Imaging probe for near-infrared I / II area

Abstract

The invention discloses an imaging probe for a near-infrared I / II area, and belongs to the field of biomedical microscopic endoscopic images. The imaging probe comprises a microscope objective group and an optical fiber bundle, the microscope objective group focuses incident light to different depths of a biological sample to be detected for high-resolution imaging; the optical fiber bundle is in coupling connection with the microscope objective group, and transmits and receives imaging information; the microscope objective group sequentially comprises 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 clear aperture range; a fourth lens corrects chromatic aberration; the fifth lens and the sixth lens form a lens group to converge light and correct aberration, and the seventh lens adopts an aspheric lens to correct spherical aberration and field curvature of the microscope objective group; and optimizing the numerical aperture and the imaging field of view of the microscope objective group according to the preset working distance of the microscope objective group. And the fluorescent wave band of indocyanine green in a near-infrared I / II region of 800-1200 nm can be effectively identified.

Description

Technical Field

[0001] The present invention belongs to the field of biomedical microendoscopic imaging, and more specifically, relates to an imaging probe for near infrared I / II region. Background Art

[0002] In recent years, endoscopes have become a better solution for detecting early, tiny, deep lesions or tumor tissues. The fiber-optic probe-type confocal microendoscope is compatible with existing endoscopes, has the ability of microendoscopic imaging at the cellular level, and provides real-time cellular structure information equivalent to pathological sections, which is of great help in the early clinical diagnosis of cancer and other malignant diseases. However, the imaging depth of existing technologies is limited. For example, only the surface of the tissue can be imaged at high resolution. When identifying whether a tumor has metastasized, it is often necessary to judge by the depth of invasion of the tumor into the tissue. Therefore, given the diversity of disease development, research on high-resolution visualization of deep tissues is particularly important.

[0003] A search of existing patent documents revealed that the Chinese invention application number is: CN201810429006.9, and the patent description with the publication date of August 14, 2020 is: "A near-infrared micro-microscope objective lens group and probe for use in the digestive tract, belonging to the field of medical imaging. The present invention relates to a near-infrared micro-microscope objective lens group for use in the digestive tract, comprising a first lens, a second lens, a third lens, and a fourth lens arranged in sequence from the object side, each of the lenses of the micro-microscope objective lens group having adapted parameters so that when the aperture of the micro-microscope objective lens group is less than 2 mm, the working distance 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. The near-infrared micro-microscope objective lens group can observe structures such as the muscularis mucosa of the digestive tract located below 200 μm on the tissue surface, and can better cooperate with the optical fiber bundle to realize the observation of tissue cells." Its shortcomings are: 1. The working distance of the microscope objective lens group is 200-300μm, which cannot break through the epithelial layer of human digestive tract tissue. For example, the thickness of the epithelial layer of the esophagus is about 260-440μm; 2. Its effective field of view is 360μm, which cannot achieve tissue imaging beyond a larger range, such as 500μm; 3. Its effective working band is 785-860nm, which is not enough to cover the fluorescence band of the clinical near-infrared fluorescent agent indocyanine green at 860-1200nm.

[0004] Therefore, the existing imaging probes that are only applicable to the near-infrared I region cannot effectively identify the near-infrared fluorescent contrast agent indocyanine green in the near-infrared I / II region fluorescence band of 860-1200nm and the imaging depth cannot achieve a larger range (such as 500μm). Summary of the invention

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

[0006] To achieve the above object, the present invention provides an imaging probe for near infrared I / II region, comprising: a mutually coupled microscope objective lens group and an optical fiber bundle;

[0007] The microscope objective lens group is used to focus incident light onto the biological sample to be tested for high-resolution imaging, and at the same time collect the fluorescence signal emitted by the biological sample to be tested under the excitation of the incident light; the optical fiber bundle is used to receive and transmit imaging information;

[0008] The microscope objective lens group includes, 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 in sequence; the first lens, the second lens and the third lens form a lens group with positive focal length, which is used to limit the light beam within the effective aperture range; the fourth lens is a double-cemented achromatic lens, which is used to correct chromatic aberration; the fifth lens and the sixth lens form a lens group with positive focal length, which is used to converge light and correct aberration; the seventh lens is an aspherical lens, which is used to correct spherical aberration and field curvature;

[0009] The numerical aperture and imaging field of view of the microscope objective lens group are calculated according to the working distance thereof by using a calculation formula for fluorescence collection efficiency.

