WO2022208629A1

WO2022208629A1 - Fluorescence observation device, photoimmunotherapy system, and fluorescence endoscope

Info

Publication number: WO2022208629A1
Application number: PCT/JP2021/013386
Authority: WO
Inventors: 周志太田; 武志菅
Original assignee: オリンパス株式会社
Priority date: 2021-03-29
Filing date: 2021-03-29
Publication date: 2022-10-06

Abstract

A fluorescence observation device according to the present invention is provided with: a first optical system; a second optical system; an image capturing element that subjects images individually formed by the first optical system and the second optical system to photoelectric conversion; an image processing unit that generates a first image based on a first observation image when the fluorescence observation device is in a normal observation mode, the first observation image being formed by the first optical system and being acquired with white light illumination, and that generates a second image based on a second observation image and a third image based on a third observation image when the fluorescence observation device is in a fluorescence observation mode, the second observation image being formed by the second optical system and being a fluorescence image acquired with excitation light illumination, and the third observation image being formed by the first optical system and being formed with excitation light and fluorescence; and a normalization unit that calculates a normalized fluorescence intensity by dividing the fluorescence intensity of the second image by the light intensity of the third image. The first optical system has a first filter having an excitation-light transmittance of 1%-30%, and the second optical system has a second filter having an excitation-light transmittance less than or equal to 0.1%.

Description

Fluorescence observation device, photoimmunotherapy system and fluorescence endoscope

The present invention relates to a fluorescence observation device, a photoimmunotherapy system, and a fluorescence endoscope.

In recent years, research has progressed on photoimmunotherapy (PIT), which treats cancer by binding antibody drugs to cancer cells and activating the antibody drugs by irradiation with near-infrared light to destroy cancer cells. ing. The antibody drug irradiated with near-infrared light absorbs light energy, causes molecular vibration, and generates heat. This heat destroys cancer cells. At this time, the antibody drug emits fluorescence when excited. The intensity of this fluorescence is used as an index of therapeutic efficacy.

PIT may be performed using an endoscope. In PIT using an endoscope, treatment is performed by irradiating a treatment site with near-infrared light while illuminating and observing with white light.

In addition, the brightness of fluorescence fluctuates depending on the distance between the subject and the imaging device even when the subject (here, cancer cells containing an antibody drug) emits the same fluorescence intensity. In order to accurately understand the therapeutic effect, it is necessary to measure the fluorescence intensity accurately regardless of the fluctuations in fluorescence brightness. On the other hand, in Patent Document 1, reference light is emitted separately from excitation light, and the ratio between the fluorescence image and the reference light image is calculated to normalize the fluorescence intensity.

JP-A-2003-036436

By the way, since excitation light has a high intensity with respect to fluorescence, an excitation cut filter with a high OD value is required in order to detect fluorescence that is weaker than excitation light. An excitation cut filter with a high OD value has a lower light transmittance near the red region than the light transmittance in other color regions, so there is a risk that color reproducibility will be impaired when observing with white light. .

The present invention has been made in view of the above. The object is to provide a fluorescence endoscope.

In order to solve the above-described problems and achieve the object, a fluorescence observation apparatus according to the present invention provides a first optical system that forms an observation image in normal observation mode, and a a second optical system for forming an observation image in the fluorescence observation mode; an imaging element for photoelectrically converting the images formed by the first optical system and the second optical system; is a first observation image formed by the first optical system, which generates a first image based on the first observation image obtained by illumination with white light, and is formed by the second optical system during the fluorescence observation mode A second observation image that generates a second observation image based on the second observation image that is a fluorescence image obtained by illumination with excitation light, and a third observation image formed by the first optical system, An image processing unit that generates a third image based on a third observation image formed by excitation light and fluorescence, and the fluorescence intensity of the second image is normalized by dividing by the light intensity of the third image. a normalization unit that calculates fluorescence intensity, the first optical system has a first filter having a transmittance of the excitation light of 1% or more and 30% or less, and the second optical system includes the It has a second filter with a transmittance of excitation light of 0.1% or less.

Further, in the fluorescence observation apparatus according to the present invention, in the above invention, the F-number of the first optical system is larger than the F-number of the second optical system.

Further, in the fluorescence observation apparatus according to the present invention, in the above invention, the excitation light has a center wavelength of 680 nm or more.

