JPH09294706A - Fluorescent diagnostic system - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a fluorescent diagnostic system with which the distribution of exciting light illuminance inside a living body can be exactly compensated. SOLUTION: Concerning the configuration of this system, a part 30 of a living body 16 is irradiated with exciting light L1 in the exciting wavelength area of a photosensitive material to emit fluorescent light and the fluorescent image formed by fluorescent light L3 emitted at that time is picked up by a fluorescent image pickup means 23. In this case, the part 30 is irradiated with near infrared light L2 longer than a wavelength 650nm, and a near infrared image formed by the reflected light is picked up by a near infrared video camera 28. Between a fluorescent image signal S1 outputted from the fluorescent image pickup means 23 and a near infrared image signal S2 outputted from the near infrared video camera 28, the division of S1/S2 is performed for each common picture element, a standardized image signal S=S1/S2 provided by that division is inputted to an image display means 25 and based on the standardized image signal S, the fluorescent image is displayed.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention irradiates a living body absorbing a fluorescent substance that emits fluorescence with excitation light and picks up an image based on the fluorescence emitted from the photosensitive substance at that time, or The present invention relates to a fluorescence diagnostic device that detects intensity and is used for diagnosis of a living body.

[0002]

2. Description of the Related Art Conventionally, PDD (Photodynamic
Various studies have been made on photodynamic diagnosis called "diagnosis". This PDD has tumor affinity,
A photosensitizer that emits fluorescence when excited by light is previously absorbed in a tumor portion of a living body, and the portion is irradiated with excitation light in the excitation wavelength region of the photosensitizer to generate fluorescence, and the fluorescence is generated. This is a technique for diagnosing a tumor part by displaying an image.

[0003] For example, Japanese Patent Publication No. 63-964, Japanese Patent Application Laid-Open No. 1-136630, and Japanese Patent Application Laid-Open No. 7-59783 disclose a fluorescence diagnostic apparatus for performing this PDD. Basically, this kind of fluorescence diagnostic apparatus basically includes an excitation light irradiating means for irradiating a living body with excitation light in an excitation wavelength region of a photosensitive substance, and a fluorescence image of the living body by detecting fluorescence emitted from the photosensitive substance. It comprises an imaging unit and an image display unit that receives the output of the imaging unit and displays the fluorescent image, and is often incorporated in an endoscope inserted into a body cavity, a surgical microscope, or the like. It is composed in the shape of

In addition, by detecting the fluorescence intensity for each point on a living body part without picking up a two-dimensional fluorescence image as described above, it is possible to diagnose whether or not one point is a tumor part. (See, for example, Japanese Patent Application No. 7-252295 by the present applicant).

In the above-described fluorescence diagnostic apparatus, the excitation light is irradiated at the part of the living body irradiated with the excitation light because the body has irregularities and the distance from the excitation light irradiation system to the living body is not uniform. Light illuminance is generally non-uniform. When the illuminance of the excitation light is non-uniform, the fluorescence intensity changes according to the level of the illuminance of the excitation light, so that the diagnosis of the tumor part may be erroneously performed.

Therefore, in order to compensate for such a distribution of the illuminance of the excitation light, for example, as disclosed in Japanese Patent Application Laid-Open No. 62-247232 and Japanese Patent Publication No. 3-58729, a biological image is taken when a fluorescent image is taken. It has been considered that a reflected image by the reflected excitation light is also captured, and the fluorescence image signal is divided by an image signal indicating the reflected image to standardize the fluorescence image signal.

[0007]

However, the wavelength range of the excitation light generally used in the fluorescence diagnostic apparatus is in the ultraviolet to visible range (about 300 to 600 nm), and such excitation light is applied to living bodies such as the human body. It is greatly absorbed. Note that FIG. 3 shows absorption spectra of main components of a living body.

When the excitation light is largely absorbed by the living body as described above, the image signal showing the reflected image reflects not only the excitation light illuminance distribution but also this absorption distribution. If so, even if the above-mentioned normalization is performed using this image signal, it is impossible to accurately compensate the distribution of the excitation light illuminance.

The present invention has been made in view of the above circumstances, and an object thereof is to provide a fluorescence diagnostic apparatus capable of accurately compensating the distribution of excitation light illuminance in a living body.

[0010]

A fluorescence diagnostic apparatus according to the present invention uses near-infrared light having a wavelength of 650 nm or more, which has a relatively small absorption in a living body, and uses an image signal or a photodetection signal for the standardization. It is characterized by obtaining.

