Fertilization capacity information generation system, fertilization capacity information generation method, and fertilization capacity information generation computer program

Abstract

This invention provides a fertilization ability information generation system, a fertilization ability information generation method, and a fertilization ability information generation computer program that can improve the accuracy of evaluating sperm fertilization ability. [Solution] The fertilization capacity information generation system 100 includes a short-axis image detection unit 124 that detects a short-axis image 210 consisting of two substantially parallel lines or one band-shaped line extending in the short-axis direction of the head in a sperm head image 200 obtained by capturing an image of at least the head of a sperm 90; a fertilization capacity information generation unit 125 that generates fertilization capacity information that can be used to evaluate fertilization capacity based on the detection result of the short-axis image 210 by the short-axis image detection unit 124; and a storage unit 123 and a display device 122 that store or output the fertilization capacity information generated by the fertilization capacity information generation unit 125.

Description

Technical Field

[0001] The present invention relates to a fertilization ability information generation system, a fertilization ability information generation method, and a fertilization ability information generation computer program that generate fertilization ability information representing the fertilization ability of sperm.

Background Art

[0002] Conventionally, sperm measurement systems, sperm measurement methods, or sperm measurement instruments that can be used to evaluate the fertilization ability of sperm with respect to eggs have been proposed. For example, Patent Document 1 below discloses a sperm concentration measurement system that can measure the sperm concentration by imaging an image of semen placed on an image for concentration measurement.

Prior Art Documents

Patent Documents

[0003]

Patent Document 1

[0004] However, in the sperm concentration measurement system described in Patent Document 1 above, since the fertilization ability of sperm based on factors other than sperm concentration cannot be evaluated, there is a problem that it may be insufficient for use in evaluating the fertilization ability of sperm.

[0005] The present invention has been made to address the above problems, and an object thereof is to provide a fertilization ability information generation system, a fertilization ability information generation method, and a fertilization ability information generation computer program that can improve the evaluation accuracy of the fertilization ability of sperm.

Summary of the Invention

[0006] To achieve the above objective, the present invention is characterized by a fertilization ability information generation system that generates fertilization ability information that can be used to evaluate the fertilization ability of sperm, comprising: a short-axis image detection unit that detects a short-axis image consisting of two substantially parallel lines or one band-shaped line extending in the short-axis direction of the head with respect to a sperm head image obtained by capturing an image of at least the head of the sperm; a fertilization ability information generation unit that generates fertilization ability information based on the detection result of the short-axis image by the short-axis image detection unit; and a storage and output means for storing or outputting the fertilization ability information generated by the fertilization ability information generation unit.

[0007] According to the features of the present invention configured in this way, the fertilization ability information generation system stores or outputs fertilization ability information generated based on the detection results of the short-axis image by the short-axis image detection unit. Therefore, by using this fertilization ability information, the accuracy of evaluating the fertilization ability of sperm can be improved.

[0008] The inventors have discovered that sperm in which a short-axis structure can be visually observed or detected from the image when observed under magnification using a microscope or the like have a higher in vitro fertilization rate compared to sperm in which the same short-axis structure cannot be visually observed or detected from the image. Here, the short-axis structure in the sperm head refers to two approximately parallel lines or one band-like line extending in the short axis direction perpendicular to the long axis direction in a two-dimensional image of the sperm head, when the sperm head is considered to be approximately elliptical in a plan view. Furthermore, this short-axis structure may be detectable as a short-axis image in the two-dimensional image of the sperm head, or it may not be detectable (it may be unclear).

[0009] The present invention is based on the above-mentioned findings obtained by the inventors. Specifically, the present invention enables the evaluation of sperm fertilization ability by performing a process to detect short-axis images of sperm head images and saving or outputting fertilization ability information generated based on the detection results of the short-axis images.

[0010] More specifically, a user of the fertilization capacity information generation system according to the present invention can evaluate the fertilization capacity of a subject's sperm based on fertilization capacity information derived from the detection results of short-axis images stored or output by the storage output means. Here, fertilization capacity information refers to information that directly or indirectly represents the presence or absence of short-axis images, the number (including the percentage) of detected short-axis images, or the detected short-axis images. Indirectly representing information refers to information that can be used as an index (reference information) for evaluating fertilization capacity, generated by image processing, analysis processing, or statistical processing of the detected short-axis images or the detection results of short-axis images. Furthermore, the fertilization capacity information may also include evaluation information of fertilization capacity based on the aforementioned index for evaluating fertilization capacity.

[0011] Another feature of the present invention is that, in the fertilization ability information generation system, the fertilization ability information generation unit generates the degree of fertilization ability as fertilization ability information based on whether or not a short-axis image is detected.

[0012] According to this, the fertilization capacity information generation system generates fertilization capacity information based on whether or not a short-axis image is detected, and therefore can provide quantitative or objective indicators of the degree of fertilization capacity based on predetermined criteria.

[0013] Another feature of the present invention is that, in the fertilization capacity information generation system, the short-axis image detection unit detects a short-axis image for each sperm head image corresponding to a plurality of sperm, and the fertilization capacity information generation unit generates fertilization capacity information based on the number or ratio of sperm head images for which a short-axis image has been detected relative to the total number of sperm head images corresponding to a plurality of sperm.

[0014] According to this, the fertilization capacity information generation system generates fertilization capacity information by determining the number or ratio of sperm head images with short-axis images detected relative to the total number of sperm head images corresponding to multiple sperm, thereby simplifying the evaluation of sperm fertilization capacity.

[0015] Another feature of the present invention is that, in the fertilization capacity information generation system, the fertilization capacity information generation unit generates information indicating that the sperm have a high degree of fertilization capacity when the ratio of the number of sperm head images in which a short-axis image is detected to the total number of sperm head images corresponding to each of the multiple sperm is 2.3% or more.