In the fluorescence observation apparatus according to the present invention, the excitation light is light in the same wavelength band as therapeutic light used in photoimmunotherapy.

Further, in the photoimmunotherapy system according to the present invention, a first optical system for forming an observation image in a normal observation mode and the first optical system are provided independently of the first optical system to form an observation image in a fluorescence observation mode. a fluorescence endoscope comprising: a second optical system that forms an image; and an imaging device that photoelectrically converts the images formed by the first optical system and the second optical system; 1 optical system generates a first observation image based on the first observation image obtained by illumination with white light; generating a second image based on a second observation image, which is an observation image, which is a fluorescent image obtained by illumination with excitation light, and generating a third observation image formed by the first optical system, wherein the excitation light and an image processing unit that generates a third image based on a third observation image formed by fluorescence; and a normalized fluorescence intensity obtained by dividing the fluorescence intensity of the second image by the light intensity of the third image. and a treatment device for emitting therapeutic light for photoimmunotherapy, wherein the first optical system has a transmittance of 1% or more for the excitation light. % or less, and the second optical system has a second filter with a transmittance of the excitation light of 0.1% or less.

Further, a fluorescence endoscope according to the present invention is a fluorescence endoscope through which a treatment instrument for emitting therapeutic light for photoimmunotherapy is inserted, wherein the first optical system forms an observation image in the normal observation mode. a second optical system that is provided independently of the first optical system and that forms an observation image in a fluorescence observation mode; and an image formed by each of the first optical system and the second optical system. the first optical system has a first filter having a transmittance of 1% or more and 30% or less for excitation light emitted in the fluorescence observation mode; and the second optical system The system has a second filter with a transmittance of 0.1% or less for said excitation light.

According to the present invention, it is possible to accurately grasp the decrease in fluorescence intensity while simultaneously ensuring the color reproducibility of the white light image.

FIG. 1 is a diagram showing a schematic configuration of an endoscope system according to one embodiment of the present invention. FIG. 2 is a block diagram showing a schematic configuration of an endoscope system according to one embodiment of the invention. FIG. 3 is a diagram for explaining the configuration of the distal end of the endoscope according to one embodiment of the present invention. FIG. 4 is a diagram illustrating the configuration of the imaging optical system of the endoscope according to one embodiment of the present invention. FIG. 5 is a diagram illustrating an example of an optical filter in the imaging optical system of the endoscope according to one embodiment of the present invention. FIG. 6 is a flow chart showing an example of processing of the processing device according to the embodiment of the present invention.

Hereinafter, a form for carrying out the present invention (hereinafter referred to as "embodiment") will be described. In the embodiment, as an example of a system including a fluorescence observation device, a photoimmunotherapy system, and a fluorescence endoscope according to the present invention, a medical endoscope system that captures and displays an image inside a subject such as a patient. will be explained. Also, the present invention is not limited by this embodiment. Furthermore, in the description of the drawings, the same parts are denoted by the same reference numerals.

(Embodiment)
FIG. 1 is a diagram showing a schematic configuration of an endoscope system according to one embodiment of the present invention. FIG. 2 is a block diagram showing a schematic configuration of the endoscope system according to this embodiment. FIG. 3 is a diagram for explaining the configuration of the distal end of the endoscope according to one embodiment of the present invention.

An endoscope system 1 shown in FIGS. 1 and 2 includes an endoscope 2 that captures an in-vivo image of a subject by inserting its distal end into the subject, and illumination light emitted from the distal end of the endoscope 2. a light source device 3 that generates a signal, a processing device 4 that performs predetermined signal processing on an imaging signal captured by the endoscope 2 and controls the overall operation of the endoscope system 1, and a signal from the processing device 4 A display device 5 for displaying an in-vivo image generated by processing and a treatment instrument device 6 are provided.

The endoscope 2 includes an insertion section 21 having a flexible and elongated shape, an operation section 22 connected to the proximal end side of the insertion section 21 and receiving input of various operation signals, and an operation section 22 to the insertion section. and a universal cord 23 extending in a direction different from the direction in which 21 extends and containing various cables connected to the light source device 3 and the processing device 4 . In PIT, the endoscope 2 corresponds to a fluorescence endoscope for observing fluorescence from the antibody drug within the subject.

