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WO2022085628A1 - Nonlinear raman scattering endoscope using optical fiber bundle - Google Patents

Nonlinear raman scattering endoscope using optical fiber bundle Download PDF

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Publication number
WO2022085628A1
WO2022085628A1 PCT/JP2021/038436 JP2021038436W WO2022085628A1 WO 2022085628 A1 WO2022085628 A1 WO 2022085628A1 JP 2021038436 W JP2021038436 W JP 2021038436W WO 2022085628 A1 WO2022085628 A1 WO 2022085628A1
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Prior art keywords
pulse laser
light
laser beam
fiber bundle
optical fiber
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French (fr)
Japanese (ja)
Inventor
守 橋本
拓希 小川
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Hokkaido University NUC
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Hokkaido University NUC
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B1/00—Instruments for performing medical examinations of the interior of cavities or tubes of the body by visual or photographical inspection, e.g. endoscopes; Illuminating arrangements therefor
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B1/00—Instruments for performing medical examinations of the interior of cavities or tubes of the body by visual or photographical inspection, e.g. endoscopes; Illuminating arrangements therefor
    • A61B1/06—Instruments for performing medical examinations of the interior of cavities or tubes of the body by visual or photographical inspection, e.g. endoscopes; Illuminating arrangements therefor with illuminating arrangements
    • A61B1/07—Instruments for performing medical examinations of the interior of cavities or tubes of the body by visual or photographical inspection, e.g. endoscopes; Illuminating arrangements therefor with illuminating arrangements using light-conductive means, e.g. optical fibres
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
    • G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
    • G01N21/65—Raman scattering

