Analysis method, analysis system, and analysis program

Abstract

To provide an analysis method, an analysis system and an analysis program capable of quantifying the anisotropy of a tissue in a specimen considering each direction in three dimensions.SOLUTION: An analysis system calculates a two-dimensional power spectrum obtained by Fourier transforming an observed image of image data using the image data showing any cross section of a tissue as input. The analysis system evaluates anisotropy information of a plane corresponding to the direction of the cross section from the angular dependence of the intensity of the two-dimensional power spectrum. The analysis system recovers the three-dimensional scattering intensity distribution from a spectrum of small-angle X-ray scattering data using the small-angle X-ray scattering data of the tissue as input. The analysis system uses the recovered scattering intensity distribution to evaluate anisotropy information in a direction different from the direction of the section by removing the influence of anisotropy information in the plane corresponding to the direction of the section.SELECTED DRAWING: Figure 3

Description

Technical Field

[0001] The present disclosure relates to an analysis method, an analysis system, and an analysis program.

Background Art

[0002] Patent Document 1 discloses a technique related to an analysis for calculating the scattering intensity of X-rays scattered by a plate-shaped sample. In this technique, the scattering intensity of X-rays is calculated under the condition that the scatterers are formed by laminating in the thickness direction of a plate-shaped sample of layers having respective shapes.

Prior Art Documents

Patent Documents

[0003]

Patent Document 1

Summary of the Invention

Problems to be Solved by the Invention

[0004] In Patent Document 1, a proposal regarding specifying the structure of a scatterer has been made. In Patent Document 1, in specifying the structure, the sample is rotated for measurement, and the angular dependence of the intensity change is analyzed. The scatterer is particles in the direction parallel to the optical axis. However, there is a problem that the configuration, control, and analysis of data of the evaluation system become complicated.

[0005] An object of the present disclosure is to provide an analysis method, an analysis system, and an analysis program that can quantify the anisotropy of tissues in a sample in consideration of each three-dimensional direction.

Means for Solving the Problems

[0006] The analysis method described in claim 1 involves a computer performing the following processes: taking image data of an arbitrary cross-section of tissue as input, calculating a two-dimensional power spectrum obtained by performing a Fourier transform on the observed image data; evaluating the anisotropy information of the plane corresponding to the direction of the cross-section from the angular dependence of the intensity of the two-dimensional power spectrum; taking small-angle X-ray scattering data of the tissue as input, reconstructing a three-dimensional scattering intensity distribution from the spectrum of the small-angle X-ray scattering data; and using the reconstructed scattering intensity distribution, evaluating the anisotropy information of a direction different from the direction of the cross-section by removing the influence of the anisotropy information of the plane corresponding to the direction of the cross-section. Furthermore, in the analysis method, the evaluation of the anisotropy information of the surface includes the ratio of the intensities in the two axes corresponding to the cross-section, and the evaluation of the anisotropy information in directions different from the cross-section is performed by solving a system of equations created using the ratio of the intensities and the intensities corresponding to the three axes of the reconstructed scattering intensity distribution, thereby calculating the intensities in directions different from the cross-section and evaluating the anisotropy information in those different directions.

[0007] The analysis method described in claim 1 evaluates the anisotropy information of the cross-sectional plane from the angular dependence of the intensity of the two-dimensional power spectrum, and then uses small-angle X-ray scattering data to remove the influence of the plane and evaluate the anisotropy information with respect to the observed image. This makes it possible to quantify the anisotropy of the tissue in the sample by considering each direction in three dimensions. Furthermore, it allows for anisotropy analysis considering all directions while keeping computation costs down.