The insertion section 21 is a flexible bendable body composed of a distal end section 24 containing an imaging device 244 in which pixels for generating signals by receiving and photoelectrically converting light are arranged two-dimensionally, and a plurality of bending pieces. It has a bending portion 25 and an elongated flexible tubular portion 26 connected to the base end side of the bending portion 25 and having flexibility. The insertion section 21 is inserted into the body cavity of the subject, and the imaging element 244 captures an image of a subject such as living tissue at a position where external light cannot reach.

The operation unit 22 includes a bending knob 221 for bending the bending portion 25 in the vertical direction and the horizontal direction, and a treatment for inserting treatment tools such as a therapeutic light irradiation device, a biopsy forceps, an electric scalpel, and an examination probe into the body cavity of the subject. It has an instrument inserting portion 222 and a plurality of switches 223 as an operation input portion for inputting operation instruction signals for peripheral devices such as air supply means, water supply means, and screen display control in addition to the processing device 4 . A treatment instrument inserted from the treatment instrument insertion portion 222 is exposed from the opening via a treatment instrument channel (not shown) of the distal end portion 24 (see FIG. 3).

The universal cord 23 incorporates at least a light guide 241 and a collective cable 245 that collects one or more signal lines. The universal cord 23 is branched at the end opposite to the side connected to the operating portion 22 . A connector 231 detachable from the light source device 3 and a connector 232 detachable from the processing device 4 are provided at the branch ends of the universal cord 23 . A part of the light guide 241 extends from the end of the connector 231 . The universal cord 23 propagates the illumination light emitted from the light source device 3 to the distal end portion 24 via the connector 231 (light guide 241 ), the operating portion 22 and the flexible tube portion 26 . In addition, the universal cord 23 transmits an image signal captured by the imaging device 244 provided at the distal end portion 24 to the processing device 4 via the connector 232 . The assembly cable 245 includes signal lines for transmitting imaging signals, signal lines for transmitting drive signals for driving the imaging element 244, and information including unique information about the endoscope 2 (imaging element 244). including signal lines for sending and receiving In this embodiment, an electric signal is transmitted using a signal line. It may transmit a signal between them.

The distal end portion 24 includes a light guide 241 made of glass fiber or the like and forming a light guide path for light emitted by the light source device 3, an illumination lens 242 provided at the distal end of the light guide 241, and an optical system for condensing light. It has a system 243 and an imaging device 244 (imaging unit) which is provided at an image forming position of the optical system 243 and receives light condensed by the optical system 243, photoelectrically converts it into an electric signal, and performs predetermined signal processing. .

The optical system 243 is configured by two optical systems (first optical system 243A and second optical system 243B) configured using one or more lenses. The first optical system 243A and the second optical system 243B form observation images at different positions of the imaging device 244 and at positions that do not overlap each other. The hole in which the optical system 243 of the distal end portion 24 is arranged is made watertight by, for example, providing a cover glass or an objective lens in the opening.
The first optical system 243A and the second optical system 243B may have an optical zoom function that changes the angle of view and a focus function that changes the focus.

The imaging element 244 photoelectrically converts the light from the optical system 243 to generate an electric signal (image signal). Specifically, the image sensor 244 has a plurality of pixels arranged in a matrix, each having a photodiode that accumulates electric charge according to the amount of light, a capacitor that converts the electric charge transferred from the photodiode into a voltage level, and the like. A light receiving section 244a in which each pixel photoelectrically converts light from the first optical system 243A and the second optical system 243B to generate an electric signal, and a pixel arbitrarily set as a readout target among the plurality of pixels of the light receiving section 244a. and a reading unit 244b for sequentially reading the electrical signals generated by the and outputting them as image signals. The imaging element 244 is implemented using, for example, a CCD (Charge Coupled Device) image sensor or a CMOS (Complementary Metal Oxide Semiconductor) image sensor.

FIG. 4 is a diagram explaining the configuration of the imaging optical system of the endoscope according to one embodiment of the present invention. The first optical system 243A and the second optical system 243B are provided inside the distal end portion 24 .

The first optical system 243A has a first lens 251A consisting of one or more optical elements, a first cut filter 252A, a first diaphragm 253A, and a second lens 254A consisting of one or more optical elements. The first cut filter 252A cuts light in the wavelength band of the excitation light. The first diaphragm 253A passes at least part of the light that has passed through the first lens 251A and the first cut filter 252A, and narrows down the light entering the second lens 254A. The excitation light here corresponds to light in the wavelength band for exciting the antibody drug in PIT.

