An imaging probe for near infrared i / ii region

Abstract

The application discloses an imaging probe for near-infrared I / II region, and belongs to the field of biomedical microscopic endoscopic images. The imaging probe comprises a microscopic objective group and a fiber bundle. The microscopic objective group focuses incident light to different depths of a biological sample to be measured for high-resolution imaging. The fiber bundle is coupled with the microscopic objective group and conducts and receives imaging information. The microscopic objective group comprises, in sequence, a first lens, a second lens, a third lens, a fourth lens, a fifth lens, a sixth lens and a seventh lens. The first lens, the second lens and the third lens jointly limit a light beam within an effective light aperture range. The fourth lens corrects chromatic aberration. The fifth lens and the sixth lens form a lens group, which converges light rays and corrects aberration. The seventh lens is a non-spherical lens, which corrects spherical aberration and field curvature of the microscopic objective group. According to a preset working distance of the microscopic objective group, the numerical aperture and the imaging field of the microscopic objective group are optimized. The imaging probe can effectively identify the near-infrared I / II region fluorescence wavelength band of indocyanine green in the range of 800-1200 nm.

Description

TECHNICAL FIELD

[0001] The present application belongs to the field of biomedical microscopic endoscopic imaging, and more particularly, to an imaging probe for near-infrared I / II region. BACKGROUND

[0002] In recent years, endoscopy is a better solution for detecting early, small, deep lesions or tumor tissues. The fiber-based probe confocal microscopic endoscope can be used with existing endoscopes, has microscopic endoscopic imaging capability at the cellular level, and provides real-time cellular structure information equivalent to pathological sections, which provides great help for early clinical diagnosis of cancer and other malignant diseases. However, the imaging depth of the existing technology is limited, such as only imaging the surface layer of the tissue when having high resolution. When identifying whether the tumor has metastasis, the invasion depth of the tumor to the tissue is often needed to determine. Therefore, given the diversity of disease development, it is particularly important to study the high-resolution visualization of deep tissues.

[0003] From the existing patent literature, the patent with the Chinese invention application number CN201810429006.9 and the publication date of August 14, 2020 describes: "Near-infrared miniature microscopic objective lens set and probe for use in the digestive tract, belong to the field of medical imaging. The present application relates to a near-infrared miniature microscopic objective lens set for use in the digestive tract, comprising a first lens, a second lens, a third lens, a fourth lens arranged in order from the object side, each lens of the microscopic objective lens set has a matching parameter so that the working distance of the miniature microscopic objective lens set is 200-300 μm, the magnification is 1.7-3.0, and the field of view can reach 360 μm at a near-infrared wavelength of 785-860 nm when the clear aperture of the miniature microscopic objective lens set is less than 2 mm. The near-infrared miniature microscopic objective lens set can observe structures such as the muscularis mucosa of the digestive tract located below the surface of the tissue 200 μm, and can better cooperate with the optical fiber bundle to observe the tissue cells." The disadvantages of this patent are: 1. The working distance of the microscopic objective lens set is 200-300 μm, which cannot break through the epithelial layer of the human digestive tract tissue, such as the epithelial layer of the esophagus, which is about 260-440 μm thick; 2. Its effective field of view is 360 μm, which cannot realize imaging of a larger range such as 500 μm of tissue; 3. Its effective working wavelength band is 785-860 nm, which is not enough to cover the fluorescence wavelength band of 860-1200 nm of the clinical near-infrared fluorescent contrast agent indocyanine green.

[0004] Therefore, the imaging probe in the existing scheme only applicable to the near-infrared I region has the problems of being unable to effectively identify the near-infrared I / II region fluorescence wavelength band of 860-1200 nm of the near-infrared fluorescent contrast agent indocyanine green and the imaging depth being unable to realize a larger range (such as 500 μm). SUMMARY

[0005] In view of the defects of the related art, the present application aims to provide an imaging probe for near-infrared I / II region, aiming to solve the problem that the imaging probe only applicable to the near-infrared I region in the prior art cannot effectively identify the near-infrared I / II region fluorescence band of the near-infrared fluorescent contrast agent indocyanine green at 860-1200 nm and the imaging depth cannot achieve a larger range.