[0010] Optionally, the preset working distance of the microscope objective lens group is 800 μm, the object numerical aperture is 0.6, and the field of view is 560 μm;

[0011] The fluorescence collection efficiency η scattering The calculation formula is:

[0012]

[0013] Among them, 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.

[0014] Optionally, the light-transmitting area diameter of the optical fiber bundle is 1200 μm, the effective image circle diameter is 1125 μm, the light-transmitting area contains N optical fibers, the value range of N is 60000±6000, the fiber core pitch is 4.38 μm, and the numerical aperture is 0.2-0.3.

[0015] Optionally, the first lens is made of H-LAF50B material;

[0016] The second lens is made of H-ZF73 material;

[0017] The third lens is made of H-ZLAF68N material;

[0018] The fourth lens is made of two materials: H-ZLAF73 and H-ZF71;

[0019] The fifth lens is made of H-ZLAF68N material;

[0020] The sixth lens is made of H-LAK7A material;

[0021] The seventh lens is made of D-LAK70 material.

[0022] Optionally, the first lens is a plano-convex lens with a refractive index of 1.75-1.76 and a center thickness of 0.954 mm;

[0023] The second lens is a plano-concave lens with a refractive index of 1.90-1.92 and a center thickness of 0.300 mm;

[0024] The third lens is a convex lens with a refractive index of 1.86 and a center thickness of 0.689 mm;

[0025] The fourth lens is a doublet lens with refractive indices of 1.85 and 1.76 respectively, the center thickness of the lens close to the object plane is 1.422 mm, and the center thickness of the lens close to the image plane is 2.087 mm;

[0026] The fifth lens is a plano-convex lens with a refractive index of 1.86 and a center thickness of 0.807 mm;

[0027] The sixth lens is a plano-convex lens with a refractive index of 1.69 and a center thickness of 0.863 mm;

[0028] The refractive index of the seventh lens is 1.65 in the wavelength range of 780-1200 nm, and the center thickness is 0.300 mm.

[0029] Optionally, the center distance between two adjacent surfaces of the first lens and the second lens is 0.050 mm;

[0030] The center distance between two adjacent surfaces of the second lens and the third lens is 0.099 mm;

[0031] The center distance between two adjacent surfaces of the third lens and the fourth lens is 0.100 mm;

[0032] The center distance between two adjacent surfaces of the fourth lens and the fifth lens is 0.351 mm;

[0033] The center distance between two adjacent surfaces of the fifth lens and the sixth lens is 0.052 mm;

[0034] The center distance between two adjacent surfaces of the sixth lens and the seventh lens is 0.075 mm;

[0035] The center distance between the seventh lens and two adjacent surfaces of the optical fiber bundle is 0.680 mm.

[0036] Optionally, the mirror curvature radius of the first lens close to the image plane is -1.334 mm, and the net aperture is 2.2 mm;

[0037] The curvature radius of the mirror surface of the second lens close to the object plane is -61.195mm, the net diameter is 2.2mm, and the curvature radius of the mirror surface close to the image plane is 2.408mm, the net diameter is 2.2mm;

[0038] The third lens has a curvature radius of 3.795 mm near the object plane and a clear aperture of 2.2 mm, and a curvature radius of -2.802 mm near the image plane and a clear aperture of 2.2 mm;

[0039] The fourth lens has a curvature radius of 3.301 mm near the object plane and a net aperture of 2.2 mm, a curvature radius of -1.529 mm at the middle cemented surface and a net aperture of 2.2 mm, and a curvature radius of 1.366 mm near the image plane and a net aperture of 1.8 mm.

[0040] The curvature radius of the mirror surface of the fifth lens close to the object plane is 22.516 mm, the clear aperture is 2.2 mm, and the curvature radius of the mirror surface close to the image plane is -1.960 mm, the clear aperture is 2.2 mm;

[0041] The sixth lens has a curvature radius of 2.375 mm near the object plane and a clear aperture of 2.2 mm, and a curvature radius of 29.269 mm near the image plane and a clear aperture of 2.2 mm;

[0042] The seventh lens has a mirror curvature radius of 1.008 mm near the object plane and a net aperture of 1.8 mm, and a mirror curvature radius of 0.476 mm near the image plane and a net aperture of 1.8 mm.

