Biological tissue identification device, biological tissue identification system, biological tissue identification method, and program

Abstract

To provide a biological tissue identification device capable of eliminating ambiguity in the superposition of mid-infrared and visible light images when acquiring microscopic images of biological tissue.SOLUTION: A biological tissue identification device (1) includes: a light source unit (10) that emits mid-infrared light and short-wavelength light having a wavelength shorter than that of mid-infrared light with the optical axis direction aligned; an objective focusing unit (20) that focuses the light beam emitted from the light source unit on an object; a first detection unit (40) that detects short wavelength light from the light beam after the same has been transmitted through or reflected by the object; and a second detection unit (50) that detects mid-infrared light from the light beam after the same has passed through or reflected by the object.SELECTED DRAWING: Figure 1

Description

[Technical Field]

[0001] The present invention relates to a biological tissue identification device, a biological tissue identification system, a biological tissue identification method, and a program. [Background technology]

[0002] For example, cancer diagnosis involves slicing lesioned biological tissue into observation sections and observing them under a microscope. Conventional tissue lesion diagnosis relies on cellular morphological changes detected using a visible light microscopy system, resulting in difficult cases. Furthermore, tissue staining to detect morphological changes or immunohistochemical staining to detect proteins specifically accumulating in lesions is required, resulting in the time required for a definitive diagnosis. Therefore, there is a need for the development of novel diagnostic techniques based on substances specifically accumulating in lesions. The inventors aim to solve this problem by developing a technology that utilizes the substance identification properties of mid-infrared light. However, mid-infrared light has a longer wavelength than visible light, resulting in reduced spatial resolution and unclear tissue boundaries. To address this issue, a method has been attempted that combines mid-infrared tissue identification with high-resolution morphological information obtained using visible light, as disclosed in Non-Patent Documents 1 and 2. [Prior art documents] [Non-patent literature]

[0003] [Non-Patent Document 1] SA Jedani et al., Analyst, 146, 5848-5854, 2021. [Non-patent document 2] R. Mankar et al., Analyst, 146, 4822-4834, 2021. Summary of the Invention [Problem to be solved by the invention]

[0004] In the methods disclosed in Non-Patent Documents 1 and 2, microscopic images using mid-infrared light and visible light are acquired using different devices. The mid-infrared light microscopic images are images obtained by focal plane array imaging and tiling processing using a Fourier transform infrared spectrometer (FT-IR) or by mapping measurement. The visible light microscopic images are images obtained by measurement using a wide-field microscope with a camera. These images are then combined to form an analytical method.

[0005] However, in the conventional techniques described above, the two images are acquired using different devices, resulting in different pixel spacing between each measurement image. Therefore, to process mid-infrared and visible light data at the same point in the tissue, interpolation calculations are required to create data for the same point between pixels where no data exists. Furthermore, the two tissue images are rotated and translated to overlay the two tissues. Furthermore, if differences in tissue shape due to distortion in the two images are observed, this correction must also be performed before overlaying the images. Furthermore, the data processing described above can be ambiguous when using interpolated data generated by calculation and when overlaying the two images, posing challenges in terms of reliability and diagnostic accuracy.

[0006] An aspect of the present invention aims to eliminate ambiguity in superimposing mid-infrared and visible light images when acquiring a microscopic image of biological tissue. [Means for solving the problem]

[0007] In order to solve the above problems, a biological tissue identification device according to one aspect of the present invention includes a light source unit that emits mid-infrared light and short-wavelength light having a wavelength shorter than the mid-infrared light with their optical axes aligned, an objective focusing unit that focuses the light beam emitted from the light source unit and irradiates the light beam onto an object, a first detection unit that detects the short-wavelength light from the light beam after it has passed through or reflected by the object, and a second detection unit that detects the mid-infrared light from the light beam after it has passed through or reflected by the object.

[0008] Furthermore, a biological tissue identification method according to one aspect of the present invention includes an emission step of emitting mid-infrared light and short-wavelength light having a wavelength shorter than the mid-infrared light with the optical axis direction aligned, an irradiation step of concentrating the emitted light beam and irradiating the object, a first detection step of detecting the short-wavelength light from the light beam after passing through or reflecting off the object, and a second detection step of detecting the mid-infrared light from the light beam after passing through or reflecting off the object.

[0009] Furthermore, a biological tissue identification system according to one aspect of the present invention includes a light source unit that emits mid-infrared light and short-wavelength light having a wavelength shorter than the mid-infrared light with their optical axes aligned; an objective focusing unit that focuses the light beam emitted from the light source unit and irradiates the object; a first detection unit that detects the short-wavelength light from the light beam after it has passed through or been reflected by the object; a second detection unit that detects the mid-infrared light from the light beam after it has passed through or been reflected by the object; an image generation unit that generates a composite image signal by combining a first detection signal detected by the first detection unit and a second detection signal detected by the second detection unit at each common detection time; and an image display control unit that displays an image based on the composite image signal on a display device.