Definitions

  • the present invention relates to a nonlinear Raman scattering endoscope that images an object such as the inner wall of the gastrointestinal tract by utilizing a nonlinear optical phenomenon.
  • the mainstream endoscopes for the gastrointestinal tract are fiberscopes that use optical fiber bundles, and videoscopes that have an image sensor such as a CCD built into the tip.
  • the current gastrointestinal endoscopy scope does not provide sufficient spatial resolution for cell observation.
  • probe-type confocal laser microendoscopes have been developed, and observation images at the same level as the pathological images of specimens can be obtained. Therefore, for example, it is not impossible to perform diagnostic imaging and endoscopic surgery at the same time. rice field.
  • a fluorescent dye fluorescein, etc.
  • This probe-type cofocal laser microendoscope is provided with an optical fiber bundle having a diameter of about 1 mm to 2 mm composed of several thousand or more small-diameter optical fibers, and a small objective lens at the tip (probe head) thereof.
  • a confocal effect can be obtained by transmitting and irradiating excitation light through individual optical fibers and back-propagating the generated fluorescence, and even the shape of cells can be observed.
  • the probe-type confocal laser microscopic endoscope has a small diameter and a small probe head, it can be inserted into the forceps hole of a bent gastrointestinal endoscopy scope, and it can be observed in a wide field of view. Both endoscopic observation and probe-type cofocal laser microscopic endoscopic observation that can be observed with high spatial resolution are compatible. However, there are concerns about the safety of intravenous administration of fluorescent dyes (Non-Patent Documents 1 and 2).
  • Non-Patent Documents 4 and 5 coherent anti-Stoke Slaman scattering (CARS)
  • SRS induced Raman scattering
  • Non-Patent Documents 8 to 10 Non-Patent Documents 8 to 10
  • a small-diameter endoscope that can be inserted into the forceps hole of a gastrointestinal endoscopy scope has not yet been developed.
  • Non-Patent Documents 9 and 10 endoscopes using a beam scanning method in which an actuator is attached to rotate an optical fiber have been developed.
  • the beam scanning mechanism is large, the rigid probe head is large, and it is difficult to insert it into the forceps hole of the gastrointestinal endoscopy scope.
  • the optical fiber bundle can be used to reduce the diameter and the probe head, but in the case of CARS, the non-linearity inside the fiber when the excitation light is transmitted by the optical fiber. Due to an optical phenomenon, four-wave mixing (FWM: Four Wave Mixing) light having the same wavelength as CARS light is generated (Non-Patent Document 11).
  • FWM Four Wave Mixing
  • This four-wave mixed light is said to be two to three orders of magnitude higher than that of the CARS light generated from the sample, and becomes noise light that interferes with the detection of CARS light.
  • Research is also being conducted to prevent the influence of this four-wave mixed light by separating the optical fiber bundle that transmits the excitation light and the optical fiber for detecting CARS light, but a probe for separating the excitation light and the CARS light.
  • the head becomes large, and the diameter can be reduced so that it can be inserted into the forceps hole (Non-Patent Document 11).
  • An object of the present invention is to provide a nonlinear Raman scattering endoscope capable of suppressing four-wave mixed light generated from an optical fiber bundle.
  • the nonlinear Raman scattering endoscope is A first laser light source that generates a first pulsed laser beam having a first wavelength, A second laser light source that generates a second pulsed laser beam having a second wavelength different from the first wavelength, A mechanism for adjusting the first pulse laser beam and the second pulse laser beam so as to irradiate an object at the same time.
  • a combined wave optical element for spatially superimposing the first pulse laser beam and the second pulse laser beam emitted from the optical fiber bundle.
  • a condensing optical system that focuses the first pulse laser light and the second pulse laser light emitted from the combined wave optical element at the same spot toward an object. It includes a photodetector that detects Raman scattered light generated by a nonlinear optical phenomenon in an object.
  • the four-wave mixed light generated from the optical fiber bundle can be suppressed.
  • FIG. 1A is a block diagram showing an example of the configuration of a nonlinear Raman scattering endoscope according to an embodiment of the present invention
  • FIG. 1B shows an example of lens arrangement inside an optical system.
  • FIG. 2A is an explanatory diagram showing how the laser beams LB1 and LB2 are incident on the end face FA of the optical fiber bundle 34.
  • FIG. 2B is a plan view of the optical fiber bundle 34 at the end face FA.
  • FIG. 3A is an explanatory diagram showing how the laser beams LB1 and LB2 are incident on the combined wave optical element 38.
  • FIG. 3B is an explanatory diagram showing how the laser beams LB1 and LB2 are incident on the wave plate 41.
  • FIG. 5A is an image showing the distribution of excitation light emitted from the end face FB without two-dimensional scanning when the laser beams LB1 and LB2 are incident on the same core.
  • FIG. 5B is an image showing the distribution of four-wave mixed light emitted from the end face FA when two-dimensional scanning is performed with the setting of FIG. 5A.
  • FIG. 5C is an image showing the distribution of excitation light emitted from the end face FB without two-dimensional scanning when the laser beams LB1 and LB2 are incident on separate cores.
  • FIG. 5A is an image showing the distribution of excitation light emitted from the end face FB without two-dimensional scanning when the laser beams LB1 and LB2 are incident on separate cores.
  • 5D is an image showing the distribution of four-wave mixed light emitted from the end face FA when two-dimensional scanning is performed with the setting of FIG. 5C.
  • 6 (A) and 6 (D) are images of an image of a sample in which one polystyrene bead (diameter 25 ⁇ m) is placed on a glass plate as an object SP in the endoscope shown in FIG. 1 (A).
  • 6 (A) shows an image of CARS light
  • FIG. 6 (D) shows a transmitted image of laser light.
  • 6 (B) and 6 (E) are images of a sample of only a glass plate as an object SP in the endoscope shown in FIG. 1 (A), and FIG. 6 (B) shows an image of CARS light.
  • FIG. 1 (A) shows an image of CARS light.
  • 6E shows a transmitted image of the laser beam.
  • 6 (C) is a difference image between the image of FIG. 6 (A) and the image of FIG. 6 (B).
  • 6 (F) is a difference image between the image of FIG. 6 (D) and the image of FIG. 6 (E).
  • FIG. 1 (A) is a block diagram showing an example of the configuration of a non-linear Raman scattering endoscope according to an embodiment of the present invention
  • FIG. 1 (B) shows an example of lens arrangement inside an optical system.
  • This endoscope includes a laser light source 11 and 21, a synchronization system 5, partial reflection mirrors 11 and 22, an optical delay adjustment mechanism including mirrors 12 to 15, mirrors 16, 23, 24, and 1/2 wavelength.
  • the laser light source 11 generates a laser beam LB1 having a wavelength ⁇ 1 as pulse excitation light on the order of picoseconds (for example, Tsunami of Spectra Physics).
  • the laser beam LB1 has, for example, linearly polarized light parallel to the paper surface.
  • the partial reflection mirror 11 reflects a part of the laser beam LB1, for example, about 1% of the light, and allows the rest of the light to pass through.
  • the light reflected by the partial reflection mirror 11 is incident on the light delay adjusting mechanism including the mirrors 12 to 15 as monitor light.
  • the mirrors 12 and 15 are fixed, the mirrors 13 and 14 are integrally displaceable, and the laser beam is adjusted by adjusting the optical path length between the mirrors 12 and 15 and the mirrors 13 and 14.
  • the time for the LB 1 to pass from the mirror 12 to the mirror 15 can be adjusted.
  • the light emitted from the optical delay adjusting mechanism is incident on the synchronization system 5 as monitor light via the mirror 16.
  • the laser light source 21 generates a laser beam LB2 having a wavelength ⁇ 2 different from the wavelength ⁇ 1 as pulse excitation light on the order of picoseconds (for example, Tsunami of Spectra Physics).
  • the laser beam LB2 has, for example, linearly polarized light parallel to the paper surface.
  • the partial reflection mirror 22 reflects a part of the laser beam LB2, for example, about 1% of the light, and allows the rest of the light to pass through. The light reflected by the partial reflection mirror 22 enters the synchronization system 5 via the mirror 23.
  • the laser light sources 11 and 21 are separate laser light sources, but for example, a part of the light of the laser light source 11 may be taken out to convert the wavelength and used instead of the laser light source 21. Alternatively, a part of the light of the laser light source 21 may be taken out, wavelength-converted, and used in place of the laser light source 11. Alternatively, the light from the laser light source may be divided into two, each of which is wavelength-converted and used in place of the laser light sources 11 and 21.
  • the synchronization system 5 detects the monitor light from the laser light sources 11 and 21 and feedback-controls so that the timings of the pulse lights in the laser light sources 11 and 21 match, for example, one or both of the laser light sources 11 and 21. By adjusting the light emission timing, the laser beams LB1 and LB2 are simultaneously irradiated on the sample.
  • One or both of the laser light sources 11 and 21 may be used as a tunable laser light source, and the synchronization system 5 may be configured to adjust the wavelengths of the laser beams LB1 and LB2.
  • the laser beam LB1 that has passed through the partially reflected mirror 11 passes through the 1/2 wave plate 17 that rotates the polarization direction of linearly polarized light by 90 °, and makes the laser beam LB1 linearly polarized light perpendicular to the paper surface.
  • the polarization directions of the laser beams LB1 and LB2 are set so as to be orthogonal to each other.
  • the dichroic mirror 18 has a function of reflecting light of a specific wavelength and transmitting light of another wavelength, and here, the laser beam LB1 having a wavelength ⁇ 1 is transmitted and the laser beam LB2 having a wavelength ⁇ 2 is transmitted. Is reflected to match the traveling directions of both.
  • the laser beams LB1 and LB2 are not coaxial, and the angle between the two beams is set to a predetermined value. The arrangement of the laser beams LB1 and LB2 will be described later.
  • the optical beam scanning mechanism 31 is composed of, for example, two galvano scanners having rotation axes substantially orthogonal to each other, and has a function of two-dimensionally scanning the laser beams LB1 and LB2.
  • the galvano scanner has a mirror that is angularly displaced according to a control signal. This enables two-dimensional scanning of the laser beam in a compact configuration.
  • a polygon mirror, a photoacoustic deflection element, an electro-optic deflection element, or the like may be used instead of scanning on both rotation axes or scanning on one rotation axis.
  • the dichroic mirror 32 has a function of transmitting the laser beams LB1 and LB2 and reflecting non-linear light generated by the object SP, for example, Raman scattered light.
  • the objective lens 33 concentrates the laser beams LB1 and LB2 in a spot shape, respectively.
  • the laser beams LB1 and LB2 are incident on different cores instead of the same core in the end face FA of the optical fiber bundle 34.
  • the optical fiber bundle 34 has a plurality of cores regularly arranged in the cladding, and for example, an image fiber in which the light distribution incident on one end face FA is reproduced as it is on the other end face FB can be used.
  • FIG. 2A is an explanatory diagram showing how the laser beams LB1 and LB2 are incident on the end face FA of the optical fiber bundle 34.
  • FIG. 2B is a plan view of the optical fiber bundle 34 at the end face FA.
  • the fiber optic bundle 34 has a plurality of cores 34a that are regularly arranged within the clad 34b.
  • the laser beam LB1 and LB2 By adjusting the beam directions of the laser beams LB1 and LB2, the light is focused in a spot shape by the objective lens 33, and is incident on the cores having different predetermined intervals.
  • the laser beam LB1 moves to the adjacent core in the end face FA by the two-dimensional scanning of the optical beam scanning mechanism 31, the laser beam LB2 also moves to the adjacent core because the cores are regularly arranged.
  • the plurality of cores 34a are arranged in a hexagonal close-packed structure. This makes it possible to increase the resolution of the image.
  • the optical fiber bundle 34 preferably has a single mode transmission or a polarization holding function. This makes it possible to extend the pulse width due to the mode dispersion and improve the storage stability of the polarized state.
  • the laser beams LB1 and LB2 are emitted in the same arrangement as in the end face FA.
  • the objective lens 35 collimates the laser beams LB1 and LB2 emitted from the end face FB of the optical fiber bundle 34.
  • the lenses 36 to 37 function as relay lenses, and the angle between the collimated laser beams LB1 and LB2 can be adjusted by selecting the focal length.
  • the combined wave optical element 38 has a function of spatially superimposing the collimated laser beams LB1 and LB2 emitted from the optical fiber bundle 34, and for example, a polarizing prism capable of combining using polarized waves can be used.
  • a polarizing prism is preferably selected from the group consisting of a Wollaston prism, a Nomalski prism, a Gran Thomson prism, a Gran tailor prism, a Nicol prism, a lotion prism and a polarizing beam splitter, whereby the combined wave optical element 38 is downsized. Is planned. With such a function, the collimated laser beams LB1 and LB2 emitted from the combined wave optical element 38 become coaxial.
  • FIG. 3A is an explanatory diagram showing how the laser beams LB1 and LB2 are incident on the combined wave optical element 38.
  • the laser beams LB1 and LB2 emitted from the end face FB of the optical fiber bundle 34 are collimated by the lens 35 and then relayed by the lenses 36 to 37, and a predetermined angle difference in a predetermined direction with respect to the combined optical element 38.
  • the plane formed by the collimated laser beam LB1 and the laser beam LB2 is parallel to the Y axis, and the laser beam LB1 and the laser beam LB2 are incident on the combined optical element 38 with a predetermined angle difference.
  • the laser beam LB1 has linear polarization along the Y direction
  • the laser beam LB2 has linear polarization along the X direction.
  • the combined wave optical element 38 coaxially emits laser beams LB1 and LB2 having linearly polarized waves orthogonal to each other.
  • the polarizations of the laser beams LB1 and LB2 are transmitted as left and right circular polarizations by the optical fiber bundle 34.
  • a 1/4 wave plate or the like is installed between the objective lens 35 and the combined wave optical element 38, and when the laser beam LB1 is incident on the combined wave optical element 38, the laser beam LB1 is linearly polarized along the Y direction.
  • the beam LB2 may be converted so as to be linearly polarized along the X direction.
  • the lenses 39 to 40 function as relay lenses, and the image magnification can be adjusted by selecting the focal length.
  • the wave plate 41 for example, a two-wavelength wave plate that gives different phase differences to light of different wavelengths can be used.
  • the wave plate 41 imparts a phase of 2n ⁇ (n is a natural number including 0) to the laser beam LB1 having the wavelength ⁇ 1 , and (2n + 1) to the laser beam LB2 having the wavelength ⁇ 2 .
  • n is a natural number including 0
  • 2n + 1 to the laser beam LB2 having the wavelength ⁇ 2 .
  • By imparting a phase of ⁇ it has a function of aligning the polarizations of the laser beams LB1 and LB2 having linear polarizations orthogonal to each other in the same direction. This increases the efficiency of Raman scattered light generation.
  • FIG. 3B is an explanatory diagram showing how the laser beams LB1 and LB2 are incident on the wave plate 41.
  • the laser beam LB2 having linear polarization in the X direction is converted into linear polarization in the Y direction by the wave plate 41, and both the laser beams LB1 and LB2 have linear polarization in the Y direction.
  • the objective lens 42 concentrates the laser beams LB1 and LB2 on the object SP, for example, the inner wall of the digestive tract in the same spot shape.
  • the spots of the laser beams LB1 and LB2 are scanned two-dimensionally in the object SP following the two-dimensional scanning by the optical beam scanning mechanism 31.
  • Raman scattered light is generated by a nonlinear optical phenomenon as described later.
  • a part of the generated Raman scattered light reverses the optical system of the endoscope, and the objective lens 42, the lens 39-40, the combined wave optical element 38, the lens 36-37, the objective lens 35, the optical fiber bundle 34, and the objective. It passes through the lens 33 and is reflected by the dichroic mirror 32.
  • the wavelength filter 45 has, for example, a band pass characteristic that allows only Raman scattered light to pass through, and attenuates light having a wavelength other than Raman scattered light. This improves the signal-to-noise ratio of the signal.
  • the photodetector 47 can use, for example, a photomultiplier tube and converts the intensity information of the light that has passed through the wavelength filter 45 into an electric signal.
  • the obtained electric signal is converted into a digital value by an A / D converter, stored in a computer memory, subsequently subjected to image processing, and displayed on a display.
  • the lens 61 and the photodiode 62 are installed to observe the laser beam transmitted through the sample and obtain the shape of the sample.
  • wave number ⁇ 3 16956 cm -1
  • frequency f 3 508.3 THz.
  • CARS light is generated.
  • an image with high spatial resolution and high contrast can be obtained as compared with visible light observation using a videoscope.
  • unstained cell observation becomes possible, intravenous administration of fluorescent dye becomes unnecessary, and the safety of the subject can be ensured.
  • the laser beams LB1 and LB2 pass through the optical fiber bundle 34, the laser beams LB1 and LB2 are set to be transmitted by different cores, respectively.
  • the probe head can be miniaturized by omitting the relay lenses 36, 37 and 39, 40 and using a GRIN (gradient index: refractive index distribution type) lens or the like for the objective lenses 35 and 42, and the optical fiber bundle 34 can be made thin. Since the diameter can be increased, it can be inserted into, for example, a forceps hole (for example, a diameter of 2 to 4 mm) of an endoscope.
  • GRIN gradient index: refractive index distribution type
  • FIG. 4 is a block diagram showing a test device for observing a four-wave mixed light generated in an optical fiber bundle.
  • This test apparatus has the same configuration as the endoscope shown in FIG. 1 (A), but the lenses 51 and 52 and the excitation light are sequentially placed after the objective lens 35 so that the end face FB of the optical fiber bundle 34 can be imaged.
  • a neutral density filter 53, a lens 54, and an image pickup camera 55 are arranged to weaken the image.
  • FIG. 5 (A) and 5 (C) show images of the end face FB
  • FIG. 5 (A) shows the laser beams LB1 and LB2 emitted from the end face FB without two-dimensional scanning when they are incident on the same core. It is an image showing the distribution of the excitation light to be generated, and it can be seen that the laser beams LB1 and LB2 are emitted from one core.
  • FIG. 5B is an image showing the distribution of four-wave mixed light emitted from the end face FA when two-dimensional scanning is performed with the setting of FIG. 5A. It can be seen that the four-wave mixed light is emitted from almost all the cores.
  • FIG. 5C is an image showing the distribution of excitation light emitted from the end face FB without two-dimensional scanning when the laser beams LB1 and LB2 are incident on separate cores, and is an image showing the distribution of the excitation light emitted from one core. It can be seen that the LB1 is emitted and the laser beam LB2 is emitted from another core.
  • FIG. 5 (D) is an image showing the distribution of four-wave mixed light emitted from the end face FA when two-dimensional scanning is performed with the setting of FIG. 5 (C). It can be seen that the four-wave mixed light is not generated in almost all the cores. The extinction rate was about 1/250 as compared with FIG. 5 (B). It is presumed that the slight noise light is caused by an optical effect different from the four-wave mixing, for example, fluorescence.
  • FIGS. 5A and 5C a white light source is installed instead of the photodetector 47 in order to show the position of the core of the optical fiber bundle, and an image is acquired by the image pickup camera 55. Further, FIGS. 5 (B) and 5 (D) are imaged using signals from the photodetector 47.
  • 6 (A) and 6 (D) are images of an image of a sample in which one polystyrene bead (diameter 25 ⁇ m) is placed on a glass plate as an object SP in the endoscope shown in FIG. 1 (A).
  • 6 (A) shows an image of CARS light
  • FIG. 6 (D) shows a transmitted image of laser light, which is measured by a photodiode 62.
  • CARS light is caused by CH 2 expansion and contraction vibration (wave number 2845 cm -1 ) of polystyrene.
  • FIG. 6 (B) and 6 (E) are images of a sample of only a glass plate as an object SP in the endoscope shown in FIG. 1 (A), and FIG. 6 (B) shows an image of CARS light.
  • FIG. 6E shows a transmitted image of the laser beam.
  • FIG. 6C is a difference image between the image of FIG. 6A and the image of FIG. 6B.
  • 6 (F) is a difference image between the image of FIG. 6 (D) and the image of FIG. 6 (E).
  • the sample is excited using the excitation light transmitted by the optical fiber bundle 34, and the generated CARS light is transmitted in the opposite direction by the optical fiber bundle 34, so that the image of the CARS light by two-dimensional scanning of the excitation light can be performed. It turns out that it is possible.
  • the present invention is extremely industrially effective in that it can suppress the four-wave mixed light generated from the optical fiber bundle.

