CN107092854B - Device and method for detecting Human Papilloma Virus (HPV) infection of cells - Google Patents
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Abstract
The invention relates to a method for detecting whether a cell is infected by a virus, which comprises the following steps: (a) capturing a cell outline of the image of the cell, the cell outline having outline pixels; (b) identifying a tangent line of the contour pixel on the cell contour to define a first side of the tangent line and a second side opposite to the first side, wherein the first side indicates an extracellular region of the cell and the second side indicates an intracellular region of the cell; (c) calculating the average value of the optical parameters of a plurality of pixels on the first side and the second side respectively; and (d) determining whether the cell is infected with the virus based on whether the average value of the optical parameter at the first side is less than the average value of the optical parameter at the second side.
Description
Technical Field
The invention relates to a device and a method for detecting Human Papilloma Virus (HPV) infection of cells, in particular to a device and a method for detecting whether cells are infected by Human Papilloma Virus (HPV) by using an image analysis technology.
Background
Human Papillomavirus (HPV) is a DNA virus of the genus papillomavirus of the family of papillomaviruses. The virus mainly infects epidermis and mucous membrane tissues of human body. At present, about 170 types of HPV are identified, some types of HPV will cause warts or cancers after invading human body, but others have no symptoms.
HPV viruses cause infections in humans and animals, primarily in epithelial cells and tissue linings of the host. The tissue type of infection can be divided into a skin type and a mucous membrane type: 1. the epidermis type mainly causes epithelial infection of hands and feet; 2. mucosal type causes infections of the mouth, throat, respiratory tract and genito-urinary tract. HPV causes the generation of skin warts of hands and feet (such as flat warts, convex warts, skin warts and the like), the mechanism of the HPV mainly causes skin keratinization hyperplasia, usually, the affected part is naturally relieved after one to five years, but partial infected faces also cause skin cancer, and some of the face also cause oral squamous cell carcinoma.
There are approximately 30 to 40 types of HPV transmission behaviors to the genitals and peripheral skin, and some of them cause genital warts. If some high-risk HPV types without wart and other symptoms are repeatedly infected, the HPV types can be possibly developed into precancerous lesion and even invasive cancer. Infection with HPV is one of the main causes of cervical cancer, and its infection pathway is generally caused by sexual behavior, whereas vertical infection via the mother is also one of the pathways causing HPV infection. Through research, 99.7% of cervical cancer is caused by HPV infection.
The conventional detection method for human papilloma virus infection of cells comprises early cytology examination, thin-layer cytology examination and the like, belongs to the traditional manual identification mode, and has the problems of accuracy, timeliness and the like. Recently, DNA detection methods such as in situ hybridization reaction, HPV DNA direct detection, amplified hybridization reaction, HPV mRNA detection and microarray analysis (micro array) have been developed due to the breakthrough of DNA technology. Molecular diagnostic techniques are currently used mostly for detection of HPV, but most of them are costly and relatively expensive, and although the us FDA has approved the use of the Cobas HPVTest of the Roche pharmaceutical factory as the first-line screening tool in 4 months 2014, the first-line screening tool accepted as a legal recommendation by the society of cancer and the like has not appeared in the us at any age group. Furthermore, although HPV Test was approved as the first line screening tool in 2015 in some regions, australia is not recommended as much. Therefore, the scientific community still returns the HPV detection method to image cytology detection and uses manual interpretation, but still has the problem that whether the cell is infected by HPV cannot be judged quickly and accurately.
In addition, the screening of the uterine cervix smear is to perform examination and judgment one by a pathologist through manpower, and to perform symptom feature selection and classification. However, the amplification speed of the pathologist is far from the growth amount of the smear to be detected, so that the overhigh workload becomes one of the worries of influencing the accuracy rate of identifying the cervical smear. It can be seen that digital pathological screening and diagnosis equipment is needed to provide a digital screening and diagnosis function for HPV infected cells (such as cervical smears), and assist pathologists in performing feature analysis and identification comparison, so as to shorten the screening time of smears and maintain accuracy and reliability.
