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WO2022107723A1 - Système d'imagerie et procédé d'imagerie utilisant la lumière proche infrarouge - Google Patents

Système d'imagerie et procédé d'imagerie utilisant la lumière proche infrarouge Download PDF

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Publication number
WO2022107723A1
WO2022107723A1 PCT/JP2021/041938 JP2021041938W WO2022107723A1 WO 2022107723 A1 WO2022107723 A1 WO 2022107723A1 JP 2021041938 W JP2021041938 W JP 2021041938W WO 2022107723 A1 WO2022107723 A1 WO 2022107723A1
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Prior art keywords
light
subject
infrared
infrared light
specimen
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PCT/JP2021/041938
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English (en)
Japanese (ja)
Inventor
譲 池原
早苗 池原
富郎 永野
健一 大澤
Original Assignee
国立大学法人千葉大学
ディー・アール・シー株式会社
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Application filed by 国立大学法人千葉大学, ディー・アール・シー株式会社 filed Critical 国立大学法人千葉大学
Priority to JP2022563743A priority Critical patent/JPWO2022107723A1/ja
Publication of WO2022107723A1 publication Critical patent/WO2022107723A1/fr

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    • 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
    • G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated

Definitions

  • the present invention relates to an imaging system and an imaging method using near-infrared light.
  • An imaging system that captures images of tissues of parts of the animal and human bodies and utilizes the images for various diagnoses, examinations, observations, and the like.
  • This imaging system illuminates a target area with light having a predetermined wavelength for imaging, and at that time, it is desired to be able to clearly image a target in a tissue. Since a silicon image sensor with high resolution can be used at a wavelength of 1 ⁇ m or less for illumination light, inspection support devices and surgery support devices that utilize near-infrared light with a wavelength of 1 ⁇ m or less have been developed. There is.
  • Non-Patent Document 1 a device for monitoring oxygen metabolism and visualizing blood vessels that are difficult to observe under direct vision has been realized (see Non-Patent Document 1).
  • the light absorption band of the main molecules constituting the living body such as water, lipid, and glucose exists in the near-infrared wavelength region having a wavelength of 1 ⁇ m or more and 2.5 ⁇ m or less.
  • the absorption band of water has peaks around wavelengths of 1500 nm and 2000 nm, and the wavelength range of about 700 to 1400 nm where absorption is small is called a window of a living body.
  • Each organ of the body has a slightly different water content depending on the type of cells that compose it and the pathological condition.
  • T2 (proton) enhancement of MRI images is used for inspection and diagnosis by utilizing this difference, but in the near-infrared wavelength region where the wavelength of 1 ⁇ m or more and 2.5 ⁇ m or less, where the efficiency of light absorption changes significantly, MRI Similar to the T2 (proton) -enhanced image of the image, it can be a means for evaluating the state of each organ.
  • Non-Patent Document 2 an example using a hyperspectral camera having a built-in spectroscopic grating has been reported (see Non-Patent Document 2).
  • the near-infrared sensor In the near-infrared region, since the absorption of multiple substances overlaps, there is a problem that the overlap between bands due to multiple overtones and hot bands is large, the spectrum is complicated, analysis is difficult, and substance identification is difficult. Analysis has been improved with advances in statistical data processing techniques.
  • the near-infrared sensor is required to have high sensitivity and low noise in order to detect weak absorption such as overtones and hot bands, and to have high sensitivity linearity to light intensity for quantitative analysis.
  • a two-dimensional array type sensor is desired in order to simultaneously perform absorption spectrum measurement and spatial position measurement.
  • the present inventor has proposed an imaging system and a surgical support system for acquiring an image of a tissue inside a living body in which the imaging time and the amount of irradiation light of the living tissue are reduced (Patent Document 1).
  • Patent Document 1 the reflected light that can be obtained when the living tissue is irradiated with infrared light having a wavelength in the infrared region based on the spectral characteristics of water and lipid, and the reflected light that can be obtained when the living tissue is irradiated with visible light. Therefore, an imaging system for acquiring an image in which the water portion is emphasized is disclosed.
  • an infrared camera using an InGaAs semiconductor is used as an infrared image pickup element.
  • Patent Document 2 an optical measuring device and an optical measuring method using near-infrared light have been proposed (Patent Document 2).
  • the position of the tissue is measured by acquiring an image showing the intensity distribution of the light reflected from the subject by irradiating the subject with near-infrared light.
  • a near-infrared composition imaging system is commercially available (Compovision (registered trademark), manufactured by Sumitomo Electric Industries, Ltd.). It is a composition imaging system consisting of a camera consisting of a two-dimensional light receiving element capable of receiving near-infrared light with a wavelength of 1000 to 2350 nm and a spectroscope, and hyperspectral analysis / imaging software, and irradiates the subject with near-infrared light. By detecting the light reflected from the subject, the composition of the subject can be analyzed.
  • lymphoid tissue cleansing is performed to prevent lymph node recurrence.
  • Surgeons and pathologists collect lymph nodes during and after surgery by relying on the tactile sensation through surgical gloves to proceed with histological diagnosis and genetic diagnosis, but recovery itself is uncertain if the size is 5 mm or less. Therefore, there is a need for a means for confirming that lymph nodes are surely contained in the collected (excised) tissue.
  • Intraoperative administration of fluorescent substances, etc. is effective in detecting such lymph nodes, but i) there is a risk of toxicity and allergic reactions in the use of contrast media, and ii) lymph nodes to which contrast media can be delivered. In addition, there are problems such as difficulty in reaching the excitation light when lymph nodes are present in the deep part of the thick stromal tissue.