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Abstract

This nonlinear Raman scattering endoscope comprises: a laser light source 11 that generates, as pulse light, a laser beam LB1 having a wavelength λ1; a laser light source 21 that generates, as pulse light, a laser beam LB2 having a wavelength λ2 different from the wavelength λ1; an optical fiber bundle 34 that has a plurality of cores 34a regularly arrayed; an optical beam scanning mechanism 31 that performs two-dimensional scanning with the laser beams LB1 and LB2 such that the laser beams LB1 and LB2 enter different cores 34a, respectively; a multiplexing optical element 38 for spatially superimposing the laser beams LB1 and LB2 emitted from the optical fiber bundle 34; an objective lens 42 that concentrates, on an object SP, the laser beams LB1 and LB2 emitted from the multiplexing optical element 38; and a light detector 47 that detects Raman scattered light generated inside the object due to a nonlinear optical phenomenon.　Such a configuration can suppress four light wave mixed light generated from the optical fiber bundle.

Description

光ファイバーバンドルを用いた非線形ラマン散乱内視鏡Non-linear Raman scattering endoscope with fiber optic bundle

　本発明は、非線形光学現象を利用して、例えば消化管内壁等の物体を撮像する非線形ラマン散乱内視鏡に関する。 The present invention relates to a nonlinear Raman scattering endoscope that images an object such as the inner wall of the gastrointestinal tract by utilizing a nonlinear optical phenomenon.

　消化管用の内視鏡は、光ファイバーバンドルを用いたファイバースコープから、ＣＣＤなどの撮像素子を先端部に内蔵したビデオスコープが主流となっている。しかし、現在の消化管内視鏡スコープでは、細胞観測には充分な空間分解能が得られていない。また、消化管がんを診断するためには、細胞を採取して染色・標本化し、病理医が顕微鏡で観察する病理検査・診断が必要になる。 The mainstream endoscopes for the gastrointestinal tract are fiberscopes that use optical fiber bundles, and videoscopes that have an image sensor such as a CCD built into the tip. However, the current gastrointestinal endoscopy scope does not provide sufficient spatial resolution for cell observation. In addition, in order to diagnose gastrointestinal cancer, it is necessary to collect cells, stain and sample them, and perform a pathological examination and diagnosis that a pathologist observes with a microscope.

　近年、プロープ型共焦点レーザ顕微内視鏡が開発され、検体標本の病理像と同等レベルの観察像が得られるため、例えば、画像診断と内視鏡手術を同時に行うことも不可能ではなくなってきた。この手法では、蛍光色素（フルオレセイン等）を静脈投与して染色された細胞からの蛍光を観察する。このプローブ型共焦点レーザ顕微内視鏡は、数千本以上の細径光ファイバーからなる直径１ｍｍ～２ｍｍ程度の光ファイバーバンドルと、その先端（プローブヘッド）に小型の対物レンズとを備える。個々の光ファイバーを通じて励起光を伝送・照射し、発生した蛍光を逆伝搬させることで共焦点効果が得られ、細胞の形状まで観察できる。また、プローブ型共焦点レーザ顕微内視鏡は、直径が細く、プローブヘッドが小さいため、曲げられた消化管内視鏡スコープの鉗子孔にも挿入することが可能であり、広い視野で観察できる通常の内視鏡観察と、高い空間分解能で観察できるプローブ型共焦点レーザ顕微内視鏡観察とが両立できる。しかしながら、蛍光色素を静脈投与することについての安全性に懸念がある（非特許文献１～２）。 In recent years, probe-type confocal laser microendoscopes have been developed, and observation images at the same level as the pathological images of specimens can be obtained. Therefore, for example, it is not impossible to perform diagnostic imaging and endoscopic surgery at the same time. rice field. In this method, a fluorescent dye (fluorescein, etc.) is intravenously administered and the fluorescence from the stained cells is observed. This probe-type cofocal laser microendoscope is provided with an optical fiber bundle having a diameter of about 1 mm to 2 mm composed of several thousand or more small-diameter optical fibers, and a small objective lens at the tip (probe head) thereof. A confocal effect can be obtained by transmitting and irradiating excitation light through individual optical fibers and back-propagating the generated fluorescence, and even the shape of cells can be observed. In addition, since the probe-type confocal laser microscopic endoscope has a small diameter and a small probe head, it can be inserted into the forceps hole of a bent gastrointestinal endoscopy scope, and it can be observed in a wide field of view. Both endoscopic observation and probe-type cofocal laser microscopic endoscopic observation that can be observed with high spatial resolution are compatible. However, there are concerns about the safety of intravenous administration of fluorescent dyes (Non-Patent Documents 1 and 2).

　一方、自発ラマン散乱分光を利用して、分子種等に敏感な分子の振動を観測する内視鏡が開発され、染色なしでがんの識別が可能であることが報告されている（非特許文献３）。しかしながら、自発ラマン散乱は非常に微弱であるため、イメージングは難しく、ポイント計測しか実現していない。 On the other hand, an endoscope for observing vibrations of molecules sensitive to molecular species has been developed using spontaneous Raman scattering spectroscopy, and it has been reported that cancer can be identified without staining (non-patented). Document 3). However, since spontaneous Raman scattering is very weak, imaging is difficult and only point measurement is realized.

　この代替手段として、コヒーレントアンチストークスラマン散乱（ＣＡＲＳ）（非特許文献４、５）、誘導ラマン散乱（ＳＲＳ）（非特許文献６、７）などの非線形ラマン散乱を用いた内視鏡が提案されている（非特許文献８～１０）。しかしながら、消化管内視鏡スコープの鉗子孔に挿入できるような細径の内視鏡は未だ開発されていない。 As an alternative to this, an endoscope using non-linear Raman scattering such as coherent anti-Stoke Slaman scattering (CARS) (Non-Patent Documents 4 and 5) and induced Raman scattering (SRS) (Non-Patent Documents 6 and 7) has been proposed. (Non-Patent Documents 8 to 10). However, a small-diameter endoscope that can be inserted into the forceps hole of a gastrointestinal endoscopy scope has not yet been developed.

　これまでにアクチュエータを取り付けて光ファイバーを旋回させるビーム走査方法を用いた内視鏡が開発されている（非特許文献９、１０）。しかし、ビーム走査機構が大きいため剛直なプローブヘッドが大きく、消化管内視鏡スコープの鉗子孔に挿入することは難しい。プローブ型共焦点レーザ顕微内視鏡と同様に光ファイバーバンドルを利用すれば細径化およびプローブヘッドの小型化が可能となるが、ＣＡＲＳの場合、励起光を光ファイバーで伝送する際にファイバー内部の非線形光学現象に起因して、ＣＡＲＳ光と同じ波長を有する四光波混合（ＦＷＭ: Four Wave Mixing）光が発生する（非特許文献１１）。この四光波混合光の強度は、試料から発生するＣＡＲＳ光と比べて２～３桁大きいとされ、ＣＡＲＳ光検出を妨害するノイズ光となる。励起光を伝送する光ファイバーバンドルとＣＡＲＳ光の検出用光ファイバーを分離することにより、この四光波混合光からの影響を防止する研究も行われているが、励起光とＣＡＲＳ光を分離するためにプローブヘッドが大きくなってしまい、鉗子孔へ挿入可能な細径化は実現されていない（非特許文献１１）。 So far, endoscopes using a beam scanning method in which an actuator is attached to rotate an optical fiber have been developed (Non-Patent Documents 9 and 10). However, since the beam scanning mechanism is large, the rigid probe head is large, and it is difficult to insert it into the forceps hole of the gastrointestinal endoscopy scope. Similar to the probe-type confocal laser microscopic endoscope, the optical fiber bundle can be used to reduce the diameter and the probe head, but in the case of CARS, the non-linearity inside the fiber when the excitation light is transmitted by the optical fiber. Due to an optical phenomenon, four-wave mixing (FWM: Four Wave Mixing) light having the same wavelength as CARS light is generated (Non-Patent Document 11). The intensity of this four-wave mixed light is said to be two to three orders of magnitude higher than that of the CARS light generated from the sample, and becomes noise light that interferes with the detection of CARS light. Research is also being conducted to prevent the influence of this four-wave mixed light by separating the optical fiber bundle that transmits the excitation light and the optical fiber for detecting CARS light, but a probe for separating the excitation light and the CARS light. The head becomes large, and the diameter can be reduced so that it can be inserted into the forceps hole (Non-Patent Document 11).