[0009] Claim 2 The analysis system described above includes a calculation unit that takes image data of an arbitrary cross-section of tissue as input and calculates a two-dimensional power spectrum obtained by performing a Fourier transform on the observed image data, and a calculation unit that uses the angle dependence of the intensity of the two-dimensional power spectrum to determine the direction of the cross-section. The system includes a first evaluation unit that evaluates anisotropy information of a plane corresponding to a direction, a restoration unit that takes X-ray small-angle scattering data of the tissue as input and reconstructs a three-dimensional scattering intensity distribution from the spectrum of the X-ray small-angle scattering data, and a second evaluation unit that uses the reconstructed scattering intensity distribution to remove the influence of anisotropy information of a plane corresponding to the direction of the cross-section, thereby evaluating anisotropy information in a direction different from the direction of the cross-section. Furthermore, in the analysis system, the evaluation of the anisotropy information of the surface includes the ratio of the intensities in the two axes corresponding to the cross-section, and the evaluation of the anisotropy information in directions different from the cross-section is performed by solving a system of equations created using the ratio of the intensities and the intensities corresponding to the three axes of the reconstructed scattering intensity distribution, thereby calculating the intensities in directions different from the cross-section and evaluating the anisotropy information in those different directions.

[0010] Claim 3The analysis program described above takes image data of an arbitrary cross-section of tissue as input, calculates a two-dimensional power spectrum obtained by performing a Fourier transform on the observed image data, evaluates the anisotropy information of the plane corresponding to the direction of the cross-section from the angular dependence of the intensity of the two-dimensional power spectrum, takes small-angle X-ray scattering data of the tissue as input, reconstructs a three-dimensional scattering intensity distribution from the spectrum of the small-angle X-ray scattering data, and uses the reconstructed scattering intensity distribution to remove the influence of the anisotropy information of the plane corresponding to the direction of the cross-section, thereby evaluating the anisotropy information of directions other than the direction of the cross-section. Furthermore, in the analysis program, the evaluation of the anisotropy information of the surface includes the ratio of the intensities in the two axes corresponding to the cross-section, and the evaluation of the anisotropy information in directions different from the cross-section is performed by solving a system of equations created using the ratio of the intensities and the intensities corresponding to the three axes of the reconstructed scattering intensity distribution, thereby calculating the intensities in directions different from the cross-section and evaluating the anisotropy information in those different directions. [Effects of the Invention]

[0011] According to the technology disclosed herein, the anisotropy of tissue in a sample can be quantified by considering each direction in three dimensions. [Brief explanation of the drawing]

[0012] [Figure 1] Figure 1 is a conceptual diagram of tissue including anisotropy. [Figure 2] Figure 2 is a schematic diagram showing the flow of the analysis method in this embodiment. [Figure 3] Figure 3 shows the functional configuration of the analysis system. [Figure 4] Figure 4 is a block diagram showing the hardware configuration of the analysis device. [Figure 5] Figure 5 is a flowchart showing the flow of the analysis process as an analysis method performed by the analysis device of this embodiment. [Modes for carrying out the invention]

[0013] An overview of embodiments of the present invention will now be described. The properties of the material are closely related to the structural characteristics within the sample. Structural characteristics refer to the size, shape, and arrangement of the dispersed or packed particles. If the shape of the particles themselves is anisotropic, the degree of orientation is also included in the structural characteristics.

[0014] When evaluating the anisotropy of particle orientation and arrangement, microscopy methods such as SEM (Scanning Electron Microscope) involve repeatedly slicing the sample little by little in the thickness direction and observing the structural features. However, this method has problems such as high data acquisition costs and the possibility of losing information from the original sample because it is a destructive observation method.

[0015] Scattering methods, such as small-angle X-ray scattering (SAXS), are non-destructive observation techniques used to evaluate the orientation of samples. However, they have the problem of not providing sufficient results for analyzing structural features in directions parallel to the optical axis, i.e., perpendicular to the observed image.

[0016] Therefore, in this embodiment, the anisotropy of the tissue is evaluated using both cross-sectional image data and small-angle X-ray scattering data. In the following description of this embodiment, the cross-sectional image data is described as an example in which the direction of the cross-section is the horizontal direction of the surface and in-plane anisotropy information is obtained, but the embodiment is not limited to this. This embodiment can also be similarly applied when the direction of the cross-section is the perpendicular direction of the surface and in-plane anisotropy information is obtained.

[0017] Figure 1 is a conceptual diagram of a tissue containing anisotropy. The tissue shown in Figure 1 exhibits anisotropy in the structural characteristics of the sample, lacking three-dimensional isotropy in the x, y, and z axes. In this case, the scattering intensity in the small-angle X-ray scattering data of the sample also contains anisotropy.