[0006] To achieve the above-mentioned purpose, the present application provides an imaging probe for near-infrared I / II region, comprising: a microscope objective group and a fiber bundle;

[0007] The microscope objective group is arranged on one side of a biological sample to be measured, for focusing incident light to different depths of the biological sample to be measured for high-resolution imaging, while collecting fluorescent signals excited by the incident light; the fiber bundle is coupled to the other side of the microscope objective group, for conducting and receiving imaging information;

[0008] The microscope objective group comprises, in order from the object side to the image side: a first lens, a second lens, a third lens, a fourth lens, a fifth lens, a sixth lens and a seventh lens; the first lens, the second lens and the third lens form a positive focal power lens group for limiting the light beam within the effective clear aperture range; the fourth lens is a double-cemented achromatic lens for correcting chromatic aberration; the fifth lens and the sixth lens form a positive focal power lens group for converging light rays and correcting aberration; the seventh lens is a aspheric lens for correcting spherical aberration and field curvature;

[0009] According to the working distance preset by the microscope objective group, the numerical aperture and the imaging field of view of the microscope objective group are optimized through a fluorescence collection efficiency calculation formula;

[0010] The microscope objective group has a total of eight lenses with focal power;

[0011] The first lens adopts a plano-convex lens with a refractive index of 1.75-1.76 and a center thickness of 0.954 mm;

[0012] The second lens adopts a double-concave lens with a refractive index of 1.90-1.92 and a center thickness of 0.300 mm;

[0013] The third lens adopts a convex lens with a refractive index of 1.86 and a center thickness of 0.689 mm;

[0014] The fourth lens adopts a double-cemented lens with refractive indices of 1.85 and 1.76, respectively, a center thickness of the lens close to the object side of 1.422 mm, and a center thickness of the lens close to the image side of 2.087 mm;

[0015] The fifth lens adopts a biconvex lens, the refractive index is 1.86, and the center thickness is 0.807 mm;

[0016] The sixth lens adopts a meniscus lens, the refractive index is 1.69, and the center thickness is 0.863 mm;

[0017] The seventh lens has a refractive index of 1.65 corresponding to a wavelength range of 780-1200 nm, and a center thickness of 0.300 mm.

[0018] Optionally, the preset working distance of the microscope objective group is 800 μm, the numerical aperture on the object side is 0.6, and the field of view is 560 μm.

[0019] The calculation formula of the fluorescence collection efficiency is as follows:

[0020]

[0021] Wherein, R FOV is the field of view radius, WD is the working distance, NA is the numerical aperture, and FOV is the imaging field of view.

[0022] Optionally, the light transmission area diameter of the optical fiber bundle is 1200 μm, the effective image circle diameter is 1125 μm, the light transmission area contains N optical fibers, the value range of N is 60000±6000, the core distance is 4.38 μm, and the numerical aperture is 0.2-0.3.

[0023] Optionally, the first lens adopts H-LAF50B material;

[0024] The second lens adopts H-ZF73 material;

[0025] The third lens adopts H-ZLAF68N material;

[0026] The fourth lens adopts two kinds of materials, H-ZLAF73 and H-ZF71;

[0027] The fifth lens adopts H-ZLAF68N material;

[0028] The sixth lens adopts H-LAK7A material;

[0029] The seventh lens adopts D-LAK70 material.

[0030] Optionally, the center distance between the two adjacent surfaces of the first lens and the second lens is 0.050 mm;

[0031] The center distance between the two adjacent surfaces of the second lens and the third lens is 0.099 mm;

[0032] The center distance between the two adjacent surfaces of the third lens and the fourth lens is 0.100 mm;

[0033] The center distance between the two adjacent surfaces of the fourth lens and the fifth lens is 0.351 mm;

[0034] The center distance between the two adjacent surfaces of the fifth lens and the sixth lens is 0.052 mm;

[0035] The center distance between the two adjacent surfaces of the sixth lens and the seventh lens is 0.075 mm;

[0036] The center distance between the two adjacent surfaces of the seventh lens and the fiber bundle is 0.680 mm.