The second optical system 243B has a third lens 251B made up of one or more optical elements, a second cut filter 252B, a second diaphragm 253B, and a fourth lens 254B made up of one or more optical elements. The second cut filter 252B cuts light in a partial wavelength band of the excitation light. The second diaphragm 253B passes at least part of the light that has passed through the third lens 251B and the second cut filter 252B, and narrows down the light entering the fourth lens 254B.

The light from the subject enters the first optical system 243A and the second optical system 243B, respectively. Here, the focal lengths of the first optical system 243A and the second optical system 243B are the same. The focal points of the first optical system 243A and the second optical system 243B need only be on the same plane, and may be at the same position on the plane.

The first optical system 243A forms an observation image on the first optical image receiving region R ₁ of the imaging device 244 . The second optical system 243B forms an observation image on the second optical image receiving region R ₂ of the imaging device 244 .

Here, the transmittance of the excitation light of the first cut filter 252A is set to 1% or more and 30% or less. Also, the transmittance of the excitation light of the second cut filter 252B is set to 0.1% or less. By setting the transmittance of the excitation light of the first cut filter 252A to 30% or less, the amount of light received by the imaging device 244 is suppressed from exceeding the upper limit of the amount of light that can be received due to the excitation light. By setting the excitation light transmittance of the first cut filter 252A to 1% or more, the imaging device 244 can receive the excitation light, so that the color reproducibility of the white light image based on the white light can be ensured. Further, by setting the excitation light transmittance of the second cut filter 252B to 0.1% or less, fluorescence can be selectively taken in during excitation light illumination.

FIG. 5 is a diagram illustrating an example of an optical filter in the imaging optical system of the endoscope according to one embodiment of the present invention. Curves Q ₁ and Q ₂ shown in FIG. 5 indicate the light transmittance of the first cut filter 252A. A curve _Q1 shows an example of a curve when the transmittance changes at a high level, and a curve _Q2 shows an example of a curve when the transmittance changes at a low level. For example, in the example shown in FIG. 5, when the center wavelength of the excitation light is 690 nm, the excitation light transmittance of the first cut filter 252A is 6% or more and 23% or less.

Also, the size of the aperture of the first diaphragm 253A is smaller than the size of the aperture of the second diaphragm 253B. That is, the F-number of the first optical system 243A is larger than the F-number of the second optical system 243B. The F value here is a numerical value representing the amount of light incident on the image sensor 244 via the optical system, and the smaller the value, the greater the amount of incident light. Although the first diaphragm 253A and the second diaphragm 253B are formed in the same member in FIG. 4, they may be formed in different members.

Also, the OD value of the first optical system 243A is smaller than the OD value of the second optical system 243B. Therefore, the second optical system 243B is composed of optical elements having a higher OD value and a smaller F value than those of the first optical system 243A.

Note that the endoscope 2 has a memory (not shown) that stores an execution program and a control program for the imaging element 244 to perform various operations, and data including identification information of the endoscope 2 . The identification information includes unique information (ID) of the endoscope 2, model year, spec information, transmission method, and the like. The memory may also temporarily store image data and the like generated by the imaging device 244 .

The configuration of the light source device 3 will be described. The light source device 3 includes a light source section 31 , an illumination control section 32 and a light source driver 33 . Under the control of the illumination control unit 32, the light source unit 31 sequentially switches illumination light with different exposure amounts and emits the illumination light toward the object (subject).

The light source unit 31 is configured using a light source, one or more lenses, etc., and emits light (illumination light) by driving the light source. The light generated by the light source section 31 is emitted from the tip of the tip section 24 toward the subject via the light guide 241 . The light source unit 31 has a white light source 311 and an excitation light source 312 .

The white light source 311 emits light (white light) having a wide visible wavelength band. The white light source 311 is realized using any light source such as a laser light source, a xenon lamp, a halogen lamp, etc., in addition to an LED light source.

The excitation light source 312 emits excitation light for exciting an excitation target (for example, an antibody drug in the case of PIT). The excitation light source 312 is implemented using a light source such as an LED light source or a laser light source.

The lighting control unit 32 controls the amount of power supplied to the light source unit 31 based on the control signal (light control signal) from the processing device 4, and also controls the light source to emit light and the driving timing of the light source.