That is, the first fluorescence diagnostic apparatus according to the present invention is, as set forth in claim 1, located at the site of the living body absorbing the photosensitizer that emits fluorescence, and in the excitation wavelength region of the photosensitizer. Excitation light irradiating means for irradiating excitation light, fluorescence image capturing means for detecting fluorescence emitted by the photosensitizer and capturing a fluorescence image of a living body, and wavelength 65 at the site of the living body.
Near-infrared light irradiation means for irradiating near-infrared light of 0 nm or more;
The near-infrared image pickup means for detecting the near-infrared light reflected at the site and picking up a near-infrared image of a living body, and the fluorescence image signal output by the fluorescence image pickup means are used for the near-infrared image pickup. And a calculating means for normalizing each pixel based on the near-infrared image signal output by the means.

In this first fluorescence diagnostic apparatus, the near infrared light irradiating means is constructed so as to change the intensity of the near infrared light, as described in claim 2, When the intensities are different from each other, at least two types of image signals output from the near-infrared image pickup means are subtracted for each pixel to obtain a difference signal.
It is desirable that the difference signal is used as a near infrared image signal for normalization.

The first fluorescence diagnostic apparatus according to the present invention described above is of a type for picking up a fluorescence image, but the technical idea of the present invention is that of a type for detecting the fluorescence intensity for each point on the living body part. It is also applicable to a fluorescence diagnostic device. That is, the latter type of the second fluorescence diagnostic apparatus according to the present invention is, as described in claim 3, the excitation wavelength of the photosensitizer at the site of the living body absorbing the photosensitizer that emits fluorescence. Excitation light irradiating means for irradiating excitation light in a region, fluorescence detecting means for detecting the intensity of fluorescence emitted by the photosensitizer for each point on the site, and near-infrared light having a wavelength of 650 nm or more at the site of the living body. Near-infrared light irradiation means for irradiating light, intensity of near-infrared light reflected at the site, near-infrared light detection means for detecting each point on the site, and the fluorescence intensity detection means output An arithmetic means for normalizing the fluorescence detection signal based on the near-infrared light detection signal output by the near-infrared light detecting means is provided.

In the second fluorescence diagnostic apparatus, as described in claim 4, the near-infrared light irradiating means is constructed so that the intensity of the near-infrared light can be changed. When the intensities are different from each other, means for subtracting at least two types of near-infrared light detection signals output from the near-infrared light detecting means to obtain a difference signal are provided, and the calculating means is for normalization. It is desirable that the difference signal be used as the near-infrared light detection signal.

Further, in the fluorescence diagnostic apparatus of the present invention, as described in claim 5, as the near-infrared light irradiation means, wavelengths 700 to 95 deviated from the fluorescence wavelength range of the photosensitizer.
It is desirable to use one that emits near infrared light of 0 nm.

[0016]

As described above, in the fluorescence diagnostic apparatus of the present invention, near-infrared light having a wavelength of 650 nm or more, which has a relatively small absorption in the living body, is used as the light for irradiating the living body portion in order to check the illuminance distribution. Therefore, the near-infrared image signal and the near-infrared light detection signal obtained by detecting this near-infrared light reflected by the living body reflect almost only the illuminance without being affected by the above absorption. Becomes Therefore, if the above-mentioned standardization is performed using such a near-infrared image signal or a near-infrared light detection signal, the distribution of excitation light illuminance can be accurately compensated for, and a fluorescence image signal with high diagnostic performance or The fluorescence detection signal can be obtained. It is clear from FIG. 3 described above that near-infrared light having a wavelength of 650 nm or more is difficult to be absorbed by the living body.

Further, as described in claim 2, at least two kinds of image signals output from the near-infrared image pickup means when the intensities of near-infrared light are different from each other are subtracted for each pixel. Then, when the difference signal is obtained, the difference signal has the change amount canceled based on the body temperature distribution of the living body part. Therefore, if the fluorescence image signal is standardized using this difference signal, the influence of the body temperature distribution can be eliminated and the distribution of the excitation light illuminance can be more accurately compensated. This point relates to claim 4.
The same applies to the configuration described in (1).

On the other hand, as described in claim 5, a wavelength outside the fluorescence wavelength region of the photosensitizer is 700 to 950 nm.
If the near-infrared light is used, the influence of absorption by the photosensitizer can be eliminated and the distribution of the excitation light illuminance can be more accurately compensated. Note that near-infrared light in such a wavelength range is very suitable because it is difficult for water contained in a large amount of living body to absorb it.