[0010] In addition, a biological tissue identification program according to one embodiment of the present invention is a program for causing a computer to execute a movement process for moving a stand on which an object is placed according to a predetermined movement distance and direction, an emission process for emitting mid-infrared light and short-wavelength light having a wavelength shorter than the mid-infrared light, a first detection process for recording data of the short-wavelength light detected from the light beam after passing through or reflecting off the object, and a second detection process for recording data of the mid-infrared light detected from the light beam after passing through or reflecting off the object. [Effects of the Invention]

[0011] According to one aspect of the present invention, when acquiring a microscopic image of biological tissue, it is possible to eliminate ambiguity in superimposing both mid-infrared light and visible light images. [Brief explanation of the drawings]

[0012] [Figure 1] FIG. 1 is a block diagram showing the configuration of a biological tissue identification device 1 according to a first embodiment of the present invention. [Figure 2] FIG. 1 is a schematic side view showing an example of a specific device configuration of the biological tissue identification device 1 according to the first embodiment. [Figure 3] 1 is a flowchart showing the flow of a biological tissue discrimination method S1 according to the first embodiment. [Figure 4] 10 is an example of an image obtained by the biological tissue identification device 1 or the biological tissue identification method S1. [Figure 5] FIG. 1 is a block diagram showing the configuration of a biological tissue identification system 2 according to a second embodiment of the present invention. [Figure 6] FIG. 2 is a block diagram showing the functions of a control unit 60. [Figure 7] 10 is a flowchart showing the flow of a biological tissue identification process S2 executed by the control unit 60. [Figure 8] FIG. 10 is a schematic diagram showing the configuration of a biological tissue identification device 3 according to a third embodiment. [Figure 9] FIG. 10 is a schematic diagram showing the configuration of a biological tissue identification device 1A according to a fourth embodiment. [Figure 10] 1 is an absorbance graph showing how the absorbance of mid-infrared light varies with wavelength between normal lung tissue and lung cancer tissue. DETAILED DESCRIPTION OF THE INVENTION

[0013] [Embodiment 1] An embodiment of the present invention will be described in detail below with reference to the drawings. However, prior to this, the current state of the art will be described. As mentioned above, biological tissue can be observed with an optical microscope by tissue staining or immunohistochemical staining. In contrast, there is a method for observing biological tissue without staining it, which uses mid-infrared light. Mid-infrared light has different natural frequencies absorbed by different molecular structures or chemical bonds. For example, FIG. 10 is an absorbance graph showing how the absorbance of mid-infrared light varies with wavelength between normal lung tissue and lung cancer tissue. The horizontal axis of FIG. 10 represents wavelength, and the vertical axis represents absorbance. The solid line represents the absorbance of normal lung tissue, and the dotted line represents the absorbance of lung cancer tissue. As shown in the figure, there is a wavelength range (wavelength range in which differences are recognized) in which the absorbance of mid-infrared light between normal lung tissue and lung cancer tissue differs significantly. In this way, by utilizing the characteristic that the absorbance of mid-infrared light differs between normal tissue and pathological tissue at specific wavelengths, normal tissue and pathological tissue can be distinguished from each other.

[0014] This method has the advantage of not requiring staining. However, because mid-infrared light has a longer wavelength than visible light, the spatial resolution of the observed image is lower than that of visible light. Therefore, image acquisition methods that compensate for the reduced resolution by superimposing an image taken with mid-infrared light and an image taken with visible light are being studied. However, when superimposing two types of images, there is the problem that it is difficult to align the two. Hereinafter, superimposing two types of images will also be referred to as "merging."

[0015] (Bio-tissue identification device 1) FIG. 1 is a block diagram showing the configuration of a biological tissue identification device 1 according to a first embodiment. Note that FIG. 1 also shows components that are not necessarily required. FIG. 2 is a schematic side view of an example of a specific device configuration of the biological tissue identification device 1. The biological tissue identification device 1 is a device that acquires two image signals using mid-infrared light of sliced ​​biological tissue and short-wavelength light having a wavelength shorter than the mid-infrared light. In the present disclosure, mid-infrared light refers to light having a wavelength of, for example, 2.5 μm or more and 20 μm or less. The biological tissue identification device 1 according to this embodiment does not require alignment between an image acquired using mid-infrared light and an image acquired using visible light.

[0016] As shown in Fig. 1, the biological tissue identification device 1 includes a light source unit 10, an objective focusing unit 20, a beam splitter 30, a first detection unit 40, a second detection unit 50, and a control unit 60. The biological tissue identification device 1 may further include an image generation unit. Fig. 2 shows each unit except for the control unit 60. The control unit 60 will be described in detail later.

[0017] The light source unit 10 emits mid-infrared light and short-wavelength light having a wavelength shorter than the mid-infrared light, with their optical axes aligned. Specifically, the light source unit 10 includes a short-wavelength light emitter 11, a mid-infrared light emitter 12, and a beam combiner 13. The short-wavelength light emitter 11 generates short-wavelength light having a wavelength shorter than the mid-infrared light. Light with a wavelength shorter than that of mid-infrared light has higher resolution than mid-infrared light, thereby improving the resolution of the superimposed image. However, if the wavelength is too short, focusing and detection become difficult. Therefore, it is preferable to use near-infrared light to ultraviolet light as light with a wavelength shorter than mid-infrared light. In the present disclosure, near-infrared light refers to light with a wavelength in the range of 0.8 μm or more and less than 2.5 μm. Visible light refers to light with a wavelength in the range of 0.36 μm or more and less than 0.8 μm. The following description will use visible light as an example of light with a wavelength shorter than mid-infrared light.

[0018] The mid-infrared light emitter 12 generates mid-infrared light. A known mid-infrared light emitting device can be used as the mid-infrared light emitter 12, and the light may be coherent or non-coherent.

[0019] It is desirable to align the optical axes of the mid-infrared light and visible light emitted from the light source unit 10. In other words, it is desirable that the respective optical axes are approximately parallel and approximately coaxial. This allows the mid-infrared light and visible light to be focused at approximately the same position on the observation object 100 (see FIG. 2; hereinafter, the observation object will be simply referred to as the "object"), thereby improving the resolution of the acquired image. Conversely, it is desirable to align the optical axes of the mid-infrared light and visible light to the extent that they each focus at approximately the same position on the object 100.

