WO2024142586A1 - Fluorescence detection apparatus - Google Patents

Abstract

A fluorescence detection apparatus 100 comprises: an excitation light source 34a that generates excitation light γ₀; a guide light source 34b that generates guide light γ_g in a visible light region; a scope 10 that is optically connected to the excitation light source and the guide light source, that is for irradiating tissue in the abdominal cavity of a subject by guiding the guide light together with the excitation light, and that condenses fluorescence emitted from the tissue by irradiation with the excitation light; and a display unit 36c that acquires a captured image of the abdominal cavity from a laparoscope device 200 for imaging the abdominal cavity of the subject and performs display control on the captured image. By superposing the guide light on the excitation light by the scope when performing the irradiation of the tissue in the abdominal cavity of the subject, it is possible to operate a probe while visually confirming an irradiation site on the captured image of the abdominal cavity.

Description

Fluorescence detection equipment

The present invention relates to a fluorescence detection device.

A method is known in which a drug is administered into a subject, and the drug is irradiated to the tissue to detect pathogens in the tissue by receiving fluorescence emitted from the tissue. For example, 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. However, 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

General Disclosure

(Item 1)
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.
(Item 2)
The fluorescence detection device may include a detector that detects the fluorescence light collected by the scope.
The display section may display the results of the detection of the fluorescence by the detector together with the captured image.
(Item 3)
The fluorescence detection device may be provided with a control unit that changes light emission parameters including one of the color, intensity, brightness, spread, beam shape, and light emission pattern of the guide light between when excitation light is being irradiated and when it is not being irradiated.
(Item 4)
The display unit may display a screen and/or provide an audio notification that the excitation light is being irradiated.

Note that the above general disclosure does not list all of the features of the present invention. Subcombinations of these features may also be inventions.

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.

The present invention will be described below through embodiments of the invention, but the following embodiments do not limit the scope of the invention as claimed. Furthermore, not all of the combinations of features described in the embodiments are necessarily essential to the solution of the invention.

FIG. 1 shows a schematic configuration of a fluorescence detection device 100 according to this embodiment. The fluorescence detection device 100 detects the fluorescence γ 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. Here, for example, indocyanine green (ICG) can be used as the drug 2. 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. In particular, 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 γ ₀ (and the guide light γ _g ) to irradiate the tissue in the abdominal cavity 1a, and collects the fluorescence γ emitted by the drug 2 in the tissue in response to the irradiation of the excitation light γ _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. Alternatively, 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. In this embodiment, 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 γ ₀ output from the light source 34. Note that the guide light γ _g in the visible light wavelength range may be superimposed on the excitation light γ ₀ so that the irradiation location of the excitation light γ 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.

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.

With the above-mentioned configuration, the scope 10 can insert the tip of its longitudinal axis into the abdominal cavity 1a of the subject 1, output the excitation light _γ0 from the tip, and collect the fluorescence γ emitted by the drug 2 in the tissue by irradiating the excitation light _γ0 from the tip. Here, the scope may output guide light _γg in the visible light wavelength range superimposed on the excitation light _γ0 to irradiate the tissue in the abdominal cavity 1a. This allows the tip of the scope 10 to approach a site of interest in the abdominal cavity 1a and examine only that site of interest.

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 flexible tube 21 is a flexible tubular member that bundles the light-transmitting optical fiber 22 and the light-receiving optical fiber 23 and holds them inside. The flexible tube 21 may be, for example, a sheathed SUS tube having a diameter of 5 mm and a length of 300 cm. One end of the flexible tube 21 is connected to the connector 14 of the scope 10, and is formed using an insulating material such as resin (for example, ABS resin) to prevent electric shock. The other end of the flexible tube 21 is connected to the connector 29 of the device main body 30.

The light transmitting optical fiber 22 and the light receiving optical fiber 23 are configured in the same manner as the light transmitting optical fiber 12 and the light receiving optical fiber 13 described above.

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 γ ₀ by pressing and releasing the SW 24a with his or her finger.