[0016] According to this, the fertilization capacity information generation system generates information indicating that the proportion of sperm head images with short-axis images is 2.3% or higher when the ratio of the number of sperm head images with short-axis images to the total number of sperm head images corresponding to each of multiple sperm is 2.3% or higher, or that the proportion of sperm head images is higher than a predetermined value or that the degree of fertilization capacity is high, thus simplifying the evaluation of sperm fertilization capacity. In this case, according to the inventor's experiments, the fertilization rate is approximately 56% when the proportion of sperm head images with short-axis images is 2.3% or higher, approximately 70.3% when the proportion is 3.6% or higher, and 73.3% when the proportion is 5.9% or higher.

[0017] Another feature of the present invention is that the fertilization capacity information generation system further includes a feature detection unit that detects external features including at least one of the number, size, shape, and movement pattern of sperm based on a sperm head image, and the fertilization capacity information generation unit generates fertilization capacity information when the external features satisfy predetermined conditions.

[0018] According to this, the fertilization capacity information generation system includes a feature detection unit that detects external features, including at least one of the number, size, shape, and movement pattern of sperm, based on sperm head images. Therefore, by generating fertilization capacity information while taking external features into account, the accuracy of evaluating sperm fertilization capacity can be improved.

[0019] Another feature of the present invention is that the fertilization ability information generation system further includes an imaging unit that captures images of at least the head of the sperm.

[0020] According to this, the fertilization capacity information generation system is equipped with an imaging unit that captures images of at least the head of the sperm, so by preparing sperm, sperm fertilization capacity information can be quickly obtained.

[0021] Another feature of the present invention is that, in the fertilization capacity information generation system, the sperm head image is captured via an optical microscope.

[0022] According to this, since the sperm head image of the fertilization capacity information generation system is captured via an optical microscope, experiments by the inventors show that high-precision short-axis images can be obtained with simpler procedures compared to when sperm are imaged via an electron microscope. In this case, experiments by the inventors confirmed that short-axis images can be obtained with higher accuracy when imaged via an objective lens with a deeper depth of field (in other words, lower resolution), such as a dry objective lens that observes through air rather than a liquid, rather than an immersion objective lens that observes through a liquid such as oil or water.

[0023] Furthermore, the present invention can be implemented not only as an invention of a fertilization capacity information generation system, but also as an invention of a fertilization capacity information generation method and a fertilization capacity information generation computer program.

[0024] Specifically, the fertilization capacity information generation method is a method for generating fertilization capacity information that can be used to evaluate the fertilization capacity of sperm, and includes a short-axis image detection step for detecting a short-axis image consisting of two substantially parallel lines or one band-shaped line extending in the short-axis direction of the head in a sperm head image obtained by capturing an image of at least the head of the sperm; a fertilization capacity information generation step for generating fertilization capacity information that serves as an indicator for evaluating fertilization capacity based on the detection result of the short-axis image obtained in the short-axis image detection step; and a storage and output step for saving or outputting the fertilization capacity information generated in the fertilization capacity information generation step.

[0025] Also, in these cases, in the fertilization ability information generation method, further include a feature detection step of detecting at least one of the number, size, shape, and movement pattern of sperm based on the sperm head image, and the fertilization ability information generation step may generate fertilization ability information when the appearance feature satisfies a predetermined condition. According to these fertilization ability information generation methods, the same operational effects as those of the above fertilization ability information generation system can be expected.

[0026] Also, the fertilization ability information generation computer program is a fertilization ability information generation computer program that can be used to evaluate the fertilization ability of sperm, and causes a computer device to execute a short-axis line image detection step of detecting a short-axis line image composed of two substantially parallel lines or one strip line extending in the short-axis direction of the head with respect to the sperm head image obtained by imaging at least the head of the sperm, a fertilization ability information generation step of generating fertilization ability information based on the detection result of the short-axis line image in the short-axis line image detection step, and a storage / output step of storing or outputting the fertilization ability information generated in the fertilization ability information generation step.

[0027] In this case, in the fertilization ability information generation computer program, the fertilization ability information generation step may generate the degree of fertilization ability as fertilization ability information based on the presence or absence of detection of the short-axis line image.

[0028] Also, in these cases, in the fertilization ability information generation computer program, further cause the computer device to execute a feature detection step of detecting at least one of the number, size, shape, and movement pattern of sperm based on the sperm head image, and the fertilization ability information generation step may generate fertilization ability information when the appearance feature satisfies a predetermined condition. According to these fertilization ability information generation computer programs, the same operational effects as those of the above fertilization ability information generation system can be expected.

Brief Description of the Drawings

[0029] [Figure 1]This is a schematic block diagram showing the overall configuration of a fertilization ability information generation system according to one embodiment of the present invention. [Figure 2] Figures (A) and (B) schematically show the external structure of human sperm, with (A) being a top view of the sperm and (B) being a side view of the sperm. [Figure 3] (A) and (B) show images of stained human sperm captured through an optical microscope (1000x magnification). (A) is a magnified portion of the sperm image, and (B) is a magnified portion of the image of one sperm within the dashed frame (B) shown in (A). [Figure 4] This flowchart shows the processing flow of the computer program that generates fertilization potential information, which is executed by the image processing device. [Figure 5] This flowchart shows the processing flow of the short-axis image detection subprogram executed by the image processing device. [Figure 6] Figures (A) and (B) simulate the process of defining a reference line for a sperm head image. Figure (A) is a schematic diagram of a binarized sperm head image, and Figure (B) is a schematic diagram showing the state in which the centroid and reference line have been set for the binarized sperm head image. [Figure 7] Figures (A), (B), and (C) simulate the process of detecting a short-axis image on a sperm head image. (A) is a schematic diagram of a grayscale image of a sperm head, (B) is a schematic diagram of a sperm head edge image obtained by performing edge processing on the grayscale image of a sperm head, resulting in the appearance of a short-axis image and a noise image, respectively. (C) is a schematic diagram of a reference line superimposed on the sperm head edge image. [Figure 8] This is a schematic diagram of a sperm head edge image showing a short-axis image and a noise image, respectively, of a single band-like line. [Modes for carrying out the invention]

[0030] Hereinafter, an embodiment of the fertilization capacity information generation system, fertilization capacity information generation method, and fertilization capacity information generation computer program according to the present invention will be described with reference to the drawings. Figure 1 is a schematic block diagram showing the overall configuration of the fertilization capacity information generation system 100 according to the present invention. Figure 2 is a schematic plan view showing the external structure of human sperm.

