JPH10225436A - Fluorescence detector - Google Patents

Abstract

PROBLEM TO BE SOLVED: To correct the fluctuation of fluorescence intensity depending on distances among an exciting light irradiation part, a fluorescence receiving part and a living body observing part without causing any arithmetic error at a fluorescence detector. SOLUTION: By an exciting light irradiation means 1, exciting light L1 irradiates a living body observing part 10. Fluorescence L3 emitted from the part 10 is guided to a fluorescence detecting means 3 and 4 by a condensing optical system 12. Fluorescence L3 is separated into desired wavelength area and detected to allow the means 3 to extract the fluorescent components of a comparatively short wavelength area and to allow the means 4 to extract the fluorescent components (or fluorescent component corresponding thereto) of all the wavelength areas. A dividing means 5 executes division based on the means 3 and 4.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a method of irradiating an observation section of a living body with a photosensitizer which emits fluorescent light having a strong affinity for a tumor in advance, to an excitation light, and then irradiating the photosensitizer and the endogenous body. The present invention relates to a fluorescence detection device for diagnosing a tumor based on the intensity of fluorescence emitted from a dye, or for diagnosing a tumor based on the intensity of autofluorescence emitted from an in-vivo dye without injecting a photosensitizer in advance.

[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 fluoresces when excited by light (ATX
-S10, 5-ALA, NPe6, HAT-D01, Photofrin-2, etc.) are absorbed in advance in a tumor part of a living body cancer or the like as a fluorescent diagnostic agent, and the part is in the excitation wavelength region of the photosensitizer. This is a technique of irradiating excitation light to generate fluorescence from a fluorescent diagnostic agent accumulated in a tumor portion, and receiving the fluorescence to display the localization / invasion range of the lesion as an image and diagnose the tumor portion.

[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, without injecting a photosensitizer into the living body in advance, the living body observation section is irradiated with excitation light in the excitation wavelength region of the living body's dye, and the fluorescent light emitted by the living body's dye is received. A technique for displaying the localization / invasion range of a part as an image to diagnose a tumor part has also been proposed.

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

In the above-described fluorescence diagnostic apparatus, the distance from the excitation light irradiation system to the living body observation unit is not uniform due to the unevenness of the part of the living body. It is uneven. Generally, the fluorescence intensity is almost proportional to the illuminance of the excitation light, and the illuminance of the excitation light decreases in inverse proportion to the square of the distance. For this reason, the normal part closer to the lesion than the light source far from the light source emits stronger fluorescence, or the fluorescence from the lesion located at a position inclined with respect to the excitation light is extremely reduced. When the illuminance of the excitation light is non-uniform, the fluorescence intensity changes in accordance with 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 the change in the fluorescence intensity due to the unevenness of the distance from the living body observation section,
For example, Japanese Patent Application Laid-Open No. 62-247232, Japanese Patent Publication No. 3-587
No. 29 has provided a fluorescence diagnostic apparatus. In the fluorescence diagnostic apparatus described in Japanese Patent Publication No. 3-58729, fluorescence generated by irradiating a part of a living body with a photosensitizer having a high affinity to a lesion in advance is irradiated with excitation light and receiving the excitation light. And the image calculation based on the division of the fluorescence component and the reflected light component is performed, and the term due to the distance from the living body observation unit is deleted by such division. However, in the result of the division of the fluorescence component and the reflected light component, a term relating to the reflectance of the part irradiated with the excitation light remains, so that a fluorescence image reflecting the distribution of the fluorescent diagnostic agent cannot be obtained as a result. Still remains.

On the other hand, "FLUORESCENCE IMAGING OF EARLY
LUNG CANCER "(Annual International Conference of
the IEEE Engineering and Biology Society, Vol. 12,
In the apparatus described in No. 3, 1990), the auto-fluorescence generated from the dyes in the living body in the living body observation section when irradiated with excitation light is referred to as a component in a green wavelength region (hereinafter, referred to as a “green region component G”). ) And a component in a red wavelength region (hereinafter, referred to as a “red region component R”), perform an image operation based on the division of the red region component R and the green region component G, and calculate the division result. indicate. This means that the spectrum of autofluorescence differs between the normal part and the diseased part, that is, the autofluorescence spectrum emitted by the in-vivo dye in the normal part is
Since the intensity of the green area in the diseased part is extremely lower than that in the normal part, the green area component G of the autofluorescence is particularly low in the diseased part.
Is extremely large as compared with the reduction rate of the red region component R, and it is possible to specifically extract the fluorescence from the lesion by R / G division and display the image. In this apparatus, although the term of the fluorescence intensity depending on the distance between the excitation light source and the fluorescence receiving unit and the living body observation unit is canceled, the S / N ratio is extremely low because the autofluorescence at the lesion is extremely small. There's a problem.

[0009] Therefore, "Fluorescence imaging diagnosis of cancer using Red / Green Ratio" presented at the 16th Annual Meeting of the Japan Society of Laser Medicine, 1995 (Tokyo Medical University, Hamamatsu Photonics)
It has been proposed that a fluorescent diagnostic agent that accumulates in a lesion and emits red fluorescence is used to amplify the intensity of red fluorescence in the lesion and perform an R / G operation. As a result, the aforementioned “FLUORESCENCE IMAGING OF EARLY LUNG C
A fluorescence image is obtained in which the fluorescence intensity from the lesion is amplified as compared with the device shown in "ANCER".

When the calculation of R / G is used as described above, the term of the fluorescence intensity depending on the distance between the excitation light source and the fluorescence receiving unit and the living body observation unit can be neglected.

[0011]

However, since the green auto-fluorescence component in the affected part is extremely weak, there is a case where both of them perform division by zero, and there still remains a problem that a calculation error tends to occur.

SUMMARY OF THE INVENTION In view of the above problems, the present invention provides a fluorescence detecting device that corrects the fluorescence intensity depending on the distance between the excitation light source and the fluorescence receiving unit and the living body observation unit irradiated with the excitation light so as not to cause a calculation error. It is intended to provide.

