Information processing device and information processing method

The information processing device addresses the challenge of determining optimal heating conditions for immunohistochemical staining by correlating staining intensity with heating temperature history, providing a solution that enhances staining quality and reduces operator variability.

JP2025073355APending Publication Date: 2025-05-13HITACHI HIGH TECH CORP
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Patent Information

Application Number
JP2023184062
Authority / Receiving Office
JP · JP
Patent Type
Applications
Current Assignee / Owner
Filing Date
2023-10-26
Publication Date
2025-05-13

AI Technical Summary

Technical Problem

Conventional heat treatment methods for immunohistochemical staining often result in suboptimal staining intensity due to inadequate or excessive heating, leading to false negatives or false positives, and require trial-and-error to determine optimal heating conditions.

Method used

An information processing device that calculates and presents optimal heating conditions for immunohistochemical staining by correlating staining intensity with the time integral value of the heating temperature, using a processor to execute a program that stores and reads information on this correlation from a memory.

Benefits of technology

The device enables the presentation of heating conditions that achieve optimal dyeing strength, reducing the need for trial-and-error and ensuring accurate pathological diagnosis through improved staining quality.

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Abstract

To provide a technology for presenting a heating condition for achieving an optimal staining intensity of a staining target.SOLUTION: Provided is an information processing device for presenting a heating condition for a staining target, comprising: a memory for storing a program; and a processor for reading and executing the program from the memory. The processor executes: processing for reading information relating to a correlation between a staining intensity of a stained specimen and a time-integrated value of a heating temperature from a storage device that stores the information relating to the correlation, where the information relating to the correlation includes a correlation approximation expression between a staining intensity calculated from a staining image of the stained specimen and a time-integrated value of a heating temperature, calculated from a heating history of the stained specimen; processing for accepting a selection of a desired staining intensity for the staining target; processing for calculating a time-integrated value corresponding to the desired staining intensity that has been selected, on the basis of the information relating to the correlation, read from the storage device, and calculating the heating condition of the staining target from the time-integrated value; and processing for displaying the calculated heating condition on a display device.SELECTED DRAWING: Figure 3
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Description

[Technical field]

[0001] The present disclosure relates to an information processing device and an information processing method. [Background technology]

[0002] In order to observe biological tissues and cells under a microscope, specimens are prepared by fixing biological tissues with a fixative such as formalin, dehydrating them with ethanol, embedding them in paraffin, and slicing the tissue into thin slices of about 3 to 5 μm using a microtome. The prepared specimens are placed on slide glasses, deparaffinized, pretreated, and stained by hybridization using a labeled probe or an antigen-antibody reaction using a labeled antibody. The pretreatment is a process for exposing target substances within cells and promoting their reaction with reagents (labeled antibodies, etc.) supplied from the outside, and is generally a heat treatment.

[0003] Regarding heat treatment, for example, paragraph 0005 of Patent Document 1 states that "both overnight incubation at 60°C or incubation at 95°C for 1 hour have been reported to be successful for use in pre-IHC AR."

[0004] Furthermore, in recent years, in order to shorten the heating time, a technique has been proposed in which heating is performed at 100°C or higher using a pressurized heater (autoclave, pressure cooker) that generates high-pressure steam (see Non-Patent Document 1). Paragraph 0008 of Patent Document 1 states that "Christensen et al. disclosed a horizontal AR device and method that achieved an AR temperature of 120°C to 130°C using an improved buffer solution." [Prior art documents] [Patent documents]

[0005] [Patent Document 1] Special Publication No. 2020-527707 [Non-patent literature]

[0006] [Non-Patent Document 1] Aichi Prefecture Clinical Laboratory System Management Survey 2014 p.217~235 Summary of the Invention [Problem to be solved by the invention]

[0007] Conventionally, the heating process was generally performed by incubation at 95 to 100°C for 1 hour. Therefore, there are few cases of staining in which heating was performed at high temperatures of 120 to 130°C using a pressure heater, and there is little knowledge of appropriate heating conditions (combination of heating temperature and heating time). Heating conditions have a significant effect on the staining intensity of the stained specimen (hereinafter referred to as the "stained specimen"). Insufficient heating may cause poor staining and result in a false negative. On the other hand, excessive heating may cause the tissue to collapse or non-specific staining may occur, resulting in a false positive. Thus, although setting the heating conditions is extremely important, there is little previous knowledge, so operators must search for optimal conditions by trial and error. However, stained specimens are often taken from patients' lesions and cannot be replaced, so trial and error search for conditions is not desirable.

[0008] The present disclosure has been made in consideration of the above-mentioned problems, and provides a technology for presenting heating conditions that achieve optimal staining intensity for an object to be stained. [Means for solving the problem]

[0009] In order to solve the above problems, an information processing device disclosed herein is an information processing device for presenting heating conditions for a stained object, and includes a memory for storing a program, and a processor for reading and executing the program from the memory, and the processor executes the following processes: reading information regarding the correlation between the staining intensity of a stained specimen and a time integral value of a heating temperature from a storage device that stores information regarding the correlation, the information regarding the correlation including a correlation approximation formula between the staining intensity calculated from a stained image of the stained specimen and the time integral value of the heating temperature calculated from the heating history of the stained specimen; accepting a selection of a desired staining intensity of the stained object; calculating the time integral value corresponding to the selected desired staining intensity based on the information regarding the correlation read from the storage device, and calculating the heating conditions for the stained object from the time integral value; and displaying the calculated heating conditions on a display device.

