CN112763417B - Digital pathological section panoramic scanning system - Google Patents

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 objects 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-size imaging device is selected, and the whole pathological section panorama can be shot once to obtain the whole pathological section panorama, so that the system cost is saved, and the acquisition efficiency is effectively improved.

Description

A digital pathological slice panoramic scanning system

technical field

The invention belongs to the field of medical devices, and relates to a panoramic scanning system for digital pathological slices.

Background technique

Microscopic examination of pathological sections is one of the gold standards for disease diagnosis.

Traditional panoramic scanning of commercial pathological sections relies on microscope objective-based microscopes integrating a high-precision motorized three-dimensional displacement stage and imaging CCD or CMOS. The imaging device can only collect a local area of the pathological slice at a time, and realize panoramic imaging through X and Y axis scanning. The high magnification objective has the problem of shallow depth of field, and the placement of pathological slices may be inclined, resulting in only a part of the entire plane on the focal plane of the high magnification objective. It is necessary to add Z-axis motorized focusing during the scanning process to obtain a clearly focused image.

The existing commercial digital pathology panorama technology uses an optical microscope objective lens to image a very small area of a pathological slice, and uses a fast X, Y, and Z three-direction scanning method to complete the image acquisition of the entire pathological slice. Taking the 40X objective lens as an example, it takes thousands of pictures to complete a 15mm*15mm pathological slice, which takes about 30s. The whole set of equipment requires a high-precision, high-stability, high-speed and durable three-dimensional motorized displacement platform and an expensive high-power microscope objective lens with excellent aberration correction in hardware; in software, it needs to be able to stitch hundreds to thousands of partial pictures To form a complete panoramic pathological slice picture, the processing speed must be fast, and the corresponding processing hardware of the computer also has high performance requirements. The above reasons determine that the existing commercial digital pathology panoramic scanning equipment must be expensive and technically difficult equipment.

SUMMARY OF THE INVENTION

The present invention proposes a digital pathological slice panoramic scanning system, which selects a large-format imaging device, completes a single shot of the panorama of the pathological slice, and obtains a full image of the entire pathological slice, eliminating the need for expensive mechanical scanning modules with high requirements and high-performance imaging. objective lens.

The technical solution of the present invention to solve the above problem is: a digital pathological slice panoramic scanning system, which is special in that it includes:

Broad-spectrum light source, tunable optical filter, photoelectric slip ring, spectroscopic device, optical fiber group, computer, object plane and image sensor; the output collimated beam of the broad-spectrum light source enters the tunable optical filter, and the tunable optical filter accepts the computer The wavelength scanning command sent will convert the output light of the broad-spectrum light source into monochromatic light that is repeatedly output in sequence; the photoelectric slip ring is linked with the spectroscopic device, and receives the computer's command to couple the monochromatic light emitted by the photoelectric slip ring into the optical fiber in sequence. The optical fiber group illuminates the objects on the object plane from multiple angles; the image sensor receives the instructions of the computer to trigger the photography, and collects the images of the objects on the object plane illuminated by the monochromatic light sequence; the computer reconstructs the collected images, Realize panorama imaging of pathological slices.

Further, the output of the broad-spectrum light source at least includes a collimated light beam in the entire wavelength range of 400-700 nm.

Further, the above-mentioned broad-spectrum light source may be a broad-spectrum light source covering a wavelength band of 400-700 nm, such as a white laser, a xenon lamp, a halogen lamp, or the like.

Further, the tunable optical filter and the optoelectronic slip ring are connected through a first optical fiber, and the optoelectronic slip ring and the optical splitting device are connected through a second optical fiber. The output light of the tunable filter is coupled into the first optical fiber, the first optical fiber and the second optical fiber are coupled in the photoelectric slip ring, the second optical fiber rotates with the turntable, and the photoelectric slip ring can make the stationary first optical fiber and the rotating second optical fiber. maintain light transmission. In order to prevent the second optical fiber from continuing to rotate during the rotation, it is necessary to synchronize the photoelectric slip ring and the turntable to make it run at the same angular velocity.