[0013]

A first fluorescence detection apparatus according to the present invention irradiates a living body observation section to which a photosensitizer (fluorescent diagnostic agent) is not injected with excitation light, and generates a living body internal part generated by the excitation light. What is claimed is: 1. A fluorescence detection device for detecting autofluorescence from a dye, comprising: an excitation light irradiating unit configured to irradiate an observation unit of a living body with excitation light in an excitation wavelength region of an in-vivo dye that emits fluorescence, First fluorescence detecting means for extracting all autofluorescent components in a visible region including a first relatively short wavelength region and a relatively long wavelength region among the autofluorescent components emitted from the dye, and among the autofluorescent components, Second
A second fluorescence detecting means for extracting a fluorescent component in a relatively short wavelength region, a fluorescent component extracted by the first fluorescent detecting means, and a fluorescent component extracted by the second fluorescent detecting means. Dividing means for performing division.

Here, the first relatively short wavelength range and the second
The relatively short wavelength region may be the same wavelength region or a different wavelength region.

Further, the second fluorescence detecting device according to the present invention irradiates the living body observation section to which the photosensitive substance (fluorescent diagnostic agent) is not injected with excitation light similarly to the first fluorescence detecting device. A fluorescence detecting device for detecting autofluorescence from an indigenous dye generated in the living body, the excitation light irradiating means for irradiating an observation unit of the living body with excitation light in an excitation wavelength region of the indwelling dye that emits fluorescence; A fluorescent component of a predetermined wavelength region within a first relatively short wavelength region among the autofluorescent components emitted from the indwelling dye, and a predetermined fluorescent component of a relatively long wavelength region of the autofluorescence. First fluorescence detection means for extracting a fluorescence sum component with a fluorescence component in a wavelength region; second fluorescence detection means for extracting a fluorescence component in a second relatively short wavelength region among the autofluorescence components; Extracted by the first fluorescence detecting means A fluorescent component which is characterized in that it has a division means for performing division of the fluorescent component extracted by said second fluorescence detecting means.

Here, the first relatively short wavelength region and the second
The relatively short wavelength region may be the same wavelength region or a different wavelength region.

In any of the above-described fluorescence detection devices according to the present invention, the fluorescence detection means is not limited to one that detects the fluorescence emitted from the observation unit for each point.
Fluorescence emitted from the observation unit is detected two-dimensionally,
A fluorescent image of the observation unit may be captured.

The fluorescence detecting means may extract each fluorescent component by any method, for example, a desired wavelength region in which the fluorescence received by the fluorescence detecting means is finally required by an optical filter or the like. May be a method of directly extracting by separately receiving light, and a fluorescent component separated and detected also in a predetermined wavelength region that is partially different from a finally required wavelength region. There is no limitation on the type of method, such as a method of extracting a fluorescent component in a desired wavelength region finally required by performing arithmetic processing such as addition and subtraction based on Hereinafter, the same applies.

[0019]

According to the above-described first and second fluorescence detection devices according to the present invention, all autofluorescent components from a relatively short wavelength region to a relatively long wavelength region, or autofluorescent components in a relatively short wavelength region are used. By using the fluorescence sum of the fluorescence component and the autofluorescence component in a relatively long wavelength region as a denominator, and performing a division operation with the autofluorescence component in a relatively short wavelength region as a numerator,
Since the denominator to perform the division can be large enough,
There is no calculation error of performing division by zero in the image calculation, and it is possible to stably remove the fluctuation of the fluorescence intensity due to the distance between the excitation light source and the living body observation unit irradiated with the excitation light. Become.

Therefore, if the autofluorescence detection device according to the present invention is applied to a fluorescence diagnostic device for observing an autofluorescence image, a fluorescence image in which the fluctuation of the fluorescence intensity due to the above distance has been removed can be obtained. Performance can be improved.

[0021]

Embodiments of the present invention will be described below in detail with reference to the drawings. FIG. 1 shows a basic configuration of a fluorescence detection device according to the present invention. The fluorescence detection device having this basic configuration includes an excitation light L1
Excitation light irradiating means 1 for irradiating light and fluorescence L3 generated from living body observation section 10 are condensed by condensing optical system 2, and then separated and detected in a desired wavelength area to thereby detect a fluorescent component in a relatively short wavelength area. Fluorescence detection means 3 to extract and fluorescence detection means 4 to extract a fluorescence component (or a fluorescence component corresponding thereto) in the entire wavelength region excited by the excitation light, and a division operation based on the outputs of the fluorescence detection means 3 and 4 Division means 5 for performing
The output of the dividing means 5 is input to a display means 6 for displaying a visible image as image information, for example.

Hereinafter, a method of correcting the fluorescence intensity depending on the distance between the excitation light source and the fluorescence receiving unit and the living body observation unit irradiated with the excitation light in the fluorescence detection apparatus having the above-described basic configuration will be described in detail. explain.

First, there is provided a fluorescence detecting apparatus for irradiating excitation light to a living body observation section into which a photosensitizer (fluorescent diagnostic agent) is not injected, and detecting autofluorescence from a dye in the living body generated by the excitation light. A fluorescent component in a relatively short wavelength region (for example, a green region component G; hereinafter, referred to as a “short wavelength component”) of the autofluorescent light and an autofluorescent component in the entire wavelength region in the visible region (total autofluorescent component). A case where the present invention is applied to division will be described. In addition, a fluorescent component in a relatively long wavelength region (for example, a red region component R) of the autofluorescence is hereinafter referred to as a “long wavelength component”. Further, the “all autofluorescent components” may be any as long as they include at least “a part of the short wavelength component and a part of the long wavelength component”. That is, the wavelength regions of the fluorescent components in the entire wavelength region are not necessarily the same as the fluorescent components in the relatively short wavelength region and the fluorescent components in the relatively long wavelength region.

The excitation light L1 having the wavelength λ _ex is supplied from the excitation light irradiation means 1.
Is emitted, and the living body observation unit 10 including the lesion 11 is irradiated with the excitation light L1. From the observation unit 10, auto-fluorescence L3 due to the in-vivo dye is generated, and the auto-fluorescence L3 is wavelength-separated into a short-wavelength region fluorescent component and a full-wavelength region fluorescent component by a dichroic mirror, an optical filter, or the like. 3 detects a short-wavelength component of the auto-fluorescence L3 generated from the dye contained in the living body of the living body observation unit 10;
All the wavelength components in the autofluorescence L3 generated from the in-vivo dye are detected. It is needless to say that the light detecting element used for the fluorescent light detecting means 3 and 4 may be a light detecting element such as a photodiode for detecting the fluorescent light L3 point by point.
May be two-dimensionally detected to capture a fluorescent image. Hereinafter, the same applies. Hereinafter, the operation of the fluorescence detection device having the above configuration will be described.