[0031] This fertilization ability information generation system 100 is a device that generates fertilization ability information representing the fertilization ability of human sperm 90 to an egg (not shown). Here, the external structure of sperm 90 will be briefly described. As shown in Figures 2(A) and (B), sperm 90 mainly consist of a head 91, a midpiece 92, and a tail 93.

[0032] The head portion 91 is the part that enters the egg and fertilizes it. In a plan view, it is formed in a roughly oval shape (see Figure 2(A)), and in a side view, it becomes thinner and pointed from the posterior end portion 91a, to which the middle portion 92 is connected, towards the apical end portion 91b, which is the front end in the direction of sperm 90's movement (see Figure 2(B)), and is formed in a wedge shape overall.

[0033] The midpiece portion 92 contains mitochondria that supply energy to move the tail portion 93, and is formed as a single thread-like extension between the head portion 91 and the tail portion 93. The tail portion 93 is the part in which the sperm 90 moves to swim toward the egg, and is formed as a single thread-like extension in the opposite direction from the head portion 91 to the midpiece portion 92.

[0034] (Configuration of the fertilization capacity information generation system 100) This fertilization ability information generation system 100 is mainly composed of an imaging device 101 and an image processing device 120, respectively.

[0035] The imaging device 101 is a device that generates an image of at least the head 91 of a sperm 90 and outputs it to the image processing device 120. The imaging device 101 mainly consists of a microscope unit 102 and an imaging unit 110.

[0036] The microscope unit 102 is an optical instrument that allows for magnified viewing of sperm 90 and guides the magnified image to the imaging unit 110. Since this microscope unit 102 is a known optical microscope, a detailed explanation will be omitted, but it is mainly composed of a mirror stand 103 which forms the frame, and a stage 104, objective lens 107, eyepiece lens 108, and illumination unit 109, respectively.

[0037] Stage 104 is a platform on which a slide 105 containing sperm-containing liquid W as a sample is detachably placed, and it moves up and down by rotating the handle 106.

[0038] Here, sperm-containing liquid W is a liquid containing human sperm 90, specifically semen, but it also includes liquids obtained by mixing semen with other liquids (e.g., physiological saline) or liquids obtained by taking sperm 90 from semen and mixing it with some other liquid (e.g., physiological saline).

[0039] The objective lens 107 is an optical lens positioned opposite the stage 104 and used to observe the sperm-containing liquid W on the slide 105 placed on the stage 104. In this embodiment, the objective lens 107 is a dry objective lens that allows observation of the sperm-containing liquid W through air. The objective lens 107 is also configured as a lens with a magnification of 100x.

[0040] The eyepiece 108 is an optical lens through which the user looks to observe the sperm-containing fluid W on the slide 105 placed on the stage 104, and is located above the objective lens 107. In this embodiment, the eyepiece 108 is composed of a lens with a magnification of 10x. Therefore, the total magnification of the microscope unit 102 is set to 1000x.

[0041] The illumination unit 109 is an optical component that illuminates the slide 105 placed on the stage 104 from below and guides the illumination light to the objective lens 107. It is composed of a light source that emits illumination light and a capacitor that focuses the illumination light.

[0042] The imaging unit 110 is an optical instrument for generating sperm head images 200 by capturing an image of the sperm-containing liquid W on a slide 105 placed on a stage 104 via an objective lens 107. Here, the sperm head image 200 is an image of at least the head 91 of the sperm 90, as shown in Figures 3(A) and (B), respectively. In this embodiment, since there are multiple sperm 90 in the sperm-containing liquid W on the slide 105, the imaging unit 110 generates a sperm imaging image 201 that captures all or some of these sperm 90, including the entire body of each sperm 90.

[0043] In this case, the imaging unit 110 captures the entire sperm 90, including the head 91, at a magnification of 1000x using the objective lens 107 and an imaging lens adapter (10x magnification) (not shown) to capture the sperm head image 200 and the sperm imaging image 201. It should be noted that in the sperm imaging image 201, it is possible that a portion of the sperm 90 may be missing from the image at the edges.

[0044] In this embodiment, the imaging unit 110 is configured using a CCD (Charge Coupled Device) image sensor that generates captured image information, which is captured color image information. However, it is sufficient for the imaging unit 110 to generate an image of sperm 90 in the sperm-containing liquid W, and other image sensors besides a CCD image sensor may be used, such as a CMOS (Complementary Metal Oxide Semiconductor) image sensor. The imaging unit 110 may also generate a sperm head image 200 or sperm image 201, which is a grayscale image instead of a color image.

[0045] In other words, in this embodiment, the imaging unit 110 is composed of a so-called digital camera. This imaging unit 110 is electrically connected to the image processing device 120 in order to output the generated image, which is the sperm image 201, to the image processing device 120.

[0046] The image processing device 120 is a computer device that generates fertilization ability information representing the fertilization ability of sperm 90 captured in the sperm imaging image 201 generated by the imaging unit 110. This image processing device 120 is composed of a microcomputer consisting of a CPU, ROM, RAM, hard disk, etc., and generates fertilization ability information by executing a fertilization ability information generation computer program that is pre-stored in the RAM.