  • a thick subject for example, a living tissue is imaged using a conventional near-infrared light imaging system that receives reflected light for imaging, it is difficult to remove noise and a sufficient S / N ratio is obtained. There is a problem that it cannot be taken and the sensitivity is not sufficient. In particular, it is difficult to detect when the imaging target is in a deep part of the subject (specimen), for example, a deep part in a living tissue (for example, a position where the depth exceeds 5 mm).
  • An object of the present invention is to provide an imaging system and an imaging method capable of easily and surely acquiring a deep image even when imaging a thick subject (specimen), for example, a living tissue.
  • the present invention is a system for imaging a subject (specimen) using transmitted light of near-infrared light, and is near-red in the near-infrared light (preferably in the wavelength range of 1000 nm to 2000 nm).
  • the subject is external light, more preferably near-infrared light in the wavelength range of 1000 nm to 1600 nm, and more preferably near-infrared light in the wavelength range of 1300 nm to 1600 nm in which the absorption of water is larger than that of lipid.
  • a near-infrared camera that receives near-infrared light transmitted through the subject (specimen), and a near-infrared light received by the near-infrared camera.
  • An imaging system comprising a control unit having an image processing unit for generating an enhanced image in which a portion in a subject (specimen) that absorbs infrared light is emphasized, the near-infrared light irradiation unit and the above.
  • the near-infrared camera is arranged at positions facing each other with the subject (specimen) to be imaged interposed therebetween, and the near-infrared camera has a plurality of light receiving elements electrically separated from adjacent light receiving elements.
  • An imaging system is provided with a light receiving element array arranged in two dimensions.
  • the near-infrared light irradiation unit and the near-infrared camera are arranged at positions facing each other with the subject (specimen) to be imaged sandwiched between them. It means that the (specimen) and the near-infrared camera are arranged in a straight line or a substantially straight line in that order, and when viewed with reference to the light emitted from the irradiation unit, it is close to the near-infrared light irradiation unit.
  • the infrared camera means that the subject (specimen) to be imaged is positioned on the optical axis connecting the two.
  • a visible camera that receives visible light reflected from the subject (specimen)
  • the image processing unit receives the near-infrared light received by the near-infrared camera.
  • the image pickup system which combines the result and the light reception result of visible light received by a visible camera to generate an enhanced image in which a portion in a subject (specimen) that absorbs near-infrared light is emphasized.
  • the image pickup system since the entire image of the subject (specimen) is captured by the visible camera, the positional relationship between the portion in the subject (specimen) that absorbs near-infrared light and the entire subject can be confirmed.
  • the near-infrared light irradiation unit is an LED module in which LED elements capable of irradiating a subject (specimen) with near-infrared light in the wavelength range of 1300 nm to 1600 nm are arranged in two dimensions.
  • the imaging system including the above is provided.
  • the near-infrared light irradiation unit is provided with the image pickup system including an inverted conical light reflector extending from the vicinity of the light source unit.
  • the near-infrared light irradiation unit is provided with the image pickup system including a filter unit made of an acrylic plate.
  • the imaging system further provided with a sample table capable of transmitting near-infrared light is provided.
  • the seventh aspect of the present invention is a method of imaging a subject (specimen) using transmitted light of near-infrared light, from near-infrared light (preferably from 1000 nm to 2000 nm, more preferably from 1000 nm).
  • An imaging method including a step of generating an enhanced image in which a portion in the subject (specimen) that absorbs the near-infrared light is emphasized based on the result of receiving the near-infrared light received by the near-infrared camera. Therefore, the near-infrared light is emitted from a position facing the near-infrared camera with the subject (specimen) to be imaged sandwiched therein, and the near-infrared camera is electrically separated from the adjacent light receiving element.
  • an imaging method which is a near-infrared camera including a light receiving element array in which a plurality of light receiving elements are arranged in two dimensions.
  • the step of receiving the visible light reflected from the subject (specimen) by the visible camera, and the light receiving result of the near infrared light received by the near infrared camera is further, the step of receiving the visible light reflected from the subject (specimen) by the visible camera, and the light receiving result of the near infrared light received by the near infrared camera.
  • An imaging method including a step of synthesizing the light reception result of the visible light received by the visible camera to generate an enhanced image in which a portion in the subject (specimen) that absorbs the near infrared light is emphasized. Is provided. In this method, since the entire image of the subject (specimen) is captured by the visible camera, the positional relationship between the portion in the subject (specimen) that absorbs near-infrared light and the entire subject can be confirmed.
  • an image is taken by irradiating with near-infrared light (preferably 1000 nm to 2000 nm, more preferably 1000 nm to 1600 nm, still more preferably near-infrared light in the wavelength range of 1300 nm to 1600 nm).
  • a container for example, a mast
  • a container based on infrared light is provided.
  • the container such as a petri dish, may itself be made of acrylic.
  • the target site existing in the subject (specimen) can be easily imaged or confirmed.
  • FIG. A shows the image pickup system shown in FIG. A is the result of imaging with a near-infrared camera arranged so as to directly receive the irradiated near-infrared light.
  • the upper figure shows the results of imaging using a near-infrared camera that does not have electrical separation between the light-receiving elements
  • the lower figure shows the results of imaging using a near-infrared camera that electrically separates each light-receiving element. It is the result of doing.
  • B is the result of taking a picture by increasing the current value of the near-infrared light using a near-infrared camera in which the photodiode cells are electrically separated.
  • the numerical value shows the current value applied to the LED module. This is the result of putting the mouse tissue (mesentery) in a petri dish containing a fixing solution and performing imaging using the apparatus of the present invention.
  • the figure on the left is the result of imaging with a visible camera, and shows the state in which each tissue (spleen, pancreas and mesentery) is separated after dissection.