[0037] Optionally, the mirror surface curvature radius of the first lens close to the image surface is -1.334 mm, and the net aperture is 2.2 mm;

[0038] The mirror surface curvature radius of the second lens close to the object surface is -61.195 mm, the net aperture is 2.2 mm, the mirror surface curvature radius close to the image surface is 2.408 mm, and the net aperture is 2.2 mm;

[0039] The mirror surface curvature radius of the third lens close to the object surface is 3.795 mm, the net aperture is 2.2 mm, the mirror surface curvature radius close to the image surface is -2.802 mm, and the net aperture is 2.2 mm;

[0040] The mirror surface curvature radius of the fourth lens close to the object surface is 3.301 mm, the net aperture is 2.2 mm, the curvature radius of the middle cemented surface is -1.529 mm, the net aperture is 2.2 mm, the mirror surface curvature radius close to the image surface is 1.366 mm, and the net aperture is 1.8 mm;

[0041] The mirror surface curvature radius of the fifth lens close to the object surface is 22.516 mm, the net aperture is 2.2 mm, the mirror surface curvature radius close to the image surface is -1.960 mm, and the net aperture is 2.2 mm;

[0042] The mirror surface curvature radius of the sixth lens close to the object surface is 2.375 mm, the net aperture is 2.2 mm, the mirror surface curvature radius close to the image surface is 29.269 mm, and the net aperture is 2.2 mm;

[0043] The mirror surface curvature radius of the seventh lens close to the object surface is 1.008 mm, the net aperture is 1.8 mm, the mirror surface curvature radius close to the image surface is 0.476 mm, and the net aperture is 1.8 mm.

[0044] Optionally, the distance between the microscopic objective lens group and the biological sample to be measured is adjustable, which is used to generate high-resolution images of different depths.

[0045] Compared with the prior art, the above technical scheme conceived by the present application can achieve the following beneficial effects:

[0046] 1. The present application provides a microscope objective group for near-infrared I / II region, which utilizes the long wavelength and low scattering characteristics of near-infrared light to realize imaging of deep tissue. The overall design adopts a combination of positive and negative lenses, and a combination of spherical and aspherical lenses, to achieve effective correction of overall aberration while ensuring high resolution. Each lens of the microscope objective group has specific matching parameters so that when the effective clear aperture of the microscope objective group is less than 1.8 mm, the magnification at a wavelength of 785-1200 nm in the near-infrared I / II region is 2.25 times, the working distance is 800 μm, the object-side NA is 0.6, and the field of view can reach 560 μm. The microscope objective group for near-infrared I / II region can be used at a wavelength of 785-1200 nm, which matches the near-infrared I / II region spectral range of the clinically available near-infrared fluorescent agent indocyanine green. Due to the 2.25 times magnification of the microscope objective group, high-resolution cell imaging can be achieved in cooperation with a fiber bundle. The microscope objective group has an object-side NA of 0.6 and a field of view of 560 μm at a working distance of 800 μm, thereby maximizing the fluorescence collection efficiency.

[0047] 2. The present application provides an imaging probe for near-infrared I / II region, which has the advantages of small size (outer diameter ~ 2.6 mm), high resolution (~ 2 μm), large depth (≥ 500 μm), large field of view (~ 500 μm), and large bandwidth (785-1200 nm). It can be compatible with the working channel of a conventional white light endoscope to enter the human body for clinical diagnosis and treatment of esophageal, gastric, or colonic diseases, and can observe structures below 500 μm, even 800 μm, on the surface of the digestive tract mucosa. The depth of high-resolution cell imaging is extended from the surface of the mucosa layer to the submucosa layer, enabling visualization of epithelial cells, tissue information, and vascular structures, thereby obtaining information on deep mucosal lesions and effectively detecting the deep structure of diseased tissue, providing a powerful tool for research and clinical application in the biomedical field. BRIEF DESCRIPTION OF DRAWINGS

[0048] Figure 1 The present application provides a schematic diagram of the optical path structure of an imaging probe for near-infrared I / II region;

[0049] Figure 2 The present application provides an image-side spot diagram of a microscope objective group 1 for an imaging probe for near-infrared I / II region;

[0050] Figure 3MTF curve diagram of the microscope objective group 1 for the imaging probe in near-infrared I / II region;

[0051] Figure 4 Image-side field curvature curve diagram and distortion curve diagram of the microscope objective group 1 for the imaging probe in near-infrared I / II region;

[0052] Figure 5 Imaging effect schematic diagram of the imaging probe in near-infrared I / II region.

