WO2023211411A1

WO2023211411A1 - Digitalization system of pathology samples

Info

Publication number: WO2023211411A1
Application number: PCT/TR2023/050355
Authority: WO
Inventors: Saim BALIN; Gülfize COŞKUN; Hasan Şahi̇n; Chingiz SEYIDBAYLI
Original assignee: Technomind Di̇ji̇tal Si̇stemler Sanayi̇ Ti̇caret Anoni̇m Şi̇rketi̇
Priority date: 2022-04-26
Filing date: 2023-04-13
Publication date: 2023-11-02
Also published as: TR2022006875A2

Abstract

The invention relates to a system for digitizing pathology samples, which enables the distance between the preparation and the objective (4) to be adjusted automatically according to the thickness of the preparation, which occurs as a result of the overlapping of cells and/or tissues while spreading or dripping the samples on the slide, and increasing the image quality of the sample by increasing the depth of focus during the scanning process.

Description

DIGITALIZATION SYSTEM OF PATHOLOGY SAMPLES

Technical Field

The invention relates to a system for digitizing pathology samples, which enables the distance between the preparation and the objective to be adjusted automatically according to the thickness of the preparation, which occurs as a result of the overlapping of cells and/or tissues while spreading or dripping the samples on the slide, and increasing the image quality of the sample by increasing the depth of focus during the scanning process.

State of the Art

Determining whether there are any lesions and abnormalities in the corresponding tissues and organs of the human body by observing a cross-sectional tissue of the human body is one of the important examination methods, and such an examination method is usual in modern medicine. The traditional way of observing a section is by observing the section texture on a slide in a bare-eyed microscope, which is labour-intensive, and the observation result is not very accurate.

Biological samples are the samples prepared suitably for the interpretation of the doctor or veterinarian on the slide for the detection of disease in humans or animals. These samples may be from certain parts of the human or animal, or from bodily fluids. By placing the samples on the slide, they can be made ready for examination without any further processing or after physical processes (washing, staining, etc.). With the microscope, specialist physicians or veterinarians interpret and diagnose these samples. The digitalization of this data, the use of data processing methods and automatic reporting by abandoning manual methods with the developing technology is an activity that reduces the labour of specialist physicians or veterinarians in this regard.

With the development of science and technology, digital cross-section scanning systems and scanning devices developed with this system are emerging that will replace the traditional section tissue observation. Digital section scanning system is a digital scanning system that can scan section tissue and create an image of a cell on the surface of section tissue. The image of the pathological section scanned by the digital section scanning system is not a normal image, but one that can be provided to the user for any zooming in or out. When magnifying a local area of the image, the user can observe a magnified view of the cell in that area and therefore a doctor can judge whether any lesions and abnormalities are present in the corresponding tissues and abnormalities of the human body by observing the tissues in the section. Being an image-based dynamic environment, Digital Pathology is a technology that allows images to be scanned or collected in digital format, managed and evaluated. Digital Pathology application areas can be stated as initial-diagnosis, diagnostic consultation, intraoperative consultation, training of medical and residency students, manual or semi-automatic quantification of immunohistochemistry (IHC) studies, clinical research, diagnostic decision making support, exchange of ideas among experts and tumour councils. In the case of performing whole slide scans in digital pathology instruments, samples are sliced and displayed for analysis as well as teaching purposes.

Digital pathology devices are frequently used for high-speed scanning of microscope slides to cover the entire slide and as a single piece, quantitative analysis of images after scanning, instant consultation by sharing images and analysis results on the web, and safe digital storage of images.

When samples are prepared in the laboratory environment during the pathology process, samples taken from the examined organ or tissue are spread on the slide. While this process is being performed, overlapping situations of cells or tissues are experienced in some areas. The resulting micrometric size differences cause problems in focusing the microscope objective. The distance to be left between the objective and the sample, which is determined during the manufacture of the objective, reveals the problem of loss of image clarity as a result of the overlapping tissues changing height. In order to adjust this distance between the objective and the sample, the distance needs to be corrected. In light microscopes, this problem is tried to be solved by moving the table on which the sample is on the z- axis.

Since the optical system (camera, objective, TV adapter and tube lens) moves completely in known devices, focus adjustment is required at a certain preparation distance as the movement area between the camera and the objective is limited. Thick prepared preparations can therefore be seen as erroneous or illegible during scanning. Thus, the quality of the image does not occur as intended, or it results in making the scanning not possible. In the scanner devices available in the market, the objective part is connected the camera (1) system and does not move in an axis perpendicular to the ground (in the Z axis). In the scanning device that is the subject of the invention, it is aimed to focus the extended depth of field (EDF) by the movement of the objective in an axis perpendicular to the ground, independent of the optical system elements. Thus, the scanning process is carried out by making the height adjustment on an axis perpendicular to the ground according to the thickness of each preparation. With this invention, it is aimed to strengthen the quality of the cell or tissue-based image by making more specific focus in the technical sense.