[0018] Figure 2 is a schematic diagram showing the flow of the analysis method of this embodiment. As shown in Figure 2, for the sample to be analyzed, (a1) image data of an arbitrary cross-section of the tissue and (a2) X-ray small-angle scattering data of the tissue are used as input. The image data in (a1) includes two-dimensional anisotropy of the x and z axes. The X-ray small-angle scattering data in (a2) is one-dimensional spectral data that includes three-dimensional anisotropy of the x, z, and y axes, and is represented as a graph with scattering intensity on the vertical axis and wavenumber on the horizontal axis. (b) is an example of a two-dimensional power spectrum obtained by Fourier transform from the image data in (a1). (b) shows the two-dimensional scattering intensity distribution of the x and z axes, with the center being the spatial frequency origin and the power spectrum spreading from the center. (c) is an example of a graph for evaluating in-plane anisotropy information. (c) shows the scattering intensity on the vertical axis and the angle in the circumferential direction of the center of the power spectrum on the horizontal axis, with the angles corresponding to the x and z axes.

[0019] An example of in-plane anisotropy information for the x and z axes is explained. In the evaluation of in-plane anisotropy information in (c), the intensity of the two-dimensional power spectrum is assumed to have an angle dependence in which, for example, angles of 0° (360°) and 180° correspond to the x axis, and angles of 90° and 270° correspond to the z axis. In this case, a certain wave number q in two-dimensional space 2D By evaluating the angular dependence of the power spectral intensity in this region, the ratio of intensity in the z-axis direction to that in the x-axis direction can be determined.

[0020] Next, we will explain an example of how to obtain y-axis anisotropy information. The X-ray small-angle scattering data in Figure 2(a2) is a one-dimensional spectrum containing anisotropy information in three axes, and the scattering intensity of the one-dimensional spectrum contains information including components in the x-axis, z-axis, and y-axis directions. Here, the wave number q in two-dimensional space. 2D There is a relationship like equation (1) in this case.

number

[0021] Furthermore, the wave number q in three-dimensional space 3DThere is a relational expression such as formula (2). Here, q x、 q y、 q z are the components of the wave number q in each axial direction.

Number

[0022] Consider the one-dimensional power spectrum obtained by integrating the two-dimensional power spectrum in the circumferential direction. The wave number q in the two-dimensional space 2D The intensity of the one-dimensional power spectrum at is denoted as a 2D (q 2D ). Similarly, the intensity of the small-angle X-ray scattering data at the wave number q in the three-dimensional space is denoted as a 3D (q 3D ).

[0023] For a certain wave number q in the two-dimensional space 2D_1 Composed of q x , q z The pair is denoted as (q x1, q z1 ). Then, the intensity of the one-dimensional power spectrum at the wave number q 2D_1 is a 2D (q 2D_1 ). Similarly, consider a certain wave number q in the three-dimensional space 3D_1 . When q 2D_1 is equal to q 3D_1 , the pair composed of q 3D_1 contains (q x , q y , q z ) is (q x1 , 0, q z1 ). Furthermore, (q x2 , q y2 , q z2 ) that satisfies formula (2) is also included. The intensity of the small-angle X-ray scattering spectrum at the wave number q 3D_1 is a 3D (q 3D_1 ).

[0024] a 2D (q​​2D_1 ) contains q x1, q z1 This includes the contribution of a. 3D (q 3D_1 ) contains q x1, q z1 In addition to the contribution of q x2 , q y2 , q z2 This includes the contribution of q. x2, q z2 The wave number of a two-dimensional space consisting of q 2D_2 Therefore, the intensity a of the one-dimensional power spectrum 2D (q 2D_2 ) contains q x2, q z2 This includes the contribution of q. x , q y , q z This is a system of equations relating to q, and by solving them, we can obtain the y-axis component of the wave number q. y The ratio of the intensities can be determined.

[0025] Thus, solving a system of equations related to wavenumber q to determine the intensity ratio of the y-axis component to the x-axis and z-axis intensities of the scattering intensity is an example of removing the influence of anisotropy information from a plane corresponding to the direction of the cross-section and evaluating anisotropy information in a direction different from the direction of the cross-section.