[0010] Further features related to the present disclosure will become apparent from the description of the present specification and the accompanying drawings. Also, the aspects of the present disclosure are achieved and realized by the elements and combinations of various elements and the following detailed description and the appended claims. The description of the present specification is merely exemplary and is not intended to limit the scope or application of the present disclosure in any way. Effect of the Invention

[0011] According to the technique of the present disclosure, it is possible to present heating conditions that realize optimal staining intensity for a stained object. Problems, configurations, and effects other than those described above will become apparent from the following description of the embodiment. [Brief description of the drawings]

[0012] [Figure 1] FIG. 1 is a diagram showing the correlation between the staining intensity of a stained specimen and the time integral value (temperature integral value) of the heating history of the staining pretreatment. [Diagram 2] FIG. 13 is a diagram for explaining the definition of a temperature integral value. [Diagram 3]1 is a functional block diagram of a heating condition presentation device according to a first embodiment. FIG. [Figure 4] FIG. 13 is a diagram for explaining image processing by a staining intensity calculation unit. [Diagram 5] 13 is a diagram for explaining a temperature integral value in the case where heating conditions are acquired from a stained image database. FIG. [Figure 6A] 11 is a diagram for explaining the process of a correlation creating unit; FIG. [Figure 6B] 11 is a diagram for explaining the process of a correlation creating unit; FIG. [Figure 7] FIG. 4 is a diagram for explaining processing of an input unit. [Figure 8] 13 is a diagram for explaining the process of a staining intensity selection request unit. FIG. [Figure 9] FIG. 4 is a diagram for explaining the processing of a calculation unit. [Figure 10] 10 is a flowchart showing a heating condition presenting method. [Figure 11] 13 is a flowchart showing details of image processing by a staining intensity calculation unit. [Figure 12] 10 is a flowchart showing details of processing by a heating history acquisition unit and a temperature integral calculation unit. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0013] [First embodiment] The present disclosure is directed to immunohistochemical staining in which heating (antigen activation) is performed as a pre-staining treatment of a staining target. In this embodiment, a heating condition presentation device and a heating condition presentation method for presenting optimal heating conditions for a staining target to a user (e.g., a clinical laboratory technician) are described. As a result of extensive research by the present inventors into heating conditions that achieve optimal staining intensity in immunohistochemical staining, they have found that a correlation can be obtained between the staining intensity of a stained specimen and the time integral value of the temperature history during heating in the staining pre-treatment (hereinafter referred to as heating history).

[0014] Fig. 1 is a diagram showing the correlation between the staining intensity of a stained specimen and the time integral value of the heating history of the staining pretreatment (hereinafter referred to as the temperature integral value). As shown in Fig. 1, it can be seen that there is a positive correlation between the staining intensity of the stained specimen and the temperature integral value.

[0015] FIG. 2 is a diagram for explaining the definition of the temperature integral value. In FIG. 2, a graph of the heating history is shown, in which the horizontal axis indicates time (minutes) and the vertical axis indicates temperature (°C). The temperature integral value of the heating history is calculated by multiplying the threshold value H th Area of ​​the region above ℃ (threshold H th It is defined as the area enclosed by a line passing through °C and parallel to the horizontal axis and the heating history curve, and this area is indicated by diagonal lines.

[0016] Threshold H th The temperature in °C is not particularly limited, but from the viewpoint of enabling effective antigen activation, it can be, for example, in the range of 80 to 95 °C or in the range of 90 to 95 °C.

[0017] In this embodiment, the method of presenting heating conditions is roughly divided into two steps. In the first step, correlation information including a correlation approximation equation between staining intensity and temperature integral value is created in advance for each test object (stained object). In the second step, the created correlation information is used to calculate heating conditions (combination of heating temperature and heating time) that realize optimal staining intensity for the stained object, and the heating conditions are presented to the user. The heating condition presenting device of this embodiment described below is configured to realize these two steps.

[0018] <Example of the configuration of the heating condition presentation device> 3 is a functional block diagram of a heating condition presentation device 1 (information processing device) according to the first embodiment. The heating condition presentation device 1 is a device that performs information processing to present optimal heating conditions for a staining object to a user. The heating condition presentation device 1 is realized by a general-purpose computer such as a workstation, a personal computer, a tablet terminal, or a smartphone. The heating condition presentation device 1 includes a memory (e.g., ROM and RAM), a processor (e.g., CPU or GPU), a storage device for storing programs, and a bus connecting these, all of which are not shown.

[0019] As shown in FIG. 3, the heating condition presentation device 1 includes an operation unit 2, a display unit 3, a web interface 4, a correlation database creation unit 10, a correlation storage unit 20, and a heating condition calculation unit 30 as software modules (functions configured by various programs being expanded in memory) executed by a processor.

[0020] The operation unit 2 is realized by input devices such as a keyboard, a mouse, a touch panel, various switches, etc. The operation unit 2 is operated by a user, accepts input of various information, and inputs the information to the correlation database creation unit 10 and the heating condition calculation unit 30.

[0021] The display unit 3 generates various screen data based on the display signals input from the correlation database creation unit 10 and the heating condition calculation unit 30, and displays it on a display device. As the display device, for example, a liquid crystal display (LCD), an EL display, a CRT display, etc. can be used.

