and outputs it to the video signal processing circuit 405 as in the first embodiment. The video signal processing circuit 405 converts the fluorescent diagnostic image signal into a video signal, and the fluorescent diagnostic image is displayed on the monitor 70.
[0077]
As is clear from the above description, in the fluorescence endoscope apparatus according to the present embodiment, the normalized fluorescence calculation value and the fluorescence yield acquired from the fluorescence emitted from the observation unit 1, as in the first embodiment. Based on the two-dimensional distribution point with the calculated value and the calculated value distribution information stored in advance in the storage unit 318, it can be determined that the measured part is an unclean biological tissue. The reliability of the result can be improved. In addition, it can be determined whether the tissue properties of the clean biological tissue are normal tissue, pre-cancerous tissue, or lesion (cancer) tissue. Other effects can be obtained in the same manner as in the first embodiment.
[0078]
Next, a third embodiment of the present invention will be described with reference to FIGS.
[0079]
Since the schematic configuration of the fluorescence endoscope apparatus according to the third embodiment is substantially the same as that of the endoscope apparatus according to the first embodiment shown in FIG. 2, only the numbers are shown in FIG. FIG. 7 is a schematic diagram of calculation value distribution information used in this embodiment.
[0080]
In the fluorescence endoscope apparatus in the present embodiment, instead of the fluorescence image processing unit 30, a signal processing circuit 301, an A / D conversion circuit 302, an image memory 303, a signal processing circuit 304, an A / D conversion circuit 305, An image memory 306, a fluorescence calculation value calculation unit 307, a storage unit 328 that stores calculation value distribution information shown in FIG. 7, and a normalized fluorescence calculation value and a fluorescence collection value calculated by the fluorescence calculation value calculation unit 307 for each pixel. A determination unit 329 for determining tissue properties using the rate calculation value and the calculation value distribution information stored in the storage unit 328, and a fluorescence diagnosis image generation unit 330 for generating a fluorescence diagnosis image based on the determination result A fluorescence calculation unit 32 is provided.
[0081]
A method for creating the calculation value distribution information stored in the storage unit 328 will be described. First, normal tissue, cancer tissue, lesions (known tissue whose tissue properties have been clarified in advance by other methods, and clean biological tissue to which no mucus or residue that emits fluorescence is attached on the tissue ( Two-dimensional correlation between normal tissue, pre-cancerous tissue, and lesion (cancer) tissue by acquiring normalized fluorescence calculation value and fluorescence yield calculation value using this fluorescent endoscope device for cancer) tissue Create a distribution graph.
[0082]
Next, an operation value distribution function as shown by a dotted line in FIG. 7 is calculated from these two-dimensional distribution graphs. The calculated value distribution function is represented by the following equation, where NF is the normalized fluorescence calculation value and AF is the fluorescence yield calculation value. ,
1 / NF = 1.1 + 0.0012 / AF
At the same time, σ is calculated as the standard deviation of the measured values obtained from the known texture. Further, the standard deviation of the measured value obtained from the known tissue is defined as σ, and the range defined by the following formula is defined as the clean biological tissue range 8.
[0083]
1 / NF = (1.1 ± σ) + 0.0012 / AF
In the storage unit 328, the clean biological tissue range 8 is stored as calculated value distribution information.
[0084]
In the determination unit 329, first, when the two-dimensional distribution point of the normalized fluorescence calculation value and the fluorescence yield calculation value for each pixel is outside the range of the clean biological tissue range 8, the determination unit 329 corresponds to the pixel. It is determined that the part 2 to be measured is an unclean biological tissue.
[0085]
If the two-dimensional distribution point is within the clean biological tissue range 8, a point on the calculated value distribution function that is closest to the two-dimensional distribution point is calculated, and the point is set as a tissue property determination point. .
[0086]
In the fluorescence diagnostic image generation unit 330, a color between green (normal tissue), yellow (precancerous tissue), and red (cancerous tissue) is continuously set in advance for each point on the calculation value distribution function. . A color corresponding to the tissue property determination point on the calculated value distribution function is assigned to each pixel in which the two-dimensional distribution points of the normalized fluorescence calculation value and the fluorescence yield calculation value are in the clean biological tissue range 8, and the non-clean biological body A pixel determined to be a tissue is assigned a green color, a fluorescent diagnostic image signal is generated, and output to the video signal processing circuit 405. The video signal processing circuit 405 converts the fluorescent diagnostic image signal into a video signal, and the fluorescent diagnostic image is displayed on the monitor 70.
[0087]
As is clear from the above description, in the fluorescence endoscope apparatus according to the present embodiment, the normalized fluorescence calculation value and the fluorescence yield acquired from the fluorescence emitted from the observation unit 1, as in the first embodiment. Whether the measurement target corresponding to each pixel is a normal tissue or a pre-cancerous tissue based on the two-dimensional distribution point with the calculated value and the calculated value distribution information stored in advance in the storage unit 328 Whether the tissue is a lesion (cancer) tissue or an unclean biological tissue can be determined.
[0088]
In addition, since the image area corresponding to the unclean biological tissue is displayed in the same green color as the normal tissue, the image corresponding to the pre-cancerous tissue or the lesion (cancer) tissue is displayed in red or yellow as the fluorescent diagnostic image. Since the area is displayed in green, the diagnostician can easily identify the precancerous tissue or the lesion (cancer) tissue.
[0089]
In each embodiment, the normal image, the fluorescence image, and the IR reflection image are picked up by one image pickup device, but may be picked up using separate image pickup devices. In such a case, it is desirable to attach an optical filter having a transmission wavelength range suitable for an image to be acquired to each image sensor. Further, a CCD image sensor may be provided in the processor unit 80, and a fluorescent image may be transmitted by an image guide from the distal end of the scope unit 10 to the CCD image sensor in the processor unit 80.
[0090]
In each embodiment, using the calculated value distribution information, whether the measurement target is an unclean biological tissue, a normal tissue, a precancerous tissue, or a lesion (cancer) tissue However, it is determined whether or not the measured part is an unclean biological tissue using the calculated value distribution information, and whether the measured part is a normal tissue, a precancerous tissue, or a lesion ( The determination of whether the tissue is cancer), that is, the determination of tissue properties, may be performed using a separate technique. Specifically, there is a method of determining using only one of the normalized fluorescence calculation value or the fluorescence yield calculation value.
[0091]
In each of the embodiments, fluorescence information is acquired as an image using a CCD image pickup device. However, the present invention is not limited to this, and one point is not measured by point measurement using a single optical fiber. The tissue property may be determined by acquiring fluorescence from the measurement point.
[Brief description of the drawings]
FIG. 1 is an explanatory diagram of feature amount distribution information.
FIG. 2 is a schematic configuration diagram of a fluorescence endoscope apparatus according to a first specific embodiment of the present invention.
FIG. 3 is a schematic configuration diagram of a mosaic filter.
FIG. 4 is a schematic configuration diagram of a switching filter.
FIG. 5 is an explanatory diagram of a tissue property determination method.
FIG. 6 is an explanatory diagram of calculation value distribution information used in the second embodiment.
FIG. 7 is an explanatory diagram of calculation value distribution information used in the third embodiment.
FIG. 8 is an explanatory diagram showing fluorescence intensity spectra of fluorescence obtained from fluorescence of normal tissue and diseased tissue.
[Explanation of symbols]
1 Observation section
2 Measured part
10 Scope section
20 Lighting unit
30,31 Fluorescence image processing unit
40 Normal image processing unit
50 CCD drive unit
60 controller
70 Monitor
101 Image sensor
106 Mosaic filter
307 Fluorescence calculation value calculator
308,318,328 Memory unit
309,319,329 Judgment part
310,330 Fluorescence diagnostic image generator