特許第５９２６０５５号公報Japanese Patent No. 5926055 特許第４８６２１６４号公報Japanese Patent No. 4862164

大宮　直木、「共焦点レーザー内視鏡Confocal laser endomicroscopy の現況と将来展望」、日本消化器内視鏡学会雑誌, 61(6), 1209-1217 (2019).  https://doi.org/10. 11280/gee.61.1209Naoki Omiya, "Current Status and Future Prospects of Confocal Laser Endoscope", Journal of Japan Gastroenterological Endoscopy Society, 61 (6), 1209-1217 (2019). Https://doi.org/10 . 11280 / gee.61.1209 斎藤豊、特定臨床研究「胃上皮性病変に対するプローブ型共焦点レーザー顕微内視鏡の診断能に関する多施設前向き研究」, https://jrct.niph.go.jp/latest-detail/jRCTs031190135Yutaka Saito, Specified clinical study "Multicenter prospective study on diagnostic ability of probe-type confocal laser microscopic endoscopy for gastric epithelial lesions", https://jrct.niph.go.jp/latest-detail/jRCTs031190135 M. S. Bergholt, W. Zheng, K. Y. Ho, M. Teh,K. G. Yeoh, et al., "Raman Endoscopy for Objective Diagnosis of Early Cancer in the Gastrointestinal System", J. Gastroint. Dig. Syst. Sl:008 (2013). doi:10.4172/2161- 069X.S1-008.M. S. Bergholt, W. Zheng, K. Y. Ho, M. Teh, K. G. Yeoh, et al., "Raman Endoscopy for Objective Diagnosis of Early Cancer in the Gastrointestinal System", J. Gastro .Syst. Sl: 008 (2013). Doi: 10.4172/2161-069X.S1-008. A. Zumbusch, G. R. Holtom, and X. S. Xie, "Three dimensional vibrational imaging by coherent anti-Stokes Raman scattering", Phys. Rev. Lett., 82, 4142-4145 (1999)A. Zumbusch, G. R. Holtom, and X. S. Xie, "Three dimensional vibrational imaging by coherent anti-Stokes Raman scattering", Phys. Rev. Lett., 82, 4142-4145 (1999) M. Hashimoto, T. Araki, and S. Kawata, "Molecular vibrational imaging in the fingerprint region by CARS microscopy with collinear configuration, "Opt. Lett., 25, 1768-1770 (2000)M. Hashimoto, T. Araki, and S. Kawata, "Molecular vibrational imaging in the fingerprint region by CARS microscopy with collinear configuration," Opt. Lett., 25, 1768-1770 (2000) C. W. Freudiger, W. Min, B. G. Saar, S. Lu, G. R. Holton, C. He, J. C. Tsai, J. X. Kang, and X. S. Xie, "Label-free biomedical imaging with high sensitivity by stimulated Raman scattering microscopy," Science 322, 1857-1861 (2008)C. W. Freudiger, W. Min, B. G. Saar, S. Lu, G. R. Holton, C. He, J. C. Tsai, J. X. Kang, and X. S. Xie, " Label-free biomedical imaging with high sensitivity by stimulated Raman scattering microscopy, "Science 322, 1857-1861 (2008) Y. Ozeki, F. Dake, S. Kajiyama, K. Fukui, and K. Itoh, "Analysis and experimental assessment of the sensitivity of stimulated Raman scattering microscopy," Opt. Express 17(5), 3651-3658 (2009)Y. Ozeki, F. Dake, S. Kajiyama, K. Fukui, and K. Itoh, "Analysis and experimental assessment of the sensitivity of stimulated Raman scattering microscopy," Opt. Express 17 (5), 3651-3 K. Hirose, T. Aoki, T. Furukawa, S. Fukushima, H. Niioka, S. Deguchi, and M. Hashimoto, "Coherent anti-Stokes Raman scattering rigid endoscope toward robot-assisted surgery", Biomedical Optics Express, 9(2), 387-396, (2018)K. Hirose, T. Aoki, T. Furukawa, S. Fukushima, H. Niioka, S. Deguchi, and M. Hashimoto, "Coherent anti-Stokes Raman scattering rigid endoscope token robot-assisted surgery", Biomed (2), 387-396, (2018) B. G. Saar, R.S. Johnston, C. W. Freudiger, X. S. Xie, and E. J. Seibel, "Coherent Raman scanning fiber endoscopy", Opt. Lett. 36(13), 2396-2398 (2011)B. G. Saar, R.S. Johnston, C. W. Freudiger, X. S. Xie, and E. J. Seibel, "Coherent Raman scanning fiber endoscopy", Opt. Lett. 36 (13), 2396-2398 (2011) ) A. Lombardini, V. Mytskaniuk, S. Sivankutty, E. R. Andresen, X. Chen , J. Wenger, M. Fabert, N. Joly, F. Louradour, A. Kudlinski and H. Rigneault. "High-resolution multimodal flexible coherent Raman endoscope", Light: Science & Applications, 7: 10, (2018)A. Lombardini, V. Mytskaniuk, S. Sivankutty, E. R. Andresen, X. Chen, J. Wenger, M. Fabert, N. Joly, F. Louradour, A. Kudlinski and H. Rigneault. multimodal flexible coherent Raman endoscope ", Light: Science & Applications, 7: 10, (2018) A. Lukic, S. Dochow, H. Bae, G. Matz, I. Latka, B. Messerschmidt , M. Schmitt, and J. Popp, "Endoscopic fiber probe for nonlinear spectroscopic imaging", Optica, 4(5), 496-501 (2017)A. Lukic, S. Dochow, H. Bae, G. Matz, I. Latka, B. Messerschmidt, M. Schmitt, and J. Popp, "Endoscopic fiber probe for non-linear spectroscopic imaging", Optica, 4 (5) 496-501 (2017)

　本発明の目的は、光ファイバーバンドルから発生する四光波混合光を抑制できる非線形ラマン散乱内視鏡を提供することである。 An object of the present invention is to provide a nonlinear Raman scattering endoscope capable of suppressing four-wave mixed light generated from an optical fiber bundle.

　本発明の一態様に係る非線形ラマン散乱内視鏡は、
　第１波長を有する第１パルスレーザ光を発生する第１レーザ光源と、
　第１波長とは異なる第２波長を有する第２パルスレーザ光を発生する第２レーザ光源と、
　前記第１パルスレーザ光および前記第２パルスレーザ光が同時に物体を照射するように調整する機構と、
　規則的に配列した複数のコアを有する光ファイバーバンドルと、
　前記第１パルスレーザ光および前記第２パルスレーザ光が異なるコアにそれぞれ入射するように、前記第１パルスレーザ光および前記第２パルスレーザ光を２次元的に走査する光学走査機構と、
　前記光ファイバーバンドルから出射された前記第１パルスレーザ光および前記第２パルスレーザ光を空間的に重ね合わせるための合波光学素子と、
　前記合波光学素子から出射された前記第１パルスレーザ光および前記第２パルスレーザ光を物体に向けて同一スポットに集光する集光光学系と、
　物体内での非線形光学現象により発生したラマン散乱光を検出する光検出器と、を備える。 The nonlinear Raman scattering endoscope according to one aspect of the present invention is
A first laser light source that generates a first pulsed laser beam having a first wavelength,
A second laser light source that generates a second pulsed laser beam having a second wavelength different from the first wavelength,
A mechanism for adjusting the first pulse laser beam and the second pulse laser beam so as to irradiate an object at the same time.
Fiber optic bundles with multiple cores arranged regularly,
An optical scanning mechanism that two-dimensionally scans the first pulse laser beam and the second pulse laser beam so that the first pulse laser beam and the second pulse laser beam are incident on different cores.
A combined wave optical element for spatially superimposing the first pulse laser beam and the second pulse laser beam emitted from the optical fiber bundle.
A condensing optical system that focuses the first pulse laser light and the second pulse laser light emitted from the combined wave optical element at the same spot toward an object.
It includes a photodetector that detects Raman scattered light generated by a nonlinear optical phenomenon in an object.

　本発明によれば、光ファイバーバンドルから発生する四光波混合光を抑制できる。 According to the present invention, the four-wave mixed light generated from the optical fiber bundle can be suppressed.

図１（Ａ）は、本発明の一実施形態に係る非線形ラマン散乱内視鏡の構成の一例を示すブロック図であり、図１（Ｂ）は、光学系内部のレンズ配置例を示す。FIG. 1A is a block diagram showing an example of the configuration of a nonlinear Raman scattering endoscope according to an embodiment of the present invention, and FIG. 1B shows an example of lens arrangement inside an optical system. 図２（Ａ）は、レーザビームＬＢ１，ＬＢ２が光ファイバーバンドル３４の端面ＦＡに入射する様子を示す説明図である。図２（Ｂ）は、光ファイバーバンドル３４の端面ＦＡでの平面図である。FIG. 2A is an explanatory diagram showing how the laser beams LB1 and LB2 are incident on the end face FA of the optical fiber bundle 34. FIG. 2B is a plan view of the optical fiber bundle 34 at the end face FA. 図３（Ａ）は、レーザビームＬＢ１，ＬＢ２が合波光学素子３８に入射する様子を示す説明図である。図３（Ｂ）は、レーザビームＬＢ１，ＬＢ２が波長板４１に入射する様子を示す説明図である。FIG. 3A is an explanatory diagram showing how the laser beams LB1 and LB2 are incident on the combined wave optical element 38. FIG. 3B is an explanatory diagram showing how the laser beams LB1 and LB2 are incident on the wave plate 41. 光ファイバーバンドルで発生する四光波混合光を観察するための試験装置を示すブロック図である。It is a block diagram which shows the test apparatus for observing the four-wave mixed light generated by an optical fiber bundle. 図５（Ａ）は、レーザビームＬＢ１，ＬＢ２を同一コアに入射した場合に、２次元走査なしで端面ＦＢから出射される励起光の分布を示す画像である。図５（Ｂ）は、図５（Ａ）の設定で２次元走査を行った場合に端面ＦＡから出射される四光波混合光の分布を示す画像である。図５（Ｃ）は、レーザビームＬＢ１，ＬＢ２を別個のコアにそれぞれ入射した場合に、２次元走査なしで端面ＦＢから出射される励起光の分布を示す画像である。図５（Ｄ）は、図５（Ｃ）の設定で２次元走査を行った場合に端面ＦＡから出射される四光波混合光の分布を示す画像である。FIG. 5A is an image showing the distribution of excitation light emitted from the end face FB without two-dimensional scanning when the laser beams LB1 and LB2 are incident on the same core. FIG. 5B is an image showing the distribution of four-wave mixed light emitted from the end face FA when two-dimensional scanning is performed with the setting of FIG. 5A. FIG. 5C is an image showing the distribution of excitation light emitted from the end face FB without two-dimensional scanning when the laser beams LB1 and LB2 are incident on separate cores. FIG. 5D is an image showing the distribution of four-wave mixed light emitted from the end face FA when two-dimensional scanning is performed with the setting of FIG. 5C. 図６（Ａ）（Ｄ）は、図１（Ａ）に示す内視鏡において、物体ＳＰとしてガラスプレート上に１つのポリスチレンビーズ（直径２５μｍ）を戴置したサンプルを撮像した画像であり、図６（Ａ）はＣＡＲＳ光の画像を示し、図６（Ｄ）はレーザ光の透過像を示す。図６（Ｂ）（Ｅ）は、図１（Ａ）に示す内視鏡において、物体ＳＰとしてガラスプレートのみのサンプルを撮像した画像であり、図６（Ｂ）はＣＡＲＳ光の画像を示し、図６（Ｅ）はレーザ光の透過像を示す。図６（Ｃ）は、図６（Ａ）の画像と図６（Ｂ）の画像の差分画像である。図６（Ｆ）は、図６（Ｄ）の画像と図６（Ｅ）の画像の差分画像である。6 (A) and 6 (D) are images of an image of a sample in which one polystyrene bead (diameter 25 μm) is placed on a glass plate as an object SP in the endoscope shown in FIG. 1 (A). 6 (A) shows an image of CARS light, and FIG. 6 (D) shows a transmitted image of laser light. 6 (B) and 6 (E) are images of a sample of only a glass plate as an object SP in the endoscope shown in FIG. 1 (A), and FIG. 6 (B) shows an image of CARS light. FIG. 6E shows a transmitted image of the laser beam. 6 (C) is a difference image between the image of FIG. 6 (A) and the image of FIG. 6 (B). 6 (F) is a difference image between the image of FIG. 6 (D) and the image of FIG. 6 (E).