[0043] Optionally, the distance between the microscope objective lens group and the biological sample to be tested is adjustable.

[0044] Compared with the prior art, the above technical solutions conceived by the present invention can achieve the following

[0045] Beneficial effects:

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

[0047] 2. The present invention provides an imaging probe for near-infrared I / II zone, which has the advantages of small size (outer diameter ~2.6mm), high resolution (~2μm), large depth (≥500μm), large field of view (~500μm), and large bandwidth (785-1200nm). 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 digestive diseases in the esophagus, stomach or colon, and can observe structures below 500μm or even 800μm on the surface of the digestive tract mucosal tissue; the depth of high-resolution cell imaging extends from the surface of the digestive tract mucosal layer to the submucosal layer, visualizing epithelial cells, tissue information and vascular structure, thereby obtaining mucosal lesion information in the deep tissue layer, and effectively detecting the deep structure of the diseased tissue, providing a powerful tool for research and clinical application in the biomedical field. BRIEF DESCRIPTION OF THE DRAWINGS

[0048] Figure 1 A schematic diagram of the optical path structure of an imaging probe for near infrared I / II region provided by the present invention;

[0049] Figure 2 The image-side spot diagram of the microscope objective lens group 1 for the imaging probe in the near-infrared I / II region;

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

[0051] Figure 4 The image field curvature curve and distortion curve of the microscope objective lens group 1 for the imaging probe in the near infrared I / II region;

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

[0053] The reference numerals are: 1, microscope objective lens 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 solutions and advantages of the present invention more clearly understood, the present invention is further described in detail below in conjunction with the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are only used to explain the present invention and are not intended to limit the present invention. In addition, the technical features involved in the various embodiments of the present invention described below can be combined with each other as long as they do not conflict with each other.

[0055] The contents involved in the above embodiment are described below in conjunction with a preferred embodiment.

[0056] like Figure 1 As shown, an imaging probe for near infrared I / II region comprises: a microscope objective lens group 1 and an optical fiber bundle 9 coupled to each other;

[0057] The microscope objective lens group 1 is used to focus incident light onto the biological sample to be tested for high-resolution imaging, and at the same time collect the fluorescence signal emitted by the biological sample to be tested under the excitation of the incident light; the optical fiber bundle 9 is used to receive and transmit imaging information;

[0058] The microscope objective lens group 1 includes, 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 lens group with positive focal length, which is used to limit the light beam within the effective aperture range; the fourth lens 5 is a double-cemented achromatic lens, which is used to correct chromatic aberration; the fifth lens 6 and the sixth lens 7 form a lens group with positive focal length, which is used to converge light and correct aberration; the seventh lens 8 adopts an aspherical lens, which is used to correct spherical aberration and field curvature.

[0059] The numerical aperture and imaging field of view of the microscope objective lens group are calculated according to the working distance thereof by using a calculation formula for fluorescence collection efficiency.

[0060] When designing the near-infrared I / II region deep-depth microscope objective lens set 1, considering that the refractive index of tissue is similar to that of water, the object environment is set to water immersion to meet the working environment of the micro objective lens. The working distance of the microscope objective lens set is the distance from the microscope objective lens set to the biological material sample.

[0061] The image telecentricity is set in the evaluation function to ensure the uniformity of the coupling efficiency between the micro-objective lens and the optical fiber bundle. The long wavelength and low scattering characteristics of near-infrared light are used to achieve 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, it can be seen that as the wavelength increases, the penetration depth increases. Therefore, the working band of the near-infrared I / II zone deep-depth microscope objective group 1 is selected in the near-infrared I / II zone that can reach the deep tissue, and is set to 785-1200nm to cover the near-infrared I / II zone spectral range of the clinical near-infrared fluorescent agent indocyanine green. In order to achieve high-resolution cell observation at a great depth, the object-side NA of the deep-depth microscope objective lens group 1 in the near-infrared I / II zone is 0.6, the magnification is 2.25 times, the image-side field of view diameter on the right side of the seventh lens 8 is 1268μm, the object-side field of view diameter on the left side of the first lens 2 is 560μm, and the working distance between the biological tissue surface and the first lens 2 is 800μm, so as to ensure high-resolution imaging of the epithelial cells on the surface of the digestive tract mucosal layer. The imaging depth can even extend to the submucosal layer, and the tissue information and vascular structure can be visualized longitudinally.