[0053] The figure marks are: 1, microscope objective group; 2, first lens; 3, second lens; 4, third lens; 5, fourth lens; 6, fifth lens; 7, sixth lens; 8, seventh lens; 9, optical fiber bundle. DETAILED DESCRIPTION

[0054] In order to make the purpose, technical scheme and advantages of the present application more clear, the present application is further described in detail below in combination with the drawings and examples. It should be understood that the specific examples described herein are only used to explain the present application and do not limit the present application. In addition, the technical features involved in each embodiment of the present application described below can be combined with each other as long as they do not conflict with each other.

[0055] The content involved in the above examples is described below in combination with a preferred embodiment.

[0056] As Figure 1 shown, an imaging probe for near-infrared I / II region includes: a microscope objective group 1 and an optical fiber bundle 9;

[0057] The microscope objective group 1 is arranged on one side of a biological sample to be measured, for focusing incident light to different depths of the biological sample to be measured for high-resolution imaging, while collecting fluorescence signals excited by the incident light; the optical fiber bundle 9 is coupled to the other side of the microscope objective group 1, for conducting and receiving imaging information;

[0058] The microscope objective group 1 includes, in order from the object side to the image side: a first lens 2, a second lens 3, a third lens 4, a fourth lens 5, a fifth lens 6, a sixth lens 7 and a seventh lens 8; the first lens 2, the second lens 3 and the third lens 4 form a positive focal power lens group for limiting the light beam within the effective clear aperture range; the fourth lens 5 is a doublet achromatic lens for correcting chromatic aberration; the fifth lens 6 and the sixth lens 7 form a positive focal power lens group for converging light rays and correcting aberration; the seventh lens 8 is a aspheric lens for correcting spherical aberration and field curvature.

[0059] In the design of the large-depth microscopic objective group 1 in the near-infrared I / II region, considering that the refractive index of the tissue is similar to that of water, the object side environment is set to be water immersion to meet the working environment of the miniature objective.

[0060] In the evaluation function, the image side telecentricity is set to ensure the uniformity of the coupling efficiency of the miniature objective and the fiber bundle. The long wavelength and low scattering characteristics of near-infrared light are used to realize imaging of deep tissues. Considering that the commonly used near-infrared dyes in clinical practice are methylene blue and indocyanine green, according to the theoretical penetration depth, as the wavelength increases, the penetration depth also increases. Therefore, the working wavelength range of the large-depth microscopic objective group 1 in the near-infrared I / II region is set to 785-1200 nm to reach the deep tissue, so as to cover the near-infrared I / II region spectral range of the clinical near-infrared fluorescent agent indocyanine green. In order to realize large-depth high-resolution cell observation, the object side NA of the large-depth microscopic objective group 1 in the near-infrared I / II region is 0.6, the magnification is 2.25, the image side field diameter on the right side of the seventh lens 8 is 1268 μm, the object side field diameter on the left side of the first lens 2 is 560 μm, and the working distance between the biological tissue surface and the first lens 2 is 800 μm, so as to ensure high-resolution imaging of the epithelial cells on the surface of the mucosa layer of the digestive tract, and the imaging depth can even extend to the submucosal layer, so as to realize longitudinal visualization of the tissue information and the vascular structure.

[0061] The designed microscopic objective group has a magnification of 2.25 when the working spectral range is 785-1200 nm and the effective clear aperture is less than 1.8 mm; the working distance of the microscopic objective group is 800 μm, the object side numerical aperture is 0.6, and the field of view is 560 μm.

[0062] The distance between the microscopic objective group and the biological sample to be measured is adjustable, and high-resolution images of different depths can be generated.

[0063] Considering the limitation of the fiber bundle on the resolution of the imaging probe, the root mean square size of the diffraction spot of the large-depth microscopic objective group 1 in the near-infrared I / II region needs to be less than the diameter of a single fiber 4.38 μm, and according to the sampling theorem, the image side MTF value of the large-depth microscopic objective group 1 in the near-infrared I / II region should be greater than 0.5 at the fiber bundle cutoff frequency 115 lp / mm. In this embodiment, the clear aperture diameter of the fiber bundle is 1200 μm, the effective image circle diameter is 1125 μm, N fibers are contained in the clear aperture region, the value range of N is 60000±6000, the core distance is 4.38 μm, and the numerical aperture is 0.2-0.3. In this embodiment, the number of fibers is preferably 60000.