[0047] Furthermore, the image processing device 120 is equipped with an input device 121 consisting of a keyboard and a mouse, and generates fertility information according to instructions from the user. The image processing device 120 is also equipped with a display device 122 consisting of a liquid crystal display, which displays the operating status of the image processing device 120, the sperm head image 200 generated by the imaging unit 110, and the fertility information based on this sperm head image 200. In other words, in this embodiment, the image processing device 120 is composed of a personal computer (so-called PC). The microcomputer constituting this image processing device 120 functions as a storage unit 123, a short-axis image detection unit 124, and a fertility information generation unit 125, respectively.

[0048] The memory unit 123 is a part that stores sperm imaging image 201, sperm head image 200, sperm head binarized image 202, sperm head grayscale image 203, sperm head edge image 204, short axis image 210, reference line RL, and fertilization potential information, and is composed of readable and writeable volatile memory.

[0049] The short-axis image detection unit 124 detects the short-axis image 210 from the sperm imaging image 201 generated by the imaging unit 110. Here, the short-axis image 210 is two linear or one band-shaped image that may appear along the short axis direction of the head 91, which is approximately elliptical in shape, in the sperm head image 200, as shown in Figure 7(B) or Figure 8, respectively. This short-axis image 210 is thought to be formed when some structure (hereinafter referred to as "short-axis structure 94") exists on or inside the head 91 of the sperm 90 along the short axis direction of the head 91, and this short-axis structure 94 is captured and forms an image when it matches the imaging conditions of the imaging unit 110. Here, the short axis direction of the head 91 is the direction perpendicular to the long axis of the head 91, which is approximately elliptical.

[0050] Although the inventors of this application have no definitive proof, this short-axis structure 94 is the equatorial region of the sperm 90, and the short-axis image 210 may be an image of this equatorial region. Here, the equatorial region is a band-shaped portion that extends in an annular manner around the head 91 of the sperm 90, located at the boundary between the protoacrosome and the posterior acrosome (also called the "posterior acrosome region"), and is also called the "posterior acrosome" or "acrosome equatorial region." In two-dimensional images such as the sperm head image 200, this equatorial region may be captured as two substantially parallel lines or a single band-shaped image extending along the short axis direction of the head 91.

[0051] The fertilization capacity information generation unit 125 generates fertilization capacity information using the short-axis image 210 detected by the short-axis image detection unit 124. The process for generating this fertilization capacity information will be described later.

[0052] (Operation of the fertilization capacity information generation system 100) The operation of the fertilization capacity information generation system 100 configured as described above will now be explained. First, the user of the fertilization capacity information generation system 100 prepares a sperm imaging image 201 including a sperm head image 200. Specifically, the user places a slide 105 containing sperm-containing liquid W, which includes the sperm 90 of the subject whose fertilization capacity is to be evaluated, on the stage 104.

[0053] In this case, the sperm-containing liquid W contains multiple sperm 90, and these sperm 90 may be alive and motile (swimming sperm 90), but it is preferable to fix them in a state where their movement is stopped using a chemical such as methanol. Furthermore, the fixed sperm 90 may be used as is without staining the head 91, but they may be stained with a staining solution to improve the accuracy of identifying the sperm head image 200 representing the head 91 or the detection accuracy of the short-axis image 210. The user may or may not know the exact number of sperm 90 contained in the sperm-containing liquid W.

[0054] Furthermore, the sperm-containing liquid W may be used either as is or in the fixed state, after removing immobile sperm 90 during or after collection from the subject. In addition, the sperm-containing liquid W may be used either as is or in the fixed state, with only sperm 90 that meet various conditions such as predetermined motility or forward velocity being used.

[0055] Next, the user operates the microscope unit 102 and the imaging unit 110 of the imaging device 101, respectively, to acquire a sperm imaging image 201, which is a color image of the sperm 90 in the sperm-containing liquid W on the slide 105. In this embodiment, the user acquires a sperm imaging image 201 at a magnification of 1000x. In this case, as shown in Figure 3(A), the sperm imaging image 201 contains multiple sperm 90, and each sperm 90 has a corresponding image. That is, as shown in Figure 3(B), the sperm imaging image 201 contains a sperm head image 200 for each sperm 90 captured in the sperm imaging image 201.

[0056] Figure 3(A) shows a further enlarged portion of a sperm image 201 taken in a fixed state with the head 91 of the sperm 90 stained. Figure 3(B) shows an enlarged image of one sperm 90 within the dashed frame (B) in Figure 3(A). Users may generate sperm images 201 by performing the imaging work themselves, or they may receive sperm images 201 generated by another person (for example, the subject who provided the sperm 90 or a person requested by this subject).

[0057] Next, the user turns on the power to the image processing device 120 and connects it to the imaging unit 110 of the imaging device 101, and operates the input device 121 and the imaging unit 110 respectively to read the sperm imaging image 201 stored in the imaging unit 110 and store a copy of it in the storage unit 123 of the image processing device 120.

[0058] Next, the user instructs the image processing device 120 to generate fertility information for the sperm image 201 captured by the image processing device 120. Specifically, the user operates the input device 121 to instruct the image processing device 120 to execute a fertility information generation computer program that generates fertility information. In response to this instruction, the image processing device 120 starts executing the fertility information generation computer program shown in Figure 4 in step S100, and performs sperm head image identification processing in step S102.

[0059] This sperm head image identification process is a process of identifying an image representing the head 91 of a sperm 90, i.e., a sperm head image 200, from a sperm image 201 captured by the image processing device 120. This sperm head image identification process can be realized by known image extraction processes. For example, the image processing device 120 stores a shape close to the shape of the head 91 of a sperm 90 (for example, an ellipse) as a reference shape (not shown), and identifies an image portion from the sperm image 201 that matches the reference shape or a close image portion that falls within a predetermined error as the sperm head image 200. In Figure 3(B), for convenience, the sperm head image 200 is shown with a dashed line to clarify the identified sperm head image 200.