[0022] The web interface 4 has a function of establishing a communication connection using a web browser. The web interface 4 is realized by, for example, a modem (and a driver) and a communication module. The heating condition presentation device 1 is configured to be connectable to an external stained image database 41, an imaging device 42, and a staining device 43 via the web interface 4 and the Internet.

[0023] The correlation database creating unit 10 creates information about correlation including an approximate correlation equation between the staining intensity of a stained specimen and the temperature integral value. A method for creating information about correlation in the correlation database creating unit 10 will be described in detail later. The correlation database creating unit 10 is connected to a stained image database 41, an imaging device 42, and a staining device 43 of an external institution via a web interface 4 and a communication network such as the Internet.

[0024] The stained image database 41 is a free and publicly available database provided by, for example, the Japanese Society of Pathology in Japan, the Digital Pathology Association (DPA) in the United States, and UKNEQAS in the United Kingdom. In the stained image database 41, stained images of stained specimens collected from medical institutions and educational and research institutions are stored as high-resolution digital images (Whole Slide Imaging: WSI).

[0025] The imaging device 42 is a device that images the stained specimen prepared by the staining device 43. The imaging device 42 includes, for example, a digital camera, an imaging sensor (for example, a charge-coupled device (CCD), a complementary metal-oxide semiconductor (CMOS) image sensor), etc.

[0026] The staining device 43 is a device for a user to stain an inspection target (staining target) and prepare a stained specimen. The staining device 43 has a storage device that stores a heating history in a pre-staining treatment of the staining target.

[0027] The correlation storage unit 20 stores information on the correlation between the staining intensity and the temperature integral value for each test subject. The correlation storage unit 20 is realized by, for example, an internal storage or an external storage. Specifically, the correlation storage unit 20 can be realized by, for example, a storage device or information storage medium such as a flash memory, a hard disk drive (HDD), a solid state drive (SSD), a storage class memory (SCM), an embedded multi media card (eMMC), an optical disk, or a magnetic tape, and a reader therefor. The storage device for realizing the correlation storage unit 20 may be the same as or different from the storage device that stores the program.

[0028] It should be noted that the correlation storage unit 20 is not limited to a configuration in which it is installed inside the heating condition presentation device 1. Alternatively, the correlation storage unit 20 may be installed in a different location apart from the heating condition presentation device 1, and can also be realized as a database or online storage connected to the heating condition presentation device 1 via a network. This allows information relating to the correlation between the staining intensity and the temperature integral value to be shared between a plurality of devices, thereby making it possible to eliminate the need for the correlation database creation unit 10 to create information relating to the correlation.

[0029] The heating condition calculation unit 30 reads out information on the correlation between the staining intensity and the temperature integral value stored in the correlation storage unit 20, and calculates heating conditions for the stained object based on the information on the correlation. The method of calculating the heating conditions in the heating condition calculation unit 30 will be described in detail later.

[0030] <Processing in correlation database creation unit 10> The correlation database creation unit 10 includes a stained image acquisition unit 11 , a staining intensity calculation unit 12 , a heating history acquisition unit 13 , a temperature integral calculation unit 14 , and a correlation creation unit 15 .

[0031] The stained image acquiring unit 11 acquires an image of a stained specimen (stained image). The stained image acquiring unit 11 can access an external stained image database 41 via the web interface 4 and the Internet. A user can select a stained image of a desired test subject by logging in to the stained image database 41 and download it from the stained image database 41 to the stained image acquiring unit 11. Note that the source from which the stained image is acquired is not limited to the stained image database 41. It is also possible to acquire the stained image from an imaging device 42 handled by the user.

[0032] Fig. 4 is a diagram for explaining image processing by staining intensity calculation unit 12. Staining intensity calculation unit 12 processes the stained image acquired by stained image acquisition unit 11 to calculate staining intensity. As shown in Fig. 4, the processing by staining intensity calculation unit 12 includes the following three steps S100, S200, and S300.

[0033] (Step S100) The staining intensity calculation unit 12 converts the color stained image into grayscale.

[0034] (Step S200) The staining intensity calculation unit 12 creates a luminance distribution of the stained image converted to grayscale. As an example, when staining is performed using DAB, a general-purpose staining reagent, a peak appears on the black side in the luminance distribution because DAB is dark brown. On the other hand, a peak appears on the white side because the background color is close to white. Therefore, the peak that appears on the black side in the luminance distribution is taken as the stained part, and the peak that appears on the white side is taken as the background color, and the parts corresponding to each peak are extracted on the stained image.

[0035] (Step S300) The staining intensity calculation unit 12 obtains RGB values ​​of, for example, 10 or more pixels for each of the extracted stained site and background color from the color stained image. Then, the staining intensity calculation unit 12 calculates the average value of each of the color information of Red, Green, and Blue.

[0036] After the above image processing, the staining intensity calculation unit 12 defines the staining intensity as the Euclidean distance in RGB space (the distance between the stained site (after staining) and the background color (before staining)), and calculates the staining intensity by the following formula (I).

[0037]

number

[0038] Returning to the explanation of Fig. 3, the heating history acquisition unit 13 accesses the stained image database 41 or the staining device 43 via the web interface 4 and the Internet, and acquires the heating history of the stained image. When acquiring the heating history of the stained specimen prepared by the staining device 43, the heating history as shown in Fig. 2 can be acquired.