[0064] Considering the machining limitation, the effective aperture of the microscopic objective lens set 1 is less than 1.8 mm, which can ensure the field of view imaging and the overall outer diameter after machining is not greater than 2.6 mm, and then can cooperate with the working channel of the gastroscope with a diameter of 2.8 mm to work.

[0065] Optionally, the working distance of the microscopic objective lens set is 800 μm; the numerical aperture and the imaging field of view of the microscopic objective lens set are optimized according to the working distance, so as to improve the fluorescence collection efficiency;

[0066] The calculation formula of the fluorescence collection efficiency is as follows:

[0067]

[0068] Wherein, R FOV is the field of view radius, WD is the working distance, NA is the numerical aperture, and FOV is the imaging field of view.

[0069] Through optimization, the design obtained is an 8-piece lens set structure combined with 7 spherical lenses and 1 aspherical lens. The overall optical length of the near-infrared I / II region large-depth microscopic objective lens set 1 is 8.8 mm, and the overall mechanical length is 9.7 mm. The overall design adopts positive and negative lens matching, and the combination of spherical and aspherical lenses, which realizes effective correction of overall aberration and ensures high resolution.

[0070] In the specific design, the second lens 3 and the third lens 4 are matched with the first lens 2 to limit the light beam within the effective aperture of the microscopic objective lens. By using materials with similar refractive index but large dispersion coefficient difference, and adopting negative-positive lens combination, the aberration can be better corrected. Due to the large field of view, a aspherical lens is placed on the last surface near the image side, which helps to correct the field curvature and other residual aberrations, and simplifies the system structure and is easy to process. Further, the stop of the system is arranged between the convex lens (third lens 4) and the double cemented lens (fourth lens 5), which further reduces the difficulty of aberration correction.

[0071] In a specific embodiment, the first lens 2 adopts H-LAF50B material;

[0072] The second lens 3 adopts H-ZF73 material;

[0073] The third lens 4 adopts H-ZLAF68N material;

[0074] The fourth lens 5 adopts H-ZLAF73 and H-ZF71 materials;

[0075] The fifth lens 6 adopts H-ZLAF68N material;

[0076] The sixth lens 7 adopts H-LAK7A material;

[0077] The seventh lens 8 adopts D-LAK70 material.

[0078] Optionally, the first lens 2 adopts a plano-convex lens with a refractive index of 1.75-1.76 and a center thickness of 0.954 mm;

[0079] The second lens 3 adopts a plano-concave lens with a refractive index of 1.90-1.92 and a center thickness of 0.300 mm;

[0080] The third lens 4 adopts a convex lens with a refractive index of 1.86 and a center thickness of 0.689 mm;

[0081] The fourth lens 5 adopts a double-cemented lens with refractive indices of 1.85 and 1.76 respectively, a center thickness of 1.422 mm near the object plane, and a center thickness of 2.087 mm near the image plane;

[0082] The fifth lens 6 adopts a plano-convex lens with a refractive index of 1.86 and a center thickness of 0.807 mm;

[0083] The sixth lens 7 adopts a plano-convex lens with a refractive index of 1.69 and a center thickness of 0.863 mm;

[0084] The seventh lens 8 has a refractive index of 1.65 corresponding to a wavelength range of 780-1200 nm and a center thickness of 0.300 mm.

[0085] Optionally, the center distance between the two adjacent surfaces of the first lens 2 and the second lens 3 is 0.050 mm;

[0086] The center distance between the two adjacent surfaces of the second lens 3 and the third lens 4 is 0.099 mm;

[0087] The center distance between the two adjacent surfaces of the third lens 4 and the fourth lens 5 is 0.100 mm;

[0088] The center distance between the two adjacent surfaces of the fourth lens 5 and the fifth lens 6 is 0.351 mm;

[0089] The center distance between the two adjacent surfaces of the fifth lens 6 and the sixth lens 7 is 0.052 mm;

[0090] The center distance between the two adjacent surfaces of the sixth lens 7 and the seventh lens 8 is 0.075 mm;

[0091] The center distance between the two adjacent surfaces of the seventh lens 8 and the fiber bundle 9 is 0.680 mm.