With the above-mentioned configuration, when the connector 14 of the scope 10 is properly connected to the gripping portion 24 of the cable 20 and the base end of the cable 20 is properly connected to the connector 29 of the device body 30, the light transmitting optical fiber 22 and the light receiving optical fiber 23 are positioned coaxially with the light transmitting optical fiber 12 and the light receiving optical fiber 13 of the scope 10, respectively, and are also positioned coaxially with the optical fibers 32, 33 of the device body 30. As a result, the light transmitting optical fiber 12 of the scope 10 is optically connected (also called optically connected) to the light source 34 (excitation light source 34a and guide light source 34b), and the light receiving optical fiber 13 is optically connected to the detector 35.

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.

Furthermore, an intake port for taking in air is provided on the front of the housing 31, and an exhaust port for sending air out is provided on the rear. By operating a fan (not shown), air flows inside the housing from the front to the rear, cooling each functional device. Also, a lamp (not shown) that uses light to indicate that the housing is in operation or that an abnormality has occurred, and a speaker (not shown) that uses sound to indicate this, are provided on the front of the housing 31. In addition, a laser key switch, a laser emergency stop button, and a start switch (all not shown) are provided on the front of the housing 31, and an AC inlet switch, a laser interlock, and a potential equalization terminal (all not shown) are provided on the rear of the housing 31.

The light source 34 is a device that generates the excitation light γ ₀ and the like, and includes an excitation light source 34a and a guide light source 34b. The excitation light source 34a employs a laser diode (e.g., 40 mW variable) that outputs near-infrared light (e.g., wavelength 785 nm) as the excitation light γ _0. The guide light source 34b employs a laser diode (e.g., 10 mW variable) that outputs visible light (light in the visible light wavelength range, e.g., green light with a wavelength of 520 nm) as the guide light γ _g . Here, since near-infrared light is difficult to see, the light source 34 outputs a guide light γ _g containing visible light superimposed on the excitation light γ ₀ so that the irradiation location of the excitation light γ ₀ can be seen. The light source 34 detects the intensity of the excitation light γ ₀ , the temperature of the excitation light source 34a, an abnormality in the power supply, and the like, and transmits the detection results to the control and arithmetic device 36.

The pumping light source 34a and the guide light source 34b send out pumping light _γ0 and guide light _γg to the optical fibers 32a and 32b, respectively, combine them via an optical fiber coupler (not shown), and send them to the light-transmitting optical fiber 22 of the cable 20 via the optical fiber 32. The pumping light source 34a and the guide light source 34b generate the pumping light _γ0 and the guide light _γg in accordance with a drive signal transmitted from the control and arithmetic device 36. Here, the pumping light source 34a may periodically output (on and off) the pumping light _γ0 .

The detector 35 is a device that detects the fluorescence γ. The detector 35 receives the fluorescence γ collected by the scope 10 via the light receiving optical fiber 23 of the cable 20 and the optical fiber 33 of the device body 30. The detector 35 has an optical filter and a spectroscope (neither shown).

The optical filter is a bandpass filter that cuts the excitation light γ ₀ that is reflected from the surface of the tissue when the tissue in the abdominal cavity 1a is irradiated with the excitation light γ ₀ and is collected by the scope 10 together with the fluorescence γ. The optical filter is disposed in front of the spectroscope.

A spectrometer is an optical device that spectrally resolves the fluorescence γ 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 detector 35 alternately obtains detection data during irradiation (on signal) and non-irradiation (off signal) in accordance with a drive signal transmitted from the control and calculation device 36, i.e., in response to the periodic on-off _of the excitation light γ 0. The detection result is transmitted to the control and calculation device 36. The control and calculation device 36 accumulates the detection data during the on signal and the off signal, respectively, and calculates the difference between the accumulated detection data, thereby canceling noise resulting from ambient light.