Further, the above-mentioned spectroscopic device is an electric turntable.

Further, the motorized turntable has an opening for placing the connector of the second optical fiber and the optical fiber collimation focusing coupling module. The collimation focusing coupling module is arranged on the opening of the turntable, and after collimating the light emitted from the second optical fiber, it sequentially focuses and couples into different optical fibers in the light group along with the rotation of the electric turntable. That is, the monochromatic light emitted from the photoelectric slip ring is sequentially coupled into the optical fiber group by receiving the instruction of the computer.

Further, the above-mentioned optical fiber group includes at least five optical fibers, and the optical fiber group is uniformly arranged at an angle from -40° to 40° with the vertical direction on a cross section, so as to realize the multi-angle illumination of the object on the object carrier plane.

Further, the distance between the above-mentioned object plane and the image sensor is 0.1 mm to 1 mm.

Further, the above-mentioned image sensor adopts an image sensor with a size larger than 15mm*15mm.

Advantages of the present invention:

1) The present invention adopts a lensless imaging method to obtain an imaging field of view of unit magnification, and by selecting a large-format image sensor, the purpose of taking a photo to achieve panoramic pathological imaging is achieved;

2) Since the panorama of the pathological slice can be obtained by taking a photo at one time, a precise displacement platform is not required, which reduces the cost;

3) The present invention adopts digital focusing and does not require physical electric focusing or manual focusing operations;

4) The present invention does not need image splicing, which reduces the difficulty of imaging;

5) The present invention reduces the shooting time from 30s to less than 2s, takes less time, and greatly improves the efficiency;

6) The system of the present invention is simple, and the hardware cost is reduced.

Description of drawings

FIG. 1 is a schematic diagram of a panoramic scanning system for digital pathological slices of the present invention.

Among them: 1. Broad-spectrum light source, 2. Tunable filter, 3. Photoelectric slip ring, 4. Spectroscopic device, 5. Optical fiber group, 6. Computer, 7. Object plane, 8. Image sensor, 9. Section One fiber, 10 second fibers.

Detailed ways

In order to make the purposes, technical solutions and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings in the embodiments of the present invention. Obviously, the described embodiments These are some embodiments of the present invention, but not all of them. Based on the embodiments of the present invention, all other embodiments obtained by persons of ordinary skill in the art without creative efforts shall fall within the protection scope of the present invention. Accordingly, the following detailed description of the embodiments of the invention provided in the accompanying drawings 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 slice panoramic scanning equipment adopts a high-magnification objective lens to image on a line scan camera or an area scan camera, and uses a precise displacement platform to perform automatic focusing, plane scanning, and clear panoramic imaging of the pathological slice.

The disadvantages of the prior art are: the imaging field of view is small; the requirements for the displacement platform are high; the electric focus is required; the image stitching is required; the time-consuming is long;

In order to solve the problems existing in the prior art, referring to FIG. 1 , the present invention proposes a panoramic scanning system for digital pathological slices, including a broad-spectrum light source 1, a tunable optical filter 2, a photoelectric slip ring 3, a spectroscopic device 4, and an optical fiber group. 5. Computer 6 , object plane 7 and image sensor 8 .

The wide-spectrum light source 1 outputs a collimated beam and enters the tunable filter 2, and the tunable filter 2 accepts the wavelength scanning instruction sent by the computer 6, and converts the output light of the wide-spectrum light source 1 into monochromatic light that is repeatedly output in sequence; The photoelectric slip ring 3 is linked with the optical device 4, and receives the instruction of the computer 6 to couple the monochromatic light emitted by the photoelectric slip ring 3 into the optical fiber group 5 in sequence; the optical fiber group 5 performs multi-angle illumination on the object on the object carrier plane 7; The sensor 8 receives the instruction of the computer 6 to trigger the photographing, and collects the image of the object on the carrier plane 7 illuminated by the monochromatic light sequence; the computer 6 reconstructs the collected image to realize the panorama imaging of the pathological slice.