When the observation unit 10 is irradiated with the excitation light L1, the observation unit 10 emits autofluorescence L3 whose spectrum is shown in FIG. This autofluorescence L2 is presumed to be superimposed with fluorescence from various in-vivo dyes such as FAD, collagen, fibronectin, porphyrin, etc. As shown in the fluorescence spectrum in FIG. In, the size of the fluorescence spectrum is different and the shape is also different, the autofluorescence L2 is large in the normal part as a whole, but the autofluorescence L2 is decreased in the lesion part as a whole. The degree of decrease of the fluorescent component having a longer wavelength than that of red is smaller than the degree of decrease of the green fluorescent component (the reason why the fluorescence spectrum differs between the lesioned part and the normal part has not been elucidated). In other words, the ratio between the near-green fluorescent component and the near-red fluorescent component changes between the affected part and the normal part, and the change in the ratio makes it possible to distinguish the affected part from the normal part.

The autofluorescence detected by the fluorescence detecting means 4
The short wavelength component Ifλ ₁ ′ of L3 is stored in the memory 6a, and the long wavelength component Ifλ ₂ ′ of the autofluorescence L3 detected by the fluorescence detection means 3 is stored in the memory 5a. On the other hand, the excitation light L1
The short-wavelength component Ifλ ₁ ″ of the auto-fluorescence L3 detected by the fluorescence detection means 4 when the irradiation of
And the autofluorescence detected by the fluorescence detection means 3
The long wavelength component Ifλ ₂ ″ of L3 is stored in the memory 5b.

Each wavelength component detected by the fluorescence detecting means 3 and 4 is represented as follows.

The apparent short wavelength component Ifλ ₁ is: Ifλ ₁ = kλ ₁ · Iλ _ex · ηFλ ₁ · N · ηD The apparent total autofluorescence component Ifλ ₂ is: Ifλ ₂ = kλ ₂ · Iλ _ex · ηFλ ₂・ N · ηD Here, the symbols used have the following meanings, respectively.

Λ _ex : excitation light wavelength Iλ _ex : distance L from the excitation light irradiation unit to the living body observation unit, power P of the excitation light source, angle θ between the excitation light beam and the observation unit
Excitation light intensity at target subject which depends on preparative, Iλ _ex = Iλ _ex
(L, P, θ) n: Apparent concentration of autofluorescent molecules contributing to fluorescence in the entire visible region (though there may be multiple types of fluorescent molecules contributing to autofluorescence, virtually one molecule Here, the term “apparent” is used in the sense that it can be treated as being present. The same applies to the following.) N: Apparent autofluorescent molecule concentration kλ ₁ that contributes to fluorescence in the short wavelength region : A constant depending on the excitation light wavelength λ _ex and the apparent fluorescent molecule contributing to the fluorescence in the short wavelength region kλ ₂ : Dependent on the excitation light wavelength λ _ex and the apparent fluorescent molecule contributing to the fluorescence in the entire visible region ΗFλ ₁ : Fluorescence quantum yield of the apparent fluorescent molecule contributing to the fluorescence in the short wavelength region to the excitation light wavelength λ _ex ηFλ ₂ : Excitation light of the apparent fluorescent molecule contributing to the fluorescence in the entire visible region fluorescence quantum yield ηD for the wavelength lambda _ex: a light emitting part and the light receiving system The detection efficiency of the fluorescence depends on the separation L ', the size D of the aperture of the light receiving system, and the efficiency の of the detector, ηD = ηD (L', ξ, D) (strictly speaking, for the fluorescence in the short wavelength region. Although the detection efficiency is different from the detection efficiency for fluorescence in the entire visible region, both can be treated as being approximately equal here.)

Next, the dividing means 5 divides the apparent short-wavelength component Ifλ ₁ and the apparent total auto-fluorescent component Ifλ ₂ . The division value Ifλ ₁ / Ifλ ₂ is expressed as follows.

Ifλ ₁ / Ifλ ₂ = (kλ ₁ · ηFλ ₁ · N) /
(kλ ₂・ ηFλ ₂・ n) where (kλ ₁・ ηFλ ₁ ) / (kλ ₂・ ηFλ ₂ ) = C, N
If / n = X, Ifλ ₁ / Ifλ ₂ = C × X, and C is a constant term, so Ifλ ₁ / Ifλ ₂ is represented as a graph in FIG. That is, the non-uniformity Iλ _ex due to the location of the excitation light illuminance is canceled. The value of X represents the number of fluorescent molecules in the normalized short-wavelength region in all the number of fluorescent molecules, that small Ifλ ₁ / Ifλ ₂ is meant to be a lesion. Thus it is possible to specifically extract lesion by performing division operation between the short wavelength components Iframuda ₁ and all autofluorescence component Ifλ _2. On this occasion,
Denominator can be increased by using whole autofluorescence component Iframuda ₂ in the denominator, it is possible to suppress the occurrence of operation error due to zero division. Therefore, for example, by using an image sensor as the fluorescence detection means 3 and 4, it is possible to display a fluorescence image whose fluorescence intensity has been corrected on the display means 6 as a visible image.

Next, there is provided a fluorescence detecting apparatus for irradiating excitation light to a living body observation part into which a fluorescent diagnostic agent is not injected, and detecting autofluorescence generated from a dye inherent in the living body,
Short wavelength component of autofluorescence (for example, green region component G)
And a case where the present invention is applied to the division of a short-wave component and a long-wave component (for example, a red region component R) with a fluorescence sum component (for example, G + R). Note that the wavelength region of the “short wavelength component” and the wavelength region of the “short wavelength component included in the fluorescence sum component” do not necessarily need to be the same.