[0039] When acquiring a stained image from an external stained image database 41, it is difficult to acquire a heating history as shown in Fig. 2. Therefore, information on the heating conditions (heating temperature H°C, heating time T minutes) accompanying the stained image is acquired from the stained image database 41 as a heating history.

[0040] The temperature integral calculation unit 14 calculates the temperature integral value based on the acquired heating history. When the heating history is acquired from the dyeing device 43, as shown in FIG. th The area of ​​the shaded area above °C is defined as the temperature integral value, and the heating history is integrated over time.

[0041] When acquiring the stained image and the heating conditions from the external stained image database 41, in many cases, the information on the heating conditions that can be acquired is only the heating temperature (H° C.) and the heating time (T min.). Therefore, when the heating conditions are acquired from the stained image database 41, the temperature integral calculation unit 14 calculates the temperature integral value by the following formula (II).

[0042] Temperature integral value = (HH th )×T (II) (In the formula, H is the heating temperature (℃), H th indicates the threshold value (℃), and T indicates the heating time (min).

[0043] Fig. 5 is a diagram for explaining the temperature integral value when the heating conditions are acquired from the stained image database 41. In Fig. 5, a curve of a virtual heating history is shown by a dotted line. The temperature integral value calculated by the formula (II) is the area of ​​the shaded region in Fig. 5.

[0044] 6A and 6B are diagrams for explaining the processing of the correlation creating unit 15. The correlation creating unit 15 creates information on the correlation including a correlation approximation formula between the staining intensity and the temperature integral value for each test object, and stores the created information on the correlation in the correlation storage unit 20. At this time, as shown in FIG. 6A, the correlation creating unit 15 first creates a graph (scatter diagram) with the staining intensity calculated by the staining intensity calculation unit 12 as the vertical axis (Y axis) and the temperature integral value calculated by the temperature integral calculation unit 14 as the horizontal axis (X axis), and plots the relationship between the staining intensity and the temperature integral value for, for example, 10 or more points. In other words, the processing of each unit of the correlation database creating unit 10 described above is performed for 10 or more stained images.

[0045] Next, as shown in FIG. 6B, correlation creating unit 15 creates an approximation curve of the plot and correlation approximation formula (III).

[0046] Y=aX+b (III) (In the formula, Y is the staining intensity, X is the temperature integral value, and a and b are coefficients.)

[0047] 6B, the correlation creating unit 15 may generate not only the correlation approximation formula (III) but also a color sample (information regarding the correlation) corresponding to the staining intensity, and store a correlation graph having the color sample in the correlation storage unit 20. By displaying the correlation graph having the color sample (information regarding the correlation) on the display device, the user can visually and easily grasp the correlation.

[0048] The above-mentioned processing of the correlation database creation unit 10 may be performed in advance by the manufacturer before shipping of the heating condition presentation device 1, or may be performed by the user after the distribution of the heating condition presentation device 1. Even if the correlation database creation unit 10 creates information on correlation before shipping of the heating condition presentation device 1, after distribution, an image of a stained specimen prepared by the user may be captured by the imaging device 42, and the correlation database creation unit 10 may further create information on correlation using the obtained stained image, thereby updating the correlation storage unit 20. The correlation storage unit 20 can be updated as described above not only when the correlation storage unit 20 is mounted inside the heating condition presentation device 1 or directly connected to the heating condition presentation device 1, but also when the correlation storage unit 20 is accessible from the heating condition presentation device 1 via the Internet.

[0049] <Processing in Heating Condition Calculation Unit 30> Returning to the description of FIG. 3, the heating condition calculation unit 30 calculates the heating conditions for the stained object using information on the correlation between the staining intensity and the temperature integral value created by the correlation database creation unit 10. As shown in FIG. 3, the heating condition calculation unit 30 includes an input unit 31, a correlation extraction unit 32, a staining intensity selection request unit 33, a calculation unit 34, and a heating condition presentation unit 35. The input unit 31 accepts input of parameters from a user, including information on the specimen to be prepared and the user's desired heating temperature or heating time. The correlation extraction unit 32 accesses the correlation storage unit 20 and extracts information on the correlation between the staining intensity and the temperature integral value corresponding to the input specimen information. The staining intensity selection request unit 33 displays a color sample included in the extracted information on the correlation on the display unit 3, and requests the user to select a desired staining intensity. The calculation unit 34 calculates the temperature integral value corresponding to the selected staining intensity from the correlation approximation formula, and calculates the heating conditions corresponding to the input items to the input unit 31. The heating condition presenting unit 35 generates a display image based on the calculated heating conditions, and displays it on the display unit 3.

[0050] Fig. 7 is a diagram for explaining the processing of the input unit 31, and shows an input screen for each parameter. As shown in Fig. 7, the input unit 31 accepts an input operation by the user via the operation unit 2 by displaying an input screen for each parameter on the display unit 3. As the parameter input screen, an input screen for inputting information on the specimen to be prepared, an input screen for inputting a heating temperature desired by the user, and an input screen for inputting a heating time desired by the user are shown as examples.