As a preferred embodiment of the present invention, the above-mentioned broad-spectrum light source 1 outputs a collimated light beam at least including the entire wavelength band of 400-700 nm.

Preferably, the above-mentioned broad-spectrum light source may be a broad-spectrum light source covering a wavelength band of 400-700 nm, such as a white laser, a xenon lamp, a halogen lamp, or the like.

As a preferred embodiment of the present invention, the tunable filter 2 and the optoelectronic slip ring 3 are connected through a first optical fiber 9 , and the optoelectronic slip ring 3 and the spectroscopic device 4 are connected through a second optical fiber 10 . The tunable filter 2 is optically 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 with the turntable, and the photoelectric slip ring 3 can make the stationary first optical fiber Light transmission is maintained between 9 and the rotating second optical fiber 10 . In order to prevent the second optical fiber 10 from continuing to rotate during the rotation, it is necessary to synchronize the photoelectric slip ring and the turntable to make it run at the same angular velocity.

The spectroscopic device 4 is composed of an open motorized turntable and a collimation focusing coupling module. The collimation focusing coupling module is arranged on the opening of the turntable, and after collimating the light emitted from the second optical fiber 10, it is sequentially focused and coupled into different optical fibers in the light group 5 along with the rotation of the electric turntable. That is, the monochromatic light emitted from the photoelectric slip ring 3 is sequentially coupled into the optical fiber group 5 by receiving the instruction of the computer.

As a preferred embodiment of the present invention, the above-mentioned light-splitting device 4 may also adopt a light-splitting module.

Further, the above-mentioned optical fiber group 5 comprises at least five optical fibers, and the optical fiber group 5 is evenly arranged on a cross-section with an included angle from -40° to 40° with the vertical direction, so as to realize multi-angle illumination on the object on the object-carrying plane 7. the goal of.

Further, the distance between the object plane 7 and the image sensor 8 is 0.1 mm to 1 mm.

Further, the above-mentioned image sensor 8 adopts an image sensor with a size larger than 15mm*15mm.

Digital holography has the characteristics of decoupling the field of view and resolution. Further, coaxial digital holography with unit magnification has the advantage of how large the effective area of the imaging device is and how large the area of the imageable object is. Therefore, a large-format imaging device is selected to obtain a full image of the entire pathological slice by taking a panorama of the pathological slice in one shot, eliminating the need for expensive mechanical scanning modules and high-performance imaging objective lenses. Combined with the fast multi-wavelength scanning technology and changing the illumination method, the color pathological panorama slice image with the resolution comparable to 40X objective lens can be realized.

Specifically, the present invention can realize high-speed, super-resolution digital holographic imaging of panoramic pathological slices:

(1) Super-resolution is performed in three intervals of 454nm-466nm, 524nm-536nm, and 624nm-636nm, the center wavelength is at 3nm intervals, and the bandwidth is <2nm, and wavelength scanning is performed. The wavelength scanning of each interval is used for sub-pixel super-resolution images. reconstruction. Three regions are used for color holographic image reconstruction, with a total of 15 scanning wavelengths. Sub-pixel super-resolution can alleviate the undersampling caused by large pixel size and synthesize reconstructed images with smaller pixel size, thereby improving image resolution. However, the loss of high-frequency spatial frequency of objects caused by the small receiving angle of image pixels needs to be alleviated by multi-angle illumination synthetic aperture super-resolution imaging. This project plans to use -40° to 40°, at 10° intervals, select 9 angles for multi-angle scanning illumination to complete synthetic aperture super-resolution imaging.