[0062] The designed microscope objective lens group has a magnification of 2.25 when the working spectrum range is 785-1200nm and the effective aperture is less than 1.8mm; the working distance of the microscope objective lens group is 800μm, the object numerical aperture is 0.6, and the field of view is 560μm.

[0063] The distance between the microscope objective lens group and the biological sample to be tested is adjustable, so as to generate high-resolution images at different depths.

[0064] Considering the limitation of the optical fiber bundle on the resolution of the imaging probe, the root mean square size of the diffuse spot of the deep depth microscope objective group 1 in the near-infrared I / II region needs to be smaller than the diameter of a single optical fiber of 4.38μm, and according to the sampling theorem, the image-side MTF value of the deep depth microscope objective group 1 in the near-infrared I / II region should be greater than 0.5 at the cutoff frequency of the optical fiber bundle of 115lp / mm. In this embodiment, the light-transmitting area diameter of the optical fiber bundle is 1200μm, the effective image circle diameter is 1125μm, and the light-transmitting area contains N optical fibers, the value range of N is 60000±6000, the core pitch is 4.38μm, and the numerical aperture is 0.2-0.3. In this embodiment, the number of optical fibers is preferably 60,000.

[0065] Taking into account the processing limitations, the effective aperture of the microscope objective lens group 1 is less than 1.8 mm, which can ensure both field imaging and the overall outer diameter after processing to be no greater than 2.6 mm, and can then work with a gastroscope with a working channel of 2.8 mm.

[0066] Optionally, the working distance of the microscope objective lens group is 800 μm; the numerical aperture and imaging field of view of the microscope objective lens group are optimized according to the working distance to improve the fluorescence collection efficiency;

[0067] The fluorescence collection efficiency η scattering The calculation formula is:

[0068]

[0069] Among them, 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.

[0070] Through optimization, the resulting design is an 8-piece lens group structure composed of 7 spherical lenses and 1 aspherical lens. The overall optical length of the near-infrared I / II zone deep-depth microscope objective group 1 is 8.8mm, and the overall mechanical length is 9.7mm. The overall design uses 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.

[0071] In the specific design, the second lens 3, the third lens 4 and the first lens 2 are matched to limit the light beam to the effective aperture of the micro-objective lens. By using materials with similar refractive indices but large differences in dispersion coefficients, and using a combination of negative and positive lenses, aberrations can be better corrected. Due to the large field of view, it is necessary to place an aspherical surface on the last side close to the image side, which helps to correct field curvature and other residual aberrations, while simplifying the system structure and facilitating processing. Furthermore, the system aperture is set between the convex lens (third lens 4) and the double cemented lens (fourth lens 5) to further reduce the difficulty of aberration correction.

[0072] In a specific embodiment, the first lens 2 is made of H-LAF50B material;

[0073] The second lens 3 is made of H-ZF73 material;

[0074] The third lens 4 is made of H-ZLAF68N material;

[0075] The fourth lens 5 is made of two materials: H-ZLAF73 and H-ZF71;

[0076] The fifth lens 6 is made of H-ZLAF68N material;

[0077] The sixth lens 7 is made of H-LAK7A material;

[0078] The seventh lens 8 is made of D-LAK70 material.

[0079] Optionally, the first lens 2 is a plano-convex lens with a refractive index of 1.75-1.76 and a center thickness of 0.954 mm;

[0080] The second lens 3 is a plano-concave lens with a refractive index of 1.90-1.92 and a center thickness of 0.300 mm;

[0081] The third lens 4 is a convex lens with a refractive index of 1.86 and a center thickness of 0.689 mm;

[0082] The fourth lens 5 is a doublet lens with refractive indices of 1.85 and 1.76 respectively. The center thickness of the lens close to the object plane is 1.422 mm, and the center thickness of the lens close to the image plane is 2.087 mm.

[0083] The fifth lens 6 is a plano-convex lens with a refractive index of 1.86 and a center thickness of 0.807 mm;

[0084] The sixth lens 7 is a plano-convex lens with a refractive index of 1.69 and a center thickness of 0.863 mm;

[0085] The refractive index of the seventh lens 8 corresponding to the wavelength range of 780-1200nm is 1.65, and the center thickness is 0.300mm.