[0092] Optionally, the first lens 2 has a mirror surface curvature radius of -1.334 mm close to the image plane, and a net aperture of 2.2 mm;

[0093] The second lens 3 has a mirror surface curvature radius of -61.195 mm close to the object plane, a net aperture of 2.2 mm, a mirror surface curvature radius of 2.408 mm close to the image plane, and a net aperture of 2.2 mm;

[0094] The third lens 4 has a mirror surface curvature radius of 3.795 mm close to the object plane, a net aperture of 2.2 mm, a mirror surface curvature radius of -2.802 mm close to the image plane, and a net aperture of 2.2 mm;

[0095] The fourth lens 5 has a mirror surface curvature radius of 3.301 mm close to the object plane, a net aperture of 2.2 mm, a mirror surface curvature radius of -1.529 mm at the middle cemented surface, a net aperture of 2.2 mm, a mirror surface curvature radius of 1.366 mm close to the image plane, and a net aperture of 1.8 mm;

[0096] The fifth lens 6 has a mirror surface curvature radius of 22.516 mm close to the object plane, a net aperture of 2.2 mm, a mirror surface curvature radius of -1.960 mm close to the image plane, and a net aperture of 2.2 mm;

[0097] The sixth lens 7 has a mirror surface curvature radius of 2.375 mm close to the object plane, a net aperture of 2.2 mm, a mirror surface curvature radius of 29.269 mm close to the image plane, and a net aperture of 2.2 mm;

[0098] The seventh lens 8 has a mirror surface curvature radius of 1.008 mm close to the object plane, a net aperture of 1.8 mm, a mirror surface curvature radius of 0.476 mm close to the image plane, and a net aperture of 1.8 mm.

[0099] The microscopic objective group 1 provided by the embodiment is used for image quality analysis, and corresponding result figures are obtained. The microscopic objective group 1 provided by the embodiment is used for fluorescence imaging experiment with indocyanine green dyeing together with the optical fiber bundle 9, and corresponding result figures are obtained Figure 5 .

[0100] Figure 2 The image side point diagram of the microscopic objective group 1 for the imaging probe in the near-infrared I / II region. As shown in Figure 2As shown, the image-side field of view diameter of the microscope objective group 1 for the near-infrared I / II region imaging probe is up to 1268 μm, therefore, the full-field image quality analysis is selected along the radial direction at the image center, 0.3 field of view, 0.5 field of view, 0.707 field of view, 0.85 field of view and full field of view, etc. The diffraction spot morphology and root mean square size of a total of 6 different positions. The Airy disk radius is 1.789 μm, and the root mean square size of the diffraction spot of all fields of view is close to the size of the Airy disk, which can be considered to reach the approximate diffraction limit. The root mean square size of the diffraction spot of all fields of view is less than or close to the diameter of the single optical fiber of the fiber bundle 4.38 μm, which meets the requirements of the miniature microscope.

[0101] Figure 3 The MTF curve of the microscope objective group 1 for the near-infrared I / II region imaging probe is shown in the figure, which shows the MTF curves of the meridional plane and the sagittal plane of the 6 radial imaging positions and the MTF curve trend under the diffraction limit condition. Although there is a certain gap between the 11 MTF curves and the MTF curve under the diffraction limit condition, the MTF at 115 lp / mm is greater than 0.5, which meets the design index, and further ensures that the resolution of the imaging probe is not limited by the imaging performance of the near-infrared I / II region microscope objective group 1 with large depth.

[0102] Figure 4 The image-side field curvature curve and the distortion curve of the microscope objective group 1 for the near-infrared I / II region imaging probe are shown in the figure; according to the field curvature curve, under the condition of four wavelengths of 785 nm, 830 nm, 1000 nm and 1200 nm, the maximum image-side field curvature is 23.48 μm, and the maximum astigmatism is 28.24 μm, which is converted to the maximum field curvature and astigmatism of the object side respectively 6.17 μm and 7.42 μm, which is less than the axial resolution of the confocal endoscope, which meets the design requirements, and can be considered that the field curvature and astigmatism are effectively corrected, and has excellent imaging performance. In the distortion curve, the distortion in the full field of view is less than 1%, which is less than the distortion that can be perceived by the general human eye, which can maximize the guarantee of the shape of the imaging target without distortion.

