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WO2024142586A1 - Appareil de détection de fluorescence - Google Patents

Appareil de détection de fluorescence Download PDF

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Publication number
WO2024142586A1
WO2024142586A1 PCT/JP2023/039161 JP2023039161W WO2024142586A1 WO 2024142586 A1 WO2024142586 A1 WO 2024142586A1 JP 2023039161 W JP2023039161 W JP 2023039161W WO 2024142586 A1 WO2024142586 A1 WO 2024142586A1
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WO
WIPO (PCT)
Prior art keywords
light
fluorescence
excitation light
abdominal cavity
light source
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/JP2023/039161
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English (en)
Japanese (ja)
Inventor
雅理 市川
智也 保坂
裕明 里村
和之 横田
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Advantest Corp
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Advantest Corp
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Filing date
Publication date
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Publication of WO2024142586A1 publication Critical patent/WO2024142586A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B1/00—Instruments for performing medical examinations of the interior of cavities or tubes of the body by visual or photographical inspection, e.g. endoscopes; Illuminating arrangements therefor
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
    • G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
    • G01N21/64—Fluorescence; Phosphorescence

Definitions

  • the present invention relates to a fluorescence detection device.
  • Patent Document 1 discloses a medical system that can display an internal region of thermal invasion that cannot be seen when illuminated with white light by irradiating a thermally invasive site with excitation light, such as blue light, and receiving the green autofluorescence emitted by the excitation light.
  • excitation light such as blue light
  • conventional laparoscopic devices including such a medical system only display images of fluorescent tissue, i.e., fluorescent images, and do not inspect specific locations in the abdominal cavity in detail.
  • Patent Document 1 International Publication No. 2020/174666
  • the fluorescence detection device may comprise a first light source that generates excitation light.
  • the fluorescence detection device may include a second light source that generates guide light in the visible light range.
  • the fluorescence detection device may include a scope that is optically connected to the first light source and the second light source, and guides the guide light together with the excitation light to irradiate tissue in the abdominal cavity of the subject, and collects fluorescence emitted from the tissue in response to irradiation with the excitation light.
  • the fluorescence detection device may include a display unit that acquires images of the abdominal cavity of the subject from an imaging device that images the abdominal cavity of the subject, and controls the display of the captured images.
  • 1 shows a schematic configuration of a fluorescence detection device according to an embodiment of the present invention.
  • 2 shows the functional configuration of a control arithmetic unit.
  • 1 shows the use of a fluorescence detection device and a laparoscopic device.
  • 1 shows an example of a screen display of a monitor device.
  • 1 shows a flow of a fluorescence detection method. An example of the change in fluorescence intensity over time and the analysis results thereof is shown. 13 shows another example of the change in fluorescence intensity over time and the analysis results thereof.
  • FIG. 1 shows a schematic configuration of a fluorescence detection device 100 according to this embodiment.
  • the fluorescence detection device 100 detects the fluorescence ⁇ emitted from tissues in the abdominal cavity 1a by a drug 2 administered to a subject (patient) 1, and allows the probe 10 to be operated by visually checking the location of the excitation light irradiated in the near-infrared region through a laparoscopic image.
  • ICG indocyanine green
  • ICG is a drug that emits fluorescence (wavelength 820-840 nm) when irradiated with near-infrared light (wavelength approximately 790 nm), and can be used in the wavelength region of the biological window (wavelength 650-900 nm), so it is suitable for biopsies such as liver function tests, circulatory function tests, sentinel lymph node identification in diseases such as breast cancer, and blood flow evaluation of blood vessels and tissues.
  • the fluorescence detection device 100 can be used in conjunction with an imaging device (i.e., a laparoscopic device 200) that images the inside of the abdominal cavity 1a of the subject 1, and includes a scope 10, a cable 20, and a device main body 30.