[0060] In other words, the image processing device 120 can identify sperm head images 200 from sperm imaging images 201 by shape (ellipse) fitting processing. In this case, ideally the image processing device 120 should be able to identify images representing all the heads 91 contained in one sperm imaging image 201 as sperm head images 200, but it is not necessary to identify images representing all the heads 91 as sperm head images 200 as long as it can identify at least a sufficient number of sperm head images 200 for evaluating fertilization ability. Therefore, the image processing device 120 may identify as sperm head images 200 only a portion (preferably 100 or more) of all the heads 91 contained in one or more sperm imaging images 201 prepared for evaluating fertilization ability.

[0061] Furthermore, the image processing device 120 can store, in addition to or instead of the shape of the head 91 of the sperm 90, a shape close to the shape of the midpiece 92 or tail 93 of the sperm 90 (for example, a straight shape or a curved shape) as a reference shape, and can identify from the sperm imaging image 201 an image portion that matches these reference shapes or an image portion that is close within a predetermined error, and identify it as a sperm head image 200, including the image portion of the head 91 adjacent to these image portions.

[0062] Furthermore, in addition to or instead of processing by the image processing device 120, the user can also directly specify or teach the image portion representing the sperm head image 200, which is the sperm head image 200, from the sperm image 201 by operating an input device 121 such as a mouse, allowing the image processing device 120 to identify the sperm head image 200.

[0063] Next, in step S104, the image processing device 120 performs a short-axis image detection process. This short-axis image detection process detects a short-axis image 210 for each sperm head 91 included in the sperm head image 200, and is performed by executing the short-axis image detection subprogram shown in Figure 5.

[0064] Specifically, the image processing device 120 starts the execution of the short-axis image detection subprogram in step S200 and performs a reference axis setting process in step S202. This reference axis setting process is the process of setting a reference line RL for each sperm head image 200, which serves as a criterion for detecting the short-axis image 210 for each sperm head image 200 representing the head 91 of the sperm 90. In this embodiment, the image processing device 120 sets the long axis of the head 91, which is formed in a substantially elliptical shape in the sperm 90, as the reference line RL. This reference axis setting process is performed by executing the following substeps 1 to 3.

[0065] Substep 1: First, as shown in Figure 6(A), the image processing device 120 creates a copy of the sperm head image 200 identified by the sperm head image identification process, and then performs a known binarization process such as "Otsu's binarization method" on the sperm head image 200 related to this copy data to generate a sperm head binarized image 202 composed of binarized images (monochrome images). Note that in Figure 6(A), the sperm head binarized image 202 is shown filled in gray instead of black for convenience.

[0066] Substep 2: Next, as shown in Figure 6(B), the image processing device 120 defines the first principal component axis, which passes through the centroid O in the binarized sperm head image 202 and through the portion where the variance with respect to the centroid O is maximum, as the reference line RL, i.e., the long axis of the head 91 which is approximately elliptical in shape, using a known method such as principal component analysis (PCA). In Figures 6(A) and (B), the upper side of the illustration is the tip 91b side of the head 91 of the sperm 90, and the lower side of the illustration is the posterior end 91a side of the head 91 (the same applies to Figures 7 and 8).

[0067] Substep 3: Next, the image processing device 120 stores the reference line RL defined in substep 2 in the storage unit 123, associating it with the sperm head image 200, which is the source data for the sperm head binarized image 202.

[0068] Next, in step S204, the image processing device 120 performs a short-axis image detection process. This short-axis image detection process is a process of detecting a short-axis image 210 for the head 91 of each sperm 90 included in the sperm head image 200, and is performed by executing the following substeps 1 to 3.

[0069] Substep 1: First, as shown in Figure 7(A), the image processing device 120 generates a sperm head grayscale image 203 by converting the sperm head image 200, which defines the reference line RL set in the reference axis setting process, into grayscale data. Specifically, the image processing device 120 creates a copy of the sperm head image 200 that defines the reference line RL, and performs grayscale processing on the sperm head image 200 related to this copy data, converting the image data into grayscale values ​​in a 256-level grayscale from 0 (white) to 255 (black). Then, the image processing device 120 stores the generated sperm head grayscale image 203 in the storage unit 123 in association with the sperm head image 200.

[0070] Substep 2: Next, the image processing device 120 performs edge detection processing on the sperm head gray image 203 generated in substep 1, as shown in Figure 7(B). This edge detection processing removes the portion representing the contour of the head 91 in the sperm head image 200 representing the head 91 of the sperm 90, and performs edge detection on the portion inside the contour of the head 91. If the sperm head image 200 contains a short-axis image 210 (i.e., if the short-axis structure 94 is captured in the head 91), this process is performed to make the short-axis image 210 visible.

[0071] Specifically, the image processing device 120 performs edge detection processing on the sperm head grayscale image 203 using a known edge detection image processing method such as the Canny edge detection method to generate a sperm head edge image 204 composed of a binarized image (monochrome image). In this case, if the sperm head image 200 contains a short-axis image 210, the short-axis image 210 will appear in the sperm head edge image 204. The image processing device 120 then stores the generated sperm head edge image 204 in the storage unit 123, associating it with the sperm head image 200, which is the original data of the sperm head grayscale image 203.

[0072] In the sperm head edge image 204 shown in Figure 7(B), two curved short-axis images 210 appear within the dotted circle, and noise images 205, resulting from the structure of the part of the head 91 inside the contour, also appear around these two short-axis images 210. Furthermore, in the sperm head edge image 204 shown in Figure 7(B), the short-axis images 210 and noise images 205 would normally appear in white, with the areas surrounding them appearing in black. However, for the sake of labeling, the short-axis images 210 and noise images 205 are shown in black, with the areas surrounding them appearing in white.

