Improved Integrated Deep Model for Pap-Smear Cell Analysis

Somasundaram DEVARAJ, Nirmala MADIAN, Gnanasaravanan SUBRAMANIAM, Rithaniya CHELLAMUTHU, Muralitharan KRISHANAN

Journal of Systems Science and Information ›› 2024, Vol. 12 ›› Issue (1) : 113-124.

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Journal of Systems Science and Information ›› 2024, Vol. 12 ›› Issue (1) : 113-124. DOI: 10.21078/JSSI-2023-0087
 

Improved Integrated Deep Model for Pap-Smear Cell Analysis

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Abstract

Cervical cancer is the fourth most common malignancy to strike a woman globally. If discovered early enough, it can be effectively treated. Although there is a chance of error owing to human error, the Pap smear is a good tool for first screening for cervical cancer. It also takes a lot of time and effort to complete. The aim of this study was to reduce the possibility of error by automating the process of classifying cervical cancer using Pap smear images. For the purpose of this study, dual convolution neural networks with LSTM were employed to classify images due to deep learning approaches inspire distinct features and powerful classifiers for many computer vision applications. The proposed deep learning model based on convolution neural networks (CNN) with the long short-term memory (LSTM) network is to learn features which give better recognition accuracy. The overall model is known as Smear-net. In which 'smear' indicates 'pap-smear cancer cells' and 'net' refers to neural network. The parameters such as, Accuracy, Precision, Recall, Accuracy, Sensitivity, and Specificity are used to validate the models. The proposed method provides the improved accuracy of 99.57 percentage for classification of the pap-smear cells. The proposed approaches demonstrate the effectiveness of our contributions by testing and comparing with the state-of-the-art techniques.

Key words

pap-smear / deep learning / convolution neural network / smear-net

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Somasundaram DEVARAJ , Nirmala MADIAN , Gnanasaravanan SUBRAMANIAM , Rithaniya CHELLAMUTHU , Muralitharan KRISHANAN. Improved Integrated Deep Model for Pap-Smear Cell Analysis. Journal of Systems Science and Information, 2024, 12(1): 113-124 https://doi.org/10.21078/JSSI-2023-0087

1 Introduction

According to World Health Organization during 2018 about 570000 women diagnosed with cervical cancer and around 311000 women died due to this cancer. Cervical cancer has now become a potential life threatening cancer. The prevention processes of cervical cancer are HIV vaccination and proper screening and treatment of precancerous lesion. One of the primary tools for cervical cancer screening is Papanicolaou (Pap) smear test. The cervical cancer occurs in the cervix region and is analysed using smear cell. Smear cell can be touching or overlapping when viewed through microscope. Many researches on segmentation and separation algorithms are proposed to analyse the overlapping and touching smear cells.
Pap smear cell segmentation is a specialized area in medical image analysis and help in early detection of cancer. There are various advanced computational techniques for identifying cervical cancer. Pap smear is a primary screening procedure for understanding the smear cell from complex microscope. The smear analysis helps in detecting abnormalities with better precision and efficiency. The efficiency is based on the classification accuracy of smear cell. The cervical cancer can be categorized into various classes like normal, precancerous and cervical cancer based on morphological features. Classification accuracy helps in reducing the morbidity and mortality rate of cancer and also leads to early diagnosis of cancer.
In recent years deep learning a subset of artificial intelligence has emerged as a transformative solution in smear cell classification. Deep learning algorithms, particularly convolutional neural networks (CNNs) are recognised for automatically and accurately categorizing cervical cells based on their morphological characteristics. This technological advancement holds immense promise in revolutionizing cervical cancer screening, offering the potential for earlier and more precise identification of abnormalities, including precancerous and cancerous cells. The limitation in classification accuracy is based on selecting the appropriate features.
Pap smear cell has cytoplasm and nucleus. Nucleus segmentation is the process of separating the nucleus region from the papsmear cell. An approach based on the image colour information was proposed which is based on colour characterization. Both single and overlapping cell clusters can be handled using the approach[15]. A fuzzy-based processing of smear cell is presented that reduces the over segmentation problems by detecting the nucleus border using the watershed transformation and classifying the nuclei using markers[68].
A method to segment the nucleus is performed using an active shape model (ASM) and a physical based model. The vibration of a spring mass system is used to represent the shape of the nuclei in the training[913]. A global and local technique for segmenting the cervical cell to separate the cytoplasm region from the background and to represent the overall scheme, a multi-way graph cut technique is adopted[1419]. As a local strategy for dividing up the nucleus region, the local adaptive graph cut is employed and separation is performed based on concave and convex points. The nucleus and cytoplasm region are enhanced using linear contrast enhancement approach while the noise is eliminated using a median filter[2022]. The maximum grey gradient difference approach is used to extract the nucleus contour.
Nucleus and cytoplasm extraction was performed using the snake method called radiating gradient vector flow (RGVF). The effort to categorise the cervical cell as normal or abnormal by the Bayes rule, which is based on two decision criteria[23, 24]. Using the parametric Bhattacharya distance formulation, texture features are retrieved. SVM-based classifier is used to categorise multispectral Pap smear images. For the purpose of distinguishing cytoplasm and nuclei, a system with a dual wavelength technique is used. Segmentation, feature extraction, and smear categorization are the first three steps of the approach. For classification, linear discrimination analysis is utilised[25-28].
The classification of Pap smear cell is based on numerical measurement and can be analysed by data analysis[29-32]. Seven groups or classes are available like squamous cell carcinoma, mild, moderate, and severe non-keratinizing squamous epithelial dysplasia, columnar epithelial dysplasia, and superficial squamous epithelial. Artificial neural networks are used for classifying cervical cells. The features are used to classify the areas of the cytoplasm and nucleus[33-36]. Six characteristics relate to the nucleus, whereas the remaining characteristics relate to the cytoplasm. A mask based regional convolutional neural network (Mask R-CNN) presented for the classification of smear cell classification[37-39]. Still, in less developed nations, their influence on cervical cancer screening has been minimal. Considerable research has been done since the first computers were made in an attempt to replace or augment human visual evaluation of Pap smears with computer-aided analysis. But the issue proved to be trickier than anticipated. The examination of Pap smears with computer assistance has proven to be a challenging procedure. The methodology presented in this study can be used to a wide range of Pap smear analysis systems, but it is especially relevant to low-cost systems that are expected to have a substantial positive impact on emerging countries. The proposed smearnet is outperforming than traditional classification methods.