Although improvements have been made in the state of the art, development of a digital pathology scanner device that enables automatic adjustment of the distance between the preparation and the objective by moving the objective in an axis perpendicular to the preparation holder, according to the thickness of the preparation resulting from the overlap of cells and/or tissues while spreading or dripping the samples on the slide and automatic adjustment of the depth of focus, which increases the image quality of the sample by increasing the depth of focus during the scanning process is needed.

American patent application with publication no US2014125776A1 in the state of the art was reviewed. In the invention that is the subject of said application, a three-dimensional pathology scanning system that comprises a sample holder to support the sample, an optical system for focusing the image of a series of parallel object planes into one of a two-dimensional detector array, multiple linear arrays, multiple TDI arrays, and multiple object planes, and a detector image plane tilted in a scanned direction relative to the array of object planes to produce a three-dimensional image of a portion of the preparation is mentioned. However, it is not mentioned that the distance between the preparation and the objective is automatically adjusted by moving the objective in a perpendicular axis to the preparation holder according to the thickness of the preparation formed as a result of the overlapping of cells and/or tissues while the sample is being spread or dripped.

The Chinese patent application with the publication number CN203688434U in the state of the art was reviewed. In the invention that is the subject of said application, a positioning device for the digital pathological section scanner platform that comprises a pathological section carrying platform, a positioning pin, a movable door, a bracket, a lever device, a left plate and a right plate, the movable door which can move up and down being arranged on a scanner casing, and a positioning hole on the transport platform through which the positioning pin can move up and down is mentioned. However, again, it is not mentioned that the distance between the preparation and the objective is automatically adjusted by moving the objective in a perpendicular axis to the preparation holder according to the thickness of the preparation formed as a result of the overlapping of cells and/or tissues while the sample is being spread or dripped.

The Turkish patent application with the publication number TR 202009926 in the state of the art was reviewed. In the invention that is the subject of said application, a digital pathological section scanning system comprising a scan end, an image processing end, a remote server, a first client end, and a second client end, the scan tip scanning a pathological slice to generate an original pathological slice image, transmitting the original pathological slice image to the image processing tip for processing; and prevents unqualified digital pathological section image formation by the image processing tip processing the original pathological section image to create a digital pathological section image and sending the digital pathological section image to the remote server is mentioned. However, in the invention as well, it is not mentioned that the distance between the preparation and the objective is automatically adjusted by moving the objective in a perpendicular axis to the preparation holder according to the thickness of the preparation formed as a result of the overlapping of cells and/or tissues while the The Invention sample is being spread or dripped.

Conclusively, due to the above described problems and the insufficiency of the existing solutions made it necessary to make an improvement in the relevant technical field.

The Aim of the Invention

The most important aim of the invention is to provide a digitalization system for pathology samples that allows scanning of samples spread on slides, photographing sample images and transferring them to a computer.

Another important aim of the invention is to provide a digitalization system for pathology samples that allows the height adjustment of the objective to be automatically adjusted on an axis perpendicular to the preparation holder, according to the thickness of the preparation. Thus, the height adjustment is made automatically according to the thickness and the scanning process is performed. With this invention, it is possible to strengthen the quality of the cell or tissue-based image by making more specific focus in the technical sense.

Another important aim of the invention is to provide a digitalization system for the pathology samples that prevents the deterioration of the image quality with focus distortion by being affected due to the elevations formed by the overlapping of the tissues in the preparation.

Another aim of the invention is to provide a digitalization system for pathology samples that allows the objective to move on an axis perpendicular to the ground independent of to the camera system. By this way, with only the movement of the objective, the tissue or cell areas on the preparation are more clearly focused and extended depth of field (EDF) focusing is achieved.

Another aim of the invention is to provide a system for digitizing pathology samples that enables to enhance the quality of images taken from cells or tissues.

A system for digitizing pathology samples, which enables the distance between the preparation and the objective to be adjusted automatically according to the thickness of the preparation, which occurs as a result of the overlapping of cells and/or tissues while spreading or dripping the samples on the slide, and increasing the image quality of the sample by increasing the depth of focus during the scanning process, to realise the aims mentioned above, comprising; at least one camera that allows viewing of tissue or organ preparations spread on a slide, at least one preparation holder that allows the preparation to be placed thereon, at least one actuator enabling said objective to move in an axis perpendicular to the preparation holder, software that allows sending commands to automatically adjust the focal depth by moving the objective on an axis perpendicular to the ground and examining the images taken from the preparation, and at least one computer that enables the transmission of the command to start the system operation and the storage of the resulting images.