The excitation light L1 having the wavelength λ _ex is supplied from the excitation light irradiation means 1.
Is emitted, and the living body observation unit 10 including the lesion 11 is irradiated with the excitation light L1. From the observation unit 10, autofluorescence L3 due to the indigenous dye in the living body is generated, and the autofluorescence L3 is a fluorescent component in a short wavelength region, a fluorescent component in a long wavelength region and a fluorescent component in a short wavelength region by an optical filter such as a dichroic mirror. The fluorescence detection means 3 is separated into wavelengths by the fluorescence sum component of
The short-wavelength component of the auto-fluorescence L3 generated from the in-vivo dye in the living body is detected, and the fluorescence detection means 4 detects the sum of the fluorescence in the auto-fluorescence L3 generated from the in-vivo dye in the living body observation unit 10. Other configurations are the same as those applied to the above-described division of the short wavelength component and the total autofluorescence component.

The means for detecting the short-wavelength component and the means for detecting the fluorescence sum component are not limited to the present configuration example. The detection is performed by separating the wavelength into a predetermined wavelength region, and the detection result is added or subtracted. By performing the above calculation, the fluorescent component in the wavelength region finally required may be obtained. For example, the wavelength is separated into a fluorescent component in a long wavelength region and a fluorescent component in a short wavelength region, the short wavelength component is detected by the fluorescence detection unit 3, the long wavelength component is detected by the fluorescence detection unit 4, and the respective outputs are added. By doing so, the fluorescence sum component may be obtained. Further, the wavelength is separated into a fluorescence component in a long wavelength region and a fluorescence sum component of a fluorescence component in a long wavelength region and a fluorescence component in a short wavelength region,
The short-wavelength component may be obtained by detecting the long-wavelength component by the fluorescence detection means 3, detecting the fluorescence sum component by the fluorescence detection means 4, and dividing the long-wavelength component from the fluorescence sum component.

Hereinafter, the operation of the fluorescence detecting device having the above configuration will be described.

As in the case described above, each wavelength component is expressed as follows.

The apparent short wavelength component Ifλ ₁ is: Ifλ ₁ = kλ ₁ · Iλ _ex · ηFλ ₁ · N · ηD The apparent long wavelength component Ifλ ₂ is: Ifλ ₂ = kλ ₂ · Iλ _ex · ηFλ ₂ · n · .eta.D fluorescence sum component Iframuda is Ifλ = Ifλ ₁ + Ifλ ₂ where the symbols used have the meaning of following described respectively.

Λ _ex : excitation light wavelength Iλ _ex : distance L from the excitation light irradiation unit to the living body observation unit, power P of the excitation light source, angle θ between the excitation light beam and the observation unit
Excitation light intensity at target subject which depends on preparative, Iλ _ex = Iλ _ex
(L, P, θ) n: apparent concentration of autofluorescent molecules that contribute to fluorescence in the long wavelength region (though there may be multiple types of fluorescent molecules that contribute to autofluorescence, virtually one molecule Here, the term “apparent” is used in the sense that it can be treated as being present. The same applies to the following.) N: Apparent autofluorescent molecule concentration kλ ₁ that contributes to fluorescence in the short wavelength region : Constant depending on the excitation light wavelength λ _ex and apparent fluorescent molecules contributing to short-wavelength fluorescence kλ ₂ : Dependent on excitation light wavelength λ _ex and apparent fluorescent molecules contributing to long-wavelength fluorescence ΗFλ ₁ : The fluorescence quantum yield of the apparent fluorescent molecule contributing to the fluorescence in the short wavelength region with respect to the excitation light wavelength λ _ex ηFλ ₂ : The excitation light of the apparent fluorescent molecule contributing to the fluorescence in the long wavelength region fluorescence quantum yield ηD for the wavelength lambda _ex: a light emitting part and the light receiving system The detection efficiency of the fluorescence depends on the separation L ', the size D of the aperture of the light receiving system, and the efficiency の of the detector, ηD = ηD (L', ξ, D) (strictly speaking, for the fluorescence in the short wavelength region. Although the detection efficiency is different from the detection efficiency for fluorescence in a long wavelength region, they can be treated as being approximately equal here.)

Next, the short-wavelength component Ifλ ₁
And the fluorescence sum component (Ifλ ₁ + Ifλ ₂ ) Is divided by Division value
Ifλ ₁ / (Ifλ ₁ + Ifλ ₂ ) is expressed as follows.

Ifλ ₁ / (Ifλ ₁ + Ifλ ₂ ) = (kλ ₁ · ηFλ ₁
・ N) / (kλ ₁・ ηFλ ₁・ N + kλ ₂・ ηFλ ₂・ n) where (kλ ₁・ ηFλ ₁ ) / (kλ ₂・ ηFλ ₂ ) = C, N
If / n = X, Ifλ ₁ / (Ifλ ₁ + Ifλ ₂ ) = C × X / (C × X + 1), and C is a constant term, so Ifλ ₁ / (Ifλ ₁ + Ifλ ₂ )
Is represented as shown in the graph of FIG. That is, the non-uniformity Iλ _ex due to the location of the excitation light illuminance is canceled. X
Represents the number of fluorescent molecules in the short wavelength region standardized by the number of fluorescent molecules in the long wavelength region, and a small value of Ifλ ₁ / (Ifλ ₁ + Ifλ ₂ ) means a lesion. Thus it is possible to specifically extract lesion by performing division operation between the short wavelength components Iframuda ₁ and the fluorescence sum component (Ifλ ₁ + Ifλ _2). At this time, the fluorescence sum component (If
λ ₁ + Ifλ ₂ ) Is used, the denominator can be increased, and the occurrence of an operation error due to division by zero can be suppressed. Therefore, for example, by using an image sensor as the fluorescence detection means 3 and 4, it is possible to display a fluorescence image whose fluorescence intensity has been corrected on the display means 6 as a visible image.

Next, an endoscope apparatus according to a first specific embodiment to which the fluorescence detecting apparatus according to the present invention is applied will be described with reference to FIGS. FIG. 5 is a schematic configuration diagram of an endoscope apparatus to which the fluorescence detection device according to the present invention is applied,
Excitation light is applied to the living body observation part where the fluorescent diagnostic agent is not injected, and the auto-fluorescence from the in-vivo dyes generated by this is detected, and the green fluorescence component and the total auto-fluorescence component of the auto-fluorescence are compared. Performs division.