2 Proposed Method

The proposed model consists of two stages as shown in Figure 1: First, the pre-processing stage for handling illumination variance and other to enhance the edges of each image. Second, the pre-processed input is given separately to the dual CNN layer which learns the spatial features and generate feature maps. Finally, the feature maps obtained from two fully connected layers are fused. Further, the global average pooling (GAP) is used to reduce feature maps and the expression is predicted using SoftMax layer. The layer information of the Smearnet as shown in Table 1.
Figure 1 Overall pap-smear cell classification

Full size|PPT slide

Table 1 Smearnet Architecture
Layer Filter Stride Size
Input 96×96
Conv 1 32 1 5×5
Maxpooling 1 2 3×3
Conv 2 32 1 5×5
Maxpooling 2 2 3×3
Conv 3 64 1 5×5
Maxpooling 3 2 3×3
Conv 4 128 1 5×5
Maxpooling 4 2 3×3
Conv 5 256 1 5×5
Maxpooling 5 2 3×3
FC1 512
FC2 7
Data Pre-Processing: Consider a video-sequence input which is converted into 16 frames per second. Then the smear cell detection is employed to detect smear regions from the successive frames. The detected face is cropped and resized to 96×96-pixel size. The probability density function of the resized image is given as,
P(Gk)=NkN,
(1)
where Gk is the greyscale image, Nk is the number of times the occurrence of Gk, and N is the total pixel. The overall process as shown in the Figure 2. The quality of image is improved with certain pre-processing techniques to learn and classify expression features effectively. The two pre-processing techniques are contrast enhancement technique, edge enhancement technique. Histogram equalization (HE) is one of the commonly used techniques for image contrast enhancement. The HE is simple and effective technique lies in mapping the gray levels based on the probability distribution function of an input. Mainly, HE technique flattens and stretches the gray level input image over the dynamic range which results in over enhancement. In smear image, over enhancement reduces the subtle edge features that results in false classification. For such reason, weighted histogram equalization (WHE) technique is adopted to eliminate illumination effect on smear image with certain thresholding conditions. Compared to other HE methods, WHE has better adaptivity and ease of control. Now the quality of an image is enhanced through certain transformation function T(). Consider the Weighted Histogram Equalization technique (WHE) which is applied over the formulated input and it is given as,
Pw(Gk)=T{P(Gk)},
(2)
Pw(Gk)={Pw^(Gk),P(Gk)>τ1,0,P(Gk)>τ2,
(3)
Figure 2 Proposed Smear-net architecture