[0073] Substep 3: Next, the image processing device 120 determines whether or not there is a short-axis image 210 in the sperm head image 200. Specifically, as shown in Figure 7(C), the image processing device 120 combines the reference line RL set in the reference axis setting process with the sperm head edge image 204 generated in substep 2 and determines whether or not there are two linear images or one band-shaped image extending for a predetermined length (e.g., number of pixels) in a direction perpendicular to this reference line RL. In this case, the predetermined length is set appropriately according to the sperm donor (subject) or the characteristics of the sperm 90, the resolution of the sperm head edge image 204, or the specifications for evaluating fertility.

[0074] Therefore, the image processing device 120 determines that "short-axis image 210 is present" if it detects two linear or one band-shaped image extending for a predetermined length in a direction perpendicular to the reference line RL in the sperm head edge image 204, while determining that "short-axis image 210 is absent" if it does not detect two linear or one band-shaped image, and stores this determination result in the storage unit 123 in association with the sperm head image 200.

[0075] Then, in step S206, the image processing device 120 finishes executing the short-axis image detection subprogram and returns to the fertility information generation computer program. This short-axis image detection subprogram is executed for all sperm head images 200 identified in the sperm head image identification process in step S102 of the fertility information generation computer program. The process of detecting this short-axis image 210 corresponds to the short-axis image detection step according to the present invention, and the image processing device 120 that performs the process of detecting this short-axis image 210 corresponds to the short-axis image detection unit according to the present invention.

[0076] Next, in step S106, the image processing device 120 generates fertilization potential information. Specifically, the image processing device 120 calculates a short-axis image detection rate, which is the ratio of the number of sperm head images 200 that were determined to have a short-axis image 210 in the short-axis image detection process in step S204 of the short-axis image detection subprogram to the total number of sperm head images 200 identified in the sperm head image identification process in step S102.

[0077] The image processing device 120 then stores the calculated short-axis image detection rate in the storage unit 123 as fertilization ability information in the original data, the sperm head image 200. The process of generating this fertilization ability information corresponds to the fertilization ability information generation step according to the present invention, and the image processing device 120 that performs the process of generating this fertilization ability information corresponds to the fertilization ability information generation unit according to the present invention. Furthermore, the storage unit 123 that stores the fertilization ability information corresponds to the storage output means according to the present invention.

[0078] Next, in step S108, the image processing device 120 displays the fertility information generated in step S106 on the display device 122. This allows the user to evaluate the fertility of the subject. In other words, the display device 122 that displays the fertility information externally corresponds to the storage output means according to the present invention. Then, in step S110, the image processing device 120 terminates the execution of the fertility information generation computer program.

[0079] In this case, the inventors' experiments have confirmed that when the short-axis image detection rate, which is the ratio of sperm head images 200 in which a short-axis image 210 was detected, is 2.3% or higher, the fertilization rate is approximately 56% when the short-axis image detection rate is 3.6% or higher, the fertilization rate is approximately 70.3% when the short-axis image detection rate is 3.6% or higher, and the fertilization rate is 73.3% when the short-axis image detection rate is 5.9% or higher. Therefore, users can evaluate the fertilization ability of a subject by checking the short-axis image detection rate based on the above experimental results.

[0080] As can be understood from the operation described above, according to the above embodiment, the fertilization ability information generation system 100 stores or outputs fertilization ability information generated based on the detection result of the short axis image 210 by the short axis image detection unit 124. Therefore, the user can improve the accuracy of evaluating the fertilization ability of sperm 90 by using this fertilization ability information.

[0081] Furthermore, the present invention is not limited to the embodiments described above, and various modifications are possible as long as they do not depart from the purpose of the present invention. In the modified examples shown below, components similar to those in the embodiments described above are denoted by corresponding reference numerals, and their descriptions are omitted.

[0082] For example, in the above embodiment, the fertility information generation system 100 is configured to include an imaging device 101. However, if sperm head images 200 or sperm imaging images 201 can be prepared separately, the fertility information generation system 100 can be configured with only an image processing device 120 (storage unit 123, short-axis image detection unit 124, and fertility information generation unit 125) by omitting the imaging device 101.

[0083] Furthermore, in the above embodiment, the fertilization capacity information generation system 100 was set to 1000x for both the magnification viewed by the user with the microscope unit 102 and the magnification captured by the imaging unit 110. However, the fertilization capacity information generation system 100 only needs to be able to detect the short-axis structure 94 or the short-axis image 210 from the sperm head image 200. Here, according to the inventor's experiments, the magnification captured by the imaging unit 110 should be set to at least 500x, preferably 800x, and more preferably 1000x. Also, the magnification viewed by the user with the microscope unit 102 should be set to at least 800x, and preferably 1000x.

[0084] Furthermore, in the above embodiment, the fertilization capacity information generation system 100 is configured to include a microscope unit 102 in the imaging unit 110 to obtain an enlarged image of the head 91 of the sperm 90 in the sperm-containing liquid W. However, the fertilization capacity information generation system 100 only needs to be able to detect the short-axis image 210 from the sperm head image 200. Therefore, the fertilization capacity information generation system 100 can be configured without the microscope unit 102 if it has an imaging unit 110 that can acquire an enlarged image or has sufficient resolution to detect the short-axis image 210 from the sperm head image 200 through image processing.