  • the scope 10 is an optical scope that is at least partially inserted into the abdominal cavity 1a of the subject 1, guides the excitation light ⁇ 0 (and the guide light ⁇ g ) to irradiate the tissue in the abdominal cavity 1a, and collects the fluorescence ⁇ emitted by the drug 2 in the tissue in response to the irradiation of the excitation light ⁇ 0.
  • the scope 10 includes a tube 11, a light-transmitting optical fiber 12, a light-receiving optical fiber 13, and a connector 14.
  • the tube 11 is a tubular or columnar member that aligns the tips of the light-transmitting optical fiber 12 and the light-receiving optical fiber 13 on one end face (i.e., the tip face) of the longitudinal axis and supports them inside.
  • the tube 11 may be, for example, a SUS tube that is completely waterproof and can be sterilized by autoclave, and the inside may be filled with a material such as resin to restrain the light-transmitting optical fiber 12 and the light-receiving optical fiber 13.
  • a plurality of through holes may be provided in the solid tube 11, and the light-transmitting optical fiber 12 and the light-receiving optical fiber 13 may be passed through each of the through holes to restrain them.
  • the tube 11 is, for example, a circular tube having a diameter of 10 mm and an axial length of 300 mm, and the tip is inserted into the abdominal cavity 1a of the subject 1, and the base end is fixed to the connector 14.
  • the light-transmitting optical fiber 12 is an optical member for transmitting the excitation light ⁇ 0 output from the light source 34. Note that the guide light ⁇ g in the visible light wavelength range may be superimposed on the excitation light ⁇ 0 so that the irradiation location of the excitation light ⁇ 0 in the near-infrared wavelength range can be visually confirmed.
  • the light-transmitting optical fiber 12 may be an optical fiber formed from a material such as quartz glass, multi-component glass, fluoride glass, chalcogenide glass, plastic, etc. Also, it may be an optical fiber such as a multimode fiber (MMF), a single mode fiber (SMF), a double clad fiber (DCF), a photonic crystal fiber (PCF), etc.
  • MMF multimode fiber
  • SMF single mode fiber
  • DCF double clad fiber
  • PCF photonic crystal fiber
  • the light-receiving optical fiber 13 is an optical component that collects the fluorescence emitted by the drug 2 in the tissue within the abdominal cavity 1a and sends it to the detector 35.
  • the number of light-receiving optical fiber 13 is not limited to one, and may be multiple.
  • the material and structure of the light-receiving optical fiber 13 are the same as those of the light-transmitting optical fiber 12.
  • the connector 14 is provided at the base end of the tube 11 and is a member for removably fixing the tube 11 to the gripping portion 24 of the cable 20.
  • the cable 20 is a tool for connecting the scope 10 to the device body 30 and optically connecting the light transmitting optical fiber 12 and the light receiving optical fiber 13 to the light source 34 and the detector 35, respectively.
  • the cable 20 includes a flexible tube 21, a light transmitting optical fiber 22, a light receiving optical fiber 23, and a gripping portion 24.
  • the grip portion 24 is provided at one end of the cable 20 and is a member that the user grips to operate the scope 10.
  • the connector 14 of the scope 10 is detachably fixed to the grip portion 24.
  • a waterproof momentary switch (SW) 24a is provided on the side of the grip portion 24. The user can start and stop the generation of the excitation light ⁇ 0 by pressing and releasing the SW 24a with his or her finger.
  • the device main body 30 is a unit equipped with various functional devices within a housing 31, including a light source 34, a detector 35, a control and calculation device 36, a recording device 37, an input/output device 38, and a communication device 39. These functional devices are connected to each other via communication lines so that they can communicate with each other.
  • the housing 31 houses functional devices such as the light source 34.
  • a connector 29 to which the flexible tube 21 is connected is fixed to the front via an insulating material such as resin (e.g., polycarbonate).
  • a power connector (not shown) is fixed to the rear, through which power is sent from a commercial power source (100V AC) to each functional device.
  • the housing 31 is grounded as a frame ground. Further connectors such as a universal serial bus (USB), digital visual interface (DVI)-D, and DVI-I are provided on the rear.
  • USB universal serial bus
  • DVI digital visual interface
  • a spectrometer is an optical device that spectrally resolves the fluorescence ⁇ and measures the fluorescence intensity for each wavelength (or frequency), and has, for example, a sensitivity wavelength range of 500 to 1100 nm and a wavelength resolution of 2.5 to 3.5 nm.