In view of the shortcomings in the prior art, the applicant has devised the present invention through careful experiments and studies and without intending to be bound by any theory, which can overcome the shortcomings in the prior art, and the following is a brief description of the present invention.
Disclosure of Invention
In order to more quickly, accurately and reliably judge whether the cells are infected by the HPV virus, the invention provides a method for directly judging whether the cells are infected by the HPV virus by using a digital pathological screening diagnostic device, so that the manual resolution smear screening time is shortened, and the accuracy and reliability of the detection are maintained.
Accordingly, the present invention provides an apparatus for detecting whether a cell is infected with Human Papillomavirus (HPV), the apparatus comprising: a color conversion unit for converting the cell image into an HSV image by converting each pixel in the cell image from red, green, and blue (RGB) color coordinates into Hue, Saturation, and lightness Value (Hue, Value, HSV) color coordinates; a cell contour capturing unit for capturing a cell contour of the cell from the HSV image; the contour pixel point capturing unit is used for selecting at least one contour pixel point from the cell contour; an identification unit for identifying a tangent line of at least one contour pixel on a cell contour to define a first side of the tangent line and a second side opposite to the first side, wherein the first side indicates an extracellular region of the cell and the second side indicates an intracellular region of the cell; a calculating unit for calculating a brightness average value or a hue average value of a plurality of pixels on the first side and the second side, respectively; and a judging unit for judging that the cell is infected with HPV when the brightness average value of the first side is less than the brightness average value of the second side or the hue average value of the first side is greater than the hue average value of the second side, and judging that the cell is not infected with HPV when the brightness average value of the first side is greater than or equal to the brightness average value of the second side or the hue average value of the first side is less than or equal to the hue average value of the second side.
The invention also provides a method for detecting whether a cell is infected by a virus, which comprises the following steps: (a) capturing a cell outline of the image of the cell and selecting at least one outline pixel point from the cell outline; (b) identifying a tangent line of at least one contour pixel on the cell contour to define a first side of the tangent line and a second side opposite to the first side, wherein the first side indicates an extracellular region of the cell and the second side indicates an intracellular region of the cell; (c) calculating the brightness average value or the hue average value of a plurality of pixels on the first side and the second side respectively; and (d) determining that the cell is infected with the virus when the mean value of the lightness of the first side is less than the mean value of the lightness of the second side or the mean value of the hue of the first side is greater than the mean value of the hue of the second side, and determining that the cell is not infected with the virus when the mean value of the lightness of the first side is greater than or equal to the mean value of the lightness of the second side or the mean value of the hue of the first side is less than or equal to the mean value of the hue of the.
The invention also provides a method for detecting whether a cell is infected by a virus, which comprises the following steps: (a) capturing a cell outline of the image of the cell, the cell outline having outline pixels; (b) identifying a tangent line of the contour pixel on the cell contour to define a first side of the tangent line and a second side opposite to the first side, wherein the first side indicates an extracellular region of the cell and the second side indicates an intracellular region of the cell; (c) calculating the average value of the optical parameters of a plurality of pixels on the first side and the second side respectively; and (d) determining whether the cell is infected with the virus based on whether the average value of the optical parameter at the first side is less than the average value of the optical parameter at the second side.
In order to make the present invention more comprehensible, embodiments accompanying with the drawings are described in detail below, but not to limit the scope of the embodiments.
Drawings
FIG. 1 is a schematic diagram of a system for detecting whether a cell is infected with Human Papillomavirus (HPV) according to the invention;
FIG. 2 is a schematic diagram of a method of detecting whether a cell is infected with Human Papillomavirus (HPV) according to the invention;
FIG. 3 is two 5 x 5 matrices in the Sobel operator of the present invention;
FIG. 4 shows 8 directions identified by the artificial neural network of the present invention;
FIG. 5 is a schematic diagram illustrating the method of using an artificial neural network to identify the tangential direction of contour pixels on the cell edge contour according to the present invention;
FIG. 6 is a schematic diagram of calculating the average brightness value or the average hue value of pixels on both sides of a tangent line according to the present invention.