[0020] The beam combining unit 13 is a device that combines visible light and mid-infrared light and outputs the combined light with the optical axis aligned. The beam combining unit 13 can be configured, for example, as a zinc selenide (ZnSe) beam combiner or a glass prism. For example, the beam combining unit 13 is configured to transmit visible light coming from a direction parallel to the combined optical axis, and to reflect mid-infrared light coming from a direction perpendicular to the combined optical axis and direct it in a direction parallel to the combined optical axis. The beam combining unit 13 is adjusted so that the optical axes of the visible light and mid-infrared light incident thereon are aligned when the combined light and the mid-infrared light are emitted.

[0021] In the example shown in FIG. 2, the light source unit 10 is located at the bottom of the figure. Visible light emitted from the short-wavelength light emitter 11 and mid-infrared light emitted from the mid-infrared light emitter 12 are combined by the beam combiner 13 to form irradiated light with aligned optical axes. The irradiated light is configured to be emitted toward the target 100. The target 100 is, for example, a biological tissue slice preparation placed on a platform 25. When measuring mid-infrared light transmitted through a sample, a preparation made of a material that transmits mid-infrared and short-wavelength light, such as ZnSe or BaF2, is used. When measuring mid-infrared light reflected from a sample, a general glass preparation can be used. The platform 25 is controlled to move sequentially to predetermined positions, and measurement data is acquired sequentially. This is called mapping measurement. Details of the platform 25 will be described later.

[0022] The objective condensing unit 20 has a function of condensing the light beam emitted from the light source unit 10 onto the target 100. The objective condensing unit 20 may condense the peripheral part of the light beam emitted from the light source unit 10 onto the target 100. The reason for this is to make it easier to detect only scattered visible light, as will be described later. In this case, the objective condensing unit 20 may block the central part of the light beam emitted from the light source unit 10. A light blocking plate for blocking light may be provided midway along the light beam before it is condensed.

[0023] The objective focusing unit 20 may be configured with a reflecting mirror. For example, the reflecting mirror may be a Schwarzschild objective mirror. A Schwarzschild objective mirror is configured with a combination of a convex mirror and a concave mirror, and since the central portion of the light beam is blocked internally, a light blocking plate is not required. Furthermore, unlike a lens, a reflecting mirror has the advantage that the focal position does not change between mid-infrared light and visible light. The objective focusing unit 20 may also be configured with a lens. However, since lenses made of glass or the like have different refractive indices for mid-infrared light and visible light, they must be combined so that the focal positions match. In the example shown in FIG. 2, the objective focusing unit 20 is configured with a Schwarzschild objective mirror. Therefore, light emitted from the objective focusing unit 20 becomes a doughnut-shaped light beam and is focused on the target 100. The objective focusing unit 20 may be any focusing optical element, and may include not only a Schwarzschild objective mirror or an objective lens, but also an aspherical lens or the like.

[0024] The beam splitter 30 has the function of splitting the light beam into two after it has passed through or reflected from the object 100. The beam splitter 30 is configured to particularly separate mid-infrared light and visible light. The beam splitter 30 may have a configuration similar to that of the beam combining unit 13. That is, the beam splitter 30 may be configured to transmit visible light and reflect mid-infrared light in a direction perpendicular to the optical axis. The light used to observe the object 100 may be transmitted light that has passed through the object 100 or reflected light that has been reflected from the object 100. In addition, both the visible light and the mid-infrared light may be transmitted light, or both may be reflected light. In addition, one of the visible light and the mid-infrared light may be transmitted light, and the other may be reflected light. If one of the visible light and the mid-infrared light is transmitted light and the other is reflected light, the beam splitter 30 is not necessary.

[0025] 2 shows an example of a configuration in which both transmitted mid-infrared light and visible light are measured, and therefore the two are separated using a beam splitter 30. However, it is also possible to use reflected light from either or both of the mid-infrared light and visible light.

[0026] The first detection unit 40 detects short wavelength light (for example, visible light) from the light beam that has passed through or reflected from the object 100 (or one of the two split light beams if the beam splitter 30 is provided). The first detection unit 40 includes a first imaging and focusing unit 42 that focuses the visible light (or one of the light beams) that has passed through or reflected from the object 100 onto the first detector 43, and a first detector 43 that detects the focused visible light. A signal detected by the first detector 43 is transmitted to the control unit 60, where it is processed and imaged (described later). The first detection unit 40 may also include a light blocking unit 41 that blocks the peripheral portion of the light beam. The reason for this is as follows.

[0027] The first detection unit 40 may detect only scattered light from the visible light transmitted through or reflected by the object 100 (dark-field observation method). In this case, the light beam irradiated onto the object 100 is preferably a donut-shaped light beam consisting of only the peripheral portion of the light beam. By providing a light-shielding unit 41 that blocks the peripheral portion of the light beam from the visible light transmitted through or reflected by the object 100, the donut-shaped transmitted or reflected light is blocked, and only scattered light that passes through the central portion can be detected. Scattered light is light scattered at the boundaries of biological tissues such as cells of the object 100. Therefore, observing the scattered light makes it easier to understand the structure of the biological tissues of the object 100.