  • the figure on the right shows the result of imaging the tissue (mesentery) irradiated with near-infrared light by receiving the transmitted light with a near-infrared camera.
  • A is the result of imaging the living tissue with visible light.
  • B and C are the results of irradiating a living tissue with near-infrared light and receiving the reflected light with a near-infrared camera for imaging.
  • D is a histological image obtained by staining with hematoxin and eosin.
  • the upper left figure is the result of imaging with a visible camera
  • the upper right figure is the result of receiving and imaging the transmitted light of a human tissue irradiated with near-infrared light with a near-infrared camera.
  • the figure below is a histological image obtained by staining with hematoxin and eosin.
  • the terms "subject” and “specimen” mean an object imaged using the apparatus and / or method of the present invention, and are used as terms that can be replaced with each other.
  • the term "near-infrared light transmitted through” means that when the subject is irradiated with near-infrared light, the subject is transmitted (penetrated) and received light on the side opposite to the irradiation side with respect to the subject. Means the light that is done.
  • the side opposite to the irradiation side means that the irradiated light is located on the optical axis in a state of traveling straight. Therefore, if there is a portion of the subject that absorbs the irradiated near-infrared light, the transmitted light of that portion becomes weaker than the surroundings depending on the degree of absorption.
  • the "visible light reflected" from the subject is the light emitted from the subject when the subject is irradiated with light, and the light received with respect to the subject on the same side as the irradiation side.
  • Irradiation of light can be performed using a specific irradiation device, but the reflected light can be detected (received) using light such as indoor light as a light source without using a special irradiation device.
  • FIG. 1 is a diagram showing an example of an imaging system according to an embodiment of the present invention.
  • the image pickup system 1000 shown in FIG. 1 includes a near-infrared irradiation unit 20 and a near-infrared camera 10.
  • FIG. 1 does not show an image processing unit for generating an image based on a light receiving result.
  • the near-infrared light irradiation unit 20 and the near-infrared camera 10 are arranged so as to face each other with the subject P to be imaged interposed therebetween.
  • the near-infrared light (indicated by an arrow in the figure) emitted from the near-infrared irradiation unit 20 is directed straight toward the near-infrared camera 10 and is received by the camera.
  • the present invention uses a near-infrared camera equipped with a light-receiving element array in which a plurality of light-receiving elements electrically separated from adjacent light-receiving elements are arranged two-dimensionally, so that the emitted near-infrared light can be emitted. Even when passing directly around the subject, the subject can be well imaged without the use of other additional structures such as a carbano scanner.
  • a plurality of light-receiving elements are two-dimensionally arranged in the light-receiving portion, and each light-receiving element is electrically separated from the adjacent light-receiving element. Therefore, optical crosstalk and blooming can be suppressed, and even when the camera directly receives the irradiated near-infrared light, good imaging of the subject is possible.
  • the structure of the light receiving element array includes a mesa type and a planar type, but any structure can be used as long as the adjacent light receiving elements are electrically separated from each other and optical crosstalk and blooming can be sufficiently suppressed.
  • a method of electrically separating a light receiving element from an adjacent cell which is used in one aspect of the present invention, for example, movement of a light generating carrier between elements adjacent to each other, that is, lateral diffusion is performed.
  • a method of providing a layer (diffusion layer) for blocking and electrically separating the layers can be mentioned.
  • a method for providing a layer between the elements a method known in the art can be used. For example, an array of light receiving elements surrounded by an impurity-doped layer (impurity diffusion layer) can be created with reference to a known light receiving element array manufacturing process.
  • the impurity diffusion layer is not particularly limited as long as it provides sufficient separation between the light receiving elements, but when a PN type light receiving element is used, impurities of a different type (p type or n type) from the light absorption layer are doped. It is a layer.
  • the light receiving element array is a PN type having a structure in which a light absorption layer is formed on a barrier layer formed on a substrate and a window layer is laminated on the light absorption layer. It is a light receiving element array. By sandwiching the light absorption layer between the barrier layer and the window layer, it is possible to reduce the dark current that affects the detection limit.
  • the light receiving element array is a planar type PN type light receiving element array, and each light receiving element is surrounded by an impurity diffusion layer extending to the barrier layer, and electricity is supplied from the light receiving elements adjacent to each other. Is separated.
  • the impurity diffusion layer is p-type.
  • the p-type impurity diffusion layer include, but are not limited to, a zinc diffusion layer.
  • a method of electrically separating the light receiving element used in one aspect of the present invention from the adjacent light receiving element for example, a method of electrically separating by providing a separation groove between the light receiving elements adjacent to each other may be mentioned. be able to.
  • a method for providing the separation groove between the elements a method known in the art can be used, and the method can be created by, for example, a standard semiconductor selective etching process.
  • the light receiving element array is provided with a separation groove between the light receiving elements adjacent to each other, and an impurity diffusion layer is formed on the side surface of the light absorption layer in the separation groove, so that each light receiving element is formed.
  • Examples of the light receiving element array having such a structure, which are electrically separated from the light receiving elements adjacent to each other, include the compound semiconductor light receiving element array described in JP-A-2019-96758.
  • a light receiving element near infrared light detection element
  • an InGaAs element having a sensitivity of at least 1.6 ⁇ m can be mentioned.
  • Photodiode arrays using InGaAs devices with extremely little crosstalk between devices are described in the above-mentioned International Publication No. WO2011 / 089949 and JP-A-2019-096758.
  • a layer doped with impurities of a type different from that of the light absorbing layer reaches the barrier layer and surrounds the element.
  • a planar type structure that electrically separates the elements it is possible to suppress noise and confine the capacitance saturation by separating the elements, obtain a sufficient S / N ratio, and enable clear imaging.