Detailed Description
The detailed features and advantages of the present invention are described in detail in the following embodiments, which are sufficient for anyone skilled in the art to understand the technical content of the present invention and to implement the present invention, and the related objects and advantages of the present invention can be easily understood by anyone skilled in the art from the disclosure of the present specification, the claims and the accompanying drawings. The following examples further illustrate aspects of the invention in detail, but are not intended to limit the scope of the invention in any way.
In various embodiments of the present invention, a method and apparatus for detecting whether a cell is infected with HPV are provided. The invention uses the detection system to capture the feature of cell morphological variation, calculates the lightness average value or hue average value of the cell interior and the cell exterior, and then judges whether the cell is infected by HPV according to the lightness average value or hue average value of two sides.
Please refer to FIG. 1 and FIG. 2, which are schematic diagrams of the detection system and method for detecting whether cells are infected by Human Papillomavirus (HPV) according to the present invention, respectively. The inspection system 100 of the present invention includes a cell image capturing device 110 and an image inspecting device 120, wherein the image inspecting device 120 includes a color conversion unit 121, a cell contour capturing unit 122, a contour pixel capturing unit 123, an identification unit 124, a calculation unit 125 and a determination unit 126.
The cell image capturing device 110 is used to capture a processed cell sample (step 201 in fig. 2), and the captured cell sample image has only one cell. In one embodiment, the cell sample may be a cervical smear or other cell sample, and the cell image capture device 110 may be a photomicrograph device. After the cell sample is sampled, the cell sample is processed by a generally known conventional method, and the processed cell sample is photographed by a photomicrograph device to obtain a cell image of a single cell.
The color conversion unit 121 then converts the red, green and blue (RGB) color coordinates of each pixel in the cell image of the single cell into Hue, Saturation and lightness values (Hue, Value, HSV) (step 202 of fig. 2) to obtain HSV images, and retains the Hue Value or lightness Value of each pixel.
After obtaining the HSV image, the cell contour capturing unit 122 performs edge detection on the cytoplasm by using Sobel operator (Sobel operator), and captures the cell contour by using a thinning method (step 203 of fig. 2), wherein the cell contour is a cell edge contour. In one embodiment, the HSV image is edge-detected with two 5 × 5 matrices (X-axis and Y-axis, respectively, as shown in fig. 3) in sobel operator.
The contour pixel capture unit 123 obtains N contour pixels on the identified cell edge contour (step 204 of fig. 2). In one embodiment, N is 1-100, preferably 10-100, and the greater the value of N, the greater the accuracy. In another embodiment, as shown in fig. 5, the contour pixel capture unit 123 takes 20 contour pixels 502 on the cell edge contour 504, and each contour pixel is spaced from the cell edge contour.
The recognition unit 124 takes the N contour pixels as the center point to obtain a square matrix (step 205 of fig. 2). In one embodiment, the square matrix is equal to or larger than 5 × 5, preferably 7 × 7. The identification unit 124 then utilizes an Artificial Neural Network (ANN) to identify the direction of the center point (i.e. the tangential direction of the center point on the cell edge contour) (step 206 of fig. 2). The artificial neural network is a training parameter obtained by training edge images of various forms, taking a 7 × 7 matrix as an example, each training takes 49 pixels in the 7 × 7 matrix as input values, and a direction value of a central point of the 7 × 7 matrix is predefined as an output value of the artificial neural network. 49 pixels in the matrix are used as input values of the neural network, and after calculation of the artificial neural network, one of 8 directions (as shown in fig. 4) is output, wherein the 8 directions are 0 °, 22.5 °, 45 °, 67.5 °, 90 °, 112.5 °, 135 °, and 157.5 °. In another embodiment, as shown in FIG. 5, the contour pixel 502 on the cell image 501 is a 7 × 7 matrix 503, and after being identified by the artificial neural network, the tangent 505 of the contour pixel 502 on the cell edge contour 504 is 135 ° (direction 7).