The control and arithmetic unit 36 is a computer device that controls each functional unit and analyzes the fluorescence state using the detection results of the fluorescence γ by the detector 35, and has a central processing unit (CPU). The CPU executes a dedicated program to cause the control and arithmetic unit 36 to perform a control and arithmetic function. The functional configuration of the control and arithmetic unit 36 will be described later. The dedicated program is activated, for example, by being stored in a ROM (not shown) and read out by the CPU, or by being stored in a storage medium such as a CD-ROM and read out by the CPU using a reading device (not shown) and expanding it into RAM.

The recording device 37 is a device that records various data, such as the results of the detection of fluorescence γ by the detector 35 and the results of the analysis of the fluorescence state by the control and arithmetic device 36, in a non-transitory storage medium (not shown). The recording device 37 may further record images (i.e., laparoscopic images) of the inside of the abdominal cavity 1a of the subject 1 captured by the laparoscopic device 200. Non-transitory storage media include tangible storage media such as hard disks, compact disks, magneto-optical disks, magnetic tapes, and flash memories. The recording device 37 is incorporated in the device main body 30, but is not limited to this, and may be disposed outside the device main body 30 so as to be communicable via an interface such as SCSI or SATA, or a network.

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 γ 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.

FIG. 2 shows the functional configuration realized by the control and calculation device 36 executing a dedicated program. The control and calculation device 36 includes a control unit 36a, an analysis unit 36b, a display unit 36c, and a recording unit 36d.

The control unit 36a is a unit that controls the operation of functional devices such as the light source 34. The control unit 36a generates a drive signal in response to a user input via the SW 24a and transmits it to the light source 34 and the detector 35. Here, the drive signal is generated so as to periodically repeat an on signal and an off signal. As a result, the light source 34 (particularly, the excitation light source 34a) periodically generates (on/off) the excitation light γ ₀ , and the detector 35 alternately acquires detection data during irradiation (on signal) and non-irradiation (off signal) of the excitation light γ ₀ , thereby canceling noise caused by disturbance light.

The control unit 36a may change light emission parameters including any one of the color, intensity, brightness, spread, beam shape, and light emission pattern of the guide light _γg when the excitation light _γ0 is being irradiated and when it is not being irradiated, so that the user can recognize that the excitation light _γ0 is being irradiated through a laparoscopic image described later. For example, when the excitation light _γ0 is irradiated, the control unit 36a may change the color of the guide light _γg 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.

The analysis unit 36b is a unit that processes the detection result of the fluorescence γ by the detector 35 and analyzes the fluorescence state of the tissue. Here, the fluorescence state includes at least one of the spectrum and intensity of the fluorescence γ, and the time change of the spectrum and intensity of the fluorescence γ. It is known that 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 γ is emitted or the tissue in which the drug 2 is located. Therefore, the analysis unit 36b may analyze the spectral shape of the fluorescence γ to identify the location or tissue in the abdominal cavity 1a that emits the fluorescence γ, i.e., the location or tissue in the abdominal cavity 1a in which the drug 2 is located. The analysis of the fluorescence state by the analysis unit 36b will be described further below.

The display unit 36c performs display control to display various information such as the results of the detection of fluorescence gamma by the detector 35, the results of the analysis of the fluorescence state by the analysis unit 36b, and the detection conditions on the display screen 41 of the monitor device 40. The display unit 36c also performs display control to acquire captured images (also called laparoscopic images) of the inside of the abdominal cavity 1a of the subject 1 from the laparoscopic device 200 that captures images of the inside of the abdominal cavity 1a of the subject 1, and to display various information together with the laparoscopic images. The screen display of various information will be described in further detail below.

The recording unit 36d is a unit that uses the recording device 37 to record various information such as the results of the detection of fluorescence γ by the detector 35, the results of the analysis of the fluorescence state by the analysis unit 36b, and the detection conditions. The recording unit 36d also reads out various data recorded in the recording device 37 and transmits it to the analysis unit 36b, etc.

FIG. 3 shows the use of the fluorescence detection device 100 in combination with the laparoscope device 200. The laparoscope device 200 is a device independent of the fluorescence detection device 100 according to this embodiment, and includes a scope 110, cables 120 and 121, and a device main body 130.