[0028] In the example shown in FIG. 2, the first detection unit 40 is configured to detect only scattered visible light. That is, a light-shielding unit 41 is provided around the first imaging and focusing unit (lens) 42. Because the irradiated light is donut-shaped, the transmitted visible light that passes through the object 100 also becomes donut-shaped. This transmitted light is almost entirely blocked by the light-shielding unit 41. On the other hand, the scattered light from the object 100 is not donut-shaped, so it reaches the first imaging and focusing unit 42, is focused, and is detected by the first detector 43. The first detector 43 is, for example, a Si (silicon) photodetector suitable for detecting visible light. The photodetector has photoelectric conversion elements arranged as pixels, and converts light into a current or voltage for each pixel and outputs it.

[0029] The second detection unit 50 detects mid-infrared light from the light beam that has passed through or reflected from the target 100 (or the other of the two split light beams if the beam splitter 30 is provided). The second detection unit 50 includes a second imaging and focusing unit 51 that focuses the mid-infrared light (or the other light beam) on the second detector 52, and a second detector 52 that detects the focused mid-infrared light. The second detection unit 50 does not include a light-shielding unit. Therefore, the second detector 52 detects both the donut-shaped mid-infrared transmitted light and the mid-infrared scattered light. The signal detected by the second detector 52 is sent to the control unit 60, where it is processed and imaged (described below).

[0030] 2, the second detection unit 50 includes a second imaging and focusing unit (lens) 51 and a second detector 52. The second detector 52 is, for example, a HgCdTe (Mercury Cadmium Telluride, MCT) photodetector suitable for detecting mid-infrared light.

[0031] The detection of visible light by the first detection unit 40 and the detection of mid-infrared light by the second detection unit 50 are performed substantially simultaneously. This is because a single light beam is split and the visible light and mid-infrared light are detected separately. In other words, if the optical path difference between the visible light and mid-infrared light is ignored, the visible light image and mid-infrared light image are detected simultaneously. Visible light and mid-infrared light are irradiated onto the object once per location on the object, and the resulting detection signals are detected by the first detector 43 and the second detector 52. Because one detection area (measurement area) is small, the irradiation position is shifted slightly, and the visible light and mid-infrared light are irradiated again and the detection signals are detected. This procedure can be repeated throughout the entire object to measure it. Then, by combining the detection signals of visible light and mid-infrared light obtained by irradiating each measurement area, a superimposed image of the measurement area is obtained. By positioning each of the superimposed images at the measurement area, an image of the entire object is obtained.

[0032] As can be seen from this processing procedure, the order of detection signals acquired by the first detector 43 and the second detector 52 is the same as the order in which the visible light and mid-infrared light were irradiated onto the object. Therefore, it is sufficient to combine the nth (n is the number of imaging locations) visible light detection signal and the nth mid-infrared light detection signal, and there is no need to align the images. Furthermore, because the order in which visible light and mid-infrared light were irradiated and the irradiation positions on the object are predetermined, it is easy to generate an entire image.

[0033] (Bio-tissue identification method S1) Next, the biological tissue identification method S1 will be explained. The biological tissue identification method S1 can be executed using the biological tissue identification device 1. Fig. 3 is a flowchart showing the flow of the biological tissue identification method S1 according to this embodiment. As shown in the figure, the biological tissue identification method S1 includes steps S11 to S17. Note that it is not necessarily necessary to execute all steps.

[0034] Step S11 is an emission step in which mid-infrared light and short-wavelength light having a wavelength shorter than the mid-infrared light are emitted with their optical axes aligned. The emission step is executed by the control unit 60 controlling the light emission of the short-wavelength light emitter 11 and the mid-infrared light emitter 12 of the light source unit 10. The short-wavelength light and mid-infrared light generated by the short-wavelength light emitter 11 and the mid-infrared light emitter 12 are combined by the beam combining unit 13 and emitted.

[0035] Step S12 is an irradiation step in which the light beam emitted from the light source unit is condensed and irradiated onto the object. The irradiation step is performed by the objective condenser unit 20.

[0036] Step S13 is a beam splitting step in which the beam that has passed through or been reflected by the object is split into two beams. Step S13 is performed by the beam splitter 30. However, step S13 is a step that is performed when both transmitted light of short wavelength light and mid-infrared light are used, or when both reflected light are used. Step S13 is not necessary when using transmitted light of one of short wavelength light and mid-infrared light and reflected light of the other.

[0037] Step S14 is a first detection step for detecting short wavelength light in one of the two split light beams. The first detection step is performed by the first detection unit 40. If step S13 is not performed, step S14 becomes the first detection step for detecting short wavelength light from either the light beam after transmission through the object or the light beam after reflection.

[0038] Step S15 is a second detection step of detecting mid-infrared light in the other of the two split light beams. The second detection step is performed by the second detection unit 50. If step S13 is not performed, step S15 becomes the second detection step of detecting mid-infrared light from the other of the light beams after transmission through the object or the light beams after reflection. Steps S14 and S15 are performed substantially simultaneously.

[0039] Step S16 is an image signal generation step in which the first detection signal detected by the first detection unit and the second detection signal detected by the second detection unit are combined at a common detection time to generate a combined image signal. The image signal generation step is executed by the image generation unit, which will be described later. As described above, "combining at a common detection time" means combining signals that were detected in the same order. In other words, it means combining the nth visible light detection signal and the nth mid-infrared light detection signal.

[0040] Step S17 is a display step for displaying the generated image. The display step is executed by the image display control unit 70, which will be described later, and causes a display device such as a display to display the synthesized image.

[0041] FIG. 4 is an example of an image obtained by the biological tissue identification device 1 or the biological tissue identification method S1. 401 in FIG. 4 is a microscopic image obtained by mid-infrared light. 402 in FIG. 4 is a microscopic image obtained by visible scattered light. As shown in the figure, mid-infrared light has a longer wavelength than visible light, so the mid-infrared light image 401 has a lower resolution than the visible light image 402. On the other hand, 403 in FIG. 4 is a composite image obtained by combining (fusing) both microscopic images. As can be seen from this, the resolution of the microscopic image obtained by mid-infrared light is increased by combining it with the microscopic image obtained by visible scattered light.

