CN112763417A - Digital pathological section panoramic scanning system - Google Patents

Digital pathological section panoramic scanning system Download PDF

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CN112763417A
CN112763417A CN202011440007.7A CN202011440007A CN112763417A CN 112763417 A CN112763417 A CN 112763417A CN 202011440007 A CN202011440007 A CN 202011440007A CN 112763417 A CN112763417 A CN 112763417A
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optical fiber
pathological section
light
slip ring
computer
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CN112763417B (en
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秦文建
曾光
何佳慧
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Shenzhen Institute of Advanced Technology of CAS
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Shenzhen Institute of Advanced Technology of CAS
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    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/01Arrangements or apparatus for facilitating the optical investigation
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/84Systems specially adapted for particular applications
    • HELECTRICITY
    • H04ELECTRIC COMMUNICATION TECHNIQUE
    • H04NPICTORIAL COMMUNICATION, e.g. TELEVISION
    • H04N23/00Cameras or camera modules comprising electronic image sensors; Control thereof
    • H04N23/60Control of cameras or camera modules
    • H04N23/67Focus control based on electronic image sensor signals

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Abstract

The invention belongs to the field of medical instruments, and relates to a panoramic scanning system for digital pathological sections, which comprises a wide-spectrum light source, a tunable filter, a photoelectric slip ring, a light splitting device, an optical fiber group, a computer, a carrying plane and an image sensor, wherein the wide-spectrum light source is connected with the tunable filter; the wide-spectrum light source outputs collimated light beams to enter the tunable filter, and the tunable filter converts the output light of the wide-spectrum light source into monochromatic light which is repeatedly output in sequence; the light splitting device receives the instruction of the computer and couples the monochromatic light emitted by the photoelectric slip ring into the optical fiber group in sequence; the optical fiber group performs multi-angle illumination on an object on the object carrying plane; the image sensor receives an instruction of a computer to realize triggering photographing and collects images of an object on a carrying plane illuminated by monochromatic light in sequence; and the computer reconstructs the acquired image to realize panoramic imaging of the pathological section. According to the invention, a large-picture imaging device is selected, and the whole pathological section full view can be obtained by shooting the pathological section panorama once, so that the system cost is saved, and the acquisition efficiency is effectively improved.