Figures to Help Understand the Invention

Figure 1: Representative exploded view of the digitization system of the pathology samples, which is the subject of the invention

Figure 2: Representative exploded view of the digitization system of the pathology samples, which is the subject of the invention

Description of Reference Numbers:

1. Camera

2. Adapter

3. Lens

4. Objective

5. Condenser

6. Light source

7. Actuator

Detailed Description of the Invention

In this detailed description, the system for digitizing the pathology samples, which is the subject of the invention, and its preferred embodiments are explained only for a better understanding of the subject, without any limiting effect. The invention describes a system for digitizing pathology samples, which enables the distance between the preparation and the objective (4) to be adjusted automatically according to the thickness of the preparation, which occurs as a result of the overlapping of cells and/or tissues while spreading or dripping the samples on the slide and increasing the image quality of the sample by increasing the depth of focus during the scanning process.

When samples are prepared in the laboratory environment, samples taken from the examined organ or tissue are spread on the slide. The digital pathology scanner device, which is the subject of the invention, comprises a camera (1) that enables the viewing of tissue or organ preparations spread on the slide, an objective (4) that allows capturing the image of the preparation viewed with the camera (1), and a light source (6) that illuminates said preparation.

Said camera (1) has a CMOS sensor (Complementary Metal Oxide Semiconductor- Active pixel sensor). The light given from said light source (6) passes through the objective (4) and falls on the preparation.

Said objective (4) is preferably an infinity correction objective (4) and the image is provided to progress smoothly to infinity.

The digital pathology scanner device, which is the subject of the invention, comprises a condenser (5) that enables the light coming from said light source (6) to be concentrated to the determined point.

The digital pathology scanner device, which is the subject of the invention, comprises a preparation holder that allows the preparation to be placed thereon, an adapter (2) that enables the size ratio of the image taken by the camera (1), and a lens (3) that allows the refraction of the received image. Said lens (3) is preferably of the tube lens (3) type.

The digital pathology scanner device, which is the subject of the invention, comprises an actuator (7) that enables said objective (4) to move on an axis perpendicular to the preparation holder. In order for the objective (4) to move in an axis perpendicular to the preparation holder, the focus is adjusted using the extended depth of field (EDF) focus method.

Said actuator (7) works with related elements in order to control the movement of the objective (4). The actuator (7) comprises a sensor that provides the necessary power to move, a sensor that enables the actuator (7), which is activated by said motion provider, to find the starting point and to determine the upper limit height that should rise, and a guide that enables the actuator (7) to move on a vertical axis on the preparation holder. It also enables the said guiding objective (4) to adjust its axis.

The digital pathology scanner device, which is the subject of the invention, comprises the software that enables the operation of the device and the automatic adjustment of the focal depth by moving the objective (4) in an axis perpendicular to the preparation holder and the examination of the image of the preparation, and the computer that enables the command to connect the operation of said system and the storage of the acquired images.

In order to start the scanning process, the preparations are placed in the preparation holder and placed in the device where the scanning process will be performed, and the scanning process starts. The preparation holder can move in a horizontal plane parallel to the ground or in an axis perpendicular to the ground. The objective (4) moves in an axis perpendicular to the preparation holder. During the production of the device used, the distance between the objective (4) and the preparation holder is determined.

After the preparation placed in the preparation holder is detected by the device, the guide inside the actuator (7) moves in a perpendicular axis to the preparation holder, touches the limit sensor and finds its initial position. Then, with the start signal from the computer, the guide descends to a certain distance. The preparation illuminated by the light source (6) is started to be viewed by the camera (1) and the images taken are transferred to the computer. By looking at the sharpness setting of the acquired image, the software compares it with the previous captured image and checks whether the value is at the predefined focus value. If the sharpness value is not in the desired range, a command is sent to the actuator (7), and the height of the objective (4) is automatically adjusted by the software as perpendicular to the preparation holder, up or down, and the shot is taken. This process is performed separately for each frame. By determining the border regions (ROI, region of interest) of cells or tissues with the software, it is ensured that the objective (4) focuses primarily on the areas to be scanned on the preparation. Then, images of the focused points are taken frame-by-frame at certain distances.

If the images taken are not at the focal value defined by the controlled value, the software sends a signal to the actuator (7) and requests it to move in an axis perpendicular to the preparation holder, thus allowing the objective (4) to move as well. The objective (4), which moves on an axis perpendicular to the preparation holder, takes the new images and these are transferred to the computer by means of the camera (1). The image acquisition process continues until the desired focal depth is reached. Once the predefined focus value is reached, the sample is photographed and saved.