[0051] The specimen information input screen has a drop-down list for selecting the staining reagent to be used during staining and the protein to be tested. The heating temperature input screen and the heating time input screen each have a drop-down list of options. Alternatively, the heating temperature input screen and the heating time input screen may each have an input box for inputting the desired heating temperature value and the desired heating time value. Note that the input screen can be configured so that if the user inputs the desired heating temperature, the heating time cannot be input, and conversely, if the user inputs the desired heating time, the heating temperature cannot be input. FIG. 7 shows an example in which specimen information, the desired heating temperature, or the heating time can be input, but alternatively, only the specimen information input screen may be displayed.

[0052] The correlation extraction unit 32 extracts information on the correlation between the staining intensity and the temperature integral value corresponding to the specimen information (staining reagent and test object) selected by the input unit 31 from the correlation storage unit 20. Then, the correlation extraction unit 32 reads out a correlation graph having a color sample (FIG. 6B) together with the correlation approximation formula (III).

[0053] FIG. 8 is a diagram for explaining the processing of the staining intensity selection request unit 33, and shows a staining intensity selection screen. As shown in FIG. 8, the staining intensity selection request unit 33 displays a color sample on the display unit 3, thereby accepting a selection operation by the user via the operation unit 2. The color sample is displayed in blocks (divided) in stages according to the color tone of the staining intensity. The user selects a desired staining intensity based on this color sample, and clicks on the screen a block showing the color tone of the corresponding staining intensity. The color intensity selection screen may include text such as "Please select the desired staining intensity."

[0054] FIG. 9 is a diagram for explaining the processing of the calculation unit 34. As shown in FIG. 9, the calculation unit 34 calculates the temperature integral value (X) corresponding to the staining intensity (Y) selected by the user using the correlation approximation formula (III) between the staining intensity and the temperature integral value extracted by the correlation extraction unit 32. Then, by substituting the obtained temperature integral value into formula (II), the heating temperature H°C or the heating time T minutes can be obtained. For example, when the user inputs a desired heating temperature H°C into the input unit 31, the corresponding heating time T minutes is calculated. On the other hand, when the user inputs a desired heating time T minutes into the input unit 31, the corresponding heating temperature H°C is calculated. Alternatively, for example, when only specimen information is input by the user on the input screen for each parameter (FIG. 7), the calculation unit 34 may generate a list of combinations of heating temperatures H°C and heating times T minutes that satisfy formula (II) of the temperature integral value.

[0055] The heating condition presenting unit 35 generates a display image based on the heating conditions (heating temperature H° C. or heating time T minutes) calculated by the calculation unit 34, and displays it on the display unit 3. This makes it possible to present the heating conditions for the dyeing object to the user. The user can set a heating device (not shown) according to the heating conditions presented by the heating condition presenting device 1, and perform dyeing pre-treatment.

[0056] <An example of processing in the heating condition presentation device 1> 10 is a flowchart showing the processing procedure of the heating condition presenting method executed by the heating condition presenting device 1. The steps for presenting heating conditions are roughly divided into two. First, in step S1, the correlation database creation unit 10 creates information on the correlation between staining intensity and temperature integral value, and stores it in the correlation storage unit 20. In step S2, the heating condition calculation unit 30 calculates heating conditions based on the information on the correlation read from the correlation storage unit 20, and presents the heating conditions to the user. Each of steps S1 and S2 will be described in detail below.

[0057] (Step S1: Creating information about correlation) The process of creating information on the correlation between staining intensity and temperature integral value in the correlation database creation unit 10 is executed when the manufacturer or user of the heating condition presentation device 1 inputs an instruction to start creating information on the correlation via the operation unit 2. The following describes the case where the process of creating information on the correlation is executed on the user side.

[0058] (Step S11) The stained image acquisition unit 11 accepts an operation for acquiring a stained image by a user. At this time, the stained image acquisition unit 11 may generate text prompting the user to acquire a stained image, transmit it to the display unit 3, and display it on the display device. The user accesses the stained image database 41 from the stained image acquisition unit 11 via the Internet. The user extracts a stained image of the inspection target and downloads it from the stained image database 41 to the stained image acquisition unit 11. Alternatively, the stained image can be acquired from an imaging device 42 used or accessible by the user. Note that the acquisition of the stained image is not limited to the above, and stained images provided by academic papers or reagent manufacturers can also be used. In any case of acquiring a stained image, it is necessary to confirm that there are heating conditions associated with the stained image.

[0059] (Step S12) The staining intensity calculation unit 12 receives the acquired stained image from the stained image acquisition unit 11. The staining intensity calculation unit 12 processes the stained image to calculate the staining intensity.

[0060] 11 is a flowchart showing details of image processing by staining intensity calculation unit 12. The image processing (steps S120 to S127) shown in FIG.

[0061] In step S120, the staining intensity calculation unit 12 acquires the stained image acquired by the stained image acquisition unit 11. In step S121, the staining intensity calculation unit 12 converts the color stained image to grayscale. In step S122, the staining intensity calculation unit 12 creates a luminance distribution of the image converted to grayscale. DAB, which is generally used as a staining reagent, is dark brown, so that the luminance distribution shows a peak on the black side. On the other hand, the background color is close to white, so that the peak shows on the white side. Therefore, in step S123, the staining intensity calculation unit 12 extracts the peak that appears on the black side in the luminance distribution as the stained part, and extracts the peak that appears on the white side as the background color. In step S124, the staining intensity calculation unit 12 displays the extracted stained part and background color so that they can be recognized on the color image, transmits them to the display unit 3, and displays them on the display device. At this time, for example, as shown in step S300 of FIG. 4, the part extracted as the stained part can be displayed by a circle on the color image.