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.

The light-transmitting optical fiber and the light-receiving optical fiber are configured in the same manner as the light-transmitting optical fiber 12 and the light-receiving optical fiber 13 described above. The light-transmitting optical fiber sends illumination light (white light) W output from the light source 131 into the abdominal cavity 1a, and the light-receiving optical fiber collects reflected light from within the abdominal cavity 1a and sends it to the camera 132.

The connector 114 is a member that supports the base end of the scope 110, and one end of the cables 120 and 121 is removably fixed to the connector 114. By connecting the cable 120 to the connector 114, the light-transmitting optical fiber in the scope 110 is optically connected to the light source 131, and by connecting the cable 121 to the connector 114, the light-receiving optical fiber in the scope 110 is optically connected to the camera 132.

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 device main body 130 is a unit equipped with various functional devices within a housing 130a, including a light source 131, a camera 132, and a communication device 133. These functional devices are connected to each other via communication lines so that they can communicate with each other.

The housing 130a houses functional devices such as the light source 131. Connectors to which the cables 120 and 121 are connected are fixed to the front. 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. Further connectors such as USB, DVI-D, and DVI-I are provided on the rear.

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 camera 132 is a device for photographing the inside of the abdominal cavity 1a, and may be, for example, a CCD camera. The camera 132 receives the reflected light collected by the scope 110 via the cable 121. An optical filter (bandpass filter) for cutting near-infrared light including the wavelength range of the excitation light _γ0 and the fluorescence γ may be disposed in front of the camera 132. The obtained laparoscopic image is transmitted to the communication device 133.

The communication device 133 is a device for communicating with the fluorescence detection device 100, and is connected to the fluorescence detection device 100 via a cable such as USB, DVI-D, or DVI-I, and can transmit various data such as laparoscopic images.

The laparoscopic device 200 and the fluorescence detection device 100 are connected using a DVI-D cable (not shown) or the like. In addition, the monitor device 40 is connected to the fluorescence detection device 100. This allows an image of the inside of the abdominal cavity 1a captured by the laparoscopic device 200 (camera 132) (i.e., a laparoscopic image) to be transmitted to the fluorescence detection device 100 and displayed on the display screen 41 of the monitor device 40 together with the analysis results of the fluorescence state processed by the fluorescence detection device 100, etc.

In the laparoscopic device 200 and fluorescence detection device 100 configured as described above, 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. Here, 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. Next, 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. As a result, 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.

4 shows an example of the screen display 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 γ 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.

In the area 42, 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. Here, the guide light _γg 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 _γ0 , and further, the direction in which the excitation light _γ0 is irradiated from the shape of the spot Sp.

In the area 44, the display unit 36c displays, for example, "laser irradiation in progress", which indicates that the excitation light _γ0 is being irradiated. This allows the display screen 41 to show that the excitation light _γ0 is emitted from the scope 10 while being superimposed on the guide light _γg , and that the tissue in the abdominal cavity 1a is being irradiated with the excitation light _γ0 . Note that, for example, when the intensity of the excitation light _γ0 exceeds a threshold, 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. Also, 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 _γ0 .

In area 43, the display unit 36c displays the results of the detection of fluorescence γ by the detector 35, in particular the peak intensity (also called the fluorescence intensity) in the fluorescence spectrum. In addition, the change in the fluorescence intensity over time is displayed in real time. As an example, the fluorescence intensity is displayed as a color bar, that is, as the fluorescence intensity increases, the bar extends from bottom to top, changing color (gradation) from blue to red.

In area 45, the display unit 36c displays the results of the detection of fluorescence gamma by detector 35. As a result of the detection, the spectrum of fluorescence gamma (which is an intensity distribution with respect to wavelength, also simply called the fluorescence spectrum) and its peak position are displayed. Furthermore, in the upper area 46, the wavelength (also called peak wavelength) and intensity (also called peak intensity) of the peak position of the fluorescence spectrum are displayed. Also, the changes over time of the fluorescence spectrum and peak intensity are displayed in real time.