  • the number of pixels of the near-infrared camera used in this embodiment is 100,000 pixels or more, preferably 200,000 pixels or more, and more preferably 300,000 pixels or more.
  • the near-infrared camera 10 has an image pickup optical system (not shown) in addition to the light receiving element.
  • This image pickup optical system includes a zoom lens for setting the image pickup magnification of the subject P and a focus lens for focusing on the subject P.
  • the near-infrared camera 10 has a lens drive system (not shown) that drives one or more of these zoom lenses and focus lenses.
  • the near-infrared camera 10 includes a synchronizable interface such as a trigger input circuit or IEEE 1394.
  • the near-infrared camera 10 is a near-infrared light, preferably near-infrared light in the wavelength range of 1000 nm to 2000 nm, more preferably 1000 nm to 1600 nm, still more preferably 1300 nm to 1600 nm. Is set so that it can receive light. Since near-infrared light having a wavelength of 1300 nm to 1600 nm is more easily absorbed by water than lipids, it is possible to acquire a target containing more water than the periphery in the subject as image data.
  • a portion containing a large amount of lipid or a portion containing a large amount of water can be obtained as an image emphasized with respect to the surroundings.
  • lymph nodes in the surrounding stromal tissue can be acquired as image data.
  • near-infrared light having a wavelength of 1000 nm to 1600 nm is absorbed more by proteins and starch than water. As described above, the absorption of near-infrared light having a specific wavelength differs depending on the component. Therefore, it is possible to obtain images reflecting the composition based on absorption of various subjects including tissues and foods.
  • the near-infrared light irradiation unit 20 irradiates the subject P from a position facing the near-infrared camera 10 with the subject P in between.
  • the camera can receive a larger amount of near-infrared light that has passed through the subject P. Therefore, the camera can detect sufficient transmitted light even for a thick subject P.
  • the subject P is irradiated from a position facing the camera 10 with the subject P in between, not only the light transmitted through the subject P but also the light directly transmitted around the subject P is received by the camera 10.
  • the near-infrared light irradiation unit 20 irradiates the subject P from directly below.
  • the near-infrared light irradiation unit 20 of the present invention includes an LED module 21 in which an LED (Light Emitting Diode) element 23 that emits near-infrared light is arranged two-dimensionally.
  • an LED Light Emitting Diode
  • one LED element 23 arranged on an independent substrate 22 is arranged two-dimensionally. It may be one, or as shown in the left figure of FIG. 3, a plurality of LED modules 23 may be arranged two-dimensionally on one substrate 22.
  • one LED element may be mounted on a single metal package, but preferably, a plurality of LED elements 23 that emit near-infrared emission wavelengths are mounted two-dimensionally.
  • an LED element 23 that emits a wavelength of 1350 nm, 1400 nm, 1450 nm, 1500 nm, or 1550 nm is mounted.
  • Each of these LED elements 23 is electrically connected to a metal terminal and further connected to a drive circuit (not shown).
  • the LED module 21 of the near-infrared light irradiation unit can arbitrarily adjust the number of LEDs mounted and the number of connected series or parallels.
  • LED elements capable of emitting the near-infrared wavelength.
  • the above, or 60 or more LED modules may be two-dimensionally integrated, preferably 16 or more, more preferably 30 or more, still more preferably 40 or more, still more preferably 50 or more, and most preferably 60. It is an LED module in which more than one LED element is integrated. It can be used in the present invention as long as it can emit near-infrared light with an amount of light that can transmit the subject, but by using the integrated LED, a sufficient amount of light can be used even if the subject is a thick object. It can transmit near-infrared light.
  • the irradiance of the light irradiating the subject P changes depending on the distance from the LED element to the subject P, the type and number of LED elements, and the current applied to the LED element. Therefore, the irradiance to irradiate the subject P may be appropriately adjusted in the amount of current according to the LED elements used, the number of LED elements, and the properties of the subject P.
  • the irradiance is not particularly limited as long as it can pass through the subject, but is, for example, 30 ⁇ W / cm 2 or more, preferably 50 ⁇ W / cm 2 or more. When the subject is sensitive to heat, for example, a living tissue, the irradiance is preferably 10 mW / cm 2 or less.
  • the near-infrared camera directly emits the near-infrared light emitted from the near-infrared light irradiation unit as a part of the near-infrared light irradiation unit 20 or as another configuration.
  • No additional configuration such as a carbano scanner, is required so that the camera does not receive light, i.e., that the camera does not receive light that does not pass through the subject and passes directly around the subject.
  • a configuration such as a carbano scanner may be added depending on the purpose of use and the application.
  • the near-infrared light irradiation unit 20 of the present invention can include a light reflector 40 and / or a filter 45 for improving irradiation to a subject as shown in FIG.
  • the material and shape of the light reflector are not particularly limited as long as they absorb less near-infrared light and can improve the irradiation of the subject with light.
  • the material for example, stainless steel, aluminum, titanium alloy, magnesium alloy can be used.
  • the shape is not particularly limited as long as it can improve the light collection and directivity to the subject, and examples thereof include an inverted conical shape, and the light reflecting surface is, for example, mirror-polished. It may be treated with alumite or the like.
  • the inverted conical reflector 40 is arranged so as to extend from the LED module.
  • the filter 45 can be used without particular limitation as long as it absorbs little near-infrared light and has high transmission efficiency, but for example, a filter made of a material such as acrylic, polycarbonate, silicon, polypropylene, or polyethylene may be used. It can be, preferably acrylic. A particularly preferred filter is an acrylic plate.
  • the filter 45 is also preferably subjected to surface treatment such as polishing in order to increase the efficiency of irradiating the subject with light, and on the other hand, a polished acrylic plate is particularly preferable.