Under the control of the illumination control unit 32, the light source driver 33 causes the light source unit 31 to emit light by supplying current to the light source to be emitted.

The configuration of the processing device 4 will be explained. The processing device 4 includes an image processing section 41 , a synchronization signal generation section 42 , an input section 43 , a control section 44 and a storage section 45 .

The image processing unit 41 receives image data of illumination light of each color imaged by the imaging element 244 from the endoscope 2 . When receiving analog image data from the endoscope 2, the image processing unit 41 performs A/D conversion to generate a digital imaging signal. Further, when image data is received as an optical signal from the endoscope 2, the image processing unit 41 performs photoelectric conversion to generate digital image data.

The image processing unit 41 performs predetermined image processing on the image data received from the endoscope 2 to generate an image and outputs the image to the display device 5, or calculates the normalized fluorescence intensity based on the image. or The image processing section 41 has a first image generation section 411 , a second image generation section 412 and a normalization section 413 .

The first image generation unit 411 generates a first image based on an image formed by white light or excitation light, which is imaged by the first optical system 243A. The first image includes a white light image generated based on white light and an excitation light image generated based on excitation light.

The second image generation unit 412 generates a second image based on the image formed by the fluorescence imaged by the second optical system 243B.

The first image generation unit 411 and the second image generation unit 412 generate images by performing predetermined image processing. Here, the predetermined image processing includes synchronization processing, gradation correction processing, color correction processing, and the like. Synchronization processing is processing for synchronizing image data of each color component of RGB. Gradation correction processing is processing for correcting the gradation of image data. Color correction processing is processing for performing color tone correction on image data. Note that the first image generation unit 411 and the second image generation unit 412 may perform gain adjustment according to the brightness of the image.

Based on the first image generated by the first image generation unit 411 and the second image generated by the second image generation unit 412, the normalization unit 413 standardizes the fluorescence intensity in the second image. Fluorescence intensity is calculated.

The image processing unit 41 is configured using a general-purpose processor such as a CPU (Central Processing Unit) or a dedicated processor such as various arithmetic circuits that execute specific functions such as an ASIC (Application Specific Integrated Circuit). Note that the image processing unit 41 may be configured to have a frame memory that holds the R image data, the G image data and the B image data.

The synchronization signal generation unit 42 generates a clock signal (synchronization signal) that serves as a reference for the operation of the processing device 4, and transmits the generated synchronization signal to the light source device 3, the image processing unit 41, the control unit 44, and the endoscope 2. Output to Here, the synchronizing signal generated by the synchronizing signal generator 42 includes a horizontal synchronizing signal and a vertical synchronizing signal.
Therefore, the light source device 3, the image processing section 41, the control section 44, and the endoscope 2 operate in synchronization with each other by the generated synchronization signal.

The input unit 43 is implemented using a keyboard, a mouse, a switch, and a touch panel, and receives inputs of various signals such as operation instruction signals for instructing the operation of the endoscope system 1 . Note that the input unit 43 may include a switch provided in the operation unit 22 or a portable terminal such as an external tablet computer.

The control unit 44 performs drive control of each component including the imaging element 244 and the light source device 3, input/output control of information to each component, and the like. The control unit 44 refers to control information data (for example, readout timing) for imaging control stored in the storage unit 45, and performs imaging as a drive signal via a predetermined signal line included in the collective cable 245. It transmits to the element 244 and switches between a normal observation mode in which an image obtained by illumination with white light is observed and a fluorescence observation mode in which fluorescence intensity of an excitation target is calculated. The control unit 44 is configured using a general-purpose processor such as a CPU or a dedicated processor such as various arithmetic circuits that execute specific functions such as an ASIC.

The storage unit 45 stores data including various programs for operating the endoscope system 1 and various parameters necessary for operating the endoscope system 1 . The storage unit 45 also stores identification information of the processing device 4 . Here, the identification information includes unique information (ID) of the processing device 4, model year, specification information, and the like.

The storage unit 45 also stores various programs including an image acquisition processing program for executing the image acquisition processing method of the processing device 4 . Various programs can be recorded on computer-readable recording media such as hard disks, flash memories, CD-ROMs, DVD-ROMs, flexible disks, etc., and can be widely distributed. The various programs described above can also be obtained by downloading via a communication network. The communication network here is realized by, for example, an existing public line network, LAN (Local Area Network), WAN (Wide Area Network), etc., and it does not matter whether it is wired or wireless.