[0019]

BEST MODE FOR CARRYING OUT THE INVENTION Hereinafter, embodiments of the present invention will be described in detail with reference to the drawings. FIG. 1 shows a side view of a fluorescence endoscope according to a first embodiment of the present invention.

This fluorescent endoscope has a wavelength of 400 n, for example.
Excitation light source 10 that emits excitation light L1 of around m, a condenser lens 11 that condenses this excitation light L1, and condensed excitation light L1
And a light guide 12 made of an optical fiber arranged so as to enter. Furthermore, this fluorescent endoscope
A near-infrared light source 13 that emits near-infrared light L2 having a wavelength of 700 to 950 nm and the near-infrared light L2 are reflected while the excitation light L1 is transmitted, and both of these lights are transmitted to the light guide 12.
And a dichroic mirror 14 for making the light incident on.

The light guide 12 is housed in a flexible probe 17 inserted into the living body 16. An image guide 18 formed of an optical fiber bundle is housed in the probe 17.

An image forming lens 20 is arranged at a position close to the tip of the image guide 18 (the left end in FIG. 1). On the rear end side of the image guide 18, a dichroic mirror 19, an excitation light cut filter 21, a condenser lens 22, and a fluorescence image pickup means 23 are arranged in this order. As the fluorescence image pickup means 23, for example, an image intensifier capable of high-sensitivity image pickup is used, and its output is inputted to the standardization calculation means 24. The calculation means 24 is connected to an image display means 25 such as a CRT.

The dichroic mirror 19 transmits the fluorescent light L3 having a peak wavelength of about 640 nm which is incident on the dichroic mirror 19 as described later, and the near infrared light L having a wavelength of 700 to 950 nm.
2 reflects. An excitation light cut filter 26, a condenser lens 27, and a near infrared video camera 28 are arranged in this order at a position where the near infrared light L2 reflected by the dichroic mirror 19 is incident. The output of the near-infrared video camera 28 is input to the calculating means 24.

The operation of the fluorescent endoscope having the above structure will be described below. The diagnostic site 30 inside the living body 16 is preliminarily absorbed with a photosensitizer having a tumor affinity and emitting fluorescence when excited by light. As the photosensitizer, for example, a porphyrin-based substance is used. Excitation light L1 and near-infrared light L are emitted from the light guide 12 to the diagnosis site 30.
2 are irradiated at the same time. Then, those lights are 30
And is irradiated with the excitation light L1 to emit fluorescence L3 from the photosensitizer.

The image forming lens 20 forms a fluorescent image of the diagnostic region 30 by the fluorescent light L3 on the end face of the image guide 18. This fluorescence image is guided to the outside of the living body 16 by the image guide 18, and is captured by the fluorescence image capturing means 23. The excitation light L1 reflected at the diagnostic site 30 and traveling toward the fluorescence image capturing means 23 is cut by the excitation light cut filter 21. The fluorescence image signal S1 representing the fluorescence image thus captured is input to the calculating means 24. Since the photosensitizer has a tumor affinity, the fluorescence image signal S1 basically shows only the tumor portion as a fluorescence image.

Here, as the fluorescence image pickup means 23, for example, an image intensifier capable of high-sensitivity image pickup is used as described above, so that a fluorescence image can be picked up with high sensitivity. High-sensitivity imaging can be performed by using a time-accumulation type imaging means as the fluorescence image capturing means 23, or by cooling the fluorescence image capturing means 23 by a cooling means.

On the other hand, the near-infrared light L2 is also reflected by the diagnosis site 30 and enters the imaging lens 20. The imaging lens 20 forms an image of the diagnostic region 30 by the near infrared light L2 on the end surface of the image guide 18. This near-infrared image is also guided to the outside of the living body 16 by the image guide 18, and is imaged by the near-infrared video camera 28. The excitation light L1 reflected by the diagnostic region 30 and traveling toward the near infrared video camera 28 is cut by the excitation light cut filter 26. The near-infrared image signal S2 indicating the near-infrared image captured in this way is input to the calculating unit 24.

The calculating means 24 performs a division S1 / S2 for each common pixel between the fluorescence image signal S1 and the near-infrared image signal S2 incident thereon, and the standard obtained thereby is obtained. The converted image signal S = S1 / S2 is input to the image display means 25. The image display means 25 displays a fluorescent image based on the standardized image signal S.