[0103] Figure 5It is an imaging effect schematic diagram for the imaging probe used in near-infrared I / II region. By combining the near-infrared I / II region confocal endoscopic imaging system, 785 nm is used as the excitation light source, and the NMPA approved near-infrared fluorescent contrast agent indocyanine green is used, the excitation light source passes through the optical fiber bundle 9 and the near-infrared I / II region large-depth microscope group 1 in turn, reaches the surface of the biological tissue marked by indocyanine green, and then the excited 800 nm-1200 nm range of fluorescent waveband is transmitted through the near-infrared I / II region large-depth microscope group 1 and the optical fiber bundle 9 in turn, and then the imaging collection process is completed. With the change of the distance between the biological tissue surface and the near-infrared I / II region large-depth microscope group 1, high-resolution images at different depths can be collected, and when 0-150 μm, the epithelial cells, goblet cells and crypt structure distribution of the colon can be seen, when 150-300 μm, the epithelial layer structure gradually disappears, and the crypt structure transitions to the lamina propria and the muscularis mucosa, at the same time, the blood vessel information begins to appear, when 300-500 μm, the blood vessel network of the submucosal layer can be clearly seen, and even when the depth is greater than or equal to 500 μm, the blood vessel information can still be seen, and will be accompanied by larger diameter blood vessel layer information, and then through real-time acquisition of large-depth, high-resolution cell information and blood vessel morphology, early screening and diagnosis and treatment of digestive tract diseases are assisted.

[0104] In the embodiment of the present application, the long wavelength and low scattering characteristics of near-infrared light are utilized to realize imaging of deep tissue. The overall design adopts positive and negative lens matching, and the combination of spherical mirrors and aspherical mirrors to realize effective correction of overall aberration while ensuring high resolution. The object side NA of the microscope objective group is 0.6, the magnification is 2.25 times, the working spectral range is 785-1200 nm, the effective clear aperture is 1.8 mm, and the effective imaging depth and field of view can reach 500 μm. It can be compatible with the working channel of the conventional white light endoscope to enter the human body for the clinical diagnosis and treatment of esophagus, stomach or colon for digestive tract diseases. The existing scheme only applies to the imaging probe in the near-infrared I region, which cannot effectively identify the near-infrared fluorescent contrast agent indocyanine green in the near-infrared I / II region of 860-1200 nm, and the imaging depth cannot realize a larger range (such as 500 μm). The problems are solved. Effective identification of near-infrared I and II region fluorescence band is realized, the application range of the imaging probe is expanded, the depth of high-resolution cell imaging is extended from the surface of the digestive tract mucosa to the submucosa, and in the case of compatible conventional white light endoscopic biopsy channel and use of indocyanine green, the clinical diagnosis and treatment of esophagus, stomach or colon in the human body can be realized. The epithelial cells, tissue information and blood vessel structure are visualized, so as to obtain the information of deep mucosal lesions of the tissue, effectively detect the deep structure of the lesion tissue, provide real-time information equivalent to pathology for early cancer staging, and provide a powerful tool for research and clinical application in the biomedical field.

[0105] Those skilled in the art will readily understand that the above description is only the preferred embodiment of the present application, and is not intended to limit the present application. Any modification, equivalent replacement and improvement made within the spirit and principle of the present application shall be included in the protection scope of the present application.

Claims

1. An imaging probe for the near infrared I / II region, characterized in that, The application relates to a microscope objective group and a fiber bundle. The microscope objective group is arranged on one side of a biological sample to be detected, is used for focusing incident light to different depths of the biological sample to be detected for high-resolution imaging, and simultaneously collects fluorescent signals excited by the incident light. The fiber bundle is coupled with the other side of the microscope objective group and is used for conducting and receiving imaging information. The microscope objective group comprises, in sequence from an object side to an image side, a first lens, a second lens, a third lens, a fourth lens, a fifth lens, a sixth lens and a seventh lens; the first lens, the second lens and the third lens form a positive-power lens group and are used for limiting a light beam within an effective light aperture range; the fourth lens is a double-cemented achromatic lens and is used for correcting chromatic aberration; the fifth lens and the sixth lens form a positive-power lens group and are used for converging light rays and correcting aberration; and the seventh lens is a non-spherical lens and is used for correcting spherical aberration and field curvature. According to a preset working distance of the microscope objective group, the numerical aperture and the imaging field of view of the microscope objective group are optimized through a fluorescent collection efficiency calculation formula. The total number of lenses with optical power of the microscope objective group is eight. The first lens is a plano-convex lens with a refractive index of 1.75-1.76 and a central thickness of 0.954 mm. The second lens is a double-concave lens with a refractive index of 1.90-1.92 and a central thickness of 0.300 mm. The third lens is a convex lens with a refractive index of 1.86 and a central thickness of 0.689 mm. The fourth lens is a double-cemented lens with refractive indexes of 1.85 and 1.76 respectively, a central thickness of 1.422 mm of the lens close to the object side and a central thickness of 2.087 mm of the lens close to the image side. The fifth lens is a double-convex lens with a refractive index of 1.86 and a central thickness of 0.807 mm. The sixth lens is a meniscus lens with a refractive index of 1.69 and a central thickness of 0.863 mm. The seventh lens has a refractive index of 1.65 corresponding to a wavelength range of 780-1200 nm and a central thickness of 0.300 mm. The preset working distance of the microscope objective group is 800 mu m, the numerical aperture of the object side is 0.6, and the field of view is 560 mu m.