Description

Digital pathological section panoramic scanning system
Technical Field
The invention belongs to the field of medical instruments, and relates to a digital pathological section panoramic scanning system.
Background
Pathological section microscopic scale examination is one of the gold standards for disease diagnosis.
Traditional commercial pathological section panoramic scanning relies on microscope based microscope integration high precision electric three-dimensional displacement platform and imaging CCD or CMOS. The imaging device can only acquire one local area of the pathological section at a time, and panoramic imaging is realized through X, Y-axis scanning. The high power objective lens has the problem of shallow depth of field, and the pathological section may be placed obliquely, so that only a part of the whole plane is located on the focal plane of the high power objective lens, and a Z-axis electric focusing is required to be added in the scanning process to obtain a clearly focused image.
The existing commercial digital pathology panoramic technology adopts an optical microscope objective to image the minimal area of a pathological section, and the whole pathological section is imaged by adopting a rapid X, Y, Z three-direction scanning mode. Taking a 40X objective as an example, several thousand pictures are required to complete a pathological section with a size of 15mm by 15mm, which takes about 30 seconds. The whole set of equipment needs a high-precision, high-stability, high-speed running and durable three-dimensional electric displacement platform and an expensive high-power microscope objective with excellent aberration correction on hardware; in terms of software, hundreds to thousands of local pictures need to be spliced into a complete panoramic pathological section picture, the processing speed must be high, and correspondingly, the processing hardware of the computer has high performance requirements. For the above reasons, it is determined that the existing commercial digital pathology panoramic scanning device must be an expensive and technically difficult device.
Disclosure of Invention
The invention provides a digital pathological section panoramic scanning system, which selects an imaging device with a large picture to complete one-time shooting of pathological section panoramic to obtain a whole pathological section full picture, and omits an expensive mechanical scanning module with high requirements and a high-performance imaging objective lens.
The technical scheme for solving the problems is as follows: a digital pathological section panoramic scanning system is characterized by comprising:
the system comprises a wide-spectrum light source, a tunable filter, a photoelectric slip ring, a light splitting device, an optical fiber group, a computer, a carrying plane and an image sensor; the wide-spectrum light source outputs collimated light beams to enter the tunable filter, and the tunable filter receives a wavelength scanning instruction sent by a computer and converts output light of the wide-spectrum light source into monochromatic light which is repeatedly output in sequence; the photoelectric slip ring is linked with the light splitting device, and receives the instruction of a computer to couple the monochromatic light emitted by the photoelectric slip ring into the optical fiber group in sequence; the optical fiber group performs multi-angle illumination on an object on the object carrying plane; the image sensor receives an instruction of a computer to realize triggering photographing and collects images of an object on a carrying plane illuminated by monochromatic light in sequence; and the computer reconstructs the acquired image to realize panoramic imaging of the pathological section.
Further, the wide-spectrum light source outputs a collimated light beam at least comprising the whole wave band of 400-700 nm.
Further, the wide-spectrum light source can be a white laser, a xenon lamp, a halogen lamp, or the like, which covers a 400-700nm band.
Furthermore, the tunable optical filter is connected with the photoelectric slip ring through a first optical fiber, and the photoelectric slip ring is connected with the light splitting device through a second optical fiber. The tunable filter is coupled with the first optical fiber in an outgoing light mode, the first optical fiber and the second optical fiber are coupled in the photoelectric slip ring, the second optical fiber rotates along with the rotary table, and the photoelectric slip ring can enable the static first optical fiber and the rotating second optical fiber to keep optical transmission. In order to prevent the second optical fiber from being continuous in the rotating process, the photoelectric slip ring and the rotating disc need to be synchronized to run at the same angular speed.
Further, the light splitting device is an electric turntable.
Furthermore, the electric rotating disc is provided with an opening for placing a joint of a second optical fiber and the optical fiber collimation and focusing coupling module. The collimation focusing coupling module is arranged on an opening of the turntable and sequentially focuses and couples different optical fibers in the optical fiber group with the rotation of the electric turntable after collimating the light emitted from the second optical fiber. The monochromatic light emitted by the photoelectric slip ring is coupled into the optical fiber group in sequence by receiving the instruction of the computer.
Furthermore, the optical fiber group comprises at least five optical fibers, and the optical fiber groups are uniformly distributed on one section at an included angle of 40 degrees to 40 degrees with the vertical direction, so that the aim of illuminating an object on the object carrying plane in multiple angles is fulfilled.
Further, the distance between the object carrying plane and the image sensor is 0.1mm to 1 mm.
Further, the image sensor is an image sensor with a frame of more than 15mm x 15 mm.
The invention has the advantages that:
1) the invention adopts a lens-free imaging mode to obtain an imaging visual field with unit magnification, and realizes the purpose of realizing panoramic pathological imaging by selecting an image sensor with a large picture by one-time photographing;
2) because the pathological section panorama can be obtained by one-time photographing, a precise displacement platform is not needed, and the cost is reduced;
3) the invention adopts digital focusing, and does not need physical electric focusing or manual focusing operation;
4) the invention does not need image splicing, thus reducing the imaging difficulty;
5) the invention reduces the shooting time from 30s to less than 2s, has short time consumption and greatly improves the efficiency;
6) the system is simple, and the hardware cost is reduced.
Drawings
Fig. 1 is a schematic diagram of a digital pathological section panoramic scanning system of the present invention.
Wherein: 1. the system comprises a wide-spectrum light source, 2, a tunable filter, 3, a photoelectric slip ring, 4, a light splitting device, 5, an optical fiber group, 6, a computer, 7, a carrying plane, 8, an image sensor, 9, a first optical fiber and 10 a second optical fiber.
Detailed Description
In order to make the objects, technical solutions and advantages of the embodiments of the present invention more apparent, the technical solutions of the embodiments of the present invention will be described clearly and completely with reference to the accompanying drawings of the embodiments of the present invention, and it is obvious that the described embodiments are some, but not all embodiments of the present invention. All other embodiments, which can be obtained by a person skilled in the art without any inventive step based on the embodiments of the present invention, are within the scope of the present invention. Thus, the following detailed description of the embodiments of the present invention, presented in the figures, is not intended to limit the scope of the invention, as claimed, but is merely representative of selected embodiments of the invention.