The operation method of the system for digitizing pathology samples, that is the subject of the invention, which enables the distance between the preparation and the objective (4) to be adjusted automatically according to the thickness of the preparation, which occurs as a result of the overlapping of cells and/or tissues while spreading or dripping the samples on the slide, and enables increasing the image quality of the sample by increasing the depth of focus during the scanning process, basically comprises the process steps of the actuator (7) moving up in an axis perpendicular to the preparation holder, touching the sensor and finding its initial position upon the detection of the preparation by the device in which it is placed, the actuator (7) descending to a predetermined distance with the start signal coming from the computer, the images being transferring to the computer by means of the camera (1), the software comparing the sharpness value of the acquired image with the previous image and moving the objective (4) in an axis perpendicular to the preparation holder by sending a signal to the actuator (7) until it equals the determined value, the objective (4) focusing on the areas to be scanned on the preparation holder in the defined ROI border regions, the images of the focused points being taken from predetermined distances frame-by- frame, and the objective (4) taking new images and transferring them to the computer via the camera (1).

Claims

1. Digitization system for pathology samples that enables automatic adjustment of the distance between the preparation and the objective (4) that captures the image of the preparation according to the thickness of the preparation resulting from the overlap of cells and/or tissues while spreading or dripping the samples on the slide enables increasing the depth of focus during the scanning process and increases the quality of the image taken from the sample, comprising: at least one camera (1) that allows viewing of tissue or organ preparations spread on a slide, at least one preparation holder that allows the preparation to be placed thereon, at least one actuator (7) enabling said objective (4) to move in an axis perpendicular to the preparation holder, software that allows sending commands to automatically adjust the focal depth by moving the objective (4) on an axis perpendicular to the ground and examining the images taken from the preparation, and at least one computer that enables the transmission of the command to start the system operation and the storage of the resulting images.

2. Digitization system for pathology samples according to Claim 1, comprising at least one condenser (5) that enables the light coming from the light source (6) to be condensed on the determined point.

3. Digitization system for pathology samples according to Claim 1, comprising at least one lens (3) that refracts the received image.

4. Digitization system for pathology samples according to Claim 1, comprising at least one light source (6) that illuminates the preparation.

5. Digitization system for pathology samples according to Claim 1, comprising at least one adapter (2) that enables performing the aspect ratio of the image taken by said camera (1).

6. Digitization system for pathology samples according to Claim 1, comprising at least one movement provider providing the necessary force for said actuator (7) to move.

7. Digitization system for pathology samples according to Claim 1, comprising at least one sensor that enables the actuator (7) to find the starting point and to determine the upper limit height that it should rise.

8. Digitization system for pathology samples according to Claim 1, comprising at least one guide that enables said actuator (7) to move in a vertical axis on the preparation holder.

9. Digitization system for pathology samples according to Claim 8, comprising the guide that provides the axis adjustment of said objective (4).

10. Digitization system for pathology samples according to Claim 1, comprising the objective (4) that enables adjusting the focus using the extended depth of field (EDF) focus method.

11. Digitization system for pathology samples according to Claim 1, wherein said camera (1) comprises a CMOS sensor (Complementary Metal Oxide Semiconductor- Sensor with Active Pixels).

12. Digitization system for pathology samples according to Claim 1, wherein the said objective (4) is an infinity correction objective (4).

13. Digitization system for pathology samples according to Claim 3, wherein said lens (3) is a tube lens (3).

14. Operating method of the digitization system for pathology samples that enables automatic adjustment of the distance between the preparation and the objective (4) that captures the image of the preparation according to the thickness of the preparation resulting from the overlap of cells and/or tissues while spreading or dripping the samples on the slide enables increasing the depth of focus during the scanning process and increases the quality of the image taken from the sample, comprising the process steps of: the actuator (7) moving in an axis perpendicular to the preparation holder, touching the sensor and finding its initial position upon the detection of the preparation by the device in which it is placed, the actuator (7) descending to a predetermined distance with the start signal coming from the computer, the images being transferring to the computer by means of the camera (1), the software comparing the sharpness value of the acquired image with the previous image and moving the objective (4) in an axis perpendicular to the preparation holder by sending a signal to the actuator (7) until it equals the determined value, the objective (4) focusing on the areas to be scanned on the preparation holder in the defined ROI border regions, the images of the focused points being taken from predetermined distances frame-by- frame, and the objective (4) taking new images and transferring them to the computer via the camera (1) operation.