2. The imaging probe of claim 1, wherein, The light transmission area diameter of the fiber bundle is 1200 mu m, the effective image circle diameter is 1125 mu m, N root fibers are contained in the light transmission area, the value range of N is 60000+ / -6000, the fiber core distance is 4.38 mu m, and the numerical aperture is 0.2-0.

3. The fluorescence collection efficiency The formula for calculating the fluorescence collection efficiency is: wherein R FOV is the field of view radius, WD is the working distance, NA is the numerical aperture, and FOV is the imaging field of view.

3. The imaging probe of claim 1, wherein, The first lens is made of H-LAF50B material.

4. The imaging probe of claim 1, wherein, The second lens is made of H-ZF73 material. The third lens is made of H-ZLAF68N material. The fourth lens is made of H-ZLAF73 and H-ZF71 materials. The fifth lens is made of H-ZLAF68N material. The sixth lens is made of H-LAK7A material. The seventh lens is made of D-LAK70 material. The central distance between the two adjacent surfaces of the first lens and the second lens is 0.050 mm.

5. The imaging probe of claim 4, wherein, The central distance between the two adjacent surfaces of the second lens and the third lens is 0.099 mm. ​ The center distance between the two adjacent surfaces of the third lens and the fourth lens is 0.100 mm; The center distance between the two adjacent surfaces of the fourth lens and the fifth lens is 0.351 mm; The center distance between the two adjacent surfaces of the fifth lens and the sixth lens is 0.052 mm; The center distance between the two adjacent surfaces of the sixth lens and the seventh lens is 0.075 mm; The center distance between the two adjacent surfaces of the seventh lens and the optical fiber bundle is 0.680 mm.

6. The imaging probe of claim 4, wherein, The mirror surface curvature radius of the first lens close to the image plane is -1.334 mm, and the net aperture is 2.2 mm; The mirror surface curvature radius of the second lens close to the object plane is -61.195 mm, and the net aperture is 2.2 mm; the mirror surface curvature radius close to the image plane is 2.408 mm, and the net aperture is 2.2 mm; The mirror surface curvature radius of the third lens close to the object plane is 3.795 mm, and the net aperture is 2.2 mm; the mirror surface curvature radius close to the image plane is -2.802 mm, and the net aperture is 2.2 mm; The mirror surface curvature radius of the fourth lens close to the object plane is 3.301 mm, and the net aperture is 2.2 mm; the curvature radius of the middle cemented surface is -1.529 mm, and the net aperture is 2.2 mm; the mirror surface curvature radius close to the image plane is 1.366 mm, and the net aperture is 1.8 mm; The mirror surface curvature radius of the fifth lens close to the object plane is 22.516 mm, and the net aperture is 2.2 mm; the mirror surface curvature radius close to the image plane is -1.960 mm, and the net aperture is 2.2 mm; The mirror surface curvature radius of the sixth lens close to the object plane is 2.375 mm, and the net aperture is 2.2 mm; the mirror surface curvature radius close to the image plane is 29.269 mm, and the net aperture is 2.2 mm; The mirror surface curvature radius of the seventh lens close to the object plane is 1.008 mm, and the net aperture is 1.8 mm; the mirror surface curvature radius close to the image plane is 0.476 mm, and the net aperture is 1.8 mm.

7. The imaging probe of claim 1, wherein, The distance between the microscopic objective lens group and the biological sample to be measured is adjustable, which is used to generate high-resolution images of different depths.

Images