  • FIG. 5 shows a side sectional view of the near-infrared light irradiation unit 20 provided with the inverted conical reflector 40 and the acrylic plate 45.
  • the light intensity that the camera can receive is attenuated in inverse proportion to the square of the distance between the light source and the subject P.
  • the distance between the light source and the subject is 20 cm
  • the brightness of the light is 1/400 of that in the case of 1 cm.
  • transmitted near-infrared light is used as in the present embodiment
  • the distance between the light source and the subject can be easily adjusted, so that such a problem does not occur and the camera can receive light of sufficient intensity.
  • the transmitted light is used as compared with the imaging using the reflected light, it is possible to take an image of an object deep in the subject.
  • the subject to be imaged by the system or method of the present invention is not particularly limited, but a subject containing a substance that absorbs near-infrared light is preferable.
  • imaging is performed using transmitted light of near-infrared light. Therefore, in the case of a subject containing a substance that absorbs near-infrared light, a portion that absorbs near-infrared light is used.
  • the imaging target of the present invention is not limited to this, but the biological tissue will be described below.
  • Light having a wavelength band of 1300 nm to 1600 nm is light in which water absorbs a large amount of energy. Therefore, in the embodiment of the present invention, when the near-infrared light in these wavelength bands is used, the energy of the light absorbed by the subject can be reduced, and the subject is heated, causing thermal damage or the like. You can prevent it from happening.
  • a near-infrared light irradiation unit that does not reach a high temperature even after continuous use for several tens of minutes, for example, can be maintained at 45 ° C. or lower.
  • the irradiation of near-infrared light and the light reception of transmitted light will be described with reference to FIG. 6 by taking as an example the present embodiment in which the subject is irradiated from directly below.
  • the near-infrared light emitted from the near-infrared light irradiation unit 20 reaches the subject P. Since light having a wavelength of 1300 nm to 1600 nm is easily absorbed by water, when a portion (for example, lymph node) T containing a large amount of water is present in the subject P, the light hitting the T is absorbed and does not pass through the subject. On the other hand, the light that hits the lipid-rich portion (for example, the stromal tissue) is not absorbed and passes through the subject. As a result, the near-infrared camera 10 can acquire image data in which the portion T containing a large amount of water and its surroundings are distinguished.
  • a visible camera 30 that receives visible light reflected from a subject (specimen) is further provided.
  • the visible camera 30 may be arranged on the same side as the near-infrared camera 10 with respect to the subject, and may be arranged at any position as long as the visible light reflected from the subject P can be received. It is not necessary to provide a dedicated visible light irradiation unit in order to receive visible light, and sufficient shooting is possible even with indoor light. However, a visible light irradiation unit may be arranged together with the visible camera 30. ..
  • the visible camera 30 is a camera having sensitivity to light having a wavelength in the visible region. Light in the visible region is sensitive to the outer shape and surface shape of the subject P.
  • a CCD camera or a CMOS camera using a silicon image pickup element such as a CCD image sensor or a CMOS image sensor capable of acquiring an image such as an external shape is used.
  • the image processing unit synthesizes the light reception result of the near infrared light received by the near infrared camera and the light reception result of the visible light received by the visible camera. Further, an imaging system for generating an enhanced image in which a portion in a subject that absorbs near-infrared light is emphasized is provided. In such a system, since the entire image of the subject is captured by the visible camera, the positional relationship between the portion inside the subject that absorbs near-infrared light and the entire subject can be confirmed. The composite image and the enhanced image can be generated by appropriately using a known image processing method.
  • the light received by the near-infrared camera is received by the near-infrared camera with reference to the light reception result of the visible light received by the visible camera.
  • the difference between the light reception result of the near infrared light and the light reception result of the visible light can be calculated.
  • the visible light irradiation unit may be used with any light source as long as it can irradiate light in the visible region, but for example, LED lighting, a laser light source, halogen lighting, or the like is used, and LED lighting is preferably used.
  • the imaging timing of the near-infrared camera 10 and the visible camera 30 may be either the case where the images are taken separately or the case where the images are taken at the same time. That is, there are cases where the near-infrared light is irradiated from the near-infrared light irradiation unit 20 and the subject P is imaged by the near-infrared camera 10, and separately, the subject P is imaged by the visible camera 30 and near-infrared. When the camera 10 and the visible camera 30 simultaneously capture images, either of them may be used.
  • the near-infrared light irradiation unit 20 when the near-infrared light irradiation unit 20 includes a shield 45 composed of an inverted conical light reflector 40 and an acrylic plate, the subject P may be arranged directly on the acrylic plate. It is possible. Alternatively, as shown in FIG. 7A, the subject P can be placed in a container 46 such as a petri dish on an acrylic plate. When the bottom of the container 46 such as a petri dish also serves as a filter, as shown in FIG. 7B, the subject P is placed directly on the near-infrared light irradiation unit 20 provided with the inverted conical reflector 40. It is also possible to place the container 46 and take an image.
  • One aspect of the present invention is to capture a subject imaged using near-infrared light (preferably near-infrared light in the wavelength range of 1000 nm to 2000 nm, more preferably 1000 nm to 1600 nm, still more preferably 1300 nm to 1600 nm).
  • near-infrared light preferably near-infrared light in the wavelength range of 1000 nm to 2000 nm, more preferably 1000 nm to 1600 nm, still more preferably 1300 nm to 1600 nm.
  • the container is preferably a petri dish.
  • the subject P can also be placed on the transmission observation sample table 50 for imaging.
  • the transmission observation sample table 50 is configured so as not to block the near-infrared light emitted from the near-infrared light irradiation unit 20.
  • the transmission observation sample table 50 at least the portion irradiated with near-infrared light (the light-transmitting portion shown by the diagonal line) is near-infrared light. It is made of a material with little interfacial reflection and absorption. Further, it is preferable that the light transmitting portion of the transmission observation sample table 50 is coated or scattered to suppress the interfacial reflection of light.