　図１（Ａ）は、本発明の一実施形態に係る非線形ラマン散乱内視鏡の構成の一例を示すブロック図であり、図１（Ｂ）は、光学系内部のレンズ配置例を示す。この内視鏡は、レーザ光源１１，２１と、同期システム５と、部分反射ミラー１１，２２と、ミラー１２～１５を含む光遅延調整機構と、ミラー１６，２３，２４と、１／２波長板１７と、ダイクロイックミラー１８，３２と、光学的ビーム走査機構３１と、対物レンズ３３，３５，４２と、光ファイバーバンドル３４と、レンズ３６～３７，３９～４０と、合波光学素子３８と、波長板４１と、波長フィルタ４５と、レンズ４６と、光検出器４７などで構成される。 FIG. 1 (A) is a block diagram showing an example of the configuration of a non-linear Raman scattering endoscope according to an embodiment of the present invention, and FIG. 1 (B) shows an example of lens arrangement inside an optical system. This endoscope includes a laser light source 11 and 21, a synchronization system 5, partial reflection mirrors 11 and 22, an optical delay adjustment mechanism including mirrors 12 to 15, mirrors 16, 23, 24, and 1/2 wavelength. Plate 17, dichroic mirrors 18, 32, optical beam scanning mechanism 31, objective lenses 33, 35, 42, optical fiber bundle 34, lenses 36 to 37, 39 to 40, combined optical element 38, It is composed of a wavelength plate 41, a wavelength filter 45, a lens 46, an optical detector 47, and the like.

　レーザ光源１１は、波長λ１を有するレーザビームＬＢ１を、ピコ秒オーダーのパルス励起光として発生する（例えば、Spectra Physics社Tsunami）。レーザビームＬＢ１は、例えば、紙面に平行な直線偏光を有する。部分反射ミラー１１は、レーザビームＬＢ１の一部、例えば、約１％の光を反射し、残りの光を通過させる。部分反射ミラー１１で反射した光は、モニタ光としてミラー１２～１５を含む光遅延調整機構に入射する。 The laser light source 11 generates a laser beam LB1 having a wavelength λ 1 as pulse excitation light on the order of picoseconds (for example, Tsunami of Spectra Physics). The laser beam LB1 has, for example, linearly polarized light parallel to the paper surface. The partial reflection mirror 11 reflects a part of the laser beam LB1, for example, about 1% of the light, and allows the rest of the light to pass through. The light reflected by the partial reflection mirror 11 is incident on the light delay adjusting mechanism including the mirrors 12 to 15 as monitor light.

　光遅延調整機構において、ミラー１２，１５が固定され、ミラー１３，１４が一体的に変位可能であり、ミラー１２，１５とミラー１３，１４との間の光路長を調整することによって、レーザビームＬＢ１がミラー１２からミラー１５までの通過する時間を調整できる。光遅延調整機構から出射した光は、モニタ光としてミラー１６を経由して同期システム５に入射する。 In the optical delay adjustment mechanism, the mirrors 12 and 15 are fixed, the mirrors 13 and 14 are integrally displaceable, and the laser beam is adjusted by adjusting the optical path length between the mirrors 12 and 15 and the mirrors 13 and 14. The time for the LB 1 to pass from the mirror 12 to the mirror 15 can be adjusted. The light emitted from the optical delay adjusting mechanism is incident on the synchronization system 5 as monitor light via the mirror 16.

　レーザ光源２１は、波長λ１とは異なる波長λ２を有するレーザビームＬＢ２を、ピコ秒オーダーのパルス励起光として発生する（例えば、Spectra Physics社Tsunami）。レーザビームＬＢ２は、例えば、紙面に平行な直線偏光を有する。部分反射ミラー２２は、レーザビームＬＢ２の一部、例えば、約１％の光を反射し、残りの光を通過させる。部分反射ミラー２２で反射した光は、ミラー２３を経由して同期システム５に入射する。 The laser light source 21 generates a laser beam LB2 having a wavelength λ 2 different from the wavelength λ 1 as pulse excitation light on the order of picoseconds (for example, Tsunami of Spectra Physics). The laser beam LB2 has, for example, linearly polarized light parallel to the paper surface. The partial reflection mirror 22 reflects a part of the laser beam LB2, for example, about 1% of the light, and allows the rest of the light to pass through. The light reflected by the partial reflection mirror 22 enters the synchronization system 5 via the mirror 23.

　なお、この例ではレーザ光源１１，２１は別々のレーザ光源であるが、例えばレーザ光源１１の一部の光を取り出して波長変換し、レーザ光源２１の代わりに用いてもよい。または、レーザ光源２１の光の一部を取り出して波長変換してレーザ光源１１の代わりに用いてもよい。あるいは、レーザ光源からの光を２分割して、それぞれを波長変換してレーザ光源１１、２１の代わりに用いてもよい。この場合、常にレーザ光源１１とレーザ光源２１は同期しているため同期システムは不要となるが、レーザビームＬＢ１あるいはレーザビームＬＢ２、または両ビームに光遅延調整機構等を挿入し、レーザビームＬＢ１とＬＢ２が試料に同時に照射されるようにする。 In this example, the laser light sources 11 and 21 are separate laser light sources, but for example, a part of the light of the laser light source 11 may be taken out to convert the wavelength and used instead of the laser light source 21. Alternatively, a part of the light of the laser light source 21 may be taken out, wavelength-converted, and used in place of the laser light source 11. Alternatively, the light from the laser light source may be divided into two, each of which is wavelength-converted and used in place of the laser light sources 11 and 21. In this case, since the laser light source 11 and the laser light source 21 are always synchronized, a synchronization system is unnecessary, but the laser beam LB1 or the laser beam LB2, or a light delay adjusting mechanism or the like is inserted into both beams to form a laser beam LB1. Allow LB2 to irradiate the sample at the same time.

　同期システム５は、レーザ光源１１，２１からのモニタ光を検出し、レーザ光源１１，２１でのパルス光のタイミングが一致するようにフィードバック制御し、例えば、レーザ光源１１，２１の一方または両方の発光タイミングを調整することでレーザビームＬＢ１とＬＢ２が試料に同時に照射されるようにする。なお、レーザ光源１１，２１のいずれか一方または両方を波長可変型のレーザ光源とし、同期システム５がレーザビームＬＢ１，ＬＢ２の波長を調整するように構成してもよい。 The synchronization system 5 detects the monitor light from the laser light sources 11 and 21 and feedback-controls so that the timings of the pulse lights in the laser light sources 11 and 21 match, for example, one or both of the laser light sources 11 and 21. By adjusting the light emission timing, the laser beams LB1 and LB2 are simultaneously irradiated on the sample. One or both of the laser light sources 11 and 21 may be used as a tunable laser light source, and the synchronization system 5 may be configured to adjust the wavelengths of the laser beams LB1 and LB2.

　部分反射ミラー１１を通過したレーザビームＬＢ１は、直線偏光の偏光方向を９０°回転させる１／２波長板１７を通過して、レーザビームＬＢ１を紙面に垂直な直線偏光にする。こうしてレーザビームＬＢ１，ＬＢ２の偏光方向は、互いに直交するように設定される。 The laser beam LB1 that has passed through the partially reflected mirror 11 passes through the 1/2 wave plate 17 that rotates the polarization direction of linearly polarized light by 90 °, and makes the laser beam LB1 linearly polarized light perpendicular to the paper surface. In this way, the polarization directions of the laser beams LB1 and LB2 are set so as to be orthogonal to each other.

　ダイクロイックミラー１８は、特定の波長の光を反射し、他の波長の光を透過させる機能を有し、ここでは、波長λ１を有するレーザビームＬＢ１を透過させ、波長λ２を有するレーザビームＬＢ２を反射して、両者の進行方向を一致させている。本実施形態では、各レーザビームＬＢ１，ＬＢ２は同軸ではなく、両ビーム間の角度は予め定めた数値に設定される。レーザビームＬＢ１，ＬＢ２の配置については後述する。 The dichroic mirror 18 has a function of reflecting light of a specific wavelength and transmitting light of another wavelength, and here, the laser beam LB1 having a wavelength λ 1 is transmitted and the laser beam LB2 having a wavelength λ 2 is transmitted. Is reflected to match the traveling directions of both. In the present embodiment, the laser beams LB1 and LB2 are not coaxial, and the angle between the two beams is set to a predetermined value. The arrangement of the laser beams LB1 and LB2 will be described later.

　光学的ビーム走査機構３１は、例えば、互いに略直交する回転軸を有する２つのガルバノスキャナで構成され、レーザビームＬＢ１，ＬＢ２を２次元的に走査する機能を有する。ガルバノスキャナは、制御信号に従って角変位するミラーを有する。これによりコンパクトな構成でレーザビームの２次元走査が可能になる。なお、ガルバノスキャナだけではなく、ポリゴンミラーや光音響偏向素子、電気光学偏向素子等を両回転軸の走査あるいは一方の回転軸の走査の代わりに用いてもよい。 The optical beam scanning mechanism 31 is composed of, for example, two galvano scanners having rotation axes substantially orthogonal to each other, and has a function of two-dimensionally scanning the laser beams LB1 and LB2. The galvano scanner has a mirror that is angularly displaced according to a control signal. This enables two-dimensional scanning of the laser beam in a compact configuration. In addition to the galvano scanner, a polygon mirror, a photoacoustic deflection element, an electro-optic deflection element, or the like may be used instead of scanning on both rotation axes or scanning on one rotation axis.

　ダイクロイックミラー３２は、レーザビームＬＢ１，ＬＢ２を透過させ、物体ＳＰで発生した非線形光、例えば、ラマン散乱光を反射する機能を有する。 The dichroic mirror 32 has a function of transmitting the laser beams LB1 and LB2 and reflecting non-linear light generated by the object SP, for example, Raman scattered light.

