CN111882561A - Cancer cell identification and diagnosis system - Google Patents
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Abstract
Description
技术领域technical field
本发明涉及细胞图像识别技术领域,具体为一种癌细胞识别诊断系统。The invention relates to the technical field of cell image recognition, in particular to a cancer cell recognition and diagnosis system.
背景技术Background technique
癌症是危害人类身体健康的常见疾病,癌症的早期诊断是治疗的关键。采用细胞学计算机辅助诊断技术,可以有效地降低医生的工作强度以及提高诊断的准确性。由于细胞图像背景复杂、细胞形态多样及重叠等问题,使得计算机检测识别难度较大。本发明对典型医学图像分割算法做出了新的技术改良,针对不重叠细胞图像及重叠细胞图像分别给出了改进算法。Cancer is a common disease that endangers human health, and early diagnosis of cancer is the key to treatment. The use of cytology computer-aided diagnosis technology can effectively reduce the work intensity of doctors and improve the accuracy of diagnosis. Due to the complex background of cell images, diverse cell shapes and overlapping problems, it is difficult to detect and identify by computer. The present invention makes new technical improvements to the typical medical image segmentation algorithm, and provides improved algorithms for non-overlapping cell images and overlapping cell images respectively.
发明内容SUMMARY OF THE INVENTION
本发明的目的是针对现有技术中存在的不足,而提供一种癌细胞识别诊断系统。这种诊断系统,可实现目标区域更精准地提取,对细胞图像进行更高效、准确地定量分析和检测识别。The purpose of the present invention is to provide a system for identifying and diagnosing cancer cells in view of the deficiencies in the prior art. This diagnostic system can achieve more accurate extraction of target areas, and perform more efficient and accurate quantitative analysis, detection and identification of cell images.
实现本发明目的的技术方案是:The technical scheme that realizes the object of the present invention is:
一种癌细胞识别诊断系统,包括,A cancer cell identification diagnostic system comprising,
细胞图像预处理模块:首先将细胞图片转化为数字图像并对其进行灰度化处理。为了更加准确的提取图像中有用细胞特征,需要将图像中小,离散正常细胞以及加性噪声一起去除。针对这一情况采用改进开闭滤波算法进行图像去噪,选取结构元素B为正常淋巴细胞的两倍。针对小于结构元素B的噪声,运用开运算消除背景中胡椒状噪声,然后利用闭运算消除砂眼噪声。针对大于结构元素B的噪声,首先将滤波的图像二值化,并对原图像进行叠加提取。图像二值化是将原图像转化为二值图像,“0”代表目标图像,“1”代表背景,用该二值图像对原图像的内容进行选择,二值图像中值为“0”的像素位置均保留原灰度值,值为“1”的像素位置灰度值为“255”。Cell image preprocessing module: First, convert the cell image into a digital image and perform grayscale processing on it. In order to more accurately extract useful cell features in the image, it is necessary to remove small, discrete normal cells and additive noise in the image together. In view of this situation, an improved open-close filter algorithm is used to denoise the image, and the structural element B is selected to be twice that of normal lymphocytes. For the noise smaller than the structuring element B, the open operation is used to eliminate the pepper noise in the background, and then the closed operation is used to eliminate the trachoma noise. For the noise larger than the structural element B, the filtered image is first binarized, and the original image is superimposed and extracted. Image binarization is to convert the original image into a binary image, "0" represents the target image, "1" represents the background, and the binary image is used to select the content of the original image. The value in the binary image is "0". The pixel position retains the original gray value, and the gray value of the pixel position with a value of "1" is "255".