[0085] Furthermore, in the above embodiment, the fertilization capacity information generation system 100 is configured with an optical microscope for its microscope unit 102 in order to obtain a magnified image of the head 91 of the sperm 90 in the sperm-containing liquid W. This is because, according to the inventors' experiments, a highly accurate short-axis image 210 can be obtained with simpler operation compared to imaging the sperm 90 through an electron microscope. In this case, according to the inventors' experiments, the objective lens of the optical microscope has a deeper depth of field (in other words, lower resolution), such as a dry objective lens that observes through air rather than liquid, rather than an immersion objective lens that observes through liquid such as oil or water, which allows for more accurate acquisition of the short-axis image 210. However, since the microscope unit 102 only needs to obtain a magnified image of the head 91 of the sperm 90 in the sperm-containing liquid W, various microscopes or magnifiers such as an optical microscope or electron microscope equipped with an immersion objective lens can be used.

[0086] Furthermore, in the above embodiment, the image processing device 120 and the fertility information generation computer program are configured to identify the sperm head image 200, which is the image portion of the head 91, from the sperm imaging image 201, which is an image of the entire sperm 90, by the sperm head image identification process in step S102. However, if the sperm head image 200, which is the image portion of the head 91 of the sperm 90, is prepared in advance, or if the sperm head image 200 is identified in advance in the sperm imaging image 201, the sperm head image identification process in step S102 can be omitted.

[0087] Furthermore, in the above embodiment, the image processing device 120 (short-axis image detection unit 124) and the short-axis image detection subprogram detected two curved images as the short-axis image 210 in the short-axis image detection process in step S204. However, the short-axis structure 94 in the head 91 of the sperm 90 may appear as a single band-like line in addition to two substantially parallel lines, as shown in Figure 8. Therefore, the image processing device 120 (short-axis image detection unit 124) and the short-axis image detection subprogram can detect a single band-like image as the short-axis image 210 in place of or in addition to the two linear images. In this case, the width of the band-like line is appropriately set according to the detection accuracy of the short-axis image 210.

[0088] Furthermore, in the above embodiment, the image processing device 120 (fertilization capacity information generation unit 125) and the fertilization capacity information generation computer program calculated the short-axis image detection rate, which is the ratio of the number of sperm head images 200 to the total number of sperm head images 200, in the fertilization capacity information generation process in step 106, and used this as fertilization capacity information. However, fertilization capacity information is information that directly or indirectly represents the presence or absence of detection of short-axis images 210, the number (including the ratio) of detected short-axis images 210, or the detected short-axis images 210. Information that indirectly represents the detected short-axis images 210 or the detection results of short-axis images 210 can be used as an index (reference information) for evaluating fertilization capacity, which is generated by image processing, analysis processing, or statistical processing.

[0089] Therefore, the image processing device 120 (fertilization capacity information generation unit 125) and the fertilization capacity information generation computer program can construct fertilization capacity information by replacing the value of the short-axis image detection rate (number) with a different number, character, figure, symbol, word, or sentence, depending on the value or degree of the short-axis image detection rate. In this case, the fertilization capacity information can be composed of numbers, characters, figures, symbols, words, or sentences corresponding to whether the short-axis image detection rate is 2.3% or higher, 3.6% or higher, or 5.9% or higher, and whether or not this threshold is met or not. In other words, in this case, the image processing device 120 (fertilization capacity information generation unit 125) and the fertilization capacity information generation computer program can generate information indicating that the short-axis image detection rate is at least 2.3% or higher, or that the degree of fertilization capacity is high, as fertilization capacity information.

[0090] Furthermore, fertilization ability information can also be represented by images that distinguish between sperm 90 in which the short-axis image 210 was detected and sperm 90 in which the short-axis image 210 was not detected (for example, by color, size, or flashing), or by graphs that show the number or percentage of images of sperm 90 in which the short-axis image 210 was detected. In addition, fertilization ability information may include evaluation information of fertilization ability based on indicators for evaluating fertilization ability (for example, an evaluation of whether fertilization ability is "present" or "absent," as well as a degree such as "high" or "low").

[0091] Furthermore, in the above embodiment, the image processing device 120 and the fertility information generation computer program are configured to generate fertility information for all sperm head images 200 identified by the sperm head image identification process in step S102, through the short-axis image detection process in step S104 and the fertility information generation process in step S106. However, the image processing device 120 and the fertility information generation computer program can also be configured not to perform the short-axis image detection process and / or the fertility information generation process for some or all of the sperm head images 200 identified by the sperm head image identification process in step S102.

[0092] Specifically, the image processing device 120 and the fertility information generation computer program may be configured to include a feature detection unit 126 that detects external features of the sperm head image 200, including at least one of the number, size, shape, and movement pattern of the sperm 90 (e.g., a predetermined motility rate or forward rate), and to execute short-axis image detection processing and / or fertility information generation processing only when these external features satisfy predetermined conditions. According to this, the fertility information generation system 100 can improve the accuracy of evaluating the fertility of the sperm 90 by generating fertility information that takes external features into account.

[0093] Furthermore, in the above embodiment, the image processing device 120 and the fertility information generation computer program are configured to generate fertility information using a plurality of sperm head images 200. However, the image processing device 120 and the fertility information generation computer program can also generate fertility information using at least one sperm head image 200. This is because, according to the inventors' experiments, the fertilization rate is approximately 56% when the proportion of sperm head images 200 in which a short-axis image 210 is detected is 2.3% or more. Therefore, if a short-axis image 210 can be detected for the sperm head image 200 of at least one sperm 90 randomly collected from a subject, it can be said that the subject may have the necessary fertility. Accordingly, the image processing device 120 or the fertility information generation computer program can also be configured to generate fertility information using the sperm head image 200 of at least one sperm 90 collected from a subject.