Even if an image is displayed using the fluorescence image signal S1 as it is, only the tumor portion can be basically displayed as a fluorescence image. In that case, the illuminance distribution of the excitation light L1 at the diagnostic site 30 is also a fluorescence image. It will be reflected in and may cause misdiagnosis. On the other hand, if a fluorescence image is displayed based on the standardized image signal S as described above, the excitation light L1
The change in fluorescence intensity due to the illuminance distribution of is canceled,
A fluorescent image accurately showing the state of the tumor at the diagnosis site 30 is displayed.

In this example, the near-infrared light L2 having a wavelength of 700 to 950 nm, which has a relatively small absorption in the living body, is used as the light with which the diagnostic region 30 is irradiated in order to check the illuminance distribution. The infrared image signal S2 is almost unaffected by the above-mentioned absorption, and almost reflects only the near-infrared light illuminance. Therefore, this near infrared image signal S2
If the above-mentioned standardization is performed by using, the distribution of the excitation light illuminance will be accurately compensated, and the standardized image signal S with high diagnostic performance will be obtained.

Next, with reference to FIG. 2, a fluorescence endoscope according to a second embodiment of the present invention will be described. In FIG. 2, elements that are the same as those shown in FIG. 1 are given the same numbers, and duplicated description thereof is omitted.

In addition to the excitation light irradiation system, the fluorescence endoscope of the second embodiment has a near infrared light source 40 that emits near infrared light L2 that is linearly polarized light having a wavelength of 700 to 950 nm, and a probe 17.
It has a polarization-maintaining fiber 41 which is housed inside and propagates the near-infrared light L2. The near infrared light source 40 is provided between the polarization maintaining fiber 41 and the near infrared light source 40.
From the side in order, a collimator lens 42 for collimating the near-infrared light L2, a λ / 2 plate 43, a polarization beam splitter 44, a fluorescence cut filter 45, and a near-infrared light L2 that is transmitted while a fluorescence L3 is reflected. A mirror 46 and a condenser lens 47 that focuses the near-infrared light L2 and makes it enter the polarization-maintaining fiber 41 are provided.

Further, an imaging lens 20 is provided at a position facing the tip (left end in FIG. 2) of the polarization-maintaining fiber 41. Further, between the imaging lens 20 and the polarization-maintaining fiber 41, a condenser lens 48, a λ / 4 plate 49, and a dichroic mirror are arranged in this order from the polarization-maintaining fiber 41 side.
50 are arranged. And this dichroic mirror
A solid-state image pickup device 51 such as a CCD image pickup device is provided at a position where the light reflected by 50 is received. This solid-state image sensor 51
Is connected to the image display means 25.

The dichroic mirror 46 reflects the fluorescent light L3 having a peak wavelength of about 640 nm which is incident thereon and transmits the near infrared light L2 having a wavelength of 700 to 950 nm as described later. At the position where the fluorescence L3 reflected by the dichroic mirror 46 enters, a light source light cut filter 52, a condenser lens 53, and a fluorescence detector 54 that cut the excitation light L1 and the near-infrared light L2 in order from the dichroic mirror 46 side. Are arranged. The output of the fluorescence detector 54 is input to the calculating means 24.

On the other hand, at the position where the light reflected by the polarization beam splitter 44 enters, a condenser lens 55 and a near infrared light detector 56 are arranged in order from the polarization beam splitter 44 side. The output of the near-infrared light detector 56 is also input to the calculating means 24.

The operation of the fluorescent endoscope having the above structure will be described below. Also in this case, the diagnostic site 30 inside the living body 16 has previously absorbed a photosensitizer having a tumor affinity and emitting fluorescence when excited by light. Then, the diagnostic region 30 is irradiated with the excitation light L1 from the light guide 12, and at the same time, the near-infrared light L2 propagated through the polarization-maintaining fiber 41 is also irradiated. These lights are reflected by the diagnostic site 30, and when the excitation light L1 is irradiated, fluorescence L3 is emitted from the photosensitizer.

The near-infrared light L2 emitted from the near-infrared light source 40 has its direction of linearly polarized light adjusted by rotating the λ / 2 plate 43, and passes through the polarization beam splitter 44. Near-infrared light L2 propagated through the polarization-maintaining fiber 41
Is converted from linearly polarized light to elliptically polarized light by the λ / 4 plate 49, is focused by the imaging lens 20, and illuminates one point on the diagnostic region 30.