The storage unit 45 having the above configuration is implemented using a ROM (Read Only Memory) in which various programs etc. are pre-installed, and a RAM, hard disk, etc. for storing calculation parameters, data, etc. for each process.

The display device 5 displays a display image corresponding to the image signal received from the processing device 4 (image processing unit 41) via the video cable. The display device 5 is configured using a monitor such as liquid crystal or organic EL (Electro Luminescence).

The treatment instrument device 6 has a treatment instrument operation section 61 and a flexible treatment instrument 62 extending from the treatment instrument operation section 61 . The treatment instrument 62 used for PIT emits light for treatment (hereinafter referred to as treatment light). The treatment instrument operation section 61 controls emission of therapeutic light from the treatment instrument 62 . The treatment instrument operation section 61 has an operation input section 611 . The operation input unit 611 is composed of, for example, switches. The treatment instrument operating section 61 causes the treatment instrument 62 to emit therapeutic light in response to an input to the operation input section 611 (for example, pressing a switch). In addition, in the treatment instrument device 6 , the light source that emits the therapeutic light may be provided in the treatment instrument 62 or may be provided in the treatment instrument operation section 61 . A light source is implemented using a semiconductor laser, an LED, or the like. For example, in the case of PIT, therapeutic light is light in a wavelength band of 680 nm or more, for example, light having a center wavelength of 690 nm.

Next, processing in the processing device 4 will be described with reference to FIG. FIG. 6 is a flow chart showing an example of processing of the processing device according to the embodiment of the present invention. FIG. 6 shows that in PIT, white light is emitted to search for a subject (here, a region containing cancer cells bound to an antibody drug), the subject is irradiated with therapeutic light, and the therapeutic effect is estimated from the fluorescence intensity. Indicates the processing for confirmation.

For example, when the endoscope 2 is activated, the processing device 4 sets the observation mode to the normal observation mode (step S101). In the normal observation mode, the controller 44 causes the light source device 3 to emit white light (step S102). By emitting the white light, the endoscope 2 irradiates the subject with the white light.

The first image generator 411 generates a white light image (first image) based on the image formed by the first optical system 243A (step S103). Specifically, the first image generating section 411 generates a white light image based on the signal value of the first optical image receiving region R ₁ of the imaging device 244 . The generated white light image is displayed on the display device 5 .

After that, the control unit 44 determines whether or not the input unit 43 has received an input instructing to change the observation mode (step S104). The observation mode change at this time is a change from normal observation mode to fluorescence observation mode. If there is no instruction to change the observation mode, that is, to change to the fluorescence observation mode (step S104: No), the controller 44 proceeds to step S102 and maintains the normal observation mode. On the other hand, when an instruction to change to the fluorescence observation mode is given (step S104: Yes), the control unit 44 proceeds to step S105.

In the fluorescence observation mode, an operator such as a doctor irradiates the subject with therapeutic light from the treatment tool 62 . At this time, in PIT, a treatment is performed in which an antibody drug is activated by irradiation with near-infrared light, which is therapeutic light, to destroy cancer cells.

The control unit 44 causes the light source device 3 to emit excitation light in the fluorescence observation mode (step S105). When the excitation light is emitted, the endoscope 2 irradiates the subject with the excitation light, and the antibody drug in the subject is excited to emit fluorescence. At this time, the second optical system 243B forms an image of the fluorescence emitted by the subject on the imaging element 244. FIG. In addition, the first optical system 243A forms an image of the excitation light reflected by the subject and the fluorescence on the imaging element 244. FIG. The excitation light and fluorescence that pass through the first optical system 243A are referred to as reference light.

In step S106, the second image generator 412 generates a fluorescence image (second image) based on the image formed by the second optical system 243B, and the first image generator 411 causes the first optical system 243A to A reference light image (third image) is generated based on the formed image. Specifically, the second image generating unit 412 generates a fluorescence image based on the signal value of the second optical image receiving region R ₂ of the imaging device 244 , and the first image generating unit 411 generates the 1 A reference light image is generated based on the signal value of the optical image receiving region _R1 .