  • the light transmitting portion may be a hole.
  • FIG. 9 shows a state in which the subject P placed in the container is placed on the sample table 50 and imaged in the system of the first aspect and the second aspect of the present invention.
  • the type of the living tissue is not particularly limited, but the tissue of the skin or the internal organ of the living body can be mentioned, and preferably the tissue of the internal organ of the living body collected or removed from the living body can be mentioned. can. Since the imaging system and method of the present invention can image a subject based on the spectral characteristics of water and lipid, a biological tissue substantially containing water and lipid is preferably used. For example, various organs and various organs in the living body can be mentioned, but not limited to.
  • parenchymal organs include lymph nodes, adrenal glands, pancreas, salivary glands, cervical cysts, and the like, and cancers that have developed in these organs and lymph nodes that have metastasized to cancer can be mentioned.
  • inflammation and infiltration of cancer in the adventitia such as lung, heart, thoracic cavity and arteriovenous blood vessels in the abdominal cavity can be mentioned.
  • the subject which is a living tissue
  • the excised biological tissue is placed in a plastic petri dish that does not absorb or has little absorption of near-infrared light, and is placed in the transmission observation sample table 50 in the petri dish.
  • the living tissue is preferably placed in a fixation solution in a petri dish.
  • the fixative that can be used in the present invention is not particularly limited as long as it can be used for fixing tissues, and examples thereof include aldehydes such as formaldehyde and glutaaldehyde, alcohols such as methanol, ethanol and isopropanol.
  • tissue fixatives such as Buan fixative and Zamboni fixative.
  • alcohols are preferable.
  • a tissue that has already been fixed and stored can also be used as the biological tissue as a subject.
  • the biological tissue in a fixed solution can be preferably transferred to a petri dish containing the above-mentioned fixative and imaged on a permeation observation sample table 50.
  • FIG. 10 is a functional block diagram showing an imaging system 1000 according to a second embodiment of the present invention.
  • the control unit 60 includes an image processing unit 61, a lighting drive unit 62, a storage device 63, an input device 64, and a display unit 65.
  • the control unit 60 is electrically connected to the near-infrared camera 10 and is electrically connected to the near-infrared irradiation unit 20 via the illumination drive unit 62.
  • the control unit 60 is also electrically connected to the visible camera 30.
  • the control unit 60 has an arithmetic processing unit such as a CPU (Central Processing Unit), and the CPU controls the image processing unit 61 and the like based on a control program stored in a storage unit such as a hard disk (not shown). Further, the control unit 60 generates a trigger signal A to be transmitted to the near-infrared camera 10 and the illumination drive unit 62, and a trigger signal A'to be transmitted to the visible camera 30.
  • a CPU Central Processing Unit
  • the image processing unit 61 processes the image signal B sent from the near-infrared camera 10 and the image signal B'sent from the visible camera 30.
  • the image processing unit 61 not only adjusts the color and contrast of the acquired image, but also performs a process of synthesizing a plurality of images sent from the respective cameras as necessary.
  • the image processing unit 61 also overlays the image from the near-infrared camera 10 and the image from the visible camera 30, if necessary.
  • the lighting drive unit 62 has a drive circuit, and lights the LED mounted on the near-infrared light irradiation unit 20 based on the trigger signal A sent from the control unit 60.
  • the storage device 63 stores various programs and stores the image processed by the image processing unit 61.
  • the storage device 63 has an input / output (IO) device compatible with a hard disk and a storage medium such as an optical disk, a CD-ROM, a DVD-ROM, a USB memory, and an SD card.
  • IO input / output
  • a pointing device such as a keyboard, a touch panel, a joystick, or a mouse is used.
  • a touch panel may be formed on the display unit 65, which will be described later, and a touch operation may be performed from the image displayed on the display unit 65.
  • the user controls the emission intensity from the near-infrared irradiation unit 20, the imaging magnification of the near-infrared camera 10 or the visible camera 30, focusing, imaging instructions, and the image processing unit 61.
  • An instruction to save the processed image in the storage device 63 or the like is given.
  • the display unit 65 a liquid crystal display device, an organic EL device, or the like is used.
  • the display unit 65 displays an image of the subject P captured by the near-infrared camera 10, an image of the subject P captured by the visible camera 30, or an image superimposed on those images.
  • the display unit 65 is not limited to one, and a plurality of display units 65 may separately display an image captured by the near-infrared camera 10, an image captured by the visible camera 30, and an overlay image thereof. Further, the image superimposed on one display screen may be displayed.
  • the embodiment of the present invention it is possible to display an image overlaid with images acquired by each of the near-infrared camera 10 and the visible camera 30.
  • a portion that absorbs near-infrared light existing in the subject, which is the subject can be easily detected or confirmed.
  • the lymph nodes existing in the living tissue can be easily detected or confirmed, and according to the embodiment of the present invention, the location of the lymph nodes in the living tissue can be easily confirmed. Lymph nodes can be collected well and tissue diagnosis and genetic diagnosis can be performed.
  • the near-infrared camera 10 When the near-infrared camera 10 receives the trigger signal A, the near-infrared camera 10 outputs an image signal B for one screen (one frame) to the control unit 60.
  • the image signal B may be either a single analog signal or a digital signal composed of a plurality of signal lines.
  • the trigger signal A is also transmitted to the lighting drive unit 62.
  • the illumination drive unit 62 Upon receiving the trigger signal A, the illumination drive unit 62 outputs an LED drive signal for each image capture (frame). As a result, the image captured by the near-infrared camera 10 is sent to the control unit 60.