The existing pathological section panoramic scanning equipment adopts a high-power objective lens to image on a linear array camera or an area array camera, and carries out automatic focusing, plane scanning and clear panoramic imaging of pathological sections through a precise displacement platform.
The defects of the prior art are as follows: the imaging field of view is small; the requirement on a displacement platform is high; electric focusing is required; image stitching is required; the time consumption is long; the system is complex.
In order to solve the problems in the prior art, referring to fig. 1, the invention provides a digital pathological section panoramic scanning system, which comprises a wide-spectrum light source 1, a tunable optical filter 2, a photoelectric slip ring 3, a light splitting device 4, an optical fiber group 5, a computer 6, a carrying plane 7 and an image sensor 8.
The wide-spectrum light source 1 outputs collimated light beams to enter the tunable filter 2, and the tunable filter 2 receives a wavelength scanning instruction sent by the computer 6 and converts the output light of the wide-spectrum light source 1 into monochromatic light which is repeatedly output in sequence; the photoelectric slip ring 3 is linked with the optical device 4, and monochromatic light emitted by the photoelectric slip ring 3 is coupled into the optical fiber group 5 in sequence by receiving an instruction of the computer 6; the optical fiber group 5 performs multi-angle illumination on an object on the object carrying plane 7; the image sensor 8 receives an instruction of the computer 6 to realize triggering photographing and collects images of objects on the carrying plane 7 illuminated by the monochromatic light in sequence; and the computer 6 reconstructs the acquired image to realize panoramic imaging of the pathological section.
As a preferred embodiment of the present invention, the wide spectrum light source 1 outputs a collimated light beam including at least the whole wavelength range of 400-700 nm.
Preferably, the wide-spectrum light source may be a white laser, a xenon lamp, a halogen lamp, or the like, which covers a wavelength band of 400-700 nm.
In a preferred embodiment of the present invention, the tunable optical filter 2 is connected to the optoelectronic slip ring 3 through a first optical fiber 9, and the optoelectronic slip ring 3 is connected to the optical splitter 4 through a second optical fiber 10. The tunable filter 2 is coupled with a first optical fiber 9 through light, the first optical fiber 9 and a second optical fiber 10 are coupled in the photoelectric slip ring 3, the second optical fiber 10 rotates along with the turntable, and the photoelectric slip ring 3 can enable the static first optical fiber 9 and the rotating second optical fiber 10 to keep light transmission. In order to prevent the second optical fiber 10 from being continuously rotated, it is necessary to synchronize the optoelectronic slip ring and the turntable so that they operate at the same angular velocity.
The light splitting device 4 is composed of an open electric turntable and a collimation focusing coupling module. The collimating and focusing coupling module is arranged on an opening of the turntable, and sequentially focuses and couples different optical fibers in the optical fiber group 5 along with the rotation of the electric turntable after the light emitted from the second optical fiber 10 is collimated. Namely, the monochromatic light emitted by the photoelectric slip ring 3 is coupled into the optical fiber group 5 in sequence by receiving the instruction of the computer.
As a preferred embodiment of the present invention, the above-mentioned optical splitter 4 may also adopt an optical splitter module.
Furthermore, the optical fiber group 5 comprises at least five optical fibers, and the optical fiber groups 5 are uniformly arranged on a cross section at an included angle of 40 degrees to 40 degrees from the vertical direction, so that the purpose of illuminating objects on the object carrying plane 7 in multiple angles is realized.
Further, the distance between the object plane 7 and the image sensor 8 is 0.1mm to 1 mm.
Further, the image sensor 8 is an image sensor with a frame size larger than 15mm by 15 mm.
The digital holography has the characteristic of decoupling the field angle and the resolution, and further, the coaxial digital holography with unit magnification has the advantages of large effective area of an imaging device and large area of an imageable object. Therefore, the imaging device with a large picture is selected to complete one-time shooting of the pathological section panorama, namely the whole pathological section full image is obtained, and an expensive mechanical scanning module and a high-performance imaging objective lens with high requirements are omitted. The color pathology panoramic section image which is comparable to 40X objective lens resolution is realized by combining a rapid multi-wavelength scanning technology and changing an illumination mode.
Specifically, the invention can realize high-speed and super-resolution digital holographic imaging of the panoramic pathological section:
(1) the super-resolution is carried out in three intervals of 454nm-466nm,524nm-536nm and 624nm-636nm, the central wavelength takes 3nm as an interval, the bandwidth is less than 2nm, wavelength scanning is carried out, and the wavelength scanning of each interval is used for sub-pixel super-resolution image reconstruction. Three areas are used for color holographic image reconstruction, and the scanning wavelength is 15 in total. The sub-pixel super-resolution can relieve insufficient sampling caused by large pixel size, and a reconstructed image with a smaller pixel size is synthesized, so that the image resolution is improved. But object high frequency spatial frequency loss due to small image pixel acceptance angles needs to be mitigated by multi-angle illuminated synthetic aperture super-resolution imaging. The project uses-40 degrees to 40 degrees, uses 10 degrees as intervals, and selects 9 degrees to carry out multi-angle scanning illumination to finish the synthetic aperture super-resolution imaging.
(2) The panoramic high-speed large-frame camera is adopted, the effective imaging area is 22mm x 22mm, standard pathological sections with the size of 15mm x 15mm can be completely covered, and the frame rate of the proposed camera can be as high as 71 frames. As can be seen from point (1), a panoramic high-resolution pathology image is obtained, 9 × 15 pictures are required, 135 pictures are taken, and finally, the total time is 135/71 ═ 1.9s in combination with the camera frame rate. Namely, a panoramic pathological section image with the same resolution as that of an image acquired by a 40X objective lens and an NA1.0 objective lens can be finished without using 2s, and the time consumption is shortened by 30s/2s to 15 times.
Compared with the commercial technology, the invention shortens the shooting time from 30s to less than 2s, and greatly improves the efficiency. The expensive precise displacement platform and the high-quality microscope objective are replaced by shooting for multiple times at the same position, so that the hardware cost and the imaging difficulty are reduced.
The above description is only an embodiment of the present invention, and not intended to limit the scope of the present invention, and all equivalent structures or equivalent flow transformations made by using the contents of the specification and the drawings, or applied directly or indirectly to other related systems, are included in the scope of the present invention.