[0042] As described above, with the biological tissue identification device 1 and biological tissue identification method S1 having the above configuration, there is no need to align the microscopic image obtained with mid-infrared light and the microscopic image obtained with short wavelength light when combining them. Therefore, when acquiring a microscopic image of biological tissue, calculations such as superposition or interpolation to generate two pieces of data at the same point on the subject are not required, and ambiguity in superimposing both mid-infrared and visible light images can be eliminated.

[0043] [Embodiment 2] Other embodiments of the present invention will be described below. For ease of explanation, the same reference numerals will be used to designate components having the same functions as those described in the above embodiment, and the description thereof will not be repeated.

[0044] (Bio-tissue Identification System 2) Fig. 5 is a block diagram showing the configuration of a biological tissue identification system 2 according to embodiment 2. As shown in the figure, the biological tissue identification system 2 comprises a light source unit 10, an objective light-collecting unit 20, a beam splitter 30, a first detection unit 40, a second detection unit 50, and a control unit 60. The configurations of the light source unit 10, the objective light-collecting unit 20, the beam splitter 30, the first detection unit 40, and the second detection unit 50 are the same as those of the biological tissue identification device 1 described in embodiment 1, so a description thereof will be omitted here. The biological tissue identification system 2 further comprises an image generation unit 69 and an image display control unit 70 in the control unit 60. The biological tissue identification system 2 may further comprise a display device (not shown) for displaying images.

[0045] The image generation unit 69 generates a composite image signal by combining the first detection signal detected by the first detection unit 40 and the second detection signal detected by the second detection unit 50 at each common detection time. A known combining method can be used to combine the first detection signal and the second detection signal. For example, predetermined calculations such as multiplication, division, or addition of the light intensity for each pixel of each detector may be performed. For example, the intensities of the two images may be normalized and the normalized two images may be added. Alternatively, a method using the data with the higher resolution for each pixel may be used. For example, the two images may be transformed into a feature space (such as spatial frequency), some components may be exchanged with the same components of a high-resolution image, and then the resulting image may be inversely transformed.

[0046] The image display control unit 70 outputs an image based on the composite image signal to a display device and displays it. The display device may be provided in the biological tissue identification system 2 or may be external to the biological tissue identification system 2. The image generation unit 69 and the image display control unit 70 may be configured as a personal computer having a display device. In that case, the biological tissue identification system 2 can be configured by the biological tissue identification device 1 and a personal computer having the functions of the image generation unit 69 and the image display control unit 70. The biological tissue identification device 1 and the personal computer may be connected via a communication network such as the Internet or an intranet. With this configuration, the biological tissue identification device 1 that measures the target and the personal computer that processes the measured data into images can be located in different places.

[0047] (control unit 60) Next, we will explain the control unit 60 of the biological tissue identification device 1 or the biological tissue identification system 2. The control unit 60 controls the light source unit 10, the first detection unit 40, the second detection unit 50, and controls the driving of the stand 25 on which the object 100 is placed. The control unit 60 may also have the functions of an image generation unit 69 and an image display control unit 70.

[0048] As shown in FIG. 1 or 5, the control unit 60 includes at least one processor 61 and at least one memory 62. The processor 61 can be configured using a general-purpose processor such as at least one MPU (Micro Processing Unit) or CPU (Central Processing Unit). The memory 62 may include multiple types of memory such as ROM (Read Only Memory) and RAM (Random Access Memory). The memory 62 may also include built-in or external memory such as HDD (Hard Disk Drive) or SSD (Solid State Drive). As an example, the processor 61 implements the functions of the control unit 60 described below by loading various control programs (such as a biological tissue identification program described below) recorded in the ROM of the memory 62 into RAM and executing them. The processor 61 may also include a dedicated processor configured using an ASIC (Application Specific Integrated Circuit), FPGA (Field Programmable Gate Array), PLD (Programmable Logic Device), or the like.

[0049] 6 is a block diagram showing the functions of the control unit 60. As shown in the figure, the control unit 60 includes a mount drive unit 63, a short-wavelength light emission control unit 64, a mid-infrared light emission control unit 65, a first detection signal acquisition unit 66, and a second detection signal acquisition unit 67. The control unit 60 may further include an image generation unit 69 and an image display control unit 70. These units are connected to each other via a bus 71.

[0050] The functions of the control unit 60 will be explained below in relation to the flow of the biological tissue identification method S1. The biological tissue identification method S1 starts when the target is set at the first imaging position. The gantry driving unit 63 sets the target at the first imaging position whose coordinates have been determined in advance. Alternatively, the user may set the target at the first imaging position.

[0051] The gantry driver 63 controls a driver that drives the gantry 25 on which the object 100 is placed. The gantry 25 may be a two-axis moving table in the X and Y directions that uses, for example, a stepping motor as a drive unit. The gantry driver 63 controls the stepping motor of the gantry 25 according to the movement direction and movement distance described in the biological tissue identification program recorded in the memory 62. The object 100 is imaged for each region (imaging range) divided into a grid pattern in the X and Y directions. The gantry driver 63 sequentially moves the gantry 25 to adjacent imaging ranges, where imaging processing is performed. This procedure is repeated to image the entire object. This is called mapping measurement. It is preferable that the width of the imaging range, i.e., the movement distance, is less than half the diameter of the beam irradiated on the object. This allows for high-resolution images to be obtained.