细胞图像分割模块:Cell Image Segmentation Module:
第一步:提取细胞核区域采取自动种子点的区域生长算法,将阈值分割和区域生长算法联合。首先设定阈值T=115,将图像分割成大于阈值T的对象点和小于阈值T的背景点两部分。原图像f(x,y)转化为输出图像g(x,y),当f(x,y)>T,g(x,y)=1;当f(x,y)≤T,g(x,y)=0。此法实现了“粗轮廓”提取细胞核的大部分区域。设置种子的生长规则为相邻像素点灰度值与种子区域平均灰度值的差的绝对值小于阈值0.15.以粗轮廓的质心作为种子的生长点,每个种子按生长规则迭代生长,差值小于阈值的加入种子,直到找不到满足规则的点就结束生长。此法实现了“细轮廓”提取细胞核。最后采用Sobel算子做边缘检测,Sobel算子的模板及对应公式如下:The first step: extracting the nucleus region adopts the region growing algorithm of automatic seed points, and combines the threshold segmentation and the region growing algorithm. First, the threshold value T=115 is set, and the image is divided into two parts: the object points larger than the threshold value T and the background points smaller than the threshold value T. The original image f(x,y) is converted into the output image g(x,y), when f(x,y)>T, g(x,y)=1; when f(x,y)≤T, g( x, y)=0. This method achieves "coarse outline" extraction of most regions of the nucleus. Set the growth rule of seeds as the absolute value of the difference between the gray value of adjacent pixels and the average gray value of the seed area is less than the threshold value of 0.15. The centroid of the thick outline is used as the growth point of the seed, and each seed grows iteratively according to the growth rule. Seeds with a value less than the threshold are added until no point that satisfies the rule is found, and the growth ends. This method achieves "fine contour" extraction of cell nuclei. Finally, the Sobel operator is used for edge detection. The template and corresponding formula of the Sobel operator are as follows:
最后输出图像。The final output image.
第二步:提取单个细胞体区域采取标记符控制的分水岭算法。为了方便确定内外标记,结合细胞显微镜图像背景量,目标暗的特点,先对细胞灰度图像做反相处理,得到目标物体较亮、背景区域较暗的图像。将图像进行二值化处理,将二值图像进行距离变化,使得分界线能保住目标物体而又不会过于接近物体边缘。最后采用分水岭变换,得到的分界线作为外部标记。将反处理的图像做基于重建的开操作和闭操作,去除目标内部细节并对局部极大值区域作为内部标记。结合内外标记,将反处理后的图像计算梯度幅值,在改进后的梯度图像上进行分水岭变换,在细胞灰度图像上显示细胞体分割轮廓。The second step: extracting a single cell body region adopts a marker-controlled watershed algorithm. In order to facilitate the determination of internal and external markers, combined with the background volume of the cell microscope image and the characteristics of the dark target, the grayscale image of the cell was first inverted to obtain an image with a brighter target object and a darker background area. The image is binarized, and the distance of the binary image is changed, so that the dividing line can keep the target object without being too close to the edge of the object. Finally, a watershed transformation is used, and the obtained dividing line is used as an external marker. Reconstruction-based opening and closing operations are performed on the inversely processed image to remove the internal details of the target and use the local maximum area as an internal marker. Combined with the inner and outer markers, the gradient magnitude is calculated from the inversely processed image, and the watershed transformation is performed on the improved gradient image, and the cell body segmentation contour is displayed on the cell grayscale image.
第三步:提取叠层的细胞图像中的细胞轮廓采用了基于snake模型的分割算法。针对snake模型对初始位置敏感的特点,采用细胞的稀疏轮廓点模型,利用环形动态轮廓搜索算法,自动定位出主体细胞的轮廓点,之后利用snake模型方法进行分割,经过曲线对细胞体边缘的拟合,最终获得细胞体轮廓。其分割精度约为94%,过分割率约为2.5%,欠分割率约3.5%。Step 3: Extract the cell contours in the stacked cell images using a segmentation algorithm based on the snake model. In view of the characteristic that the snake model is sensitive to the initial position, the sparse contour point model of the cell is used, and the circular dynamic contour search algorithm is used to automatically locate the contour points of the main cell. Finally, the outline of the cell body is obtained. Its segmentation accuracy is about 94%, the over-segmentation rate is about 2.5%, and the under-segmentation rate is about 3.5%.
癌细胞图像特征提取模块:计算分割后每个区域的核质比,细胞核大小是否均匀,核染色异常以及核间距是否均匀。Cancer cell image feature extraction module: Calculate the nuclear-to-cytoplasmic ratio of each region after segmentation, whether the size of the nucleus is uniform, whether the nuclear staining is abnormal, and whether the nuclear spacing is uniform.