Full size|PPT slide

τ1 and τ2 are the upper and lower thresholds which are defined as
τ1βmax{P(Gk)},
(4)
τ2Gk<1,
(5)
where weight function and it takes a value <1 and not zero.
Hence, the WHE based on thresholding can be calculated using the formula:
Pw(Gk)=[(P(Gk)τ2)/(τ1τ2)]τ1 for τ1<ττ2.
(6)
The image is processed with the above function to handle distinct illumination conditions and considered as one of the inputs for CNN. Edge enhancement technique plays a vital role in image classification. Mainly, the convolutional neural network (CNN) classifies the images based on the edge features. In facial expression recognition, edge enhancement technique enriches the latent features which identifies the subtle expression variations. Hence it is essential to improve and preserve edge features to get better expression classification results. The edge enhancement is performed on the same set of video-sequence using distance map and geometric distance map method which are discussed below.

2.1 Distance Map Method

In distance map method, each pixel in the image is labelled with a distance value, which is nearest to the active neighbourhood pixel. Hence the distance between two prominent edge points is calculated using Euclidean distance metric. The mathematical representation of the Euclidean metric is given in an equation (7).
Deuc(p,q)=i=1n(piqi)2.
(7)

2.2 Geometric Distance Map Method

The geometric distance map describes geometric information of a set of pixels in the 3D space image based on the distance calculated between the member pairs using a chamfer distance metric. The computation is between each foreground voxel to the nearest background voxel. The chamfer distance is the average distance between two points M and N and is presented in the following equation:
CD(M,N)=1/pmiMminnjN|minj|,
(8)
where M={mi}, N={nj} and p is the number of points in M. The distance map and geometric distance map techniques are superimposed to get good edge information as resultant image that assists in detecting expressions better.

2.3 Feature Learning

As mentioned in CNN is composed of convolutional layer, MaxPooling layer with an activation function, and a fully connected layer. In the proposed architecture, after each convolutional layer and before maxpooling, batch normalization (BN) and rectified linear unit (ReLU) activation function are added. The function of batch normalization boosts the network to learn the features very effectively during training and reduces overfitting. Mainly, the effective classification is highly subjective to the image features which are associated with an edge and the depth of the network. In this research, two pre-processing techniques are applied for image sequences to preserve edge features and the connectivity of each edge for better classification. If the input of the 2D convolutional layer is I(x,y), and the corresponding feature map s(x,y) will be obtained by convolving the input data with a convolution kernel w(x,y) of size m×n.
s(x,y)=I(x,y)w(x,y),
(9)
s(x,y)=m=0M1n=0N1I(m,n)w(xm,yn),
(10)
After each convolution operation, the input to the successive hidden layer is changed. Such distributions in all the hidden layers may limit the performance of layer parameters which also reduce the learning rate during training. To address such issue, BN technique is introduced in the proposed architecture to regularize the internal co-variate shift of each convolution layer.
The activations of a given input is normalized before it passes to the next layer in the network. If x is considered as the mini-batch of activations, then the normalized input x^ can be computed using the following equation,
x^=(xiμB)/σβ2+ϵ  (normalize),
(11)
where μB and σβ2 are the respective mean and variance over each mini-batch of training images, β. ϵ is the error, which set equal to a small positive value. Hence, the activation of convolution layer will have approximately a zero mean and unit variance.
μB1mi=1mxi  (Mini-batch Mean),
(12)
σβ21mi=1m(xiμβ)2  (Mini batch Variance),
(13)
yiγxl^+βBNγ,β(xi)  (Scale and Shift).
(14)
Hence, the output of the convolution layer is multiplied by a standard deviation (γ-gamma) and adds a mean (β-beta), which ranges of 0 and 1. The γ and β are the two parameters learned in each layer which preserves the network ability. The main advantages of using BN as follows, it reduces overfitting, Minimizes the loss, Stabilizes the network by allowing for a wide variety of learning rate and regularization techniques. Now the normalised features obtained using BN are given to the max-pooling layer. The function of maxpooling learns significant value of invariant feature maps. Also, max-pooling layer reduces the dimensional of previous layer output images by a factor of kI(x,y) through a non-linear down-sampling technique. Hence maxpooling improves generalisation and reduces overfitting. Here, the sampling size of max-polling is 3×3. Further, adopted the ReLU (Rectified Linear Unit) non-linear activation function. The use of ReLU increases the non-linearity and avoids the vanishing gradient problem. It is defined as,
ReLU(x)=max(0,x).
(15)
The neurons of the fully connected layer which connects all the convolutional layer, maxpooling layer, and its activation together. It is a special form of a convolutional layer that acts as a multilayer perceptron. It is given as
F(x)=σ(Wx),
(16)
where σ is an identity function, W is the weight matrix, and x is the input.
Finally, the output from the dual CNN structure are fused and given to Global average pooling layer, which reduces the dimensionality of spatial features globally by averaging all the feature vectors obtained from the previous layer. For further classification, the softmax layer is used. It classifies and predicts the probability of each expression labels based on the obtained feature maps. The softmax layer has an ability to classify a non-linear functions and is given as,
P(x)j=exji=1Nexi.
(17)
The proposed architecture is composed of five convolutional layers with 32, 64, 128, 256, and 512 filters of size 5×5, respectively. After each convolutional layer and before maxpooling layer, batch normalization and ReLU activation functions are considered. The main purpose of BN is to reduce overfitting and optimizes the network by increasing the non-linearity. The obtained features from the convolutional layer are further down-sampled using max-pooling layer. The activations of all the previous layers are connected to a fully connected layer[29]. Further, the fully connected layer of the dual CNN architecture is fused and given to global average pooling (GAP).
Sensitivity(Se=TP/(TP+FN)),
(18)
Specificity(Sp=TN/(TN+FP)),
(19)
Accuracy(Acc=(TP+TN)/(TP+FN+TN+FP)).
(20)
Finally, the Soft-Max layer predicts the expression categories. The use of dual CNN architecture with Pre-processing techniques enhances the edges of each input image and boost the network to learn higher level of feature abstractions. The proposed network is compact in design and has the capability to train faster.