[0062] In step S125, the staining intensity calculation unit 12 transmits the above-mentioned color image and image data of a dialog box for the user to input a judgment result as to whether or not there is a problem with the extraction of the stained portion to the display unit 3, and causes the display unit to display the image. In this way, the staining intensity calculation unit 12 accepts an input of the judgment result by the user as to whether or not the extraction result of the stained portion is appropriate. The dialog box can include, for example, a text "Is the extraction of the stained portion appropriate?" and selection buttons of "Yes" and "No". If the user judges that the extraction of the stained portion is appropriate and inputs "Yes", the process proceeds to step S126. If the user judges that the extraction of the stained portion is inappropriate and inputs "No", the process returns to step S123. When returning to step S123, the staining intensity calculation unit 12 redoes the extraction of the stained portion on the luminance distribution. At this time, it is also possible to display a grayscale luminance distribution so that the user can manually select the stained portion while viewing the luminance distribution.

[0063] In step S126, staining intensity calculation unit 12 obtains RGB values ​​of, for example, 10 or more pixels from the color image for the extracted stained site and background color, and calculates the average value of each of the red, green, and blue color information.

[0064] In step S127, the staining intensity calculation unit 12 defines the staining intensity as the Euclidean distance in RGB space (the distance between the stained site (after staining) and the background color (before staining)), and calculates the staining intensity by the above-mentioned formula (I).

[0065] (Step S13) Returning to the description of Fig. 10, in step S13, the heating history acquisition unit 13 accesses the stained image database 41 or the staining device 43 to acquire the heating history of the stained image. Then, the temperature integral calculation unit 14 calculates a time integral value (temperature integral value) of the heating history.

[0066] 12 is a flowchart showing details of the processing by the heating history acquisition unit 13 and the temperature integral calculation unit 14. The processing (steps S131 to S134) shown in FIG.

[0067] In step S131, the heating history acquisition unit 13 determines whether the heating history as shown in Fig. 2 can be acquired. Specifically, when a stained specimen is prepared by the staining device 43 and a stained image is prepared by the imaging device 42, the heating history of the stained image can be acquired from the staining device 43, and therefore it is determined that it can be acquired (Yes). On the other hand, when a stained image is acquired from an external database such as the stained image database 41, it is determined that the heating history cannot be acquired (No). If the heating history can be acquired (Yes), the process proceeds to step S132. If the heating history cannot be acquired (No), the process proceeds to step S134.

[0068] In step S132, the heating history acquisition unit 13 accesses the dyeing device 43 and acquires the heating history as shown in FIG. 2. In step S133, the temperature integral calculation unit 14 calculates the threshold value H th The area of ​​the region above ℃ (shaded area in Figure 2) is calculated and used as the temperature integral value.

[0069] On the other hand, when acquiring a stained image from the stained image database 41, in step S134, the heating history acquisition unit 13 acquires the heating conditions (heating temperature H°C, heating time T minutes) associated with the stained image as an alternative heating history. The temperature integral calculation unit 14 calculates the temperature integral value from the above-mentioned formula (II).

[0070] (Step S14) Returning to the explanation of Fig. 10, the correlation creating unit 15 receives the staining intensity calculated by the staining intensity calculation unit 12 in step S12 and the temperature integral calculated by the temperature integral calculation unit 14 in step S13. The correlation creating unit 15 creates a graph with the staining intensity on the vertical axis (Y axis) and the time integral on the horizontal axis (X axis), and plots the relationship between the staining intensity and the temperature integral (Fig. 6A). Then, the correlation creating unit 15 creates a correlation graph (Fig. 6B) including an approximation curve of the plot and the above-mentioned correlation approximation formula (III).

[0071] (Step S15) The correlation creating unit 15 accesses the correlation storage unit 20 and stores the correlation approximation formula (III) and the correlation graph created in step S14 as information relating to the correlation between the staining intensity and the temperature integral value.

[0072] The above describes an embodiment in which the processes for generating information on correlation in step S1 are performed by the user. Alternatively, the processes in step S1 may be performed by the manufacturer before shipping the heating condition presentation device 1.

[0073] (Step S2: Calculation of heating conditions) The heating condition calculation process in the heating condition calculation unit 30 is executed when the user inputs a heating condition calculation request via the operation unit 2.

[0074] (Step S21) When the input unit 31 receives a calculation request for heating conditions, it transmits input screen data (FIG. 7) for various parameters related to the staining target to the display unit 3, displays it on the display device, and accepts input of various parameters. The information input by the user is the staining reagent to be used during staining, the protein to be tested, and the desired heating temperature or desired heating time. If the user inputs the desired heating temperature, the heating time is calculated as a heating condition in the subsequent step. If the user inputs the desired heating time, the heating temperature is calculated as a heating condition in the subsequent step.

[0075] (Step S22) The correlation extraction unit 32 receives user input information from the input unit 31 and accesses the correlation storage unit 20. Then, the correlation extraction unit 32 extracts information on the correlation between the input staining reagent and the staining intensity and the temperature integral value corresponding to the test subject from the correlation storage unit 20 and downloads it.

