JP2022066737A - Non-linear Raman scattering endoscope with fiber optic bundle - Google Patents

Abstract

To provide a non-linear Raman scattering endoscope capable of suppressing four-wave mixed light generated from an optical fiber bundle.SOLUTION: A non-linear Raman scattering endoscope includes: a laser light source 11 that generates a laser beam LB1 having a wavelength λ1 as pulsed light; a laser light source 21 that generates a laser beam LB2 having a wavelength λ2 different from the wavelength λ1 as pulsed light; a Fiber optic bundle 34 with multiple cores 34a arranged regularly; an optical beam scanning mechanism 31 that two-dimensionally scans the laser beams LB1 and LB2 so that the laser beams LB1 and LB2 are incident on different cores 34a, respectively; a combining wave optical element 38 for spatially superimposing the laser beams LB1 and LB2 emitted from the optical fiber bundle 34; an objective lens 42 that focuses on an object SP, the laser beams LB1 and LB2 emitted from the combining wave optical element 38; and a photodetector 47 that detects Raman scattered light generated by nonlinear optical phenomena in the object.SELECTED DRAWING: Figure 1

Description

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. 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 under a microscope by a pathologist.

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 cofocal 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).

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.

As an alternative to this, an endoscope using non-linear Raman scattering such as coherent anti-Stoke Raman 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.

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 cofocal 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 nonlinearity inside the fiber when the excitation light is transmitted by the optical fiber. Due to an optical phenomenon, four wave mixing (FWM) 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-light 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).

Japanese Patent No. 5926055 Japanese Patent No. 4862164

Naoki Omiya, "Current Status and Future Prospects of Confocal Laser Endomicroscopy", Journal of Japan Gastroenterological Endoscopy Society, 61 (6), 1209-1217 (2019). Https://doi.org/10 . 11280 / gee. 61.1209 Yutaka 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. 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) 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) 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) 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. 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)

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 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 light and the second pulse laser light so that the first pulse laser light and the second pulse laser light are incident on different cores, respectively.
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.

According to the present invention, 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 non-linear Raman scattering endoscope according to an embodiment of the present invention, and 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. It is a block diagram which shows the test apparatus for observing the four-wave mixed light generated by an optical fiber bundle. 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. 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).

FIG. 1A 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. 1B 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.

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.

In the optical delay adjustment mechanism, the mirrors 12 and 15 are fixed, the mirrors 13 and 14 can be integrally displaced, 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 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.

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, the 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 the laser beam LB1. Allow LB2 to irradiate the sample at the same time.

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 the 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.

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 both beams is set to a predetermined numerical 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. 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.

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 focuses 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.

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 directly reproduced 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. 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.

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.

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.

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. 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.

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 wave 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.

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.

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.

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.

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.

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.

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.

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.

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).

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.

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.

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.

FIG. 4 is a block diagram showing a test device for observing a four-wave mixed light generated by 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.

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.

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. 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. 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.

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.

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.

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).

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.

The present invention is extremely industrially effective in that it can suppress four-wave mixed light generated from an optical fiber bundle.

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)

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 light and the second pulse laser light so that the first pulse laser light and the second pulse laser light are incident on different cores, respectively.
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 photodetector that detects Raman scattered light generated by a nonlinear optical phenomenon in an object. The nonlinear Raman scattering endoscope according to claim 1, further comprising a wave plate for aligning the polarization of the first pulse laser beam and the polarization of the second pulse laser beam into the same deflection state. The nonlinear Raman scattering endoscope according to claim 1, wherein the plurality of cores are arranged in a hexagonal close-packed structure in the optical fiber bundle. 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. The nonlinear Raman scattering endoscope according to claim 1, wherein the combined wave optical element is 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 polarized beam splitter. 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. The non-linear Raman scattering endoscope according to claim 1, wherein the Raman scattered light is coherent anti-Stoke Raman scattered light. The nonlinear Raman scattering endoscope according to claim 1, wherein the optical fiber bundle has a single mode transmission or a polarization holding function. 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. 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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