　対物レンズ３３は、レーザビームＬＢ１，ＬＢ２をそれぞれスポット状に集光する。本実施形態では、ダイクロイックミラー１８の角度調整およびレーザビームＬＢ１，ＬＢ２の光軸調整により、光ファイバーバンドル３４の端面ＦＡにおいてレーザビームＬＢ１，ＬＢ２が、同じコアではなく、異なるコアにそれぞれ入射するように設定される。 The objective lens 33 concentrates the laser beams LB1 and LB2 in a spot shape, respectively. In the present embodiment, by adjusting the angle of the dichroic mirror 18 and adjusting the optical axis of the laser beams LB1 and LB2, the laser beams LB1 and LB2 are incident on different cores instead of the same core in the end face FA of the optical fiber bundle 34. Set.

　光ファイバーバンドル３４は、クラッド内に規則的に配列した複数のコアを有しており、例えば、一方の端面ＦＡに入射した光分布が他方の端面ＦＢにそのまま再現されるイメージファイバーが使用できる。 The optical fiber bundle 34 has a plurality of cores regularly arranged in the cladding, and for example, an image fiber in which the light distribution incident on one end face FA is reproduced as it is on the other end face FB can be used.

　図２（Ａ）は、レーザビームＬＢ１，ＬＢ２が光ファイバーバンドル３４の端面ＦＡに入射する様子を示す説明図である。図２（Ｂ）は、光ファイバーバンドル３４の端面ＦＡでの平面図である。光ファイバーバンドル３４は、クラッド３４ｂ内に規則的に配列した複数のコア３４ａを有する。レーザビームＬＢ１，ＬＢ２のビームの方向を調整することにより、対物レンズ３３によりスポット状に集光され、予め定めた間隔の異なるコアにそれぞれ入射する。光学的ビーム走査機構３１の２次元走査により、端面ＦＡにおいてレーザビームＬＢ１が隣りのコアに移動すると、コアが規則的に配列されているためレーザビームＬＢ２も同様に隣りのコアに移動する。 FIG. 2A is an explanatory diagram showing how the laser beams LB1 and LB2 are incident on the end face FA of the optical fiber bundle 34. FIG. 2B is a plan view of the optical fiber bundle 34 at the end face FA. The fiber optic bundle 34 has a plurality of cores 34a that are regularly arranged within the clad 34b. By adjusting the beam directions of the laser beams LB1 and LB2, the light is focused in a spot shape by the objective lens 33, and is incident on the cores having different predetermined intervals. When the laser beam LB1 moves to the adjacent core in the end face FA by the two-dimensional scanning of the optical beam scanning mechanism 31, the laser beam LB2 also moves to the adjacent core because the cores are regularly arranged.

　また、光ファイバーバンドル３４において、複数のコア３４ａは六方最密充填構造で配列されることが好ましい。これにより画像の分解能を高めることができる。さらに光ファイバーバンドル３４は、シングルモード伝送または偏光保持機能を有することが好ましい。これによりモード分散によるパルス幅の伸長、偏光状態の保存性を改善できる。 Further, in the optical fiber bundle 34, it is preferable that the plurality of cores 34a are arranged in a hexagonal close-packed structure. This makes it possible to increase the resolution of the image. Further, the optical fiber bundle 34 preferably has a single mode transmission or a polarization holding function. This makes it possible to extend the pulse width due to the mode dispersion and improve the storage stability of the polarized state.

　図１に戻って、光ファイバーバンドル３４の端面ＦＢでは、端面ＦＡでの配置と同じ配置でレーザビームＬＢ１，ＬＢ２が出射する。 Returning to FIG. 1, in the end face FB of the optical fiber bundle 34, the laser beams LB1 and LB2 are emitted in the same arrangement as in the end face FA.

　対物レンズ３５は、光ファイバーバンドル３４の端面ＦＢから出射したレーザビームＬＢ１，ＬＢ２をコリメートする。レンズ３６～３７は、リレーレンズとして機能し、焦点距離の選択によりコリメートされたレーザビームＬＢ１，ＬＢ２間の角度が調整できる。 The objective lens 35 collimates the laser beams LB1 and LB2 emitted from the end face FB of the optical fiber bundle 34. The lenses 36 to 37 function as relay lenses, and the angle between the collimated laser beams LB1 and LB2 can be adjusted by selecting the focal length.

　合波光学素子３８は、光ファイバーバンドル３４から出射されたコリメートされたレーザビームＬＢ１，ＬＢ２を空間的に重ね合わせる機能を有し、例えば、偏光を利用して合波できる偏光プリズムが使用できる。こうした偏光プリズムは、ウォラストンプリズム、ノマルスキープリズム、グラントムソンプリズム、グランテーラープリズム、ニコルプリズム、ロションプリズムおよび偏光ビームスプリッタからなるグループから選ばれることが好ましく、これにより合波光学素子３８の小型化が図られる。こうした機能により、合波光学素子３８を出射したコリメートされたレーザビームＬＢ１，ＬＢ２は同軸となる。 The combined wave optical element 38 has a function of spatially superimposing the collimated laser beams LB1 and LB2 emitted from the optical fiber bundle 34, and for example, a polarizing prism capable of combining using polarized waves can be used. Such a polarizing prism is preferably selected from the group consisting of a Wollaston prism, a Nomalski prism, a Gran Thomson prism, a Gran tailor prism, a Nicol prism, a lotion prism and a polarizing beam splitter, whereby the combined wave optical element 38 is downsized. Is planned. With such a function, the collimated laser beams LB1 and LB2 emitted from the combined wave optical element 38 become coaxial.

　図３（Ａ）は、レーザビームＬＢ１，ＬＢ２が合波光学素子３８に入射する様子を示す説明図である。光ファイバーバンドル３４の端面ＦＢから出射したレーザビームＬＢ１，ＬＢ２は、レンズ３５によりコリメートされ、続いてレンズ３６～３７によってリレーされ、合波光学素子３８に対して予め定めた方向の予め定めた角度差で入射する。一例として、コリメートされたレーザビームＬＢ１とレーザビームＬＢ２がつくる平面はＹ軸に平行であり、レーザビームＬＢ１とレーザビームＬＢ２は予め定めた角度差で合波光学素子３８に入射する。また、レーザビームＬＢ１は、Ｙ方向に沿った直線偏光を有し、レーザビームＬＢ２は、Ｘ方向に沿った直線偏光を有する。合波光学素子３８は、互いに直交する直線偏光を有するレーザビームＬＢ１，ＬＢ２を同軸に出射する。 FIG. 3A is an explanatory diagram showing how the laser beams LB1 and LB2 are incident on the combined wave optical element 38. The laser beams LB1 and LB2 emitted from the end face FB of the optical fiber bundle 34 are collimated by the lens 35 and then relayed by the lenses 36 to 37, and a predetermined angle difference in a predetermined direction with respect to the combined optical element 38. Incident at. As an example, the plane formed by the collimated laser beam LB1 and the laser beam LB2 is parallel to the Y axis, and the laser beam LB1 and the laser beam LB2 are incident on the combined optical element 38 with a predetermined angle difference. Further, the laser beam LB1 has linear polarization along the Y direction, and the laser beam LB2 has linear polarization along the X direction. The combined wave optical element 38 coaxially emits laser beams LB1 and LB2 having linearly polarized waves orthogonal to each other.

　なお、図１に戻って、例えば対物レンズ３３とダイクロイックミラー３２の間に１／４波長板等を設置することよってレーザビームＬＢ１，ＬＢ２の偏光を左、右円偏光として、光ファイバーバンドル３４で伝送し、対物レンズ３５と合波光学素子３８の間に１／４波長板等を設置して、合波光学素子３８に入射する際にはレーザビームＬＢ１をＹ方向に沿った直線偏光に、レーザビームＬＢ２を、Ｘ方向に沿った直線偏光となるように変換してもよい。 Returning to FIG. 1, for example, by installing a 1/4 wave plate or the like between the objective lens 33 and the dichroic mirror 32, the polarizations of the laser beams LB1 and LB2 are transmitted as left and right circular polarizations by the optical fiber bundle 34. Then, a 1/4 wave plate or the like is installed between the objective lens 35 and the combined wave optical element 38, and when the laser beam LB1 is incident on the combined wave optical element 38, the laser beam LB1 is linearly polarized along the Y direction. The beam LB2 may be converted so as to be linearly polarized along the X direction.

　図１に戻って、レンズ３９～４０は、リレーレンズとして機能し、焦点距離の選択により結像倍率が調整できる。 Returning to FIG. 1, the lenses 39 to 40 function as relay lenses, and the image magnification can be adjusted by selecting the focal length.

　波長板４１は、例えば、異なる波長の光に対して異なる位相差を与える二波長波長板が使用できる。本実施形態では、波長板４１は、波長λ１を有するレーザビームＬＢ１に対して２ｎπ（ｎは０を含む自然数）の位相を付与し、波長λ２を有するレーザビームＬＢ２に対して（２ｎ＋１）πの位相を付与することにより、互いに直交する直線偏光を有するレーザビームＬＢ１，ＬＢ２の偏光を同一方向に揃える機能を有する。これによりラマン散乱光の発生効率が高くなる。 As the wave plate 41, for example, a two-wavelength wave plate that gives different phase differences to light of different wavelengths can be used. In the present embodiment, the wave plate 41 imparts a phase of 2nπ (n is a natural number including 0) to the laser beam LB1 having the wavelength λ 1 , and (2n + 1) to the laser beam LB2 having the wavelength λ 2 . By imparting a phase of π, it has a function of aligning the polarizations of the laser beams LB1 and LB2 having linear polarizations orthogonal to each other in the same direction. This increases the efficiency of Raman scattered light generation.

　図３（Ｂ）は、レーザビームＬＢ１，ＬＢ２が波長板４１に入射する様子を示す説明図である。Ｘ方向の直線偏光を有するレーザビームＬＢ２は、波長板４１によってＹ方向の直線偏光に変換され、レーザビームＬＢ１，ＬＢ２はともにＹ方向の直線偏光を有するようになる。 FIG. 3B is an explanatory diagram showing how the laser beams LB1 and LB2 are incident on the wave plate 41. The laser beam LB2 having linear polarization in the X direction is converted into linear polarization in the Y direction by the wave plate 41, and both the laser beams LB1 and LB2 have linear polarization in the Y direction.