  • the input/output device 38 is a device for receiving user input and sending it to the control and arithmetic device 36, as well as outputting various data to the user, such as the results of the detection of fluorescence ⁇ by the detector 35 and the results of the analysis of the fluorescence state by the control and arithmetic device 36.
  • the input/output device 38 can receive user input from an input panel provided on the front of the housing 31, or from external devices such as a keyboard, mouse, or touch panel (none of which are shown) via an interface on the back of the housing 31.
  • the input/output device 38 can also transmit various data to an external monitor device 40 via an interface on the back of the housing 31, and display it on its display screen 41.
  • the communication device 39 is a device for communicating with external devices, particularly the laparoscopic device 200, and is connected to the laparoscopic device 200 via a cable such as USB, DVI-D, or DVI-I, and can receive various data such as laparoscopic images, which will be described later.
  • the received data is sent to the input/output device 38, and via this to the control and arithmetic device 36, etc.
  • the control unit 36a may change the color of the guide light ⁇ g from green to a brighter color (e.g., orange), the intensity to be stronger, the brightness to be brighter, the spread to be narrower, the beam shape from a circle to an x or +, and the light emission pattern to be blinking at regular intervals.
  • a brighter color e.g., orange
  • the analysis unit 36b is a unit that processes the detection result of the fluorescence ⁇ by the detector 35 and analyzes the fluorescence state of the tissue.
  • the fluorescence state includes at least one of the spectrum and intensity of the fluorescence ⁇ , and the time change of the spectrum and intensity of the fluorescence ⁇ .
  • the drug 2 exhibits different fluorescence spectra when bound to, for example, blood, and it is expected that the shape of the fluorescence spectrum will change depending on the location when the fluorescence ⁇ is emitted or the tissue in which the drug 2 is located.
  • the scope 110 is an optical tube that is at least partially inserted into the abdominal cavity 1a of the subject 1, emits illumination light W to illuminate the abdominal cavity 1a, and collects reflected light.
  • the scope 110 includes a tube 111, a light-transmitting optical fiber and a light-receiving optical fiber (not shown), and a connector 114.
  • the tube 111 is a tubular member that aligns the tips of the light-transmitting optical fiber and the light-receiving optical fiber on one end face (i.e., the tip face) of the longitudinal axis and supports them internally.
  • the tip of the tube 111 is inserted into the abdominal cavity 1a of the subject 1, and the base end is fixed to the connector 114.
  • Cables 120 and 121 are devices for connecting scope 110 to device body 130 and optically connecting the light transmitting optical fiber and light receiving optical fiber of scope 110 to light source 131 and camera 132, respectively. Cables 120 and 121 are flexible, and each transmits illumination light W output from light source 131 to the light transmitting optical fiber of scope 110, and transmits reflected light focused on the light receiving optical fiber of scope 110 to camera 132.
  • the light source 131 is a device that generates illumination light W, and may be, for example, an LED that outputs white light.
  • the illumination light W is sent to the scope 110 via the cable 120.
  • the user inserts the tip of the longitudinal axis of the scope 110 of the laparoscopic device 200 and the tip of the longitudinal axis of the scope 10 of the fluorescence detection device 100 into the abdominal cavity 1a of the subject 1, respectively.
  • a cylindrical holder may be fitted into the outer skin of the abdomen of the subject 1, and the scopes 110, 10 may be inserted into the abdominal cavity 1a through it.
  • the user operates the light source 131 of the laparoscopic device 200 to generate illumination light W, which is sent to the scope 110 via the cable 120.
  • the illumination light W is emitted from the tip of the scope 110 to illuminate the abdominal cavity 1a, and at the same time, the reflected light from within the abdominal cavity 1a is collected by the scope 110 and sent to the camera 132 via the cable 121.
  • the camera 132 receives reflected light to capture images of the abdominal cavity 1a, and the images are sequentially transmitted to the fluorescence detection device 100 by the communication device 133, received by the communication device 39 of the fluorescence detection device 100, processed by the input/output device 38, and sequentially displayed on the display screen 41 of the monitor device 40.