[0026] Figure 3 shows the functional configuration of the analysis system 100. As shown in Figure 4, in the analysis system 100, the user terminal 102 and the analysis device 110 are connected via a network N such as the Internet.

[0027] The user terminal 102 is a terminal for inputting data related to the analysis. The user terminal 102 consists of a control unit 104 and a display unit 106, and is equipped with an interface that allows selection and specification of various data stored in the storage unit 112 of the analysis device 110. The control unit 104 of the user terminal 102 specifies the processing target. When specifying the processing target, image data of an arbitrary cross-section of the tissue and small-angle X-ray scattering data of the tissue are specified and transmitted to the analysis device 110. The user terminal 102 also receives the evaluation results of the anisotropy information processed by the analysis device 110 and displays them on the display unit 106. Note that the user terminal 102 may be configured as an integrated unit with the analysis device 110.

[0028] Figure 4 is a block diagram showing the hardware configuration of the analysis device 110. As shown in Figure 4, the analysis device 110 has a CPU (Central Processing Unit) 11, ROM (Read Only Memory) 12, RAM (Random Access Memory) 13, storage 14, input unit 15, display unit 16, and communication interface (I / F) 17. Each component is connected to the others via a bus 19 so that they can communicate with each other. The user terminal 102 may have a similar hardware configuration.

[0029] The CPU 11 is a central processing unit that executes various programs and controls various components. Specifically, the CPU 11 reads a program from the ROM 12 or storage 14 and executes the program using the RAM 13 as a working area. The CPU 11 controls each of the above components and performs various calculations according to the program stored in the ROM 12 or storage 14. In this embodiment, the ROM 12 or storage 14 stores an analysis program.

[0030] ROM12 stores various programs and data. RAM13 temporarily stores programs or data as a working area. Storage14 consists of a storage device such as an HDD (Hard Disk Drive) or SSD (Solid State Drive) and stores various programs, including the operating system, and various data.

[0031] The input unit 15 includes a pointing device such as a mouse and a keyboard, and is used for various types of input.

[0032] The display unit 16 is, for example, a liquid crystal display and displays various information. The display unit 16 may also function as an input unit 15 by employing a touch panel system.

[0033] The communication interface 17 is an interface for communicating with other devices such as terminals. For such communication, a wired communication standard such as Ethernet® or FDDI, or a wireless communication standard such as 4G, 5G, or Wi-Fi® may be used.

[0034] The functional configuration of the analysis device 110 shown in Figure 3 will now be explained. Functionally, the analysis device 110 consists of a storage unit 112, a calculation unit 120, and an evaluation unit 122. The evaluation unit 122 includes a first evaluation unit 122A, a restoration unit 122B, and a second evaluation unit 122C. Each functional configuration is realized by the CPU 11 reading the analysis program stored in the ROM 12 or storage 14, expanding it into the RAM 13, and executing it. The analysis device 110 receives the specification of image data and X-ray small-angle scattering data from the user terminal 102 and executes the processing of each unit. The analysis device 110 transmits the evaluation result of the anisotropy information to the user terminal 102.

[0035] The memory unit 112 pre-stores the collected image data and small-angle X-ray scattering data of the target of analysis. The image data is a digital image of the x-axis and z-axis cross-section of the tissue, and includes the anisotropy of the tissue. The small-angle X-ray scattering data is associated with the tissue in the image data. Note that the storage method is not limited to the memory unit 112; the image data and small-angle X-ray scattering data may also be received from the user terminal 102.

[0036] The calculation unit 120 takes image data as input and calculates a two-dimensional power spectrum obtained by performing a Fourier transform on the observed image data.

[0037] The evaluation unit 122 will now be described. The first evaluation unit 122A evaluates the in-plane anisotropy information corresponding to the x-axis and z-axis directions of the cross-section from the angular dependence of the intensity of the calculated two-dimensional power spectrum. In the first evaluation unit 122A, for example, a graph showing the intensity according to the angle, as described in (c) above, is obtained by integrating the intensity of the two-dimensional power spectrum in the circumferential direction. In the first evaluation unit 122A, the intensity a in the direction of the two axes (x-axis and z-axis) is obtained from the angular dependence of the intensity in the graph. 2D (q 2D_1 The ratio of ) is calculated as one of the evaluations of the anisotropy information within the plane. Alternatively, the intensity corresponding to the height h of the distribution and the width W of the midpoint (h / 2) of the distribution height may be determined as part of the evaluation.