　図１に戻って、対物レンズ４２は、レーザビームＬＢ１，ＬＢ２を同一スポット状に物体ＳＰ、例えば、消化管内壁に集光する。レーザビームＬＢ１，ＬＢ２のスポットは、光学的ビーム走査機構３１による２次元走査に追従して、物体ＳＰにおいて２次元的に走査される。 Returning to FIG. 1, the objective lens 42 concentrates the laser beams LB1 and LB2 on the object SP, for example, the inner wall of the digestive tract in the same spot shape. The spots of the laser beams LB1 and LB2 are scanned two-dimensionally in the object SP following the two-dimensional scanning by the optical beam scanning mechanism 31.

　物体ＳＰでは、後述するような非線形光学現象によりラマン散乱光が発生する。発生したラマン散乱光の一部は、内視鏡の光学系を逆行して、対物レンズ４２、レンズ３９～４０、合波光学素子３８、レンズ３６～３７、対物レンズ３５、光ファイバーバンドル３４、対物レンズ３３を通過し、ダイクロイックミラー３２で反射する。 In the object SP, Raman scattered light is generated by a nonlinear optical phenomenon as described later. A part of the generated Raman scattered light reverses the optical system of the endoscope, and the objective lens 42, the lens 39-40, the combined wave optical element 38, the lens 36-37, the objective lens 35, the optical fiber bundle 34, and the objective. It passes through the lens 33 and is reflected by the dichroic mirror 32.

　波長フィルタ４５は、例えば、ラマン散乱光のみを通過させるバンドパス特性を有し、ラマン散乱光以外の波長を有する光を減衰させる。これにより信号のＳＮ比が向上する。 The wavelength filter 45 has, for example, a band pass characteristic that allows only Raman scattered light to pass through, and attenuates light having a wavelength other than Raman scattered light. This improves the signal-to-noise ratio of the signal.

　光検出器４７は、例えば、光電子増倍管が使用でき、波長フィルタ４５を通過した光の強度情報を電気信号に変換する。得られた電気信号は、Ａ／Ｄコンバータによりデジタル値に変換されてコンピュータのメモリに保存され、続いて画像処理が施されてディスプレイに表示される。 The photodetector 47 can use, for example, a photomultiplier tube and converts the intensity information of the light that has passed through the wavelength filter 45 into an electric signal. The obtained electric signal is converted into a digital value by an A / D converter, stored in a computer memory, subsequently subjected to image processing, and displayed on a display.

　レンズ６１とフォトダイオード６２は、試料を透過したレーザ光を観測し、試料の形状を得るために設置されている。 The lens 61 and the photodiode 62 are installed to observe the laser beam transmitted through the sample and obtain the shape of the sample.

　次に動作について説明する。波長が異なるレーザビームＬＢ１，ＬＢ２が非線形光学効果を有する物質を進行する場合、四光波混合によりｆ３（＝２ｆ１－ｆ２）を有する光と周波数ｆ４（＝２ｆ２－ｆ３）を有する光が発生する。このうち、レーザビームＬＢ１，ＬＢ２の周波数差（ｆ１－ｆ２）が物質の分子振動の周波数と一致して、分子振動に共鳴して周波数ｆ３（＝２ｆ１－ｆ２）の光が発生する現象は、コヒーレントアンチストークスラマン散乱（ＣＡＲＳ）と称される。 Next, the operation will be described. When laser beams LB1 and LB2 having different wavelengths travel through a substance having a non-linear optical effect, light having f 3 (= 2f 1 − f 2 ) and frequency f 4 (= 2 f 2 −f 3 ) are generated by four-wave mixing. The light it has is generated. Of these, the frequency difference (f 1 − f 2 ) of the laser beams LB 1 and LB 2 coincides with the frequency of the molecular vibration of the substance, and the light having the frequency f 3 (= 2 f 1 − f 2 ) resonates with the molecular vibration. The phenomenon that occurs is called coherent anti-Stoke Raman scattering (CARS).

　一例として、レーザビームＬＢ１が、波長λ１＝７０８．７３ｎｍ、波数ν１＝１４１０９ｃｍ－１、周波数ｆ１＝４２３．０ＴＨｚを有し、レーザビームＬＢ２が、波長λ２＝８８７．８４ｎｍ、波数ν２＝１６９５６ｃｍ－１、周波数ｆ２＝３３７．７ＴＨｚを有する場合、ＣＡＲＳ光は、波長λ３＝５８９．７５ｎｍ、波数ν３＝１６９５６ｃｍ－１、周波数ｆ３＝５０８．３ＴＨｚを示す。なお、波長λ、波数ν、周波数ｆ、角周波数ω、光速ｃの関係は、ｆ＝ｃ／λ、ω＝２πｆ、ν＝１／λで表される。 As an example, the laser beam LB1 has a wavelength λ 1 = 708.73 nm, a wave number ν 1 = 14109 cm -1 , a frequency f 1 = 423.0 THz, and the laser beam LB 2 has a wavelength λ 2 = 887.84 nm, a wave number ν. When having 2 = 16956 cm -1 , frequency f 2 = 337.7 THz, CARS light indicates wavelength λ 3 = 589.75 nm, wave number ν 3 = 16956 cm -1 , frequency f 3 = 508.3 THz. The relationship between the wavelength λ, the wave number ν, the frequency f, the angular frequency ω, and the light velocity c is represented by f = c / λ, ω = 2πf, and ν = 1 / λ.

　例えば、消化管内壁などにレーザビームＬＢ１，ＬＢ２を同軸に集光して照射すると、ＣＡＲＳ光が発生する。物体に対してレーザビームＬＢ１，ＬＢ２を走査しながらＣＡＲＳ光の強度を計測することによって、ビデオスコープを用いた可視光観察と比べて高い空間分解能かつ高いコントラストの画像が得られる。また無染色細胞観察が可能になるため、蛍光色素の静脈投与が不要になり、被検体の安全性も確保できる。 For example, when the laser beams LB1 and LB2 are coaxially focused and irradiated on the inner wall of the digestive tract, CARS light is generated. By measuring the intensity of CARS light while scanning the laser beams LB1 and LB2 with respect to an object, an image with high spatial resolution and high contrast can be obtained as compared with visible light observation using a videoscope. In addition, since unstained cell observation becomes possible, intravenous administration of fluorescent dye becomes unnecessary, and the safety of the subject can be ensured.

　さらに本実施形態では、レーザビームＬＢ１，ＬＢ２が光ファイバーバンドル３４を通過する際、レーザビームＬＢ１，ＬＢ２は異なるコアでそれぞれ伝送されるように設定される。これにより光ファイバーバンドル３４での非線形光学現象に起因した四光波混合光の発生を大幅に抑制できる。リレーレンズ３６、３７および３９、４０を省略し、対物レンズ３５、４２にＧＲＩＮ（ｇｒａｄｉｅｎｔ　ｉｎｄｅｘ： 屈折率分布型）レンズ等を用いることでプローブヘッドの小型化が可能で、また光ファイバーバンドル３４の細径化が可能であるため、例えば、内視鏡の鉗子孔（例えば、直径２～４ｍｍ）へ挿入することも可能である。 Further, in the present embodiment, when the laser beams LB1 and LB2 pass through the optical fiber bundle 34, the laser beams LB1 and LB2 are set to be transmitted by different cores, respectively. As a result, the generation of four-wave mixed light due to the nonlinear optical phenomenon in the optical fiber bundle 34 can be significantly suppressed. The probe head can be miniaturized by omitting the relay lenses 36, 37 and 39, 40 and using a GRIN (gradient index: refractive index distribution type) lens or the like for the objective lenses 35 and 42, and the optical fiber bundle 34 can be made thin. Since the diameter can be increased, it can be inserted into, for example, a forceps hole (for example, a diameter of 2 to 4 mm) of an endoscope.

　図４は、光ファイバーバンドルで発生する四光波混合光を観察するための試験装置を示すブロック図である。この試験装置は、図１（Ａ）に示す内視鏡の構成と同様であるが、光ファイバーバンドル３４の端面ＦＢを撮像できるように、対物レンズ３５の後段に順次、レンズ５１，５２、励起光を弱めるニュートラルデンシティフィルタ５３、レンズ５４、撮像カメラ５５を配置している。 FIG. 4 is a block diagram showing a test device for observing a four-wave mixed light generated in an optical fiber bundle. This test apparatus has the same configuration as the endoscope shown in FIG. 1 (A), but the lenses 51 and 52 and the excitation light are sequentially placed after the objective lens 35 so that the end face FB of the optical fiber bundle 34 can be imaged. A neutral density filter 53, a lens 54, and an image pickup camera 55 are arranged to weaken the image.

　図５（Ａ）、（Ｃ）は、端面ＦＢの画像を示しており、図５（Ａ）は、レーザビームＬＢ１，ＬＢ２を同一コアに入射した場合に、２次元走査なしで端面ＦＢから出射される励起光の分布を示す画像であり、１つのコアからレーザビームＬＢ１，ＬＢ２が出射されている様子が判る。 5 (A) and 5 (C) show images of the end face FB, and FIG. 5 (A) shows the laser beams LB1 and LB2 emitted from the end face FB without two-dimensional scanning when they are incident on the same core. It is an image showing the distribution of the excitation light to be generated, and it can be seen that the laser beams LB1 and LB2 are emitted from one core.

　図５（Ｂ）は、図５（Ａ）の設定で２次元走査を行った場合に端面ＦＡから出射される四光波混合光の分布を示す画像である。ほぼ全てのコアから四光波混合光が出射されている様子が判る。 FIG. 5B is an image showing the distribution of four-wave mixed light emitted from the end face FA when two-dimensional scanning is performed with the setting of FIG. 5A. It can be seen that the four-wave mixed light is emitted from almost all the cores.

　図５（Ｃ）は、レーザビームＬＢ１，ＬＢ２を別個のコアにそれぞれ入射した場合に、２次元走査なしで端面ＦＢから出射される励起光の分布を示す画像であり、１つのコアからレーザビームＬＢ１が出射され、他のコアからレーザビームＬＢ２が出射されている様子が判る。 FIG. 5C is an image showing the distribution of excitation light emitted from the end face FB without two-dimensional scanning when the laser beams LB1 and LB2 are incident on separate cores, and is an image showing the distribution of the excitation light emitted from one core. It can be seen that the LB1 is emitted and the laser beam LB2 is emitted from another core.

　図５（Ｄ）は、図５（Ｃ）の設定で２次元走査を行った場合に端面ＦＡから出射される四光波混合光の分布を示す画像である。ほぼ全てのコアにおいて四光波混合光が発生していない様子が判る。消光率は、図５（Ｂ）と比べて約１／２５０となった。なお、僅かなノイズ光は、四光波混合とは別の光学効果、例えば、蛍光に起因するものと推測される。 FIG. 5 (D) is an image showing the distribution of four-wave mixed light emitted from the end face FA when two-dimensional scanning is performed with the setting of FIG. 5 (C). It can be seen that the four-wave mixed light is not generated in almost all the cores. The extinction rate was about 1/250 as compared with FIG. 5 (B). It is presumed that the slight noise light is caused by an optical effect different from the four-wave mixing, for example, fluorescence.