In the area 47, 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 γ, an irradiation time for irradiating the excitation light _γ0 (also called an irradiation timer), a standard intensity of the excitation light _γ0 (which may be the intensity of the excitation light _γ0 received from the light source 34), a standard intensity of the guide light _γg , 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). In particular, 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 γ ₀ , and thereby collect and inspect the fluorescence γ 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.

Figure 5 shows the flow of the fluorescence detection method. Before the flow starts, the laparoscope device 200 and the fluorescence detection device 100 are connected as described above, and the monitor device 40 is connected to the fluorescence detection device 100. As an example, the fluorescence detection flow for evaluating blood flow in blood vessels and tissues in which a drug 2 is administered to the blood vessels of a subject 1 and the circulation of the drug 2 through the tissues in the abdominal cavity 1a is evaluated will be described here.

In 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.

In step S2, the control unit 36a displays an image (i.e., a laparoscopic image) of the inside of the abdominal cavity 1a of the subject 1 captured by the laparoscopic device 200 on the display screen 41 (area 42) of the monitor device 40 connected to the fluorescence detection device 100, as shown in FIG. 4. Here, the guide light _γg in the visible light wavelength _range is output from the tip of the scope 10 so that the position in the abdominal cavity 1a to which the tip of the scope 10 is directed, i.e., the irradiation spot (spot Sp) of the excitation light γ0 and the irradiation direction can be visually confirmed. As a result, 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 _γ0 .

In step S3, the control unit 36a judges whether or not SW24a has been turned on. If the control unit 36a judges that SW24a has been turned on, it proceeds to step S4 assuming that the user has turned SW24a on, and if it judges that SW24a has not been turned on, it repeats step S3 assuming that the user has not turned SW24a on. Note that if a certain amount of time has passed without proceeding to step S4 or if step S3 has been repeated a predetermined number of times, it may return to step S1.

In step S4, the control unit 36a transmits a drive signal to the light source 34 to generate excitation light γ ₀ , which is superimposed on the guide light γ _g and emitted from the tip of the scope 10 to irradiate the spot Sp. At this time, as shown in FIG. 4, "laser irradiation in progress" is displayed in an area 44 of the display screen 41. By irradiating the excitation light γ ₀ , the drug 2 located in the tissue in the spot Sp absorbs the excitation light γ ₀ and emits fluorescence γ. The fluorescence γ emitted by the drug 2 is collected from the tip of the scope 10 and sent to the detector 35. The light source 34 generates the excitation light γ ₀ and simultaneously detects its intensity, and transmits the detection result to the control and calculation device 36 (analysis unit 36b).

In step S5, the control unit 36a operates the detector 35 to detect the collected fluorescence γ. As a result, the fluorescence γ is detected at regular intervals, and the results are sequentially transmitted to the control and calculation device 36 (analysis unit 36b).

In step S6, the analysis unit 36b analyzes the fluorescence state using the detection result of the fluorescence γ by the detector 35. The fluorescence state includes, for example, the fluorescence spectrum, its peak wavelength and peak intensity, and their changes over time.

The fluorescence state may include the spectral shape of the fluorescence γ. The analysis unit 36b may analyze the spectral shape of the fluorescence γ to identify the location or tissue that emits the fluorescence γ, i.e., the location or tissue where the drug is located. The result may be displayed on the display screen 41 in the next step S7.

In step S7, the display unit 36c displays various information such as the detection result of the fluorescence γ and the analysis result of the fluorescence state, the detection conditions, etc. on the display screen 41 of the monitor device 40. As a result, as shown in Fig. 4, the fluorescence intensity is displayed in area 43 of the display screen 41, the fluorescence spectrum is displayed in area 45, and the peak wavelength and peak intensity of the fluorescence spectrum are displayed in area 46. These displays are updated every time a fluorescence spectrum is detected (i.e., displayed in real time). In addition, the recording unit 36d records, using the recording device 37, various information such as the detection result of the fluorescence γ and the analysis result of the fluorescence state, the detection conditions including the intensity of the excitation light _γ0 , together with the detection time, every time a fluorescence spectrum is detected.