The excitation light L1 reflected by the diagnostic site 30 is reflected by the dichroic mirror 50, and the near infrared light L2 and the fluorescent light L3 also reflected by the diagnostic site 30 are dichroic mirrors.
Penetrate 50. The imaging lens 20 receives the reflected excitation light L.
An image (normal image) of the diagnosis region 30 according to 1 is formed on the solid-state image sensor 51. The solid-state image sensor 25 captures this normal image,
The image signal Sm representing the normal image is input to the image display means 25.

The image display means 25 displays the normal image represented by the image signal Sm. Therefore, the surgeon or assistant observes this displayed normal image to determine the state of the diagnosis site 30,
The positional relationship between the probe 17 and the diagnostic site 30 can be confirmed. In order to capture such a normal image, in addition to using the reflected excitation light L1 as described above, a system for irradiating the diagnostic site 30 with illumination light such as white light may be separately provided.

The near-infrared light L2 and the fluorescence L3 which have passed through the dichroic mirror 50 are condensed by the condenser lens 48 and enter the polarization plane preserving fiber 41. Guided outside. When the near-infrared light L2 is reflected by the diagnosis site 30, the direction of its elliptically polarized light is inverted, and then passes through the λ / 4 plate 49 to travel from the near-infrared light source 40 to the diagnosis site 30 side. The direction of linearly polarized light is rotated by 90 ° compared with.

The fluorescence L3 emitted from the polarization plane preserving fiber 41 is reflected by the dichroic mirror 46, and the condenser lens 53
The light is collected by and is received by the fluorescence detector 54. The excitation light L1 and the near-infrared light L2 directed to the fluorescence detector 54 are cut by the light source light cut filter 52. The fluorescence detector 54 outputs a fluorescence detection signal Sp1 indicating the intensity of the fluorescence L3, and this fluorescence detection signal Sp1 is input to the calculating means 24.

On the other hand, the near-infrared light L2 emitted from the polarization-maintaining fiber 41 has a linear polarization direction of 90 as described above.
The light beam is reflected by the polarization beam splitter 44 by being rotated by ° and is condensed by the condenser lens 55.
Received. The fluorescent light L3 traveling toward the polarization beam splitter 44 is cut by the fluorescent light cut filter 45. The near infrared light detector 56 outputs a near infrared light detection signal Sp2 indicating the intensity of the near infrared light L2, and the near infrared light detection signal S
p2 is input to the calculating means 24.

The calculating means 24 calculates the Sp1 between the fluorescence detection signal Sp1 and the near-infrared light detection signal Sp2 which are incident thereon.
/ Sp2 is divided, and the standardized fluorescence detection signal Sp = Sp1 / Sp2 obtained thereby is input to the image display means 25.

Since the photosensitizer has a tumor affinity, it can be considered that the fluorescence L3 basically originates from the tumor portion when the normalized fluorescence detection signal Sp exceeds a predetermined level. On the other hand, since the detection location of the fluorescence L3 in the diagnostic region 30 and the normal image capturing range of the solid-state image sensor 25 can be associated with each other, for example, the center point of the normal image capturing range is set as the detection location of the fluorescence L3. If the center point of the image pickup range is aligned with the screen center of the image display means 25 and a mark is displayed at the screen center when the normalized fluorescence detection signal Sp exceeds a predetermined level, the mark is displayed in the normal image. It is possible to determine that the part overlapping with is the tumorous part.

Further, regardless of such a display, an alarm sound is emitted when the standardized fluorescence detection signal Sp exceeds a predetermined level, and when the alarm sound is emitted, the center of the screen of the image display means 25 is displayed. It is also possible to determine that the location of the normal image in is the tumorous part.

Even if the fluorescence detection signal Sp1 is used as it is,
Basically, the presence or absence of a tumor can be determined as described above,
In that case, the amount of change in the fluorescence intensity based on the illuminance distribution of the excitation light L1 at the diagnosis site 30 is reflected in the fluorescence detection signal Sp1, which may lead to misdiagnosis. On the other hand,
If the presence / absence of a tumor is determined based on the standardized fluorescence detection signal Sp as described above, the change in fluorescence intensity due to the illuminance distribution of the excitation light L1 is canceled, and the presence / absence of a tumor can be accurately determined.