Claims (9)

1. The utility model provides a digital pathological section panorama scanning system which characterized in that:
the device comprises a wide-spectrum light source (1), a tunable filter (2), a photoelectric slip ring (3), a light splitting device (4), an optical fiber group (5), a computer (6), a carrying plane (7) and an image sensor (8);
the wide-spectrum light source (1) outputs collimated light beams to enter the tunable filter (2), and the tunable filter (2) receives a wavelength scanning instruction sent by the computer (6) and converts the output light of the wide-spectrum light source (1) into monochromatic light which is repeatedly output in sequence; the photoelectric slip ring (3) is linked with the light splitting device (4), and monochromatic light emitted by the photoelectric slip ring (3) is coupled into the optical fiber group (5) in sequence by receiving an instruction of the computer (6);
the optical fiber group (5) performs multi-angle illumination on an object on the object carrying plane (7);
the image sensor (8) receives an instruction of the computer (6) to trigger photographing, and images of objects on the object carrying plane (7) illuminated by the monochromatic light in sequence are collected; and the computer (6) reconstructs the acquired image to realize panoramic imaging of the pathological section.
2. The digital pathological section panoramic scanning system of claim 1, wherein:
the wide-spectrum light source (1) outputs a collimated light beam at least comprising the whole wave band of 400-700 nm.
3. The digital pathological section panoramic scanning system of claim 2, wherein:
the wide-spectrum light source (1) is a white laser, a xenon lamp or a halogen lamp covering a 400-700nm wave band.
4. The digital pathological section panoramic scanning system of claim 3, wherein:
the tunable optical filter (2) is connected with the photoelectric slip ring (3) through a first optical fiber (9), the photoelectric slip ring (3) is connected with the light splitting device (4) through a second optical fiber (10), the tunable optical filter (2) emits light to be coupled into the first optical fiber (9), the first optical fiber (9) and the second optical fiber (10) are coupled in the photoelectric slip ring (3), the second optical fiber (10) rotates along with the turntable, and the photoelectric slip ring (3) can enable the static first optical fiber (9) and the rotating second optical fiber (10) to keep light transmission.
5. The digital pathological section panoramic scanning system of claim 3, wherein:
the light splitting device (4) is an electric turntable.
6. The digital pathological section panoramic scanning system of claim 5, wherein:
the electric turntable is provided with an opening for placing a joint of a second optical fiber (10) and an optical fiber collimation and focusing coupling module, and the collimation and focusing coupling module collimates the emergent light of the second optical fiber (10) and then sequentially focuses and couples different optical fibers in the optical fiber group (5) along with the rotation of the electric turntable.
7. The system of any one of claims 1-6, wherein:
the optical fiber group (5) comprises at least five optical fibers, and the optical fiber group (5) is uniformly distributed on one cross section at an included angle of 40 degrees to 40 degrees from minus one vertical direction, so that the purpose of illuminating objects on the object carrying plane (7) in multiple angles is realized.
8. The digital pathological section panoramic scanning system of claim 7, wherein:
the distance between the carrying plane (7) and the image sensor (8) is 0.1mm to 1 mm.
9. The digital pathological section panoramic scanning system of claim 8, wherein:
the image sensor (8) is an image sensor with a frame of more than 15mm x 15 mm.
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