The user can view the laparoscopic images, etc. displayed on the display screen 41 of the monitor device 40 and select the images, etc. that they wish to play back later via the input/output device 38. In response to this user input, the recording unit 36d marks the laparoscopic images and records them using the recording device 37.

When step S7 is completed, the detection mode ends and the process returns to step S1.

In step S11, the recording unit 36d reads out various information such as the laparoscopic image, the fluorescence gamma detection results, the analysis results of the fluorescence state, and the detection conditions recorded by the recording device 37. When the user selects the desired laparoscopic image by inputting an ID number identifying the subject 1 and/or the ID number of the scope 10 via the input/output device 38, the recording unit 36d reads out various information such as the laparoscopic image, the fluorescence gamma detection results, the analysis results of the fluorescence state, and the detection conditions corresponding to those ID numbers, and the display unit 36c displays these on the display screen 41 of the monitor device 40. The user can reach the desired scene by marking the laparoscopic image displayed on the screen.

Figures 6 and 7 show examples of the time change in fluorescence intensity and its analysis results read out by the recording unit 36d and displayed on the display screen 41. The fluorescence intensity is, for example, the peak intensity of the fluorescence spectrum, and the time change in fluorescence intensity is the time series change in peak intensity recorded in the recording device 37 each time the fluorescence spectrum is detected. In the example shown in Figure 6, for example, a significant change in fluorescence intensity occurs between 17 and 35 seconds as drug 2 is administered to a blood vessel and circulates through the tissues in the abdominal cavity 1a. In the example shown in Figure 7, a significant change in fluorescence intensity occurs between 0 and 54 seconds.

In step S12, the analysis unit 36b selects a time range for calculating the change over time in the intensity of the fluorescence γ. The user looks at the change over time in the fluorescence intensity displayed on the display screen 41 and inputs the start time and end time of the time range via the input/output device 38. The analysis unit 36b determines that the intensity of the excitation light γ ₀ is constant or its fluctuation is within a certain range in that time range, and selects the time range input by the user if the determination is affirmative.

In step S13, the analysis unit 36b calculates the change in fluorescence intensity over time in the time range selected in step S12. The analysis unit 36b calculates the change in fluorescence intensity over time, for example, by least-squares fitting the fluorescence intensity for the selected time range using a first-order polynomial (linear model) for time. The calculation results quantify the rise rate when the fluorescence intensity increases over time, and the fall rate when the fluorescence intensity decreases.

In step S14, the display unit 36c displays the calculation results from step S13 on the display screen 41. Note that steps S12 to S14 may be repeated multiple times to calculate the change in fluorescence intensity over time for multiple time ranges, and the calculation results may be displayed sequentially on the display screen 41.

In the example shown in Figure 6, the fluorescence intensity increases at a rise rate of 77/sec in time range A, increases at a rise rate of 33/sec in time range B, increases further at a rise rate of 137/sec in time range C, and decays at a fall rate of -134/sec in time range D. From this result, it can be seen that the drug 2 administered into the blood vessels is circulating within the tissues in the abdominal cavity 1a along with the blood flow, and that the blood is flowing without stagnation, as the fluorescence intensity represents the drug concentration in the blood.

On the other hand, in the example shown in Figure 7, the fluorescence intensity increases at a rise rate of 3.9/sec in time range A, increases at a rise rate of 20/sec in time range B, increases at a rise rate of 7.8/sec in time range C, decays at a fall rate of -3.3/sec in time range D, and increases slightly at a rise rate of 0.4/sec in time range E (saturating at a constant value). From these results, it can be seen that the drug 2 administered to the blood vessels is retained in the tissues of the abdominal cavity 1a, and that the fluorescence intensity represents the drug concentration in the blood, indicating congestion.