[0086] Optionally, the center distance between two adjacent surfaces of the first lens 2 and the second lens 3 is 0.050 mm;

[0087] The center distance between two adjacent surfaces of the second lens 3 and the third lens 4 is 0.099 mm;

[0088] The center distance between two adjacent surfaces of the third lens 4 and the fourth lens 5 is 0.100 mm;

[0089] The center distance between two adjacent surfaces of the fourth lens 5 and the fifth lens 6 is 0.351 mm;

[0090] The center distance between two adjacent surfaces of the fifth lens 6 and the sixth lens 7 is 0.052 mm;

[0091] The center distance between two adjacent surfaces of the sixth lens 7 and the seventh lens 8 is 0.075 mm;

[0092] The center distance between the seventh lens 8 and two adjacent surfaces of the optical fiber bundle 9 is 0.680 mm.

[0093] Optionally, the mirror curvature radius of the first lens 2 close to the image plane is -1.334 mm, and the net aperture is 2.2 mm;

[0094] The mirror curvature radius of the second lens 3 close to the object plane is -61.195 mm, the net diameter is 2.2 mm, and the mirror curvature radius close to the image plane is 2.408 mm, the net diameter is 2.2 mm;

[0095] The third lens 4 has a curvature radius of 3.795 mm near the object plane and a clear aperture of 2.2 mm, and a curvature radius of -2.802 mm near the image plane and a clear aperture of 2.2 mm;

[0096] The fourth lens 5 has a curvature radius of 3.301 mm near the object plane, a net aperture of 2.2 mm, a curvature radius of -1.529 mm at the middle cemented surface, a net aperture of 2.2 mm, and a curvature radius of 1.366 mm near the image plane, a net aperture of 1.8 mm.

[0097] The curvature radius of the mirror surface of the fifth lens 6 close to the object plane is 22.516 mm, the clear aperture is 2.2 mm, and the curvature radius of the mirror surface close to the image plane is -1.960 mm, the clear aperture is 2.2 mm;

[0098] The mirror curvature radius of the sixth lens 7 close to the object plane is 2.375 mm, the net diameter is 2.2 mm, and the mirror curvature radius close to the image plane is 29.269 mm, the net diameter is 2.2 mm;

[0099] The seventh lens 8 has a mirror curvature radius of 1.008 mm near the object plane and a clear aperture of 1.8 mm, and a mirror curvature radius of 0.476 mm near the image plane and a clear aperture of 1.8 mm.

[0100] The microscope objective lens set 1 provided in this embodiment is used to perform image quality analysis, and the corresponding result graph is obtained. The microscope objective lens set 1 provided in this embodiment and the optical fiber bundle 9 are used to perform a fluorescence imaging experiment using indocyanine green staining, and the corresponding result is obtained. Figure 5 .

[0101] Figure 2 : is the image point diagram of the microscope objective lens group 1 for the imaging probe in the near infrared I / II region. Figure 2 As shown in the figure, the image field diameter of the microscope objective lens group 1 for the imaging probe in the near-infrared I / II region is as high as 1268μm. Therefore, different fields of view such as 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 were selected along the radial direction for full-field image quality analysis, and the diffuse spot morphology and root mean square size of 6 different positions were analyzed. The radius of the Airy disk is 1.789μm, and the root mean square size of the diffuse spots in all fields of view is close to the Airy disk size. It can be considered that the design has reached the approximate diffraction limit. The root mean square size of the diffuse spots in all fields of view is less than or close to the diameter of a single optical fiber in the optical fiber bundle, which is 4.38μm, meeting the requirements of the micro-microscope objective lens.

[0102] Figure 3 The MTF curve of the microscope objective lens set 1 for the imaging probe in the near-infrared I / II region shows the MTF curves of the meridian and sagittal planes at 6 radial imaging positions and the MTF curve trend under the diffraction limit. Although there is a certain gap between the 11 MTF curves and the MTF curve under the diffraction limit condition, the MTF at 115lp / mm is greater than 0.5, which meets the design indicators and further ensures that the resolution of the imaging probe is not limited to the imaging performance of the microscope objective lens set 1 with a large depth in the near-infrared I / II region.

[0103] Figure 4 The image side field curvature curve and distortion curve of the microscope objective lens group 1 for the imaging probe in the near infrared I / II region are shown in the figure. According to the field curvature curve, at the four wavelengths of 785nm, 830nm, 1000nm and 1200nm, the maximum image side field curvature is 23.48μm, and the maximum astigmatism is 28.24μm. The maximum values ​​of the object side field curvature and astigmatism are 6.17μm and 7.42μm respectively, which are less than the axial resolution of the confocal endoscope and meet the design requirements. It can be considered that both the field curvature and astigmatism have been effectively corrected, and the imaging performance is excellent. 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 human eye, and the shape of the imaging target can be guaranteed to be undistorted to the greatest extent.