[0076] (Step S23) The staining intensity selection request unit 33 receives the downloaded information on the correlation from the correlation extraction unit 32. Then, the staining intensity selection request unit 33 generates a staining intensity selection screen (FIG. 8) based on the color sample of the information on the correlation, transmits it to the display unit 3, and displays it on the display device. The color sample can be composed of a plurality of blocks showing the shades of staining intensity in stages.

[0077] (Step S24) The staining strength selection request unit 33 accepts the selection of a color tone of a desired staining strength based on a color sample by the user. At this time, the user clicks on a block indicating a color tone of a desired staining strength on the color sample screen.

[0078] (Step S25) The calculation unit 34 receives information on the color selected by the user from the staining intensity selection request unit 33. The calculation unit 34 substitutes the staining intensity corresponding to the color into the correlation approximation formula (III) to calculate the temperature integral value.

[0079] (Step S26) The calculation unit 34 calculates the heating time corresponding to the desired heating temperature, or the heating temperature corresponding to the desired heating time, by substituting the calculated temperature integral value into formula (II). Note that, if the user does not input either the desired heating time or the heating temperature in step S21, the calculation unit 34 calculates a combination of the heating temperature and the heating time that satisfies formula (II) of the temperature integral value.

[0080] (Step S27) The heating condition presenting unit 35 receives the calculated heating conditions (heating temperature or heating time) from the calculation unit 34. The heating condition presenting unit 35 generates image data based on the heating conditions, transmits the image data to the display unit 3, and displays the image data on the display device. This makes it possible to present the calculated heating conditions to the user.

[0081] <Summary of the First Embodiment> As described above, the heating condition presentation device 1 (information processing device) of this embodiment includes a memory that stores a program, and a processor that reads and executes the program from the memory. The heating condition presentation device 1 includes a heating condition calculation unit 30 as a software module executed by the processor. The correlation extraction unit 32 of the heating condition calculation unit 30 reads out information on correlation, including a correlation approximation equation between the staining intensity calculated from the stained image of the stained specimen and the time integral value of the heating temperature calculated from the heating history of the stained specimen, stored in the correlation storage unit 20 (storage device). The staining intensity selection request unit 33 accepts the selection of a desired staining intensity of the stained object. The calculation unit 34 calculates a time integral value corresponding to the selected desired staining intensity based on the information on correlation read out from the correlation storage unit 20, and calculates the heating conditions of the stained object from the time integral value. The heating condition presentation unit 35 displays the calculated heating conditions on the display unit 3 (display device).

[0082] This allows the user to know the heating conditions that will achieve the optimal staining intensity of the stained specimen without having to go through trial and error to search for heating conditions, thus reducing the burden on the user and enabling appropriate pathological diagnosis based on good stained images.

[0083] [Second embodiment: Example in which Euclidean distance in Lab space is used as staining intensity] In the first embodiment, the staining intensity is defined as the Euclidean distance in the RGB space. The staining intensity can also be expressed in another color space. In the second embodiment, the staining intensity is defined as the Euclidean distance in the Lab space. * a * b *The space is expressed in three dimensions, just like the RGB space, and the L * represents brightness, and a * represents the saturation of green to red, and b * represents the saturation of blue to yellow. * a * b * The space is closer to how humans perceive color compared to the RGB space.

[0084] L * a * b * The Euclidean distance in space can be calculated based on the RGB values ​​obtained from the stained image through the following three steps (i) to (iii).

[0085] (i) Conversion of RGB values ​​to tristimulus values ​​XYZ

[0086]

number

[0087]

number

[0088] (ii) Tristimulus values ​​XYZ to L * a * b * Converting to a value

[0089]

number

[0090] (iii) Calculation of staining intensity (Euclidean distance)

[0091]

number

[0092] In the above-mentioned step S14, the correlation creation unit 15 can create a correlation using the staining intensity calculated by the staining intensity calculation unit 12 using the formula (VII). * a * b * By expressing the color by values, the color sample presented to the user can be made closer to the color that the user actually sees. Therefore, the user can correctly select the desired staining intensity from the color sample. As a result, the possibility of presenting the optimal heating conditions is improved compared to when RGB values ​​are used.

[0093] [Third embodiment: Example including a stained image acquisition unit that captures a stained image of a specimen] In the first embodiment, it has been described that the stained image acquisition unit 11 accesses an external stained image database 41 or an imaging device 42 via the Internet to acquire stained images. However, the source of the stained images is not limited to an external device. It is also possible to adopt a configuration in which the stained image acquisition unit 11 has a function of capturing stained images, that is, a configuration in which the stained image acquisition unit 11 also functions as the imaging device 42. This makes it possible to acquire stained images within the heating condition presentation device 1. Therefore, the processing of the stained image acquisition unit 11 is simplified. The heating history can be configured to be acquired from an external staining device 43, as in the first embodiment.