  • the frame rate of the near-infrared camera 10 is 10 fps, and one frame is 1/10 second, the near-infrared camera 10 is 1 Acquires 10 near-infrared light images per second.
  • the visible camera 30 when the visible camera 30 receives the trigger signal A', it outputs an image signal B'for one screen (one frame) to the control unit 60.
  • the image signal B' may be either a single analog signal or a digital signal composed of a plurality of signal lines. As a result, the image captured by the visible camera 30 is sent to the control unit 60.
  • control unit 60 has an image processing unit 61 that generates an image that overlays an image acquired by the near-infrared camera 10 and an image acquired by the visible camera 30, and is a visible image. It is possible to generate an enhanced image in which a portion of the subject that absorbs near-infrared light is emphasized on the top.
  • imaging by a visible camera is not performed, only imaging by a near-infrared camera is performed, and an enhanced image in which a portion in a subject that absorbs near-infrared light is emphasized can be generated. can.
  • the near-infrared light transmitted through the subject is received to generate an image
  • the light in the living tissue which becomes a problem when the subject P such as the living tissue is irradiated with light, is generated. Scattering is suppressed, targets existing in deep areas, for example, deeper than 5 mm, can be detected or imaged, and a thick subject P can be imaged.
  • the deep structure of the subject P and the near-infrared light corresponding to a specific component are irradiated. Since the image is taken by the near-infrared camera 10, it is possible to acquire the composition / component information of the subject P. Further, according to another embodiment, it is possible to take an image with the visible camera 30 by using visible light (for example, a wavelength of 800 nm or less) sensitive to the outer shape and surface shape of the subject P, so that the composition of the subject P can be taken. -It is possible to acquire the contour information of the subject P at the same time in addition to the component information, and it is possible to acquire an image with good visibility in a short time.
  • visible light for example, a wavelength of 800 nm or less
  • near-infrared light is used to detect near-infrared light transmitted through the subject. Therefore, when the subject is a living tissue, the subject is in a thick tissue, for example, a stroma. It is possible to detect a target (for example, a lymph node) located at a position deeper than 5 mm in the tissue. Therefore, by using this embodiment, it is possible to detect a target (for example, a lymph node) present in a living tissue having a thickness of 10 mm, preferably 20 mm or more.
  • an overlay display of a visible light image and a near infrared light image is possible, and imaging in an open system is possible.
  • the imaging guide it becomes possible to collect a part in a living tissue that absorbs near-infrared light, for example, a lymph node.
  • the InGaAs light-receiving element used in the light-receiving part of the near-infrared camera does not react to the lighting of the operating room or the examination room. It doesn't have to be dark. Therefore, it is possible to improve the accuracy and efficiency of "searching for lymph nodes" in the pathological examination department or the operating room.
  • the imaging method using the imaging system of the above-described embodiment is as follows. First, in the near-infrared camera unit 10, the near-infrared light transmitted through the subject P is electrically separated in two dimensions by irradiating the subject P with the near-infrared light from the near-infrared irradiation unit 20. Image data by near-infrared light is acquired by receiving light with a light receiving element. When a visible image is required in addition to the near-infrared light image, visible light is obtained by acquiring an image showing the intensity distribution of the light emitted from the subject with the visible camera 30 before, after, or at the same time. Acquires image data by. After that, based on each of the acquired image data, the image processing unit 61 generates an enhanced image in which the portion in the subject that absorbs the near-infrared light is emphasized.
  • FIG. 11A is a result of taking an image with a near-infrared camera arranged so as to directly receive the irradiated near-infrared light using an LED module in which 60 LED elements having an emission wavelength of 1450 nm are integrated.
  • the figure above is a near-infrared camera (manufactured by Nikon, model number NIR-P01S near red) that has multiple light receiving elements arranged in two dimensions, but each light receiving element is not electrically separated from the adjacent light receiving element. This is the result of imaging using a near-infrared camera mounted on an external sample photographing device.
  • the figure below shows a plurality of two-dimensionally arranged light-receiving elements, and each light-receiving element is electrically separated from an adjacent light-receiving element. This is the result of imaging using a near-infrared camera (NVU3VLI manufactured by IR Spec Co., Ltd.).
  • the numerical values shown below are the current values applied to the LED module.
  • the optical crosstalk and blooming between the elements cannot be suppressed and the image cannot be taken only by applying a small amount of current to the LED element.
  • the state of the integrated LEDs can be photographed well.
  • FIG. 11B when the near-infrared camera shown in the lower figure of FIG. 11A was used, optical crosstalk and blooming between the elements could be satisfactorily suppressed even if the amount of current was further increased by 30 times or more.
  • FIG. 12 is a result of acquiring a transmitted image by near-infrared LED irradiation of 1450 nm (the current value applied to the LED module is 0.1 A) using the system of the present invention.
  • Mice were dissected, tissue was removed and the mesentery was separated from the tissue.
  • This is the result of obtaining a transmitted image of the separated mesentery by putting it in a petri dish containing a fixed solvent and irradiating it with near-infrared light.
  • the left figure is a photograph of the mesentery after separation from the tissue, and the right figure is a transmission image using near-infrared light.
  • the darkened areas are the lymph nodes.
  • the mesentery is composed primarily of adipocytes, the tissue of which contains lymph nodes. An image was obtained that emphasized the lymph nodes containing a large amount of water. Circles in the figure indicate the location of lymph nodes.
  • FIG. 13 is the result of imaging using the reflected light of the conventional near-infrared light.
  • A is the result of taking a picture with visible light. Lymph nodes are present in the area indicated by the arrow.
  • B and C are the results of imaging using near-infrared reflected light. The location of the lymph nodes is indicated by a dotted circle.