[0094] Furthermore, in the above embodiment, the image processing device 120 or the fertility information generation computer program is configured to store fertility information in the storage unit 123 and display it on the display device 122. That is, the storage unit 123 and the display device 122 correspond to the storage output means according to the present invention, and the process of storing fertility information in the storage unit 123 or displaying it on the display device 122 corresponds to the storage output step according to the present invention. However, the image processing device 120 or the fertility information generation computer program only needs to perform at least one of storing fertility information in the storage unit 123 and displaying it on the display device 122. Also, the image processing device 120 or the fertility information generation computer program can be configured to store or display information via a communication line to a storage device or display device that is physically separated from the image processing device 120. In addition, the storage unit 123 may be a portable storage device such as a so-called USB memory that is physically detachable from the image processing device 120. [Explanation of symbols]

[0095] W...Sperm-containing fluid, O...Centricular center of the head binarized image, RL...Reference line 90...Sperm, 91...Sperm head, 91a...Back end, 91b...Tip, 92...Medium piece, 93...Tail, 94...Short axis structure, 100... Fertilization potential information generation system, 101... Imaging device, 102... Microscope unit, 103... Microscope stand, 104... Stage, 105... Slide, 106... Handle, 107... Objective lens, 108... Eyepiece, 109... Illumination unit, 110... Imaging unit, 120...Image processing device, 121...Input device, 122...Display device, 123...Storage unit, 124...Short axis image detection unit, 125...Fertilization ability information generation unit, 126...Feature detection unit, 200...Sperm head image, 201...Sperm imaging image, 202...Sperm head binarized image, 203...Sperm head grayscale image, 204...Sperm head edge image, 205...Noise image, 210...Short-axis image.

Claims

1. A fertilization ability information generation system that generates fertilization ability information that can be used to evaluate the fertilization ability of sperm, A short-axis image detection unit detects a short-axis image consisting of two substantially parallel lines or one band-shaped line extending in the short-axis direction of the sperm head, with respect to a sperm head image obtained by capturing an image of at least the head of the sperm. A fertilization ability information generation unit generates fertilization ability information based on the detection result of the short-axis image by the short-axis image detection unit, A fertilization ability information generation system characterized by comprising storage and output means for storing or outputting the fertilization ability information generated by the fertilization ability information generation unit.

2. In the fertilization ability information generation system described in claim 1, The fertilization ability information generation unit is, A fertilization ability information generation system characterized by generating the degree of fertilization ability as fertilization ability information based on whether or not the short-axis image is detected.

3. In the fertilization ability information generation system described in claim 2, The aforementioned short-axis image detection unit is The method involves detecting the short-axis image for each of the sperm head images corresponding to each of the multiple sperm, The fertilization ability information generation unit is, A fertilization ability information generation system characterized by generating the number or ratio of the sperm head images in which the short-axis image is detected relative to the total number of sperm head images corresponding to each of the plurality of sperm as fertilization ability information.

4. In the fertilization ability information generation system described in claim 3, The fertilization ability information generation unit is, A fertilization ability information generation system characterized in that, when the ratio of the number of sperm head images in which the short axis image is detected to the total number of sperm head images corresponding to each of the plurality of sperm is 2.3% or more, it generates information indicating that the sperm have a high degree of fertilization ability or to that effect as fertilization ability information.

5. In the fertilization ability information generation system described in claim 1, further, The system includes a feature detection unit that detects external features, including at least one of the number, size, shape, and movement pattern of the sperm, based on the sperm head image. The fertilization ability information generation unit is, A fertilization ability information generation system characterized by generating fertilization ability information when the aforementioned external characteristics satisfy predetermined conditions.

6. In the fertilization ability information generation system described in claim 1, further, A fertilization ability information generation system characterized by comprising an imaging unit that captures an image of at least the head of the sperm.

7. In the fertilization ability information generation system described in claim 1, The aforementioned sperm head image is A system for generating fertilization potential information, characterized by being imaged via an optical microscope.

8. A method for generating fertilization ability information that can be used to evaluate the fertilization ability of sperm, A short-axis image detection step involves detecting a short-axis image consisting of two substantially parallel lines or one band-shaped line extending in the short-axis direction of the sperm head, with respect to a sperm head image obtained by capturing an image of at least the head of the sperm. A fertilization ability information generation step generates fertilization ability information that serves as an indicator for evaluating fertilization ability based on the detection results of the short-axis image obtained by the short-axis image detection step, A method for generating fertilization ability information, characterized by including a save / output step for saving or outputting the fertilization ability information generated in the fertilization ability information generation step.

9. In the method for generating fertilization ability information described in claim 8, further, The feature detection step includes detecting external features, including at least one of the number, size, shape, and movement pattern of the sperm, based on the sperm head image. The fertilization ability information generation step is, A method for generating fertilization ability information, characterized in that the fertilization ability information is generated when the aforementioned external characteristics satisfy predetermined conditions.

10. A computer program for generating fertilization ability information that can be used to evaluate the fertilization ability of sperm, In a computer device, A short-axis image detection step involves detecting a short-axis image consisting of two substantially parallel lines or one band-shaped line extending in the short-axis direction of the sperm head, with respect to a sperm head image obtained by capturing an image of at least the head of the sperm. A fertilization ability information generation step that generates fertilization ability information based on the detection result of the short-axis image obtained in the short-axis image detection step, A computer program for generating fertilization ability information, characterized by causing the program to execute a save / output step for saving or outputting the fertilization ability information generated in the fertilization ability information generation step.

11. In the fertilization ability information generation computer program described in claim 10, The fertilization ability information generation step is, A computer program for generating fertilization ability information, characterized by generating the degree of fertilization ability as fertilization ability information based on whether or not the short-axis image is detected.

12. In the fertilization ability information generation computer program described in claim 10, further, The aforementioned computer device, This involves performing a feature detection step to detect external features, including at least one of the number, size, shape, and movement pattern of the sperm, based on the sperm head image. The fertilization ability information generation step is, A computer program for generating fertilization ability information, characterized in that it generates fertilization ability information when the aforementioned external characteristics satisfy predetermined conditions.

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