An endoscope apparatus according to an embodiment of the present invention is an endoscope 100 inserted into a site suspected of a lesion of a patient.
An illumination device 110 having a light source for emitting white light for normal image observation and excitation light for fluorescent image observation; an optical path switching unit 120 for switching the optical path between normal image observation and fluorescent image observation; A color CCD camera 130 for receiving reflected light from the living body observation unit, a high-sensitivity camera unit 140 for receiving fluorescence generated from the living body observation unit due to the excitation light when observing a fluorescent image, and a reflected light image or a fluorescence image The image processing apparatus 150 includes an image processing device 150 that performs image processing, and a display 160 that displays image information processed by the image processing device 150 as a visible image.

The endoscope 100 has a light guide 106 and an image fiber 104 extending to the end of the endoscope insertion portion 101 inside the endoscope insertion portion 101. The light guide 106 and the tip of the image fiber 104 are provided. An illumination lens 102 and an objective lens 103 are provided at the end of the section, that is, the endoscope insertion section 101, respectively. One end of the light guide 106 reaches the inside of the lighting device 110 through a connecting portion 107 that connects the lighting device 110 to the operation unit 105. The image fiber 10
One end of 4 extends into the operation section 105 and is in contact with an eyepiece section 108 having an eyepiece lens 109.

The illumination device 110 includes a xenon lamp 118 that emits white light L2 for normal image observation, and an excitation light for fluorescence observation.
A mercury lamp 111 for emitting L1, an optical filter 112 for setting a transmission wavelength of the excitation light L1 emitted from the mercury lamp 111
And a switching mirror 115 driven by a driver 116 to switch between white light L2 and excitation light L1 during normal observation and fluorescence observation.

The optical path switching unit 120 converts the reflected light passing through the image fiber 104 during normal observation into a color C signal.
A switching mirror 121 driven by a driver 123 is provided to switch the optical path to the CD camera 130 so as to send the fluorescence L3 passing during fluorescence observation to the high sensitivity camera unit 140.

The high-sensitivity camera unit 140 switches the fluorescence L3 transmitted through the image fiber 104 through the long pass filter 142a for transmitting all fluorescence and the band-pass filter 142b for transmitting near green light at the time of fluorescence observation. And a cooled CCD camera 144 on which the fluorescent light L3 transmitted through the switching optical filter 142 is imaged.
The switching optical filter 142 uses a long-pass filter 142a for transmitting all fluorescence and a band-pass filter 142b for transmitting near-green light by switching with a driver 143.

The image processing device 150 includes the color CCD camera 13
A / D conversion circuit for digitizing the video signal obtained at 0
1, a normal image memory 154 for storing a digitized normal image signal, and a near-green fluorescence image memory 152 for storing a digitized video signal reflecting a fluorescence component near green
, A full fluorescent image memory 153 for storing a digitized video signal reflecting all the fluorescent light, and a near green fluorescent image memory 15
2 and the output of the total fluorescence image memory 153, and stores a result of the division in the division memory 155. The video signals stored in the normal image memory 154 and the division memory 155 are displayed as a visible image on the display 160. Signal generation circuit 156 for performing image processing for the same, switching mirrors 115 and 121 for the illumination device 110, high-sensitivity camera unit 140 and optical path switching unit 120, and a timing controller 15 for sending signals to drivers 116, 123 and 143 for driving a switching optical filter 142.
8 and a video processor 157 for controlling the timing controller 158.

Hereinafter, the operation of the endoscope apparatus having the above configuration to which the fluorescence detecting device according to the present invention is applied will be described. First, the operation of the present endoscope apparatus during normal image observation will be described.

At the time of normal observation, the switching mirror 115 in the illuminating device 110 is driven by the driver 116 based on a signal from the timing controller 158 and moves to the position indicated by the broken line so as not to disturb the progress of the white light L2. The white light L2 output from the xenon lamp 118 passes through the lens 117 to the switching mirror 115. The white light L2 that has passed through the switching mirror 115 is incident on the light guide 106 by the lens 114, and is guided to the end of the endoscope.
2 to the region (biological observation unit) 10 including the lesion 11.

The reflected light of the white light L2 is condensed by the objective lens 103, and travels through the image fiber 104 and the eyepiece lens 109 provided in the eyepiece section 108 to the switching mirror 121 in the switching unit 120.

The switching mirror 121 is driven by a driver 123 based on a signal from the timing controller 312 and moves to a position indicated by a solid line during normal observation. The reflected light is reflected by the switching mirror 121 and is imaged on the color CCD camera 130 by the lens 122.

The video signal from the color CCD camera 130 is A /
After being input to the D conversion circuit 151 and digitized for each of the RGB video signals, it is stored in the normal image memory 154 corresponding to the RGB image. The normal image signal stored in the normal image memory 154 is subjected to color matrix processing and encoding processing after DA conversion by the video signal generation circuit 156, input to the display 160 as an NTSC signal, and displayed on the display 160 as a visible image. .

The above series of operations are performed by the video processor 157
And a timing controller 158.

Next, the operation at the time of observing the autofluorescent image will be described. The switching mirror 115 is a timing controller 158
Is driven by the driver 116 on the basis of the signal from the controller and moves to the position indicated by the solid line so as to block the passage of the white light L2 and reflect the excitation light L1. The excitation light L1 emitted from the mercury lamp 111 is supplied to the optical filter 112 and the lens 11
3 and travels to the switching mirror 115. Switching mirror 115
The excitation light L1 reflected by the light source is incident on the light guide 106 by the lens 114, and is guided to the end of the endoscope.
Area including the lesion 11 from the illumination lens 102 (living body observation section)
Irradiate to 10. It should be noted that a bright line spectrum having a center wavelength of 405 nm is transmitted from the mercury lamp 111 by the optical filter 112.

The fluorescence L3 from the irradiated portion 10 generated by the irradiation of the excitation light is condensed by the objective lens 103, and travels through the image fiber 104 and the eyepiece lens 109 to the switching mirror 121. The switching mirror 121 is driven by the driver 123 based on a signal from the timing controller 158 and moves to the position shown by the broken line so as not to hinder the progress of the fluorescent light L3. Switching mirror 12
The fluorescence L3 that has passed through one portion passes through the lens 141 and the switching optical filter 142, and forms an image on the cooled CCD camera 144. The switching optical filter 142 has a configuration as shown in FIG. 6, and has a wavelength 460n as shown in FIGS. 7a and 7b, respectively.
m, a long-pass filter 142a that transmits all fluorescence of at least m,
A band pass filter 142b that transmits a fluorescent component near green having a wavelength of 510 +/− 10 nm, and the filter is switched by a driver 143 that operates based on a signal from a timing controller 158.