核质比:对于不叠层的细胞图像,通过segment子程序将图像分为一个分块一个单细胞,调用ncratio子程序计算出每个细胞的核质比。当该细胞的核质比远超于正常细胞核质比0.5:1时,判定疑似癌细胞。对于叠层的细胞图像,调用segment子程序,将图像分区,计算整个区域的核质比,当其比值远超于正常细胞核质比0.5:1时,可判定疑似癌细胞。Nucleocytoplasmic ratio: For non-overlapping cell images, the segment subroutine divides the image into a block and a single cell, and calls the ncratio subroutine to calculate the nucleocytoplasmic ratio of each cell. When the nucleocytoplasmic ratio of the cell is much higher than the normal cell nucleocytoplasmic ratio of 0.5:1, it is determined to be a suspected cancer cell. For the stacked cell images, the segment subroutine is called, the image is divided into sections, and the nuclear-cytoplasmic ratio of the entire area is calculated. When the ratio is much higher than the normal cell nuclear-cytoplasmic ratio of 0.5:1, a suspected cancer cell can be determined.
细胞核大小:将分割后得到的图像通过segment分块处理,将得到的单个细胞核大小。若细胞核大小分布比较分散,则符合癌细胞特征。Nucleus size: The image obtained after segmentation is processed into segments to obtain the size of a single nucleus. If the nuclear size distribution is relatively scattered, it is consistent with the characteristics of cancer cells.
核染色体异常:通过计算核深染面积与细胞核面积的比值,若占比大于31.91%,可以判定疑似癌细胞。Nuclear chromosome abnormality: By calculating the ratio of nuclear hyperchromatic area to nuclear area, if the proportion is greater than 31.91%, it can be determined as a suspected cancer cell.
成团细胞相邻核间距:通过调用distant计算成团细胞相邻核间距,若成团细胞细胞核分布不均匀,可以判定疑似癌细胞。The distance between adjacent nuclei of agglomerated cells: Calculate the distance between adjacent nuclei of agglomerated cells by calling distance. If the nuclei of agglomerated cells are not uniformly distributed, a suspected cancer cell can be determined.
细胞图像分类识别模块:采用BP神经网络识别技术识别癌细胞。首先初始化网络的权值和阈值。网络权值的初始值即为网络从误差曲面的哪一点开始训练,该点影响网络的训练时间。开始向前计算,求出所有神经元的所有输出。计算输出层误差梯度。然后向后计算各隐层误差梯度,计算并保存各权值修正量,修正权值。判断是否达到训练目标。如达到,训练结束,达不到则转入向前计算。Cell image classification and recognition module: using BP neural network recognition technology to identify cancer cells. First initialize the weights and thresholds of the network. The initial value of the network weight is the point at which the network starts to train on the error surface, which affects the training time of the network. Start computing forward, finding all outputs of all neurons. Calculate the output layer error gradient. Then calculate the error gradient of each hidden layer backward, calculate and save the correction amount of each weight, and correct the weight. Determine whether the training goal is achieved. If it is reached, the training is over. If it is not reached, it will be transferred to the forward calculation.
附图说明Description of drawings
图1为实施例的结构示意图。FIG. 1 is a schematic structural diagram of an embodiment.
图2为实施例中提取细胞核区域的流程示意图。FIG. 2 is a schematic flow chart of extracting the nucleus region in the embodiment.
图3为实施例中BP神经网络识别算法的流程示意图FIG. 3 is a schematic flowchart of the BP neural network identification algorithm in the embodiment
具体实施方式Detailed ways
下面结合附图及具体实施例对本发明作进一步的详细描述,但不是对本发明的限定The present invention will be described in further detail below in conjunction with the accompanying drawings and specific embodiments, but it is not intended to limit the present invention.