　このようにレーザビームＬＢ１，ＬＢ２を異なるコアでそれぞれ伝送することによって、光ファイバーバンドル３４で発生する四光波混合光を大幅に抑制できる。なお、図５（Ａ）と（Ｃ）は、光ファイバーバンドルのコアの位置を示すために、光検出器４７の代わりに白色光源を設置し、撮像カメラ５５で画像を取得している。また、図５（Ｂ）と（Ｄ）は、光検出器４７からの信号を用いて画像化している。 By transmitting the laser beams LB1 and LB2 in different cores in this way, the four-wave mixed light generated in the optical fiber bundle 34 can be significantly suppressed. In FIGS. 5A and 5C, a white light source is installed instead of the photodetector 47 in order to show the position of the core of the optical fiber bundle, and an image is acquired by the image pickup camera 55. Further, FIGS. 5 (B) and 5 (D) are imaged using signals from the photodetector 47.

　図６（Ａ）（Ｄ）は、図１（Ａ）に示す内視鏡において、物体ＳＰとしてガラスプレート上に１つのポリスチレンビーズ（直径２５μｍ）を戴置したサンプルを撮像した画像であり、図６（Ａ）はＣＡＲＳ光の画像を示し、図６（Ｄ）はレーザ光の透過像を示しており、フォトダイオード６２で計測している。ＣＡＲＳ光は、ポリスチレンのＣＨ２伸縮振動（波数２８４５ｃｍ－１）に起因している。 6 (A) and 6 (D) are images of an image of a sample in which one polystyrene bead (diameter 25 μm) is placed on a glass plate as an object SP in the endoscope shown in FIG. 1 (A). 6 (A) shows an image of CARS light, and FIG. 6 (D) shows a transmitted image of laser light, which is measured by a photodiode 62. CARS light is caused by CH 2 expansion and contraction vibration (wave number 2845 cm -1 ) of polystyrene.

　図６（Ｂ）（Ｅ）は、図１（Ａ）に示す内視鏡において、物体ＳＰとしてガラスプレートのみのサンプルを撮像した画像であり、図６（Ｂ）はＣＡＲＳ光の画像を示し、図６（Ｅ）はレーザ光の透過像を示す。 6 (B) and 6 (E) are images of a sample of only a glass plate as an object SP in the endoscope shown in FIG. 1 (A), and FIG. 6 (B) shows an image of CARS light. FIG. 6E shows a transmitted image of the laser beam.

　図６（Ｃ）は、図６（Ａ）の画像と図６（Ｂ）の画像の差分画像である。図６（Ｆ）は、図６（Ｄ）の画像と図６（Ｅ）の画像の差分画像である。 FIG. 6C is a difference image between the image of FIG. 6A and the image of FIG. 6B. 6 (F) is a difference image between the image of FIG. 6 (D) and the image of FIG. 6 (E).

　これらの画像から、光ファイバーバンドル３４で伝送した励起光を用いてサンプルを励起し、発生したＣＡＲＳ光を光ファイバーバンドル３４で逆方向に伝送することによって、励起光の２次元走査によるＣＡＲＳ光のイメージングが可能であることが判る。 From these images, the sample is excited using the excitation light transmitted by the optical fiber bundle 34, and the generated CARS light is transmitted in the opposite direction by the optical fiber bundle 34, so that the image of the CARS light by two-dimensional scanning of the excitation light can be performed. It turns out that it is possible.

　本発明は、光ファイバーバンドルから発生する四光波混合光を抑制できる点で産業上極めて有効である。 The present invention is extremely industrially effective in that it can suppress the four-wave mixed light generated from the optical fiber bundle.

　　　５　同期システム
　　１１，２１　レーザ光源
　　１１，２２　部分反射ミラー
　　１２～１５　ミラー（光遅延調整機構）
　　１７　１／２波長板
　　１８，３２　ダイクロイックミラー
　　１６，２３，２４　ミラー
　　３１　光学的ビーム走査機構
　　３３，３５，４２　対物レンズ
　　３４　光ファイバーバンドル
　　３４ａ　コア
　　３４ｂ　クラッド
　　３６～３７，３９～４０，６１　レンズ
　　３８　合波光学素子
　　４１　波長板
　　４５　波長フィルタ
　　４７　光検出器
　　６２　フォトダイオード
　　ＦＡ，ＦＢ　端面
　　ＬＢ１，ＬＢ２　レーザビーム
　　ＳＰ　物体 5 Synchronous system 11,21 Laser light source 11,22 Partial reflection mirror 12 to 15 Mirror (light delay adjustment mechanism)
17 1/2 Wave Plate 18, 32 Dycroic Mirror 16, 23, 24 Mirror 31 Optical Beam Scanning Mechanism 33, 35, 42 Objective Lens 34 Optical Fiber Bundle 34a Core 34b Clad 36-37, 39-40, 61 Lens 38 Combined Wave Optical element 41 Wave plate 45 Wavelength filter 47 Optical detector 62 Photo diode FA, FB End face LB1, LB2 Laser beam SP Object

Claims (10)

　第１波長を有する第１パルスレーザ光を発生する第１レーザ光源と、
　第１波長とは異なる第２波長を有する第２パルスレーザ光を発生する第２レーザ光源と、
　前記第１パルスレーザ光および前記第２パルスレーザ光が同時に物体を照射するように調整する機構と、
　規則的に配列した複数のコアを有する光ファイバーバンドルと、
　前記第１パルスレーザ光および前記第２パルスレーザ光が異なるコアにそれぞれ入射するように、前記第１パルスレーザ光および前記第２パルスレーザ光を２次元的に走査する光学走査機構と、
　前記光ファイバーバンドルから出射された前記第１パルスレーザ光および前記第２パルスレーザ光を空間的に重ね合わせるための合波光学素子と、
　前記合波光学素子から出射された前記第１パルスレーザ光および前記第２パルスレーザ光を物体に向けて同一スポットに集光する集光光学系と、
　物体内での非線形光学現象により発生したラマン散乱光を検出する光検出器と、を備える非線形ラマン散乱内視鏡。 A first laser light source that generates a first pulsed laser beam having a first wavelength,
A second laser light source that generates a second pulsed laser beam having a second wavelength different from the first wavelength,
A mechanism for adjusting the first pulse laser beam and the second pulse laser beam so as to irradiate an object at the same time.
Fiber optic bundles with multiple cores arranged regularly,
An optical scanning mechanism that two-dimensionally scans the first pulse laser beam and the second pulse laser beam so that the first pulse laser beam and the second pulse laser beam are incident on different cores.
A combined wave optical element for spatially superimposing the first pulse laser beam and the second pulse laser beam emitted from the optical fiber bundle.
A condensing optical system that focuses the first pulse laser light and the second pulse laser light emitted from the combined wave optical element at the same spot toward an object.
A nonlinear Raman scattering endoscope comprising a light detector that detects Raman scattered light generated by a nonlinear optical phenomenon in an object. 　前記第１パルスレーザ光の偏光および前記第２パルスレーザ光の偏光を同一な偏向状態に揃えるための波長板をさらに備える請求項１記載の非線形ラマン散乱内視鏡。 The nonlinear Raman scattering endoscope according to claim 1, further comprising a wave plate for aligning the polarization of the first pulse laser light and the polarization of the second pulse laser light in the same deflection state. 　前記光ファイバーバンドルにおいて、複数のコアは六方最密充填構造で配列される請求項１記載の非線形ラマン散乱内視鏡。 The nonlinear Raman scattering endoscope according to claim 1, wherein in the optical fiber bundle, a plurality of cores are arranged in a hexagonal close-packed structure. 　前記第１パルスレーザ光および前記第２パルスレーザ光は、前記光ファイバーバンドル内で互いに直交した直線偏光を有する請求項１記載の非線形ラマン散乱内視鏡。 The nonlinear Raman scattering endoscope according to claim 1, wherein the first pulse laser light and the second pulse laser light have linear polarization orthogonal to each other in the optical fiber bundle. 　前記合波光学素子は、ウォラストンプリズム、ノマルスキープリズム、グラントムソンプリズム、グランテーラープリズム、ニコルプリズム、ロションプリズムおよび偏光ビームスプリッタからなるグループから選ばれる請求項１記載の非線形ラマン散乱内視鏡。 The nonlinear Raman scattering endoscope according to claim 1, wherein the combined wave optical element is selected from a group consisting of a Wollaston prism, a Nomalski prism, a Gran Thomson prism, a Gran tailor prism, a Nicol prism, a lotion prism, and a polarized beam splitter. 　前記波長板は、前記第１パルスレーザ光および前記第２パルスレーザ光に対して異なる位相差を与える二波長波長板である請求項２記載の非線形ラマン散乱内視鏡。 The non-linear Raman scattering endoscope according to claim 2, wherein the wave plate is a two-wavelength wave plate that gives different phase differences to the first pulse laser light and the second pulse laser light. 　前記ラマン散乱光は、コヒーレントアンチストークスラマン散乱光である請求項１記載の非線形ラマン散乱内視鏡。 The non-linear Raman scattering endoscope according to claim 1, wherein the Raman scattered light is coherent anti-Stoke Raman scattered light. 　前記光ファイバーバンドルは、シングルモード伝送または偏光保持機能を有する請求項１記載の非線形ラマン散乱内視鏡。 The nonlinear Raman scattering endoscope according to claim 1, wherein the optical fiber bundle has a single-mode transmission or a polarization holding function. 　前記光学走査機構は、ガルバノスキャナ、ポリゴンミラー、光音響偏向素子または電気光学偏向素子である請求項１記載の非線形ラマン散乱内視鏡。 The nonlinear Raman scattering endoscope according to claim 1, wherein the optical scanning mechanism is a galvano scanner, a polygon mirror, an opto-acoustic deflection element, or an electro-optical deflection element. 　前記第１パルスレーザ光および前記第２パルスレーザ光は、前記光ファイバーバンドル内で右回りと左回りの偏光を有し、前記光ファイバーバンドル射出後、直交した直線偏光へ変換される請求項１記載の非線形ラマン散乱内視鏡。 The first pulse laser light and the second pulse laser light have right-handed and left-handed polarization in the optical fiber bundle, and are converted into orthogonal linear polarization after the optical fiber bundle is ejected. Non-linear Raman scattering endoscope.
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