Also in this example, the near-infrared light L2 having a wavelength of 700 to 950 nm, which has a relatively small absorption in the living body, is used as the light for irradiating the diagnostic region 30 to check the illuminance distribution. The infrared light detection signal Sp2 is almost unaffected by the above-mentioned absorption, and substantially reflects only the near infrared light illuminance. Therefore, if the above-mentioned normalization is performed using this near-infrared light detection signal Sp2, the distribution of the excitation light illuminance can be accurately compensated, and the standardized fluorescence detection signal Sp with high diagnostic performance can be obtained.

Although the fluorescence diagnostic apparatus according to the two embodiments described above is configured as a fluorescence endoscope, the present invention is not limited to such a fluorescence endoscope, and a surgical microscope. The present invention can be applied to a fluorescence diagnostic device and the like incorporated in a computer and has the same effect.

[Brief description of drawings]

FIG. 1 is a schematic side view showing a fluorescent endoscope according to a first embodiment of the present invention.

FIG. 2 is a schematic side view showing a fluorescence endoscope which is a second embodiment of the present invention.

FIG. 3 is a graph showing absorption spectra of main components of a living body.

[Explanation of symbols]

 10 Excitation light source 11 Condenser lens 12 Light guide 13 Near-infrared light source 14 Dichroic mirror 16 Living body 17 Probe 18 Image guide 19 Dichroic mirror 20 Imaging lens 21 Excitation light cut filter 22 Condenser lens 23 Fluorescent image capturing means 24 Standardization Calculation means 25 Image display means 26 Excitation light cut filter 27 Condenser lens 28 Near infrared video camera 30 Diagnostic site 40 Near infrared light source 41 Polarization preserving fiber 42 Collimator lens 43 λ / 2 plate 44 Polarization beam splitter 45 Fluorescence cut Filter 46 Dichroic mirror 47 Condenser lens 48 Condenser lens 49 λ / 4 plate 50 Dichroic mirror 51 Solid-state image sensor 52 Light source light cut filter 53 Condenser lens 54 Fluorescence detector 55 Condenser lens 56 Near infrared detector L1 Excitation Light L2 Near infrared light L3 Fluorescence

Claims (5)

[Claims] 1. Excitation light irradiating means for irradiating a site of a living body absorbing a photosensitizer that emits fluorescence with excitation light in the excitation wavelength region of the photosensitizer, and fluorescence emitted by the photosensitizer. Fluorescence image capturing means for detecting and capturing a fluorescence image of a living body, near-infrared light irradiating means for irradiating the site of the living body with near-infrared light having a wavelength of 650 nm or more, and the near-infrared light reflected by the site A near-infrared image capturing means for detecting a near-infrared image of a living body, and a fluorescence image signal output by the fluorescence image capturing means, and a near-infrared image signal output by the near-infrared image capturing means. And a calculation unit for normalizing each pixel based on the above. 2. The near-infrared light irradiation means is configured to change the intensity of the near-infrared light, and outputs from the near-infrared image pickup means when the intensities of the near-infrared light are different from each other. Means for obtaining a difference signal by subjecting each of the at least two types of image signals obtained by subtraction to each pixel is provided, and the arithmetic means uses the difference signal as the near-infrared image signal for standardization. The fluorescence diagnostic apparatus according to claim 1, wherein the fluorescence diagnostic apparatus is configured. 3. Excitation light irradiating means for irradiating a site of a living body absorbing a photosensitizer that emits fluorescence with excitation light in the excitation wavelength region of the photosensitizer; Fluorescence detection means for detecting intensity for each point on the site, near-infrared light irradiation means for irradiating the site of the living body with near-infrared light having a wavelength of 650 nm or more, and the near-infrared light reflected by the site Near-infrared light detection means for detecting the intensity of light for each point on the site, and a fluorescence detection signal output by the fluorescence intensity detection means, near-infrared light detection output by the near-infrared light detection means A fluorescent diagnostic device, comprising: an arithmetic means for normalizing based on a signal. 4. The near-infrared light irradiation means is configured to change the intensity of the near-infrared light, and outputs the near-infrared light detection means when the intensities of the near-infrared light differ from each other. Means for obtaining a difference signal by subtracting at least two types of detected near-infrared light detection signals is provided, and the arithmetic means uses the difference signal as the near-infrared light detection signal for standardization. The fluorescence diagnostic apparatus according to claim 3, wherein the fluorescence diagnostic apparatus is configured as described above. 5. The near-infrared light irradiation means has a wavelength of 700 to 950 nm outside the fluorescence wavelength region of the photosensitizer.
5. The fluorescence diagnostic apparatus according to claim 1, which emits near-infrared light.