实施例:Example:
参照图1,一种癌细胞识别诊断系统,包括,Referring to Figure 1, a cancer cell identification and diagnosis system includes,
细胞图像预处理模块:Cell image preprocessing module:
首先将细胞图片转化为数字图像并对其进行灰度化处理。为了更加准确的提取图像中有用细胞特征,需要将图像中小,离散正常细胞以及加性噪声一起去除。针对这一情况采用改进开闭滤波算法进行图像去噪,选取结构元素B为正常淋巴细胞的两倍。针对小于结构元素B的噪声,运用开运算消除背景中胡椒状噪声,然后利用闭运算消除砂眼噪声。针对大于结构元素B的噪声,首先将滤波的图像二值化,并对原图像进行叠加提取。图像二值化是将原图像转化为二值图像,“0”代表目标图像,“1”代表背景,用该二值图像对原图像的内容进行选择,二值图像中值为“0”的像素位置均保留原灰度值,值为“1”的像素位置灰度值为“255”。如图2所示,细胞图像分割模块:The cell pictures are first converted into digital images and grayscaled. In order to more accurately extract useful cell features in the image, it is necessary to remove small, discrete normal cells and additive noise in the image together. In view of this situation, an improved open-close filter algorithm is used to denoise the image, and the structural element B is selected to be twice that of normal lymphocytes. For the noise smaller than the structuring element B, the open operation is used to eliminate the pepper noise in the background, and then the closed operation is used to eliminate the trachoma noise. For the noise larger than the structural element B, the filtered image is first binarized, and the original image is superimposed and extracted. Image binarization is to convert the original image into a binary image, "0" represents the target image, "1" represents the background, and the binary image is used to select the content of the original image. The value in the binary image is "0". The pixel position retains the original gray value, and the gray value of the pixel position with a value of "1" is "255". As shown in Figure 2, the cell image segmentation module:
第一步:提取细胞核区域采取自动种子点的区域生长算法,将阈值分割和区域生长算法联合。首先设定阈值T=115,将图像分割成大于阈值T的对象点和小于阈值T的背景点两部分。原图像f(x,y)转化为输出图像g(x,y),当f(x,y)>T,g(x,y)=1;当f(x,y)≤T,g(x,y)=0。此法实现了“粗轮廓”提取细胞核的大部分区域。设置种子的生长规则为相邻像素点灰度值与种子区域平均灰度值的差的绝对值小于阈值0.15.以粗轮廓的质心作为种子的生长点,每个种子按生长规则迭代生长,差值小于阈值的加入种子,直到找不到满足规则的点就结束生长。此法实现了“细轮廓”提取细胞核。最后采用Sobel算子做边缘检测,Sobel算子的模板及对应公式如下:The first step: extracting the nucleus region adopts the region growing algorithm of automatic seed points, and combines the threshold segmentation and the region growing algorithm. First, the threshold value T=115 is set, and the image is divided into two parts: the object points larger than the threshold value T and the background points smaller than the threshold value T. The original image f(x,y) is converted into the output image g(x,y), when f(x,y)>T, g(x,y)=1; when f(x,y)≤T, g( x, y)=0. This method achieves "coarse outline" extraction of most regions of the nucleus. Set the growth rule of seeds as the absolute value of the difference between the gray value of adjacent pixels and the average gray value of the seed area is less than the threshold value of 0.15. The centroid of the thick outline is used as the growth point of the seed, and each seed grows iteratively according to the growth rule. Seeds with a value less than the threshold are added until no point that satisfies the rule is found, and the growth ends. This method achieves "fine contour" extraction of cell nuclei. Finally, the Sobel operator is used for edge detection. The template and corresponding formula of the Sobel operator are as follows:
最后输出图像。The final output image.
第二步:提取单个细胞体区域采取标记符控制的分水岭算法。为了方便确定内外标记,结合细胞显微镜图像背景量,目标暗的特点,先对细胞灰度图像做反相处理,得到目标物体较亮、背景区域较暗的图像。将图像进行二值化处理,将二值图像进行距离变化,使得分界线能保住目标物体而又不会过于接近物体边缘。最后采用分水岭变换,得到的分界线作为外部标记。将反处理的图像做基于重建的开操作和闭操作,去除目标内部细节并对局部极大值区域作为内部标记。结合内外标记,将反处理后的图像计算梯度幅值,在改进后的梯度图像上进行分水岭变换,在细胞灰度图像上显示细胞体分割轮廓。The second step: extracting a single cell body region adopts a marker-controlled watershed algorithm. In order to facilitate the determination of internal and external markers, combined with the background volume of the cell microscope image and the characteristics of the dark target, the grayscale image of the cell was first inverted to obtain an image with a brighter target object and a darker background area. The image is binarized, and the distance of the binary image is changed, so that the dividing line can keep the target object without being too close to the edge of the object. Finally, a watershed transformation is used, and the obtained dividing line is used as an external marker. Reconstruction-based opening and closing operations are performed on the inversely processed image to remove the internal details of the target and use the local maximum area as an internal marker. Combined with the inner and outer markers, the gradient magnitude is calculated from the inversely processed image, and the watershed transformation is performed on the improved gradient image, and the cell body segmentation contour is displayed on the cell grayscale image.