[0104] Figure 5 The diagram is a schematic diagram of the imaging effect of the imaging probe for the near infrared I / II region. By combining the near infrared I / II region confocal endoscopic imaging system, using 785nm as the excitation light source, and coordinating with the near infrared fluorescent contrast agent indocyanine green approved by NMPA, the excitation light source sequentially passes through the optical fiber bundle 9 and the near infrared I / II region deep microscope objective lens group 1 to reach the surface of the biological tissue labeled with indocyanine green, and then the excited fluorescence band in the range of 800nm-1200nm is sequentially transmitted through the near infrared I / II region deep microscope objective lens group 1 and the optical fiber bundle 9, thereby completing the imaging acquisition process. As the distance between the biological tissue surface and the deep-depth microscope objective group 1 in the near-infrared I / II zone changes, high-resolution images at different depths can be collected. At 0-150μm, the distribution of epithelial cells, goblet cells and crypt structures of the colon can be seen. Starting from 150-300μm, the epithelial layer structure gradually disappears, and the crypt structure transitions to the lamina propria and muscularis mucosa. At the same time, vascular information begins to appear. At 300-500μm, the vascular network of the submucosal layer is clearly visible. Even when the depth is ≥500μm, the vascular information is still visible and will be accompanied by information on the vascular layer with a larger diameter. Therefore, by acquiring deep, high-resolution cell information and vascular morphology in real time, it can assist in the early screening and diagnosis and treatment of digestive tract diseases.

[0105] In the embodiment of the present invention, the long wavelength and low scattering characteristics of near-infrared light are used to realize imaging of deep tissues. The overall design adopts a combination of positive and negative lenses, and a spherical mirror and an aspherical mirror to achieve effective correction of overall aberration while ensuring high resolution, so that the object side NA of the microscope objective group is 0.6, the magnification is 2.25 times, the working spectrum range is 785-1200nm, and the effective aperture is 1.8mm. It is adapted to the near-infrared I / II zone spectrum range of 785-1200nm of the clinically available near-infrared fluorescent agent indocyanine green, and the effective imaging depth and field of view can reach 500μm. It can be compatible with the working channel of conventional white light endoscopes to enter the human body for clinical diagnosis and treatment of digestive tract diseases in the esophagus, stomach or colon. It solves the problem that the imaging probe only applicable to the near-infrared I zone in the existing solution cannot effectively identify the near-infrared fluorescent contrast agent indocyanine green in the near-infrared I / II zone fluorescence band of 860-1200nm and the imaging depth cannot achieve a larger range (such as 500μm). It has achieved effective identification of near-infrared zone I and zone II fluorescence bands, expanded the application range of the imaging probe, and extended the depth of high-resolution cell imaging from the surface of the gastrointestinal mucosal layer to the submucosal layer. While being compatible with conventional white light endoscopic biopsy channels and using indocyanine green, it can enter the human body for clinical diagnosis and treatment of the esophagus, stomach, or colon, visualize epithelial cells, tissue information, and vascular structure, thereby obtaining information on mucosal lesions deep in the tissue, effectively detecting the deep structure of the diseased tissue, and providing real-time information equivalent to pathology for the staging of early cancers, providing a powerful tool for research and clinical applications in the biomedical field.

[0106] It will be easily understood by those skilled in the art that the above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions and improvements made within the spirit and principles of the present invention should be included in the protection scope of the present invention.

Claims

1. An imaging probe for near infrared I / II region, characterized in that: include: A mutually coupled microscope objective lens set and optical fiber bundle; The microscope objective lens group is used to focus incident light onto the biological sample to be tested for high-resolution imaging, and to collect fluorescence signals emitted by the biological sample to be tested under the excitation of the incident light; The optical fiber bundle is used to receive and transmit imaging information; The microscope objective lens group includes, 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 lens group with positive focal length, which is used to limit the light beam within the effective aperture range; the fourth lens is a double cemented achromatic lens, which is used to correct chromatic aberration; the fifth lens and the sixth lens form a lens group with positive focal length, which is used to converge light and correct aberration; the seventh lens is an aspherical lens, which is used to correct spherical aberration and field curvature; The numerical aperture and imaging field of view of the microscope objective lens group are calculated according to the working distance thereof by using a calculation formula for fluorescence collection efficiency.