As described above, the switching optical filter 142 is driven by the driver 143, and first, a filter 142a that transmits all the fluorescent light of blue-green or more is selected. Long pass filter
The total fluorescence transmitted through 142a forms an image on the cooled CCD camera 144. The video signal reflecting the total fluorescence is input to the A / D conversion circuit 151, digitized, and stored in the total fluorescence image memory 153.

Next, based on the signal from the timing controller 158, a band-pass filter 142b that transmits only the near green fluorescent component is selected. Cooled CCD camera 144
Outputs a video signal reflecting near-green fluorescence.
The video signal reflecting the near-green fluorescence is digitized by the A / D conversion circuit 151 and stored in the near-green fluorescence image memory 152.

After the video signal reflecting both fluorescent components is obtained, the video signal reflecting the green fluorescent component stored in the near-green fluorescent image memory 152 and the video signal reflecting the green fluorescent component stored in the full fluorescent image memory 153 are stored in the division memory 155. The division with the video signal reflecting all the fluorescent components is performed, and the divided image signal is stored in the division memory 155.

The divided image signal stored in the division memory 155 is subjected to an encoding process after DA conversion by the video signal generation circuit 156, and is displayed on the display 160 as a visible image. It should be noted that a normal image and a divided image can be displayed on the display screen in an overlay manner.

Next, an endoscope apparatus according to a second specific embodiment to which the fluorescence detection apparatus according to the present invention is applied will be described with reference to FIGS. In FIG. 8, the same elements as those in FIG. 5 are denoted by the same reference numerals, and description thereof will be omitted unless otherwise required. FIG.
1 is a schematic configuration diagram of an endoscope apparatus to which a fluorescence detection device according to the present invention is applied, and irradiates excitation light to a living body observation unit to which a fluorescent diagnostic agent has not been injected, thereby generating an autogenous dye from a living body endogenous dye. The fluorescence is detected, and the green fluorescence component and the long-wavelength fluorescence component of the auto-fluorescence are divided.

The endoscope device according to the embodiment of the present invention is an endoscope 100 inserted into a site suspected of a lesion of a patient.
An illumination device 110 having a light source for emitting white light for normal image observation and excitation light for fluorescent image observation; an optical path switching unit 120 for switching the optical path between normal image observation and fluorescent image observation; A color CCD camera 130 for receiving the reflected light from the living body observation unit, a high-sensitivity camera unit 200 for receiving the fluorescence generated from the living body observation unit by the excitation light when observing the fluorescent image, a reflected light image or a fluorescent image The image processing apparatus 210 includes an image processing device 210 that performs image processing, and a display 160 that displays image information processed by the image processing device 210 as a visible image. The endoscope apparatus includes a high-sensitivity camera unit 200 and an image processing apparatus 210.
Is different from the endoscope apparatus according to the first specific embodiment described above.

The high-sensitivity camera unit 200 includes a long-pass filter 202 for removing the excitation light component, and separates the fluorescent light L3 transmitted through the long-pass filter 202 into fluorescent light in the green wavelength region and fluorescent light in the green wavelength region that is green or higher. A dichroic mirror 201 is provided for imaging fluorescence in the wavelength region to the first cooled CCD camera 205 and fluorescence in the green wavelength region or longer (long wavelength) to the second cooled CCD camera 204.

The image processing device 210 is a color CCD camera
130, an A / D conversion circuit 211 for digitizing video signals obtained by the first cooled CCD camera 205 and the second cooled CCD camera 204, a normal image memory 214 for storing digitized normal image signals, Near-green fluorescent image memory for storing digitized video signals reflecting fluorescent components
213, a long-wavelength fluorescent image memory 212 for storing a digitized video signal reflecting a long-wavelength fluorescent component, an output of the near-green fluorescent image memory 213 and an output of the long-wavelength image memory 212, and the addition result is obtained. Addition memory 215 to save,
A division memory 216 for dividing the output of the near-green fluorescence image memory 213 and the output of the addition memory 215 and storing the result of the division.
A video signal generation circuit 217 that performs image processing for displaying the video signal stored in the normal image memory 214 and the division memory 216 as a visible image on the display 160;
Switching mirrors 115 and 121 for the illumination device 110, the high-sensitivity camera unit 200, and the optical path switching unit 120, and a switching optical filter
It comprises a timing controller 219 for sending signals to drivers 116, 123, 143 for driving 142, and a video processor 218 for controlling the timing controller 219.

The operation of the endoscope apparatus having the above configuration will be described below. The operation of the present endoscope apparatus at the time of normal image observation is the same as that of the endoscope apparatus according to the first specific embodiment. Therefore, only the operation at the time of observing an autofluorescent image will be described.

Excitation light L1 irradiates the living body observation section similarly to the endoscope apparatus according to the first specific embodiment. Excitation light
Fluorescence from irradiated part 10 caused by irradiation with L1
L3 is condensed by the objective lens 103, passes through the image fiber 104 and the eyepiece 109, and travels to the switching mirror 121. This switching mirror 121 is a timing controller
Based on the signal from 219, it is driven by the driver 123 to move to the position indicated by the broken line so as not to hinder the progress of the fluorescence L3. The fluorescent light L3 that has passed through the switching mirror 121
Passes through a lens 203 and a long-pass filter 202 and travels to a dichroic mirror 201. The long-pass filter 202 has the transmission characteristics shown in FIG. 9A, and transmits only the fluorescence having a wavelength of 480 nm or more. As a result, the excitation light L1 having a center wavelength of 405 nm is cut. The dichroic mirror 201 has the characteristics shown in FIG.
The long-wavelength fluorescent component near the green color (wavelength 540 nm or more) is transmitted and forms an image on the first cooled CCD camera 205, and the fluorescent component near the green color (wavelength 480 nm to 540 nm) is reflected by the dichroic mirror 20.
The light is reflected by 1 and forms an image on the second cooled CCD camera 204.