(2) The panoramic high-speed adopts an ultra-high-speed large-format camera, and the effective imaging area is 22mm*22mm, which can completely cover standard pathological slices of 15mm*15mm size, and the frame rate of the proposed camera can be as high as 71 frames. It can be seen from point (1) that to obtain a panoramic high-resolution pathological image, a total of 9*15=135 photos need to be taken. Combined with the camera frame rate, the total time taken is 135/71=1.9s. That is, a panoramic pathological slice image with the same resolution as the image obtained by the 40X, NA1.0 objective lens can be completed without 2s, and the time-consuming is shortened by 30s/2s=15 times.

Compared with the commercial technology, the present invention reduces the shooting time from 30s to less than 2s, and greatly improves the efficiency. Replacing expensive precision displacement stages and high-quality microscope objectives with multiple shots at the same location reduces hardware costs and imaging difficulty.

The above descriptions are only the embodiments of the present invention, and are not intended to limit the protection scope of the present invention. Any equivalent structure or equivalent process transformation made by using the contents of the description and drawings of the present invention, or directly or indirectly applied to other related The system field is similarly included in the protection scope of the present invention.

Claims (6)

1. a digital pathological slice panoramic scanning system, is characterized in that: Including a broad-spectrum light source (1), a tunable filter (2), a photoelectric slip ring (3), a spectroscopic device (4), an optical fiber group (5), a computer (6), an object plane (7) and an image sensor (8); A broad-spectrum light source (1) outputs a collimated beam into a tunable filter (2), The tunable filter (2) accepts the wavelength scanning instruction sent by the computer (6), and converts the output light of the broad-spectrum light source (1) into monochromatic light that is repeatedly output in sequence; the photoelectric slip ring (3) and the spectroscopic device ( 4) Linkage, receiving the instruction of the computer (6) to couple the monochromatic light emitted from the photoelectric slip ring (3) into the optical fiber group (5) in sequence; The optical fiber group (5) performs multi-angle illumination on the object on the object carrier plane (7); The tunable filter (2) is connected with the optoelectronic slip ring (3) through a first optical fiber (9), and the optoelectronic slip ring (3) and the light splitting device (4) are connected through a second optical fiber (10) , the output of the tunable filter (2) is 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), and the second optical fiber (10) When the turntable rotates, the photoelectric slip ring (3) can keep light transmission between the stationary first optical fiber (9) and the rotating second optical fiber (10); The spectroscopic device (4) is an electric turntable; The motorized turntable has an opening for placing the connector of the second optical fiber (10) and the optical fiber collimation focusing coupling module. The rotation of the focus is sequentially coupled into different fibers in the fiber group (5); The image sensor (8) receives an instruction from the computer (6) to trigger a photograph, and collects images of the object on the object carrier plane (7) illuminated sequentially by monochromatic light; the computer (6) reconstructs the collected images to realize the panorama of the pathological slice imaging. 2. a kind of digital pathological slice panoramic scanning system according to claim 1, is characterized in that: The broad-spectrum light source (1) outputs at least a collimated light beam that includes the entire wavelength band of 400-700 nm. 3. a kind of digital pathological slice panoramic scanning system according to claim 2, is characterized in that: The broad-spectrum light source (1) is a broad-spectrum light source covering a wavelength band of 400-700 nm by a white laser, a xenon lamp or a halogen lamp. 4. according to the arbitrary described a kind of digital pathological slice panoramic scanning system of claim 1-3, it is characterized in that: The optical fiber group (5) includes at least five optical fibers, and the optical fiber group (5) is uniformly arranged on a section at an included angle from -40° to 40° with the vertical direction, so as to realize the detection of objects on the object-carrying plane (7) The purpose of multi-angle lighting. 5. a kind of digital pathological slice panoramic scanning system according to claim 4, is characterized in that: The distance between the object plane (7) and the image sensor (8) is 0.1 mm to 1 mm. 6. a kind of digital pathological slice panoramic scanning system according to claim 5, is characterized in that: The image sensor (8) adopts an image sensor with a format larger than 15mm*15mm.

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