After identifying the tangent 505 of the contour pixel 502 on the cell edge contour 504, the identification unit 124 identifies the left or right of the tangent 505 as being inside or outside the cell, and selects M pixels on both sides of the tangent (step 207 of fig. 2). In one embodiment, as shown in fig. 6, the identification unit 124 takes M pixels perpendicular to the tangent 505 and passing through two sides of the contour pixel 502, i.e. an intra-cell pixel 601 and an extra-cell pixel 602. The number of M depends on the resolution of the cell image capturing device 110, and M may be any positive integer. Preferably, M is 1000-3000. The number of M may be user defined.
The calculating unit 125 calculates the average value of the optical parameters of the M pixels inside the cell (step 208 of fig. 2) and the average value of the optical parameters of the M pixels outside the cell (step 209 of fig. 2). Wherein the optical parameter includes hue and/or brightness.
The determining unit 126 determines whether the cell is infected with HPV according to the hue average value and/or brightness average value of the pixels inside and outside the cell (step 210 in FIG. 2) (step 211 in FIG. 2). Wherein when the extracellular lightness average value is less than the intracellular lightness average value or the extracellular hue average value is greater than the intracellular hue average value, the cell is judged to be infected with HPV, and when the extracellular lightness average value is greater than or equal to the intracellular lightness average value or the extracellular hue average value is less than or equal to the intracellular hue average value, the cell is judged not to be infected with HPV.
Examples
1. An apparatus for detecting whether a cell is infected with Human Papilloma Virus (HPV), the apparatus comprising:
a color conversion unit for converting a cell image into an HSV image by converting each pixel in the cell image from red, green and blue (RGB) color coordinates to Hue, Saturation and lightness (HSV) color coordinates;
a cell contour capturing unit for capturing a cell contour of the cell from the HSV image;
a contour pixel point capturing unit for selecting at least one contour pixel point from the cell contour;
an identification unit for identifying a tangent line of the at least one contour pixel on the cell contour to define a first side of the tangent line and a second side opposite to the first side, wherein the first side indicates the extracellular region of the cell and the second side indicates the intracellular region of the cell;
a calculating unit for calculating the brightness average value or the hue average value of a plurality of pixels on the first side and the second side respectively; and
a judging unit for judging that the cell is infected by HPV when the brightness average value of the first side is less than the brightness average value of the second side or the hue average value of the first side is greater than the hue average value of the second side, and judging that the cell is not infected by HPV when the brightness average value of the first side is greater than or equal to the brightness average value of the second side or the hue average value of the first side is less than or equal to the hue average value of the second side.
2. The apparatus of embodiment 1, wherein the cell image is an image of a single cell, and the single cell and the cell are the same cell.
3. The apparatus of embodiment 1, wherein the cell contour capturing unit detects the cell in the image by a sobel operator (Sobeloperator), and captures the cell contour by a thinning algorithm.
4. The apparatus of embodiment 1, wherein the calculating unit calculates a brightness average or a hue average of a plurality of pixels of a straight line perpendicular to the tangent line and passing through the center point.
5. A method of detecting whether a cell is infected with a virus, the method comprising:
(a) capturing a cell contour of an image of the cell and selecting at least one contour pixel point from the cell contour;
(b) identifying a tangent line of the at least one contour pixel on the cell contour to define a first side of the tangent line and a second side opposite to the first side, wherein the first side indicates the extracellular region of the cell and the second side indicates the intracellular region of the cell;
(c) calculating the brightness average value or the hue average value of a plurality of pixels on the first side and the second side respectively; and
(d) when the average value of the lightness of the first side is less than the average value of the lightness of the second side or the average value of the hue of the first side is greater than the average value of the hue of the second side, the cell is judged to be infected by the virus, and when the average value of the lightness of the first side is greater than or equal to the average value of the lightness of the second side or the average value of the hue of the first side is less than or equal to the average value of the hue of the second side, the cell is judged not to be infected by the virus.