The image signal obtained by the first cooled CCD camera 205 which reflects a fluorescent component having a long wavelength near green or higher is A
The signal is input to the / D conversion circuit 211, digitized, and stored in the long-wavelength image memory 212. Similarly, the image signal obtained by the second cooled CCD camera 204 reflecting the fluorescent component near green is input to the A / D conversion circuit 211, and is digitized and stored in the near-green image memory 213.

After the video signal reflecting both the fluorescent components is obtained, the addition memory 215 stores the video signal reflecting the green fluorescent component stored in the near-green fluorescent image memory 152 and the total fluorescent image memory 153. The addition is performed with the video signal reflecting all the fluorescent components, and the added image signal is stored in the addition memory 215. This added image signal corresponds to the fluorescence in the entire wavelength region, and is equivalent to a video signal reflecting all the fluorescence components in the endoscope apparatus according to the first specific embodiment.

Next, the division memory 216 divides the video signal reflecting the green fluorescence component stored in the near-green fluorescence image memory 213 and the video signal reflecting all the fluorescence components stored in the addition memory 215. Then, the divided image signal is stored in the division memory 216.

The divided image signal stored in the division memory 216 is subjected to DA conversion by the video signal generation circuit 217 and then subjected to encoding processing and displayed on the display 160 as a visible image. It should be noted that a normal image and a divided image can be displayed on the display screen in an overlay manner.

Next, an endoscope apparatus according to a third specific embodiment to which the fluorescence detecting apparatus according to the present invention is applied will be described with reference to FIGS. In FIG. 10, the same elements as those in FIG. 5 and FIG.
Descriptions of them will be omitted unless otherwise required.
FIG. 10 is a schematic configuration diagram of an endoscope apparatus to which the fluorescence detection device according to the present invention is applied. The auto-fluorescence is detected, and the green fluorescence component of the auto-fluorescence and the sum of the fluorescence components of the green and red fluorescence components are divided.

The endoscope apparatus according to the embodiment of the present invention includes an endoscope 100 inserted into a site suspected of a lesion of a patient.
An illumination device 110 having a light source for emitting white light for normal image observation and excitation light for fluorescent image observation; an optical path switching unit 120 for switching the optical path between normal image observation and fluorescent image observation; A color CCD camera 130 for receiving the reflected light from the living body observation unit, a high-sensitivity camera unit 300 for receiving the fluorescence generated from the living body observation unit by the excitation light when observing the fluorescent image, a reflected light image or a fluorescent image The image processing apparatus 310 includes an image processing apparatus 310 that performs image processing, and a display 160 that displays image information processed by the image processing apparatus 310 as a visible image. The endoscope apparatus includes a high-sensitivity camera unit 300 and an image processing apparatus 310.
Is different from the endoscope device according to the first and second specific embodiments.

The high-sensitivity camera unit 300 includes an excitation light cut filter 302 for cutting the transmitted light and the excitation light component of the fluorescent light L3, and a cooling CCD for forming an image of the reflected light and the fluorescent light L3 transmitted through the filter 302. It consists of a camera 303. Note that a color mosaic filter is mounted on the light receiving surface of the cooled CCD camera 303.

The image processing device 310 includes a cooled CCD camera 303
A / D conversion circuit that digitizes the video signal obtained by
311, an R image memory 314, a G image memory 313, and a B image memory 31 for storing digitalized RGB image signals.
2. an addition memory 315 for adding the components stored in each of these image memories to obtain a fluorescence sum component and storing the addition result;
Red fluorescent component and addition memory stored in image memory 314
A division memory 316 that divides the fluorescence sum component stored in 315 and stores the result of the division, and generates a video signal that performs image processing for displaying the video signal stored in the division memory 316 on the display 160 as a visible image. Circuit 317, switching mirrors 115 and 12 for lighting device 110 and optical path switching unit 120
A timing controller 319 for sending a signal to drivers 116 and 123 for driving
9 comprises a video processor 318 for controlling.

Hereinafter, the operation of the endoscope apparatus having the above configuration will be described. First, the operation of the present endoscope apparatus during normal image observation will be described in detail. Similar to the endoscope apparatus according to the first specific embodiment, white light L2 irradiates the living body observation unit. The reflected light of the white light L2 applied to the living body is collected by the objective lens 103, and the image fiber 104 and the eyepiece
Through the eyepiece 109 provided in 108, it goes to the high sensitivity camera unit 300. The reflected light of the white light 119 transmitted through the eyepiece 109 passes through the lens 301 and the excitation light cut filter 302, and forms an image on the cooled CCD camera 303. Note that the light receiving surface of the cooled CCD camera 303 is shown in FIG.
Are attached. The optical transmission characteristics of the color mosaic filter are as shown in FIG. 11 (B), and each color filter transmits only a component in the wavelength region of each color. The video signal from the cooled CCD camera 303 is
After being input to the A / D conversion circuit 311 and digitizing each of the RGB video signal components, the R image memory 31
4, stored in the G image memory 313 and the B image memory 312.

R image memory 314, G image memory 313, B
The normal image signal stored in each of the image memories 312 is subjected to color matrix processing and encoding processing after DA conversion by the video signal generation circuit 317, and then input to the display 160, where it is displayed as a visible image. .

Next, the operation when observing the fluorescent image will be described in detail. Excitation light L1 irradiates the living body observation unit similarly to the endoscope apparatus according to the first specific embodiment. The fluorescent light 30 from the living body irradiated portion 10 generated by the irradiation of the excitation light is received by the objective lens 103, passes through the image fiber 104 and the eyepiece 109, passes through the excitation light cut filter 302, and removes the excitation light component. After cooling the CCD
An image is formed on the camera 303. Since the fluorescence intensity is lower than that of the normal observation light, the imaging rate of the cooled CCD camera 303 is made sufficiently slower in the fluorescent image observation than in the normal image observation.

As in the normal image observation, the cooled CCD camera 30
3 is input to the A / D conversion circuit 311.
After digitizing each of the R image, the G image, and the B image, the R image memory 314, the G image memory 313,
The image is stored in the B image memory 312. After the RGB fluorescent image is obtained, the addition memory 315 adds the video signal reflecting the red fluorescent component stored in the R image memory 314 and the video signal reflecting the green fluorescent component stored in the G image memory 313. Is performed, and the addition image signal is stored in the addition memory 315.