  • the display screen 41 of the monitor device 40 has an area 42 on the left that displays a laparoscopic image, an area 44 in the upper center that displays that excitation light ⁇ 0 is being irradiated, an area 43 on the right center that displays the peak value (fluorescence intensity) of the fluorescence spectrum, an area 45 on the right that displays the fluorescence spectrum, and an area 47 below that displays detection conditions, etc.
  • the display unit 36c displays a laparoscopic image of the inside of the abdominal cavity 1a of the subject 1 transmitted from the laparoscopic device 200.
  • the guide light ⁇ g is emitted from the tip of the scope 10, so that the user can confirm, on the display screen 41, the position and spread of the spot Sp irradiated with the excitation light ⁇ 0 , and further, the direction in which the excitation light ⁇ 0 is irradiated from the shape of the spot Sp.
  • the display unit 36c displays, for example, "laser irradiation in progress", which indicates that the excitation light ⁇ 0 is being irradiated.
  • This allows the display screen 41 to show that the excitation light ⁇ 0 is emitted from the scope 10 while being superimposed on the guide light ⁇ g , and that the tissue in the abdominal cavity 1a is being irradiated with the excitation light ⁇ 0 .
  • the display unit 36c may notify the user by displaying the display "laser irradiation in progress" in the area 44 in red or by blinking the display.
  • the user may be notified by voice, for example, by emitting a beep sound that becomes louder or has a faster cycle depending on the intensity of the excitation light ⁇ 0 .
  • the display unit 36c displays the results of the detection of fluorescence gamma by detector 35.
  • the spectrum of fluorescence gamma which is an intensity distribution with respect to wavelength, also simply called the fluorescence spectrum
  • the wavelength (also called peak wavelength) and intensity (also called peak intensity) of the peak position of the fluorescence spectrum are displayed.
  • the changes over time of the fluorescence spectrum and peak intensity are displayed in real time.
  • the display unit 36c displays the detection conditions, etc.
  • the detection conditions include, for example, an ID number for identifying the subject 1, an ID number of the scope 10 used to detect the fluorescence ⁇ , an irradiation time for irradiating the excitation light ⁇ 0 (also called an irradiation timer), a standard intensity of the excitation light ⁇ 0 (which may be the intensity of the excitation light ⁇ 0 received from the light source 34), a standard intensity of the guide light ⁇ g , and a date, time, and minute of the biopsy.
  • the user can operate the fluorescence detection device 100 while viewing the laparoscopic image displayed on the monitor device 40 (area 42).
  • the user can bring the tip of the scope 10 close to a site of interest in the abdominal cavity 1a, irradiate the spot Sp located at the site of interest with excitation light ⁇ 0 , and thereby collect and inspect the fluorescence ⁇ emitted by the drug 2 in the tissue in the spot Sp.
  • the display unit 36c may read various information such as the laparoscopic image, the fluorescence gamma detection result, the fluorescence state analysis result, and the detection conditions recorded by the recording device 37 via the recording unit 36d, and play and display them on the display screen 41 of the monitor device 40.
  • the recording unit 36d may also mark the laparoscopic image by user input via the input/output device 38 or at a specified timing (for example, the timing when the fluorescence intensity exceeds a predetermined threshold intensity), and record it in the recording device 37.
  • the marking may be to decorate the image by making the outer frame of the laparoscopic image red, to display a mark on the display screen 41, to record information such as the time, etc. This allows the user to easily reach and confirm the desired scene when the desired laparoscopic image is later played back and displayed.
  • step S1 the control unit 36a determines the operation mode of the fluorescence detection device 100.
  • the operation mode can be selected, for example, on the front panel of the housing 31, and may include, for example, a detection mode in which the fluorescence gamma collected from within the abdominal cavity 1a is detected, and an analysis mode in which the fluorescence state is analyzed using the detection results of the fluorescence gamma. If the control unit 36a determines that the detection mode is selected, it proceeds to step S2 and executes the detection flow, and if it determines that the analysis mode is selected, it proceeds to step S11 and executes the analysis flow.
  • the user confirms the position of the spot Sp in the laparoscopic image displayed on the monitor device 40, and moves the scope 10 to direct and/or bring the tip of the scope 10 close to the site of interest in the abdominal cavity 1a. Then, the user turns on the SW 24a to irradiate the site of interest with the excitation light ⁇ 0 .