6. The method of embodiment 5, wherein the virus is Human Papilloma Virus (HPV) and the cell image is captured by photomicrography.
7. The method of embodiment 5 wherein each pixel in the captured image of the cell is converted from red, green and blue (RGB) color coordinates to Hue, Saturation and lightness (Hue, Value, HSV) color coordinates into an HSV image with the cell outline.
8. The method of embodiment 5, wherein the step (a) further comprises:
(a1) detecting the cell contour in the cell image by using respective X-axis and Y-axis 5 × 5 matrixes of a Sobel operator (Sobel operator); and
(a2) the cell contour is captured using a fine-line algorithm.
9. The method of embodiment 5, wherein step (a) selects a plurality of contour pixels, the contour pixels being spaced apart from each other.
10. The method of embodiment 5, wherein the cut is identified using an Artificial Neural Network (ANN).
11. The method of embodiment 5, wherein the step (c) comprises calculating the average brightness or the average hue of a plurality of pixels of a straight line perpendicular to the tangent line and passing through the center point.
12. A method of detecting whether a cell is infected with a virus, the method comprising:
(a) capturing a cell contour of an image of the cell, the cell contour having a contour pixel;
(b) identifying a tangent line of the contour pixel on the cell contour to define a first side of the tangent line and a second side opposite to the first side, wherein the first side indicates the extracellular region of the cell and the second side indicates the intracellular region of the cell;
(c) calculating an average value of optical parameters of a plurality of pixels on the first side and the second side; and
(d) and judging whether the cell is infected by the virus according to whether the average value of the optical parameters of the first side is smaller than that of the second side.
13. The method of embodiment 12, wherein the average optical parameter comprises at least one of a brightness average and a hue average, and the cell is determined to be infected by the virus when the brightness average of the first side is less than the brightness average of the second side or the hue average of the first side is greater than the hue average of the second side, and the cell is determined to be not infected by the virus when the brightness average of the first side is greater than or equal to the brightness average of the second side or the hue average of the first side is less than or equal to the hue average of the second side.
The invention belongs to a difficult innovation, has high industrial value and is applied by law. Furthermore, the invention may be modified in any way by a person skilled in the art, without departing from the scope of protection as claimed in the appended claims.
[ notation ] to show
100 detection system
110 cell image capture device
120 image detection device
121 color conversion unit
122 cell contour capture unit
123 contour pixel point capturing unit
124 identification cell
125 computing unit
126 judging unit
S201-S211 steps
501 cell image
502 outline pixel point
5037 × 7 matrix
504 cell edge contour
505 tangent line
601 intracellular pixel points
602 extracellular pixel
Claims (13)
1. An apparatus for detecting whether a cell is infected with Human Papilloma Virus (HPV), the apparatus comprising:
a color conversion unit for converting a cell image into a hue, saturation and lightness value (HSV) image by converting each pixel in the cell image from red, green and blue (RGB) color coordinates into HSV color coordinates;
a cell contour capturing unit for capturing a cell contour of the cell from the HSV image;
a contour pixel point capturing unit for selecting at least one contour pixel point from the cell contour;
an identification unit for identifying a tangent line of the at least one contour pixel on the cell contour to define a first side of the tangent line and a second side opposite to the first side, wherein the first side indicates the extracellular region of the cell and the second side indicates the intracellular region of the cell;
a calculating unit for calculating the brightness average value or the hue average value of a plurality of pixels on the first side and the second side respectively; and
a judging unit for judging that the cell is infected by HPV when the brightness average value of the first side is less than the brightness average value of the second side or the hue average value of the first side is greater than the hue average value of the second side, and judging that the cell is not infected by HPV when the brightness average value of the first side is greater than or equal to the brightness average value of the second side or the hue average value of the first side is less than or equal to the hue average value of the second side.