The normalization unit 413 normalizes the fluorescence image based on the fluorescence image and the reference light image generated in step S106 (step S107). The normalization unit 413 calculates the normalized fluorescence intensity (normalized fluorescence intensity) by dividing the fluorescence intensity in the fluorescence image by the light intensity of the reference light image. The fluorescence intensity and light intensity at this time correspond to the luminance value of each pixel, and are calculated for each pixel. That is, normalized fluorescence intensity is generated for each pixel.

The operator can confirm the therapeutic effect at each position (pixel position) on the subject by confirming the normalized fluorescence intensity. At this time, since the fluorescence intensity is standardized, it is possible to confirm an accurate therapeutic effect by eliminating fluctuations in the fluorescence intensity caused by the distance between the optical system (eg, the first lens 251A or the third lens 251B) and the subject. It can be carried out.

After that, the control unit 44 determines whether or not to end the process (step S108). The control unit 44 determines whether or not to end the process based on the presence or absence of an end instruction to the input unit 43 and the power on/off state of the endoscope 2 . Here, when the control unit 44 determines to end the process (step S108: Yes), the process ends. On the other hand, when the control unit 44 determines to continue the process (step S108: No), the process proceeds to step S109.

In step S109, the control unit 44 determines whether or not to reacquire the normalized fluorescence intensity. The control unit 44 determines whether or not to end the process based on whether or not there is a reacquisition instruction to the input unit 43 . Here, if the control unit 44 determines to reacquire the normalized fluorescence intensity (step S109: Yes), the control unit 44 proceeds to step S105 and performs normalized fluorescence intensity calculation processing. On the other hand, when the control unit 44 determines not to acquire the normalized fluorescence intensity again (step S109: No), the process proceeds to step S101 and switches to the normal observation mode.

In the embodiment described above, the first optical system 243A that forms an optical image for generating a white light image in the normal observation mode has a first excitation light transmittance of 1% or more and 30% or less. A first optical system 243A having a cut filter 253A and a second optical system 243B for generating a fluorescence image in the fluorescence observation mode, the second excitation cut filter 253B having an excitation light transmittance of 0.1% or less. A reference image is generated based on the image formed by the first optical system 243A in the fluorescence observation mode, and the normalized fluorescence intensity is calculated using this reference image. In addition, since the transmittance of the excitation light of the first excitation cut filter 253A of the first optical system 243A is 1% or more and 30% or less, it is possible to suppress deterioration in color reproducibility of the white image due to the cut filter. . Furthermore, since the excitation light transmittance of the second excitation cut filter 253B of the second optical system 243B is set to 0.1% or less, it is possible to suppress saturation of the amount of light received by the imaging device 244 due to the excitation light. According to the present embodiment, it is possible to ensure the color reproducibility of the white light image by adjusting the transmittance of the excitation cut filter while accurately grasping the decrease in the fluorescence intensity by standardizing the fluorescence intensity. can.

Further, in the above-described embodiment, the F-number of the first optical system 243A is larger than the F-number of the second optical system 243B. The ratio of the fluorescence to the reference light can be accurately calculated by taking the order of the intensity of the light (reference light) as a close order.

Further, in the above-described embodiment, the excitation light and the treatment light may be in the same wavelength band (same center wavelength) or different wavelength bands (center wavelength). Among them, for example, if the wavelength band of the excitation light is set to 690 nm, which is the same as that of the therapeutic light, the light penetrates to the inside because the 690 nm is in the near-infrared region. When the light penetrates into the living body, stable reference light can be obtained that does not depend on the fine uneven structure of the surface. When the excitation light and the therapeutic light are used in common, the therapeutic light (excitation light) may be emitted from the treatment tool 62, and the excitation light source 312 may not be provided.

Further, in the above-described embodiment, the first optical system 243A has a therapeutic light (excitation light) transmittance of 1% or more and 30% or less in the therapeutic light (center wavelength 690 nm) in photoimmunotherapy. , the irradiation range of the therapeutic light can be confirmed in the image. According to this embodiment, the irradiation range can be adjusted while checking the image, and the irradiation position of the therapeutic light can be set accurately.

Although the light source device 3 is separate from the processing device 4 in the above-described embodiment, the light source device 3 and the processing device 4 may be integrated. Further, in the embodiment, an example in which the therapeutic light is emitted by the treatment tool has been described, but the light source device 3 may be configured to emit the therapeutic light.