[0038] The reconstruction unit 122B takes X-ray small-angle scattering data as input and reconstructs a three-dimensional scattering intensity distribution from the spectrum of the X-ray small-angle scattering data. From the three-dimensional scattering intensity distribution, the intensities a in the x, z, and y axes are obtained. 3D (q 3D_1 ) can be obtained.

[0039] The second evaluation unit 122C evaluates the anisotropy information in the y-axis direction by using the reconstructed scattering intensity distribution to remove the influence of in-plane anisotropy information corresponding to the direction of the cross-section. The y-axis direction is perpendicular to the observed image, and is different from the cross-sectional directions of the x and z axes.

[0040] An example of a specific configuration of the processing by the second evaluation unit 122C will be described. The second evaluation unit 122C uses the scattering intensity distribution to determine the intensity a corresponding to the three axes. 3D (q 3D_1 The second evaluation unit 122C determines the intensity a in the z-axis direction and the x-axis direction. 2D (q 2D_1 The ratio of ) and the intensity a corresponding to the three axes of the reconstructed three-dimensional scattering intensity distribution. 3D (q 3D_1 A system of linear equations is created using ). The second evaluation unit 122C solves the created system of linear equations to determine the strength in the y-axis, thereby removing the influence of the x-axis and y-axis. In this way, the second evaluation unit 122C calculates the strength in the y-axis, which is in a direction different from the cross-section, and obtains this as an evaluation of the anisotropy information of the y-axis.

[0041] (Control flow) Figure 5 is a flowchart showing the flow of the analysis process as an analysis method performed by the analysis device 110 of this embodiment.

[0042] In step S100, the CPU 11 acquires the specified image data and X-ray small-angle scattering data from the storage unit 112.

[0043] In step S102, the CPU 11 takes the acquired image data as input and calculates a two-dimensional power spectrum obtained by performing a Fourier transform on the observed image data.

[0044] In step S104, the CPU 11 evaluates the in-plane anisotropy information corresponding to the x and z axis directions of the cross-section from the angular dependence of the intensity of the calculated two-dimensional power spectrum.

[0045] In step S106, the CPU 11 takes the acquired small-angle X-ray scattering data as input and reconstructs a three-dimensional scattering intensity distribution from the spectrum of the small-angle X-ray scattering data.

[0046] In step S108, the CPU 11 evaluates the anisotropy information in the y-axis direction by using the in-plane anisotropy information and the reconstructed scattering intensity distribution to remove the influence of the in-plane anisotropy information corresponding to the direction of the cross-section.

[0047] In step S110, the CPU 11 outputs the anisotropy information in the plane corresponding to the evaluated x and z axis directions, as well as the anisotropy information of the y axis, to the user terminal 102 as evaluation results.

[0048] As described above, the analysis system 100 of this embodiment can quantify the anisotropy of tissue in a sample by considering each direction in three dimensions.

[0049] In addition, the various processes that the CPU 11 reads and executes in the above embodiment may be executed by various processors other than the CPU. Examples of such processors include PLDs (Programmable Logic Devices) such as FPGAs (Field-Programmable Gate Arrays) whose circuit configuration can be changed after manufacturing, GPUs (Graphics Processing Units), and ASICs (Application Specific Integrated Circuits), which are dedicated electrical circuits that have a circuit configuration specifically designed to execute a particular process. Furthermore, each of the above processes may be executed by one of these various processors, or by a combination of two or more processors of the same or different types (for example, multiple FPGAs, and a combination of a CPU and an FPGA). More specifically, the hardware structure of these various processors is an electrical circuit that combines circuit elements such as semiconductor elements.