When step S14 is completed, the analysis mode ends and the process returns to step S1.

The fluorescence detection flow ends when the user, for example, turns off the switch on the front panel.

The fluorescence detection device 100 according to this embodiment includes an excitation light source 34a that generates excitation light _γ0 , a guide light source 34b that generates guide light _γg in the visible light region, a scope 10 that is optically connected to the excitation light source 34a and the guide light source 34b and guides the guide light _γg together with the excitation light _γ0 to irradiate tissues in the abdominal cavity 1a of the subject 1 and collects the fluorescence γ emitted from the tissues by irradiation with the excitation light _γ0 , and a display unit 36c that acquires photographed images of the abdominal cavity 1a from a laparoscope device 200 that photographs the inside of the abdominal cavity 1a of the subject 1 and controls the display of the photographed images. By irradiating the tissues in the abdominal cavity 1a of the subject 1 with the guide light _γg superimposed on the excitation light _γ0 by the scope 10, it becomes possible to operate the probe 10 by visually recognizing the irradiation location on the photographed image of the abdominal cavity 1a.

The present invention has been described above using an embodiment, but the technical scope of the present invention is not limited to the scope described in the above embodiment. It will be clear to those skilled in the art that various modifications and improvements can be made to the above embodiment. It is clear from the claims that forms incorporating such modifications or improvements can also be included in the technical scope of the present invention.

The order of execution of each process, such as operations, procedures, steps, and stages, in the devices, systems, programs, and methods shown in the claims, specifications, and drawings is not specifically stated as "before" or "prior to," and it should be noted that the processes can be performed in any order, unless the output of a previous process is used in a later process. Even if the operational flow in the claims, specifications, and drawings is explained using "first," "next," etc. for convenience, it does not mean that it is necessary to perform the processes in that order.

1 ... subject (patient), 1a ... abdominal cavity, 2 ... drug, 10 ... scope, 11 ... tube, 12 ... light transmitting optical fiber, 13 ... light receiving optical fiber, 14 ... connector, 20 ... cable, 21 ... flexible tube, 22 ... light transmitting optical fiber, 23 ... light receiving optical fiber, 24 ... gripping portion, 24a ... switch, 29 ... connector, 30 ... device main body, 31 ... housing, 32, 33 ... optical fiber, 32a, 32b ... optical fiber, 34 ... light source, 34a ... excitation light source, 34b ... guide light source, 35 ... detector , 36...control calculation device, 36a...control unit, 36b...analysis unit, 36c...display unit, 36d...recording unit, 37...recording device, 38...input/output device, 39...communication device, 40...monitor device, 41...display screen, 42-47...area, 100...fluorescence detection device, 110...scope, 111...tube, 114...connector, 120, 121...cable, 130...device main body, 130a...housing, 131...light source, 132...camera, 133...communication device, 200...laparoscopic device, Sp...spot, γ...fluorescence, γ ₀ ...excitation light, γ _g ...guide light.

Claims (4)

A first light source that generates excitation light;
A second light source that generates guide light in the visible light region;
a scope that is optically connected to the first light source and the second light source, guides the guide light together with the excitation light to irradiate tissue in an abdominal cavity of a subject, and collects fluorescence emitted from the tissue in response to irradiation with the excitation light;
a display unit that acquires an image of the abdominal cavity from an imaging device that images the abdominal cavity of the subject and controls display of the acquired image;
A fluorescence detection device comprising: a detector for detecting the fluorescence collected by the scope,
The fluorescence detection device according to claim 1 , wherein the display section displays a result of the fluorescence detection by the detector together with the captured image. The fluorescence detection device according to claim 2, further comprising a control unit that changes light emission parameters including any one of the color, intensity, brightness, spread, beam shape, and light emission pattern of the guide light when the excitation light is irradiated and when it is not irradiated. The fluorescence detection device according to claim 2 or 3, wherein the display unit displays on a screen and/or issues an audio notification that the excitation light is being irradiated.

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