[0052] The short-wavelength light emission control unit 64 controls the short-wavelength light emitter 11 to emit light for a predetermined period of time after the object is moved to the imaging position. The mid-infrared light emission control unit 65 controls the mid-infrared light emitter 12 to emit light for a predetermined period of time after the object is moved to the imaging position. These controls are performed substantially simultaneously. Therefore, one emission control unit may control the emission of light from the short-wavelength light emitter 11 and the mid-infrared light emitter 12, causing both to emit light at the same time. This causes steps S11 and S12 to be executed. Furthermore, step S13 is executed when the light beam emitted from the light source unit 10 passes through the beam splitter 30.

[0053] The first detection signal acquisition unit 66 acquires the first detection signal output from the first detector 43, converts it into a digital signal, and records it in the memory 62. The second detection signal acquisition unit 67 acquires the second detection signal output from the second detector 52, converts it into a digital signal, and records it in the memory 62. This executes steps S14 and S15. When the light emission and imaging are complete, the gantry driving unit 63 moves the gantry 25 to the next imaging position.

[0054] The image generation unit 69 acquires and combines the first detection signal and the second detection signal recorded in the memory 62 to generate a composite image signal (composite image data), and records the composite image signal in the memory 62. This executes step S16. Step S16 is executed by an image generation program that causes the computer to execute a signal combination process that combines the first detection signal detected by the first detection unit and the second detection signal detected by the second detection unit for each common detection time to generate a composite image signal.

[0055] The image display control unit 70 acquires the image data recorded in the memory 62 and transmits it to a display device (not shown) for display, thereby executing step S17.

[0056] The control executed by the processor 61 of the control unit 60 in accordance with the biological tissue identification program will be described below as biological tissue identification processing (biological tissue imaging processing) S2. The biological tissue identification program is stored in the memory 62. FIG. 7 is a flowchart showing the flow of the biological tissue identification processing S2 executed by the control unit 60. As shown in the figure, the biological tissue identification processing S2 includes steps S21 to S24. The biological tissue identification processing S2 may further include steps S25 to S27.

[0057] Step S21 is a step of executing a movement process to move the gantry 25 on which the target 100 is placed to an imaging position according to a predetermined movement distance and direction. Specifically, the processor 61 controls the driving of the driving unit of the gantry 25. The process of moving the gantry 25 to the initial imaging position may be performed by a user.

[0058] Step S22 is a step of executing a light emission process to emit mid-infrared light and short-wavelength light having a wavelength shorter than that of the mid-infrared light. Specifically, the processor 61 controls the short-wavelength light emitter 11 and the mid-infrared light emitter 12 to emit light for a predetermined period of time.

[0059] Step S23 is a step of executing a first detection process to record data of short wavelength light detected from the light beam after it has been transmitted through or reflected by the target 100. Specifically, the processor 61 records the signal from the first detector 43 in the memory 62.

[0060] Step S24 is a step of executing a second detection process to record data of mid-infrared light detected from the light beam after it has passed through or been reflected by the target 100. Specifically, the processor 61 records a signal from the second detector 52 in the memory 62.

[0061] Step S25 is a determination step for determining whether all predetermined data has been recorded. Specifically, the processor 61 determines whether all data of a predetermined location (area) to be imaged has been recorded. If it is determined that all data has not been recorded (locations to be imaged remain) (step S25: NO), the process returns to step S21, and the gantry 25 is moved to the next imaging location. If it is determined that all data has been recorded (step S25: YES), the process proceeds to step S26.

[0062] Step S26 is a step of executing a synthesis process for synthesizing the short wavelength light data and the mid-infrared light data for each imaging region.

[0063] Step S27 is a step of executing a display process to display an image based on the combined data on the display device. Through the above steps, an image of the entire object is displayed on the display device.

[0064] According to the biological tissue identification system 2 having the above configuration, there is no need to align the microscopic image obtained by mid-infrared light and the microscopic image obtained by short wavelength light when combining them. Therefore, when acquiring a microscopic image of biological tissue, it is possible to eliminate the ambiguity that occurs when the mid-infrared light and the visible light images are combined. Furthermore, the combined image can be displayed on a display device.

[0065] In the first or second embodiment, the control unit 60 can perform mapping measurement of the target according to a program that records predetermined procedures. Therefore, after the user sets the target on the stand, the user can execute measurement according to the program. Note that the control unit 60 of the biological tissue identification device 1 or the biological tissue identification system 2 may be provided with a measurement condition setting unit (function) that allows the user to change the measurement conditions (not shown).

[0066] [Embodiment 3] Other embodiments of the present invention will be described below. For ease of explanation, the same reference numerals will be used to designate components having the same functions as those described in the above embodiment, and the description thereof will not be repeated.

[0067] FIG. 8 is a schematic diagram showing the configuration of a biological tissue identification device 3 according to a third embodiment. As described above, the mid-infrared light and visible light may be transmitted light or reflected light. Furthermore, the irradiated light may or may not be doughnut-shaped light. In the example shown in FIG. 8, mid-infrared light and visible light with aligned optical axes are emitted from the light source unit 10, and are condensed by the objective condenser lens 20A and directed toward the target 100. In this example, the light beam is not doughnut-shaped.