2. The apparatus of claim 1, wherein the image of the cell is an image of a single cell, and the single cell and the cell are the same cell.
3. The apparatus of claim 1, wherein the cell contour capturing unit detects the cell in the image by a sobel operator and captures the cell contour by a thinning algorithm.
4. The apparatus of claim 1, wherein the computing unit computes the average of brightness or the average of hue of pixels of a line perpendicular to the tangent line and passing through the at least one contour pixel.
5. A method of detecting whether a cell is infected with a virus, the method comprising:
(a) capturing a cell contour of an image of the cell and selecting at least one contour pixel point from the cell contour;
(b) identifying a tangent line of the at least one contour pixel on the cell contour to define a first side of the tangent line and a second side opposite to the first side, wherein the first side indicates the extracellular region of the cell and the second side indicates the intracellular region of the cell;
(c) calculating the brightness average value or the hue average value of a plurality of pixels on the first side and the second side respectively; and
(d) when the average value of the lightness of the first side is less than the average value of the lightness of the second side or the average value of the hue of the first side is greater than the average value of the hue of the second side, the cell is judged to be infected by the virus, and when the average value of the lightness of the first side is greater than or equal to the average value of the lightness of the second side or the average value of the hue of the first side is less than or equal to the average value of the hue of the second side, the cell is judged not to be infected by the virus.
6. The method of claim 5, wherein the virus is Human Papilloma Virus (HPV) and the cell image is captured by photomicrography.
7. The method of claim 5, wherein each pixel in the captured image of the cell is converted from red, green and blue (RGB) color coordinates to hue, saturation and lightness values (HSV) color coordinates into an HSV image with the cell outline.
8. The method of claim 5, wherein the step (a) further comprises:
(a1) detecting the cell contour in the cell image by utilizing respective X-axis and Y-axis 5X 5 matrixes of a Sobel operator; and
(a2) the cell contour is captured using a fine-line algorithm.
9. The method of claim 5, wherein the step (a) selects a plurality of contour pixels, and the contour pixels are spaced apart from each other.
10. The method of claim 5, wherein the tangent is identified using an Artificial Neural Network (ANN).
11. The method of claim 5, wherein the step (c) is performed by calculating a brightness average or a hue average of pixels of a straight line perpendicular to the tangent line and passing through the center point.
12. A method of detecting whether a cell is infected with a virus, the method comprising:
(a) capturing a cell contour of an image of the cell, the cell contour having a contour pixel;
(b) identifying a tangent line of the contour pixel on the cell contour to define a first side of the tangent line and a second side opposite to the first side, wherein the first side indicates the extracellular region of the cell and the second side indicates the intracellular region of the cell;
(c) calculating an average value of optical parameters of a plurality of pixels on the first side and the second side; and
(d) and judging whether the cell is infected by the virus according to whether the average value of the optical parameters of the first side is smaller than that of the second side.
13. The method of claim 12, wherein the average optical parameter comprises at least one of a brightness average and a hue average, and the cell is determined to be infected by the virus when the brightness average of the first side is less than the brightness average of the second side or the hue average of the first side is greater than the hue average of the second side, and the cell is determined not to be infected by the virus when the brightness average of the first side is greater than or equal to the brightness average of the second side or the hue average of the first side is less than or equal to the hue average of the second side.
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| CN111539354B (en) * | 2020-04-27 | 2020-12-15 | 易普森智慧健康科技（深圳）有限公司 | Liquid-based cytology slide scanning area identification method |
| CN116883323A (en) * | 2023-06-16 | 2023-10-13 | 中国医学科学院肿瘤医院 | Multiple immunofluorescence image analysis system based on computer vision |
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