[0094] [Variations] The present disclosure is not limited to the above-described embodiments, and includes various modified examples. For example, the above-described embodiments have been described in detail to clearly explain the present disclosure, and it is not necessary to include all of the configurations described. In addition, a part of an embodiment can be replaced with a configuration of another embodiment. In addition, a configuration of another embodiment can be added to a configuration of an embodiment. In addition, a part of the configuration of each embodiment can be added to, deleted from, or replaced with a part of the configuration of another embodiment. [Explanation of symbols]

[0095] 1...Heating condition presentation device 2...Operation unit 3...Display section 4. Web interface 10…Correlation Database Creation Department 11…Staining image acquisition section 12... Staining intensity calculation section 13…Heating history acquisition section 14...Temperature integral calculation section 15…Correlation Creation Section 20…Correlation storage section 30…Heating condition calculation section 31...Input section 32…Correlation extraction section 33…Staining Intensity Selection Request Section 34...Arithmetic section 35...Heating condition presentation section 41...Dyeing image database 42...Imaging device 43...Dyeing equipment

Claims

1. An information processing device for presenting heating conditions for a dyeing object, A memory for storing a program and a processor for reading and executing the program from the memory, The processor, A process of reading out information on the correlation between the staining intensity of a stained specimen and a time integral value of a heating temperature from a storage device that stores the information on the correlation, the information on the correlation including a correlation approximation formula between the staining intensity calculated from a stained image of the stained specimen and the time integral value of the heating temperature calculated from a heating history of the stained specimen; receiving a selection of a desired staining intensity of the stained object; A process of calculating the time integral value corresponding to the selected desired staining intensity based on the information on the correlation read from the storage device, and calculating a heating condition for the stained object from the time integral value; A process of displaying the calculated heating conditions on a display device; An information processing device that executes the above.

2. The storage device further stores a color sample corresponding to the staining intensity as information related to the correlation; The processor, In the process of receiving the selection of the desired staining intensity, the color sample is displayed on the display device; In the process of calculating the heating conditions, input of information on the object to be dyed and a desired heating temperature or a desired heating time is accepted; calculating the time integral value corresponding to the selected desired staining intensity from the correlation approximation formula, and calculating, as the heating condition, a heating time corresponding to the input desired heating temperature or a heating temperature corresponding to the input desired heating time; The information processing device according to claim 1 , wherein the display process displays the calculated heating time or heating temperature on the display device.

3. The processor further comprises: A process of acquiring the stained image of the stained specimen; A process of calculating the staining intensity of the acquired stained image; A process of acquiring the heating history of the stained specimen; A process of calculating the time integral value of the heating history; The information processing apparatus according to claim 1 , wherein the information regarding the correlation is obtained by executing the following: and the information regarding the correlation is stored in the storage device.

4. The information processing apparatus according to claim 1 , wherein the staining intensity is a Euclidean distance between a stained site and a background color in an RGB color space of the stained image.

5. The staining intensity is the L * a * b * The information processing apparatus according to claim 1 , wherein the distance is a Euclidean distance between the stained site and a background color in a color space.

6. The processor, The information processing apparatus according to claim 4 , wherein the stained site and the background color are extracted from a grayscale luminance distribution of the stained image.

7. The processor, The information processing apparatus according to claim 3 , further comprising: accessing an external stained image database via a communication network; and acquiring the stained image from the stained image database.

8. The processor, The information processing apparatus according to claim 3 , further comprising: accessing an external imaging device that captures the stained image of the stained specimen via a communication network; and acquiring the stained image from the imaging device.

9. The processor, The information processing apparatus according to claim 3 , further comprising: accessing an external stained image database via a communication network; and acquiring the heating history of the stained specimen from the stained image database.

10. The processor, The information processing apparatus according to claim 3 , further comprising: accessing an external staining device that stains the stained specimen via a communication network; and acquiring the heating history from the staining device.

11. The information processing apparatus according to claim 1 , further comprising an imaging device that captures the stained image of the stained specimen.

12. The information processing apparatus according to claim 1 , wherein the heating conditions include a heating temperature and a heating time.

13. The information processing device according to claim 1 , wherein the time integral value of the heating temperature is calculated by (heating temperature−temperature threshold)×heating time.

14. The information processing device according to claim 2 , wherein the information on the staining target includes names of a staining reagent and a protein.

15. The information processing device according to claim 2 , wherein the color sample is displayed divided into stages according to the color tone of the staining intensity.

16. An information processing method for presenting heating conditions for a dyeing object, which is realized by a processor of an information processing device executing a program stored in a memory, comprising: The processor: Reading out information on the correlation between the staining intensity of the stained specimen and a time integral value of the heating temperature from a storage device that stores information on the correlation, the information on the correlation including a correlation approximation formula between the staining intensity calculated from a stained image of the stained specimen and the time integral value of the heating temperature calculated from a heating history of the stained specimen; Accepting a selection of a desired staining intensity of the stained object; calculating the time integral value corresponding to the selected desired staining intensity based on the information on the correlation read from the storage device, and calculating a heating condition for the stained object from the time integral value; Displaying the calculated heating conditions on a display device; An information processing method comprising:

17. The storage device further stores a color sample corresponding to the staining intensity as information related to the correlation; Accepting a selection of the desired staining intensity includes: and accepting a selection of the desired staining intensity by displaying the color sample on the display device; Calculating the heating conditions includes: Receiving input of information regarding the object to be dyed and a desired heating temperature or a desired heating time; calculating the time integral value corresponding to the selected desired staining intensity from the correlation approximation formula, and calculating, as the heating condition, a heating time corresponding to the input desired heating temperature or a heating temperature corresponding to the input desired heating time; The displaying step includes: Displaying the calculated heating time or heating temperature on the display device. The information processing method according to claim 16 , comprising:

Citation Information

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