[0068] Of the light beams irradiated onto the object, visible light is transmitted and forms an image on the first detector 43 by the first imaging condenser 42. Meanwhile, part of the mid-infrared light is reflected from the object 100 and returns toward the objective condenser lens 20A. It is further bent at a right angle by the reflecting mirror 30A arranged along the way and forms an image on the second detector 52 by the second imaging condenser 51. The reflecting mirror 30A is not a beam splitter but a half mirror for guiding the mid-infrared light reflected from the object 100 to the second detector 52. The signals output from the first detector 43 and the second detector 52 are processed as described above.

[0069] The modified configurations described in the first or second embodiment can also be applied to the third embodiment. The third embodiment can also achieve the same effects as those achieved by the configurations of the first or second embodiment.

[0070] [Embodiment 4] Other embodiments of the present invention will be described below. For ease of explanation, the same reference numerals will be used to designate components having the same functions as those described in the above embodiment, and the description thereof will not be repeated.

[0071] FIG. 9 is a schematic diagram showing the configuration of a biological tissue identification device 1A according to a fourth embodiment. The configuration of the biological tissue identification device 1A is basically the same as that of the biological tissue identification device 1 shown in FIG. 2. The biological tissue identification device 1A differs from the biological tissue identification device 1 in that the beam combining unit 13 and the beam splitter 30 are configured to be movable. Specifically, the beam combining unit 13 and the beam splitter 30 can be inserted into or removed from the optical path. This allows visible light and short-wavelength light to be collected separately. That is, when both the beam combining unit 13 and the beam splitter 30 are inserted into the optical path, the visible light is guided to the first detector 43 and the mid-infrared light is guided to the second detector 52, as shown in FIG. 2. On the other hand, when both the beam combining unit 13 and the beam splitter 30 are removed from the optical path, only the visible light is guided to the first detector 43, as shown in FIG. 9. In this case, the measurement time differs between the mid-infrared light measurement and the visible light measurement, but since the mid-infrared light image and the visible light image are obtained at the same measurement point on the object 100, it is easy to combine the two.

[0072] [Software implementation example] The functions of the biological tissue identification device 1 (hereinafter referred to as the "device") can be realized by a program that causes a computer to function as the device, and a program that causes a computer to function as each control block of the device (particularly each part included in the control unit 60).

[0073] In this case, the device includes a computer having at least one control device (e.g., a processor) and at least one storage device (e.g., a memory) as hardware for executing the program. The control device and storage device execute the program, thereby realizing the functions described in each of the above embodiments.

[0074] The program may be non-transitory and may be recorded on one or more computer-readable recording media. The recording media may or may not be included in the device. In the latter case, the program may be supplied to the device via any wired or wireless transmission medium.

[0075] Furthermore, some or all of the functions of the control blocks can be realized by logic circuits. For example, an integrated circuit in which a logic circuit that functions as each of the control blocks is formed is also included in the scope of the present invention. In addition, the functions of the control blocks can also be realized by, for example, a quantum computer.

[0076] Furthermore, each process described in each of the above embodiments may be executed by AI (Artificial Intelligence). In this case, the AI ​​may run on the control device or on another device (for example, an edge computer or a cloud server).

[0077] The present invention is not limited to the above-described embodiments, and various modifications are possible within the scope of the claims. Embodiments obtained by appropriately combining the technical means disclosed in different embodiments are also included in the technical scope of the present invention.

[0078] (summary) (Aspect 1) A biological tissue identification device comprising: a light source unit that emits mid-infrared light and short-wavelength light having a wavelength shorter than the mid-infrared light with the optical axis direction aligned; an objective focusing unit that focuses the light beam emitted from the light source unit on a target; a first detection unit that detects the short-wavelength light from the light beam after it has passed through or reflected by the target; and a second detection unit that detects the mid-infrared light from the light beam after it has passed through or reflected by the target.

[0079] (Aspect 2) 2. The biological tissue identification device according to aspect 1, wherein the objective light-collecting unit collects the light beam emitted from the light source unit at a peripheral portion thereof.

[0080] (Aspect 3) The biological tissue identification device according to aspect 1 or 2, wherein the first detection unit includes a light-shielding unit that blocks a peripheral portion of the short-wavelength light, a first imaging and focusing unit that focuses the short-wavelength light scattered from the object, and a first detector that detects the focused scattered light.

[0081] (Aspect 4) 4. The biological tissue identification device according to any one of aspects 1 to 3, wherein the second detection unit includes a second imaging and focusing unit that focuses the mid-infrared light, and a second detector that detects the focused mid-infrared light.

[0082] (Aspect 5) 5. The biological tissue identification device of any one of aspects 1 to 4, further comprising a beam splitter that splits the light beam into two after passing through or reflecting off the object, wherein the first detection unit detects the short-wavelength light in one of the two light beams, and the second detection unit detects the mid-infrared light in the other of the two light beams.

[0083] (Aspect 6) 6. The biological tissue identification device according to any one of aspects 1 to 5, wherein the objective light-collecting unit is configured with a reflecting mirror.

[0084] (Aspect 7) The biological tissue identification device of any one of aspects 1 to 6, wherein the light source unit includes a mid-infrared light emitter, a short-wavelength light emitter, and a beam combining unit that combines the mid-infrared light emitted from the mid-infrared light emitter and the short-wavelength light emitted from the short-wavelength light emitter.

[0085] (Aspect 8) The biological tissue identification device according to any one of aspects 1 to 7, further comprising an image generation unit that generates a composite image signal by combining a first detection signal detected by the first detection unit and a second detection signal detected by the second detection unit at each common detection time.

[0086] (Aspect 9) A biological tissue identification method comprising: an emission step of emitting mid-infrared light and short-wavelength light having a wavelength shorter than the mid-infrared light with the optical axis direction aligned; an irradiation step of concentrating the emitted light beam and irradiating the object; a first detection step of detecting the short-wavelength light from the light beam after it has passed through or been reflected by the object; and a second detection step of detecting the mid-infrared light from the light beam after it has passed through or been reflected by the object.