Further, in the above-described embodiment, the light that has passed through the first optical system 243A and the light that has passed through the second optical system 243B are received by a single imaging element 244 in a divided light receiving area. As described above, an image sensor that receives light that has passed through the first optical system 243A and an image sensor that receives light that has passed through the second optical system 243B may be provided separately.

Further, in the above-described embodiment, the endoscope system according to the present invention is explained as being the endoscope system 1 using the flexible endoscope 2 whose observation target is the biological tissue in the subject. However, there are many types of endoscopes, such as rigid endoscopes, industrial endoscopes for observing material properties, fiberscopes, optical viewing tubes, and other optical endoscopes with a camera head connected to the eyepiece. It can also be applied to a scope system.

INDUSTRIAL APPLICABILITY As described above, the fluorescence observation device, photoimmunotherapy system, and fluorescence endoscope according to the present invention are useful for both ensuring the color reproducibility of white light images while accurately grasping the decrease in fluorescence intensity. is.

Reference Signs List 1 endoscope system 2 endoscope 3 light source device 4 processing device 5 display device 6 treatment device device 21 insertion section 22 operation section 23 universal cord 24 distal end section 25 bending section 26 flexible tube section 31 light source section 32 illumination control section 33 Light source driver 41 Image processing unit 42 Synchronization signal generation unit 43 Input unit 44 Control unit 45 Storage unit 61 Treatment instrument operation unit 62 Treatment instrument 311 White light source 312 Excitation light source 411 First image generation unit 412 Second image generation unit 413 Normalization unit

Claims

a first optical system that forms an observation image in normal observation mode;
a second optical system provided independently of the first optical system for forming an observation image in a fluorescence observation mode;
an imaging device that photoelectrically converts images respectively formed by the first optical system and the second optical system;
During the normal observation mode, the first observation image formed by the first optical system is generated based on the first observation image obtained by illumination with white light, and during the fluorescence observation mode, the first observation image is generated. generating a second image based on a second observation image formed by two optical systems, which is a fluorescent image obtained by illumination with excitation light, and a third observation formed by the first optical system; an image processing unit that generates a third image based on a third observation image formed by excitation light and fluorescence;
a normalization unit that calculates a normalized fluorescence intensity by dividing the fluorescence intensity of the second image by the light intensity of the third image;
with
The first optical system has a first filter having a transmittance of the excitation light of 1% or more and 30% or less,
The second optical system has a second filter with a transmittance of the excitation light of 0.1% or less,
Fluorescence observation device.
The F-number of the first optical system is larger than the F-number of the second optical system,
The fluorescence observation device according to claim 1.
The excitation light has a center wavelength of 680 nm or more,
The fluorescence observation device according to claim 1.
The excitation light is light in the same wavelength band as the therapeutic light used in photoimmunotherapy,
The fluorescence observation device according to claim 1.
a first optical system that forms an observation image in normal observation mode;
a second optical system provided independently of the first optical system for forming an observation image in a fluorescence observation mode;
an imaging device that photoelectrically converts images respectively formed by the first optical system and the second optical system;
a fluorescence endoscope having
During the normal observation mode, the first observation image formed by the first optical system is generated based on the first observation image obtained by illumination with white light, and during the fluorescence observation mode, the first observation image is generated. generating a second image based on a second observation image formed by two optical systems, which is a fluorescence image obtained by illumination with excitation light, and a third observation formed by the first optical system; an image processing unit that generates a third image based on a third observation image formed by excitation light and fluorescence;
a normalization unit that calculates a normalized fluorescence intensity by dividing the fluorescence intensity of the second image by the light intensity of the third image;
a processing device having
a treatment device for emitting therapeutic light for photoimmunotherapy;
with
The first optical system has a first filter having a transmittance of the excitation light of 1% or more and 30% or less,
The second optical system has a second filter with a transmittance of the excitation light of 0.1% or less,
Photoimmunotherapy system.
A fluorescence endoscope through which a treatment instrument for emitting therapeutic light for photoimmunotherapy is inserted,
a first optical system that forms an observation image in normal observation mode;
a second optical system provided independently of the first optical system for forming an observation image in a fluorescence observation mode;
an imaging device that photoelectrically converts images respectively formed by the first optical system and the second optical system;
with
The first optical system has a first filter having a transmittance of 1% or more and 30% or less for excitation light emitted during the fluorescence observation mode,
The second optical system has a second filter with a transmittance of the excitation light of 0.1% or less,
fluorescence endoscopy.