  • B is the result of imaging under the condition that the whole image can be taken, but the lymph node is unknown.
  • C is the result of imaging under the condition that the lymph node can be photographed, but the whole image is blurred and cannot be understood.
  • D is the result of hematoxin-eosin staining of the vertical cross section of the tissue.
  • B and C are taken from the direction of the black arrow.
  • the lymph node existing at a position exceeding 5 mm from the surface could not be detected.
  • FIG. 14 shows a transmitted image of a human tissue (right closed lymph node) irradiated with near-infrared light of 1450 nm (the current value applied to the LED module was 0.8 A) using the system of the present invention. Is the result of obtaining.
  • the left figure is a photograph of the tissue separated from the tissue, and the right figure is a transmitted image using near-infrared light.
  • the black part indicated by the circle is the lymph node, and an image emphasizing the lymph node containing a large amount of water was obtained.
  • FIG. 15 shows the results of similar imaging of human tissue resected as left closed lymph node dissection in prostate cancer surgery.
  • the upper left figure is a photograph of the excised tissue, and the upper right figure is a transmitted image using near infrared light.
  • the black part indicated by the circle is the lymph node, and an image emphasizing the lymph node containing a large amount of water was obtained.
  • the figure below shows the results of staining the tissue with hematoxin and eosin.
  • P Subject, 1000 ... Imaging system, 10 ... Near infrared camera, 20 ... Near infrared irradiation unit, 21 ... LED module, 22 ... Metal package, 23 ... Light receiving element, 30 ... Visible Camera, 40 ... Reflector, 45 ... Shield, 46 ... Share, 50 ... Transmission observation sample stand, 60 ... Control unit, 61 ... Image processing unit, 62 ... Lighting drive unit 63 ... Memory Device, 64 ... Input device, 65 ... Display unit

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Abstract

L'objet de la présente invention est de fournir un système d'imagerie et un procédé d'imagerie qui permettent, même lors de l'imagerie d'un sujet épais, d'acquérir simplement et de manière fiable une image d'une partie profonde du sujet. La présente invention concerne un système d'imagerie qui est destiné à imager un sujet à l'aide d'une lumière infrarouge proche transmise et comprend : une unité d'émission de lumière proche infrarouge qui est capable d'émettre une lumière proche infrarouge sur le sujet ; un appareil de prise de vues à proche infrarouge destiné à recevoir la lumière proche infrarouge qui a traversé le sujet ; et une unité de commande comprenant une unité de traitement d'image destinée à utiliser le résultat de la réception de la lumière infrarouge proche transmise par l'appareil de prise de vues à proche infrarouge pour générer une image accentuée dans laquelle une portion d'absorption de lumière proche infrarouge à l'intérieur du sujet est accentuée. L'unité d'émission de lumière proche infrarouge et l'appareil de prise de vues à proche infrarouge sont disposés avec le sujet à imager interposé entre eux. L'appareil de prise de vues à proche infrarouge comprend un réseau d'éléments de réception de lumière dans lequel une pluralité d'éléments de réception de lumière qui sont chacun séparés électriquement des éléments de réception de lumière adjacents à ceux-ci sont disposés de façon bidimensionnelle.
PCT/JP2021/041938 2020-11-18 2021-11-15 Système d'imagerie et procédé d'imagerie utilisant la lumière proche infrarouge WO2022107723A1 (fr)

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JP2852096B2 (ja) * 1990-03-29 1999-01-27 オリンパス光学工業株式会社 被検体通過中の散乱光成分抑制方法およびその装置
US20080218732A1 (en) * 2005-07-27 2008-09-11 University Of Massachusetts Lowell Infrared Scanner for Biological Applications
WO2011089949A1 (fr) * 2010-01-25 2011-07-28 アイアールスペック株式会社 Réseau d'éléments de réception de lumière à semi-conducteurs composés
WO2014192876A1 (fr) * 2013-05-30 2014-12-04 独立行政法人産業技術総合研究所 Système et procédé d'imagerie
JP2016168231A (ja) * 2015-03-13 2016-09-23 キヤノン株式会社 撮影装置、撮影システム、撮影方法及び撮影装置で用いられる支持部材
JP2018132465A (ja) * 2017-02-17 2018-08-23 株式会社Ｓｃｒｅｅｎホールディングス 撮像方法および撮像装置
JP2019096758A (ja) * 2017-11-24 2019-06-20 アイアールスペック株式会社 化合物半導体フォトダイオードアレイ

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Publication number Priority date Publication date Assignee Title
JP2852096B2 (ja) * 1990-03-29 1999-01-27 オリンパス光学工業株式会社 被検体通過中の散乱光成分抑制方法およびその装置
US5451785A (en) * 1994-03-18 1995-09-19 Sri International Upconverting and time-gated two-dimensional infrared transillumination imaging
US20080218732A1 (en) * 2005-07-27 2008-09-11 University Of Massachusetts Lowell Infrared Scanner for Biological Applications
WO2011089949A1 (fr) * 2010-01-25 2011-07-28 アイアールスペック株式会社 Réseau d'éléments de réception de lumière à semi-conducteurs composés
WO2014192876A1 (fr) * 2013-05-30 2014-12-04 独立行政法人産業技術総合研究所 Système et procédé d'imagerie
JP2016168231A (ja) * 2015-03-13 2016-09-23 キヤノン株式会社 撮影装置、撮影システム、撮影方法及び撮影装置で用いられる支持部材
JP2018132465A (ja) * 2017-02-17 2018-08-23 株式会社Ｓｃｒｅｅｎホールディングス 撮像方法および撮像装置
JP2019096758A (ja) * 2017-11-24 2019-06-20 アイアールスペック株式会社 化合物半導体フォトダイオードアレイ

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