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Surgery (AREA)
  • General Health & Medical Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Physics & Mathematics (AREA)
  • Pathology (AREA)
  • Medical Informatics (AREA)
  • Public Health (AREA)
  • Engineering & Computer Science (AREA)
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  • Heart & Thoracic Surgery (AREA)
  • Optics & Photonics (AREA)
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  • Animal Behavior & Ethology (AREA)
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  • Veterinary Medicine (AREA)
  • Chemical & Material Sciences (AREA)
  • Analytical Chemistry (AREA)
  • Biochemistry (AREA)
  • General Physics & Mathematics (AREA)
  • Immunology (AREA)
  • Endoscopes (AREA)
  • Investigating, Analyzing Materials By Fluorescence Or Luminescence (AREA)

Abstract

Un appareil de détection de fluorescence 100 comprend : une source de lumière d'excitation 34a qui génère une lumière d'excitation γ0 ; une source de lumière de guidage 34b qui génère une lumière de guidage γg dans une région de lumière visible ; un endoscope 10 qui est optiquement connecté à la source de lumière d'excitation et à la source de lumière de guidage, qui est utilisé pour irradier un tissu de la cavité abdominale d'un sujet en guidant la lumière de guidage conjointement avec la lumière d'excitation et qui condense la fluorescence émise par le tissu suite à son exposition à la lumière d'excitation ; et une unité d'affichage 36c qui acquiert une image capturée de la cavité abdominale en provenance d'un dispositif de laparoscopie 200 servant à prendre des images de la cavité abdominale du sujet et qui effectue une commande d'affichage sur l'image capturée. La superposition de la lumière de guidage sur la lumière d'excitation effectuée par l'endoscope lors de la mise en œuvre de l'irradiation du tissu dans la cavité abdominale du sujet permet de faire fonctionner une sonde tout en confirmant visuellement un site d'irradiation sur l'image capturée de la cavité abdominale.
PCT/JP2023/039161 2022-12-28 2023-10-30 Appareil de détection de fluorescence Ceased WO2024142586A1 (fr)

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JP2022212677A JP2024095404A (ja) 2022-12-28 2022-12-28 蛍光検出装置
JP2022-212677 2022-12-28

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Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2001212070A (ja) * 2000-01-31 2001-08-07 Olympus Optical Co Ltd 蛍光観察内視鏡装置
JP2011101763A (ja) * 2009-11-12 2011-05-26 Fujifilm Corp 画像表示装置
JP2013153951A (ja) * 2012-01-30 2013-08-15 Reimei Ri 腹腔鏡診断装置及びセンチネルリンパ節の検査方法
WO2016111043A1 (fr) * 2015-01-07 2016-07-14 オリンパス株式会社 Dispositif d'endoscope
WO2018220908A1 (fr) * 2017-05-31 2018-12-06 オリンパス株式会社 Système d'endoscope
CN210842944U (zh) * 2019-01-31 2020-06-26 广东欧谱曼迪科技有限公司 一种指导曝光型荧光内窥镜系统

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2001212070A (ja) * 2000-01-31 2001-08-07 Olympus Optical Co Ltd 蛍光観察内視鏡装置
JP2011101763A (ja) * 2009-11-12 2011-05-26 Fujifilm Corp 画像表示装置
JP2013153951A (ja) * 2012-01-30 2013-08-15 Reimei Ri 腹腔鏡診断装置及びセンチネルリンパ節の検査方法
WO2016111043A1 (fr) * 2015-01-07 2016-07-14 オリンパス株式会社 Dispositif d'endoscope
WO2018220908A1 (fr) * 2017-05-31 2018-12-06 オリンパス株式会社 Système d'endoscope
CN210842944U (zh) * 2019-01-31 2020-06-26 广东欧谱曼迪科技有限公司 一种指导曝光型荧光内窥镜系统

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