Next, in the division memory 316, the video signal reflecting the green fluorescence component stored in the G image memory 313 is divided by the addition image signal stored in the addition memory 315, and the division image signal is divided. Stored in 316. The divided image signal stored in the division memory 316 is subjected to color matrix processing and encoding processing after D / A conversion by the video signal
Displayed as a visible image at 160. By providing a memory for storing the normal image signal separately from each of the RGB memories (312 to 314), the divided image and the normal image can be displayed in an overlay manner.

In addition, in the addition memory 315, a video signal reflecting the red fluorescent component stored in the R image memory 314,
By adding the video signal reflecting the green fluorescent component stored in the G image memory 313 and the video signal reflecting the blue fluorescent component stored in the B image memory 312, an entire region fluorescent image reflecting all the fluorescent components is obtained. Addition memory 31 as signal
5 and in the division memory 316, the G image memory 31
It is also possible to divide the video signal reflecting the green fluorescent component stored in 3 and the whole area fluorescent image signal stored in the addition memory 315.

Further, as a color mosaic filter, FIG.
Four types of color filters having the transmission characteristics shown in FIG.
(A) By using the filter array shown, it is also possible to perform a division operation such as G1 fluorescence image / (R fluorescence image + G1 fluorescence image + G2 fluorescence image + B fluorescence image).

Further, since the configuration of the high-sensitivity camera unit of the present endoscope apparatus is simple, it can be easily applied to an electronic endoscope having an imaging element at the end of the endoscope.

On the other hand, in the embodiment described above, the fluorescence detection apparatus according to the present invention is applied to the image pickup optical system. However, the present invention is not limited to the image pickup optical system but can be applied to a scanning optical system. It is. In this case, the change η in the detection efficiency due to the distance between the light emitting part and the light receiving system, etc.
D can be canceled.

[Brief description of the drawings]

FIG. 1 is a basic configuration diagram of a fluorescence detection device according to the present invention.

FIG. 2 is an explanatory diagram showing a fluorescence spectrum of autofluorescence.

FIG. 3 shows the division of the short wavelength component Ifλ ₁ and the total autofluorescence component Ifλ ₂ Ifλ ₁ / Ifλ ₂ and the variable N / n = X in which the number of fluorescent molecules in the short wavelength region is normalized by the total number of fluorescent molecules. Principle explanatory diagram showing the relationship

FIG. 4 shows division of a short wavelength component Ifλ ₁ and a fluorescence sum component Ifλ.
Principle explanatory diagram showing the relationship between λ ₁ / Ifλ and the variable N / n = X that standardizes the number of fluorescent molecules in the short wavelength region with the number of fluorescent molecules in the short wavelength region.

FIG. 5 is a schematic configuration diagram of an endoscope apparatus which is a first specific embodiment to which the fluorescence detection device according to the present invention is applied.

FIG. 6 is a structural diagram of a switching optical filter used in the endoscope apparatus according to the first embodiment.

FIGS. 7A and 7B are light transmission characteristic diagrams of the switching optical filter.

FIG. 8 is a schematic configuration diagram of an endoscope apparatus which is a second specific embodiment to which the fluorescence detection device according to the present invention is applied.

FIG. 9 is a light transmission characteristic diagram (A) of a long-pass filter used in the endoscope apparatus according to the second embodiment and a light transmission characteristic diagram of a dichroic mirror (B).

FIG. 10 is a schematic configuration diagram of an endoscope apparatus which is a third specific embodiment to which the fluorescence detection device according to the present invention is applied.

FIG. 11 is a diagram illustrating a filter arrangement of a color mosaic filter used in the endoscope apparatus according to the third embodiment (A) and a light transmission characteristic diagram of each color filter (B).

FIG. 12 is a diagram showing a filter arrangement of another color mosaic filter usable in the endoscope apparatus according to the third embodiment (A) and a light transmission characteristic diagram of each color filter (B).

[Explanation of symbols]

 DESCRIPTION OF SYMBOLS 1 Excitation light irradiation means 2 Condensing optical system 3 Fluorescence detection means 4 Fluorescence detection means 5 Division means 6 Display means L1 Excitation light L3 Fluorescence 100 Endoscope 104 Image fiber 106 Light guide 110 Illumination device 111 Mercury lamp 115 Switching mirror 118 Xenon Lamp 120 Optical path switching unit 130 Color CCD camera 140,200,300 High-sensitivity camera unit 150,210,310 Image processing device 151,211,311 A / D conversion circuit 155,216,316 Division image memory 156,217,317 Video signal generation circuit 157,218,318 Video processor 158,219,319 Timing controller 160 Display

Claims (3)

[Claims] 1. An excitation light irradiating means for irradiating an observation section of a living body with excitation light in an excitation wavelength region of an in-vivo dye that emits fluorescence, and an auto-fluorescent component emitted from the in-vivo dye in the observation section. First fluorescence detecting means for extracting all autofluorescent components in a visible region including a first relatively short wavelength region and a relatively long wavelength region; and a second relatively short wavelength region of the autofluorescent components. A second fluorescence detection unit for extracting a fluorescence component, a fluorescence component extracted by the first fluorescence detection unit,
A fluorescence detecting device comprising: a dividing means for dividing the fluorescent component extracted by the second fluorescence detecting means. 2. An excitation light irradiating means for irradiating an observation section of a living body with excitation light in an excitation wavelength region of an in-vivo dye that emits fluorescence, and an auto-fluorescent component emitted from the in-vivo dye in the observation section. Extracting a first fluorescent sum component of a fluorescent component of a predetermined wavelength region in the first relatively short wavelength region and a fluorescent component of a predetermined wavelength region in the relatively long wavelength region of the autofluorescence; Fluorescence detection means, a second fluorescence detection means for extracting a fluorescence component in a second relatively short wavelength region of the autofluorescence component, and a fluorescence component extracted by the first fluorescence detection means When,
A fluorescence detecting device comprising: a dividing means for dividing the fluorescent component extracted by the second fluorescence detecting means. 3. The fluorescence detecting means according to claim 1, wherein said fluorescence detecting means is configured to two-dimensionally detect fluorescence emitted from said observation part and to pick up a fluorescence image of said observation part.
The fluorescence detection device according to claim 1.