[0087] (Aspect 10) a first detection unit that detects the short wavelength light from the light beam after it has been transmitted through or reflected by the object; a second detection unit that detects the mid-infrared light from the light beam after it has been transmitted through or reflected by the object; an image generation unit that generates a composite image signal by combining a first detection signal detected by the first detection unit and a second detection signal detected by the second detection unit at a common detection time; and an image display control unit that displays an image based on the composite image signal on a display device.

[0088] (Aspect 11) A biological tissue identification program that causes a computer to execute a movement process that moves a platform on which an object is placed according to a predetermined movement distance and direction, an emission process that emits mid-infrared light and short-wavelength light having a wavelength shorter than the mid-infrared light, a first detection process that records data of the short-wavelength light detected from the light beam after it has passed through or been reflected by the object, and a second detection process that records data of the mid-infrared light detected from the light beam after it has passed through or been reflected by the object.

[0089] (Aspect 12) A computer-readable non-transitory recording medium having recorded thereon the biological tissue identification program according to embodiment 11. [Explanation of symbols]

[0090] 1...Bio-tissue identification device 2. Biological tissue identification system 10...Light source section 11...Short wavelength light emitting unit 12...Mid-infrared light emitting unit 13...Beam joint 20, 20A...Objective focusing part (objective focusing lens) 30, 30A...Beam splitter (reflector) 40...First detection unit 41...Light blocking part 42...First imaging condenser 43...First detector 50...Second detection unit 51...Second imaging condenser 52...Second detector 60...Control unit 61...Processor 62...Memory 63... Platform drive unit 64...Short wavelength light emission control section 65...Mid-infrared light emission control unit 66...First detection signal acquisition unit 67...Second detection signal acquisition unit 69...Image generation unit 70...Image display control unit

Claims

1. a light source unit that emits mid-infrared light and short-wavelength light having a wavelength shorter than that of the mid-infrared light, with optical axes aligned; an objective condensing unit that condenses the light beam emitted from the light source unit onto an object; a first detection unit that detects the short wavelength light from the light beam after it has been transmitted through or reflected by the object; a second detection unit that detects the mid-infrared light from the light beam after it has been transmitted through or reflected by the object; A biological tissue identification device comprising:

2. The biological tissue identification device according to claim 1 , wherein the objective light-condensing unit condenses the peripheral portion of the light beam emitted from the light source unit onto a target.

3. 3. The biological tissue identification device according to claim 2, wherein the first detection unit comprises: a light-shielding unit that blocks a peripheral portion of the short-wavelength light; a first imaging and focusing unit that focuses the short-wavelength light scattered from the object; and a first detector that detects the focused scattered light.

4. 3. The biological tissue identification device according to claim 2, wherein the second detection section comprises a second image forming and focusing section that focuses the mid-infrared light, and a second detector that detects the focused mid-infrared light.

5. 3. The biological tissue identification device according to claim 1, further comprising a beam splitter that splits the light beam into two after passing through or reflecting off the object, wherein the first detection unit detects the short wavelength light in one of the two light beams, and the second detection unit detects the mid-infrared light in the other of the two light beams.

6. 3. The biological tissue identification device according to claim 1, wherein the objective light-condensing unit is configured with a reflecting mirror.

7. 3. The biological tissue identification device according to claim 1, wherein the light source unit comprises: a mid-infrared light emitter; a short-wavelength light emitter; and a beam combiner that combines the mid-infrared light emitted from the mid-infrared light emitter and the short-wavelength light emitted from the short-wavelength light emitter.

8. 3. The biological tissue identification device according to claim 1, further comprising an image generation unit that generates a composite image signal by combining a first detection signal detected by the first detection unit and a second detection signal detected by the second detection unit for each common detection time.

9. an emission step of emitting mid-infrared light and short-wavelength light having a wavelength shorter than that of the mid-infrared light with their optical axes aligned; an irradiation step of concentrating the emitted light beam and irradiating the target with the light beam; a first detection step of detecting the short wavelength light from the light beam after it has been transmitted through or reflected by the object; a second detection step of detecting the mid-infrared light from the light beam after it has been transmitted through or reflected by the object; A method for identifying biological tissue, comprising:

10. a light source unit that emits mid-infrared light and short-wavelength light having a wavelength shorter than that of the mid-infrared light, with optical axes aligned; an objective condensing unit that condenses the light beam emitted from the light source unit onto an object; a first detection unit that detects the short wavelength light from the light beam after it has been transmitted through or reflected by the object; a second detection unit that detects the mid-infrared light from the light beam after it has been transmitted through or reflected by the object; an image generating unit that generates a composite image signal by combining the first detection signal detected by the first detecting unit and the second detection signal detected by the second detecting unit at each common detection time; an image display control unit that displays an image based on the composite image signal on a display device; A biological tissue identification system comprising:

11. On the computer, a movement process for moving the platform on which the object is placed according to a predetermined movement distance and direction; a light emission process for emitting mid-infrared light and short wavelength light having a wavelength shorter than that of the mid-infrared light; a first detection process for recording data of the short wavelength light detected from the light beam after it has been transmitted through or reflected by the object; a second detection process for recording data of the mid-infrared light detected from the light beam after it has been transmitted through or reflected by the object; A biological tissue identification program for executing the above.

12. A computer-readable non-transitory recording medium on which the biological tissue identification program according to claim 11 is recorded.

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