Claims (6)

In the fluorescence determination device for determining the tissue property of the measurement target part based on the fluorescence emitted from the measurement target part by the irradiation of the excitation light,
Storage means for preliminarily storing distribution information of a plurality of feature amounts acquired based on fluorescence information of fluorescence emitted from clean biological tissue irradiated with excitation light;
Excitation light irradiating means for irradiating the portion to be measured with excitation light;
Detecting means for detecting fluorescence information of fluorescence emitted from the measurement target portion by irradiation of the excitation light;
Feature quantity acquisition means for acquiring a plurality of feature quantities based on the fluorescence information detected by the detection means;
A determination unit that determines that the measurement target is an unclean biological tissue based on the plurality of feature amounts acquired by the feature amount acquisition unit and the distribution information stored in the storage unit; A fluorescence determination apparatus comprising: Wherein the plurality of feature amounts, fluorescent determination apparatus according to claim 1, wherein the a fluorescence yield calculation value reflecting the fluorescence yield of the normalized fluorescence calculating value and the fluorescence reflecting the spectral shape of the fluorescence . The clean biological tissue is composed of a plurality of known property tissues,
The storage means stores in advance distribution information of a plurality of feature amounts for each known characteristic tissue,
The determination unit determines a tissue property of the measured part based on a plurality of feature amounts acquired by the feature amount acquisition unit and distribution information of the feature amount for each known property tissue. The fluorescence determination apparatus according to claim 1 or 2, wherein: The excitation light irradiation means irradiates the observation part with the excitation light,
The detection means detects fluorescence information of fluorescence emitted from the observation unit as an image,
The feature amount acquisition means acquires a plurality of feature amounts for each pixel of the image based on the fluorescence information,
The determination unit determines, for each pixel, the measurement target corresponding to the pixel is an unclean biological tissue based on the plurality of feature amounts and the distribution information stored in the storage unit. Is what
A fluorescent diagnostic image generating means for generating a fluorescent diagnostic image based on a determination result by the determining means;
The fluorescence determination apparatus according to claim 3 , further comprising display means for displaying the fluorescence diagnostic image. When the ratio of the number of pixels determined to be an image of unclean biological tissue to the number of pixels of a pixel unit composed of a predetermined number of pixels is greater than or equal to a predetermined value, 5. The fluorescence determination apparatus according to claim 4 , wherein display correction processing is performed on the pixel unit. The fluorescence diagnostic image generation means provides the pixel unit with reliability information corresponding to the ratio of the number of pixels determined to be an image of an unclean biological tissue to the number of pixels of the pixel unit including a predetermined number of pixels. The fluorescence determination apparatus according to claim 4 or 5 , wherein the fluorescence determination apparatus is added.

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