第三步:提取叠层的细胞图像中的细胞轮廓采用了基于snake模型的分割算法。针对snake模型对初始位置敏感的特点,采用细胞的稀疏轮廓点模型,利用环形动态轮廓搜索算法,自动定位出主体细胞的轮廓点,之后利用snake模型方法进行分割,经过曲线对细胞体边缘的拟合,最终获得细胞体轮廓。其分割精度约为94%,过分割率约为2.5%,欠分割率约3.5%。Step 3: Extract the cell contours in the stacked cell images using a segmentation algorithm based on the snake model. In view of the characteristic that the snake model is sensitive to the initial position, the sparse contour point model of the cell is used, and the circular dynamic contour search algorithm is used to automatically locate the contour points of the main cell. Finally, the outline of the cell body is obtained. Its segmentation accuracy is about 94%, the over-segmentation rate is about 2.5%, and the under-segmentation rate is about 3.5%.
癌细胞图像特征提取模块:计算分割后每个区域的核质比,细胞核大小是否均匀,核染色异常以及核间距是否均匀。Cancer cell image feature extraction module: Calculate the nuclear-to-cytoplasmic ratio of each region after segmentation, whether the size of the nucleus is uniform, whether the nuclear staining is abnormal, and whether the nuclear spacing is uniform.
核质比:对于不叠层的细胞图像,通过segment子程序将图像分为一个分块一个单细胞,调用ncratio子程序计算出每个细胞的核质比。当该细胞的核质比远超于正常细胞核质比0.5:1时,判定疑似癌细胞。对于叠层的细胞图像,调用segment子程序,将图像分区,计算整个区域的核质比,当其比值远超于正常细胞核质比0.5:1时,可判定疑似癌细胞。Nucleocytoplasmic ratio: For non-overlapping cell images, the segment subroutine divides the image into a block and a single cell, and calls the ncratio subroutine to calculate the nucleocytoplasmic ratio of each cell. When the nucleocytoplasmic ratio of the cell is much higher than the normal cell nucleocytoplasmic ratio of 0.5:1, it is determined to be a suspected cancer cell. For the stacked cell images, the segment subroutine is called, the image is divided into sections, and the nuclear-cytoplasmic ratio of the entire area is calculated. When the ratio is much higher than the normal cell nuclear-cytoplasmic ratio of 0.5:1, a suspected cancer cell can be determined.
细胞核大小:将分割后得到的图像通过segment分块处理,将得到的单个细胞核大小。若细胞核大小分布比较分散,则符合癌细胞特征。Nucleus size: The image obtained after segmentation is processed into segments to obtain the size of a single nucleus. If the nuclear size distribution is relatively scattered, it is consistent with the characteristics of cancer cells.
核染色体异常:通过计算核深染面积与细胞核面积的比值,若占比大于31.91%,可以判定疑似癌细胞。Nuclear chromosome abnormality: By calculating the ratio of nuclear hyperchromatic area to nuclear area, if the proportion is greater than 31.91%, it can be determined as a suspected cancer cell.
成团细胞相邻核间距:通过调用distant计算成团细胞相邻核间距,若成团细胞细胞核分布不均匀,可以判定疑似癌细胞。The distance between adjacent nuclei of agglomerated cells: Calculate the distance between adjacent nuclei of agglomerated cells by calling distance. If the nuclei of agglomerated cells are not uniformly distributed, a suspected cancer cell can be determined.
如图3所示,细胞图像分类识别模块:采用BP神经网络识别技术识别癌细胞。首先初始化网络的权值和阈值。网络权值的初始值即为网络从误差曲面的哪一点开始训练,该点影响网络的训练时间。开始向前计算,求出所有神经元的所有输出。计算输出层误差梯度。然后向后计算各隐层误差梯度,计算并保存各权值修正量,修正权值。判断是否达到训练目标。如达到,训练结束,达不到则转入向前计算。As shown in Figure 3, cell image classification and recognition module: using BP neural network recognition technology to identify cancer cells. First initialize the weights and thresholds of the network. The initial value of the network weight is the point at which the network starts to train on the error surface, which affects the training time of the network. Start computing forward, finding all outputs of all neurons. Calculate the output layer error gradient. Then calculate the error gradient of each hidden layer backward, calculate and save the correction amount of each weight, and correct the weight. Determine whether the training goal is achieved. If it is reached, the training is over. If it is not reached, it will be transferred to the forward calculation.
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