[0050] Furthermore, in the above embodiment, the information processing program was described as being pre-stored (installed) on a computer-readable non-temporary recording medium. For example, the information processing program is pre-stored on ROM 12 or storage 14. However, it is not limited to this, and each program may be provided in a form recorded on a non-temporary recording medium such as CD-ROM (Compact Disc Read Only Memory), DVD-ROM (Digital Versatile Disc Read Only Memory), and USB (Universal Serial Bus) memory. Also, the analysis program may be downloaded from an external device via a network.

[0051] The processing flow described in the above embodiment is just one example, and unnecessary steps may be deleted, new steps added, or the processing order rearranged, as long as it does not deviate from the main point. [Explanation of Symbols]

[0052] 100 Analysis Systems 102 User terminals 104 Control Unit 106 Display section 110 Analysis equipment 112 Storage section 120 Calculation Department 122 Evaluation Department 122A First Evaluation Department 122B Restoration Section 122C Second Evaluation Department

Claims

1. Taking image data of an arbitrary cross-section of tissue as input, a two-dimensional power spectrum is calculated by performing a Fourier transform on the observed image data. From the angular dependence of the intensity of the two-dimensional power spectrum, the anisotropy information of the plane corresponding to the direction of the cross-section is evaluated. Taking the X-ray small-angle scattering data of the aforementioned tissue as input, a three-dimensional scattering intensity distribution is reconstructed from the spectrum of the X-ray small-angle scattering data. By using the reconstructed scattering intensity distribution, the influence of anisotropy information of a plane corresponding to the direction of the cross-section is removed, thereby evaluating anisotropy information in a direction different from the direction of the cross-section. An analysis method in which a computer performs the processing, The evaluation of the anisotropy information of the aforementioned surface includes the ratio of the intensity in the two axial directions corresponding to the cross-section, An analysis method for evaluating anisotropy information in directions different from the cross-section involves solving a system of equations created using the ratio of the intensities and the intensities corresponding to the three axes of the reconstructed scattering intensity distribution to calculate the intensities in directions different from the cross-section and evaluate the anisotropy information in those different directions.

2. A calculation unit that takes image data of an arbitrary cross-section of tissue as input and calculates a two-dimensional power spectrum obtained by performing a Fourier transform on the observed image data, A first evaluation unit evaluates the anisotropy information of the plane corresponding to the direction of the cross-section from the angular dependence of the intensity of the two-dimensional power spectrum, A reconstruction unit takes X-ray small-angle scattering data of the aforementioned tissue as input and reconstructs a three-dimensional scattering intensity distribution from the spectrum of the X-ray small-angle scattering data, A second evaluation unit evaluates anisotropy information in directions different from the direction of the cross-section by removing the influence of anisotropy information of the plane corresponding to the direction of the cross-section using the reconstructed scattering intensity distribution, An analysis system comprising, The evaluation of the anisotropy information of the aforementioned surface includes the ratio of the intensity in the two axial directions corresponding to the cross-section, An analysis system for evaluating anisotropy information in directions different from the cross-section involves solving a system of equations created using the ratio of the intensities and the intensities corresponding to the three axes of the reconstructed scattering intensity distribution to calculate the intensity in directions different from the cross-section and evaluate the anisotropy information in those different directions.

3. Taking image data of an arbitrary cross-section of tissue as input, a two-dimensional power spectrum is calculated by performing a Fourier transform on the observed image data. From the angular dependence of the intensity of the two-dimensional power spectrum, the anisotropy information of the plane corresponding to the direction of the cross-section is evaluated. Taking the X-ray small-angle scattering data of the aforementioned tissue as input, a three-dimensional scattering intensity distribution is reconstructed from the spectrum of the X-ray small-angle scattering data. By using the reconstructed scattering intensity distribution, the influence of anisotropy information of a plane corresponding to the direction of the cross-section is removed, thereby evaluating anisotropy information in a direction different from the direction of the cross-section. An analysis program that causes a computer to perform the processing, The evaluation of the anisotropy information of the aforementioned surface includes the ratio of the intensity in the two axial directions corresponding to the cross-section, An analysis program that evaluates anisotropy information in directions different from the cross-section by solving a system of equations created using the ratio of the intensities and the intensities corresponding to the three axes of the reconstructed scattering intensity distribution, thereby calculating the intensity in directions different from the cross-section and evaluating the anisotropy information in those different directions.

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