2. The imaging probe according to claim 1, characterized in that: The microscope objective lens group has a working distance of 800 μm, an object numerical aperture of 0.6, and a field of view of 560 μm; The fluorescence collection efficiency η scattering The calculation formula is: Among them, 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 according to claim 1, characterized in that: The optical fiber bundle has a light-transmitting area diameter of 1200 μm, an effective image circle diameter of 1125 μm, contains N optical fibers in the light-transmitting area, the value range of N is 60000±6000, the fiber core distance is 4.38 μm, and the numerical aperture is 0.2-0.

3.

4. The imaging probe according to claim 1, characterized in that: The first lens is made of H-LAF50B material; The second lens is made of H-ZF73 material; The third lens is made of H-ZLAF68N material; The fourth lens is made of two materials: H-ZLAF73 and H-ZF71; 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.

5. The imaging probe according to claim 4, characterized in that: The first lens is a plano-convex lens with a refractive index of 1.75-1.76 and a center thickness of 0.954 mm; The second lens is a plano-concave lens with a refractive index of 1.90-1.92 and a center thickness of 0.300 mm; The third lens is a convex lens with a refractive index of 1.86 and a center thickness of 0.689 mm; The fourth lens is a doublet lens with refractive indices of 1.85 and 1.76 respectively, the center thickness of the lens close to the object plane is 1.422 mm, and the center thickness of the lens close to the image plane is 2.087 mm; The fifth lens is a plano-convex lens with a refractive index of 1.86 and a center thickness of 0.807 mm; The sixth lens is a plano-convex lens with a refractive index of 1.69 and a center thickness of 0.863 mm; The refractive index of the seventh lens is 1.65 in the wavelength range of 780-1200 nm, and the center thickness is 0.300 mm.

6. The imaging probe according to claim 4, characterized in that: The center distance between the two adjacent surfaces of the first lens and the second lens is 0.050 mm; The center distance between two adjacent surfaces of the second lens and the third lens is 0.099 mm; The center distance between two adjacent surfaces of the third lens and the fourth lens is 0.100 mm; The center distance between two adjacent surfaces of the fourth lens and the fifth lens is 0.351 mm; The center distance between two adjacent surfaces of the fifth lens and the sixth lens is 0.052 mm; The center distance between two adjacent surfaces of the sixth lens and the seventh lens is 0.075 mm; The center distance between the seventh lens and two adjacent surfaces of the optical fiber bundle is 0.680 mm.

7. The imaging probe according to claim 4, characterized in that: The curvature radius of the mirror surface of the first lens close to the image plane is -1.334mm, and the net aperture is 2.2mm; The curvature radius of the mirror surface of the second lens close to the object plane is -61.195mm, the net diameter is 2.2mm, and the curvature radius of the mirror surface close to the image plane is 2.408mm, the net diameter is 2.2mm; The third lens has a curvature radius of 3.795 mm near the object plane and a clear aperture of 2.2 mm, and a curvature radius of -2.802 mm near the image plane and a clear aperture of 2.2 mm; The fourth lens has a curvature radius of 3.301 mm near the object plane and a net aperture of 2.2 mm, a curvature radius of -1.529 mm at the middle cemented surface and a net aperture of 2.2 mm, and a curvature radius of 1.366 mm near the image plane and a net aperture of 1.8 mm. The curvature radius of the mirror surface of the fifth lens close to the object plane is 22.516 mm, the clear aperture is 2.2 mm, and the curvature radius of the mirror surface close to the image plane is -1.960 mm, the clear aperture is 2.2 mm; The sixth lens has a curvature radius of 2.375 mm near the object plane and a clear aperture of 2.2 mm, and a curvature radius of 29.269 mm near the image plane and a clear aperture of 2.2 mm; The seventh lens has a mirror curvature radius of 1.008 mm near the object plane and a net aperture of 1.8 mm, and a mirror curvature radius of 0.476 mm near the image plane and a net aperture of 1.8 mm.

8. The imaging probe according to claim 1, characterized in that: The distance between the microscope objective lens group and the biological sample to be tested is adjustable.

Images