3 Experimental Set Up and Result Discussion

The effectiveness of the proposed integrated model is evaluated on publicly available database. The experiment is carried out in Ubuntu16.04 with Intel® coreTM i7, 2.70 GHz processor and 16 GB RAM memory with 8 GB external NVIDIA graphics card. Database Mendeley datasets, MDE-lab datasets, DTU/Herlev and Own datasets collected form hospitals are used, respectively. The DTU/Herlev Pap Smear Database (2005) contains Pap-smear data acquired from images of healthy & cancerous smears coming from the Herlev University Hospital (Denmark). The number of sequences considered from each dataset for the proposed model evaluation. The DTU/Herlev Pap Smear Database details is shown in Table 2.
Table 2 DTU/Herlev Pap smear Database
class category cell Type Number of sample
1 Normal Superficial squamous epithelial 74
2 Normal Intermediate squamous epithelial 70
3 Normal Columnar squamous epithelial 98
4 Abnormal Mild squamous non-keratinizing dysplasia 182
5 Abnormal Moderate squamous 146
6 Abnormal Severe squamous 197
7 Abnormal Squamous cell carcinoma 150
The proposed model is implemented using KERAS deep learning library. The model is trained initially with each dataset as mentioned above, based on subject-independent and cross-dataset validation method and also evaluated the performance of the proposed model. First, pre-processing techniques are implemented to correct illumination and to improve the edges. Second, employ a data augmentation technique to overcome the issue of limited data, during training. The use of data augmentation technique avoids overfitting and accurately predicts the unseen data. all the datas are combined and trained based on the evaluation method. Also, the datas are fed into the dual CNN layers and the corresponding layer parameters are shown in Table. The parameters are set to 250 epochs with mini-batch size 80 and the initial learning rate as 0.001. Using Stochastic Gradient Decent method, the model parameters are updated with a momentum of 0.95 and the total loss function is optimized. The parameters are fine-tuned at the fully connected layers and the GAP.
Two different experiment protocols are used for analysis: Subject-independent and cross-dataset protocol tasks. In subject-independent method, the images in the dataset have been divided into training set and validation set in a subject independent manner. It is also called as K-fold cross validation. Then, the model is iteratively repeated as per the K-folds and averaging the recognition accuracy over the K-folds. In cross-dataset evaluation one dataset is used for testing and the other for training. Similarly, the model is iteratively trained and evaluated for all the datasets based on K-fold cross-validation manner. In this experiment, each dataset follows the 10-fold cross-validation method (i.e., the datasets are split into 10 groups during the CNN training, with 9 groups for training and the remaining 1 group for validation each time and repeat it for 10 times) to evaluate the proposed model. From confusion matrix, the classification accuracy is measured for each expression. From the literature, the evaluation differs for six class and seven class (including neutral) expression classification. Also, the classification accuracy depends on choosing the annotated expression frames for training. The process is carried out with 10-fold cross validation protocol in which the nine folds are used for training and remaining one for validation. In this various folding is used, such as 8-fold and 5-fold cross-validation technique and experimented for 6 class expression labels. The confusion matrix is shown is Table 3. In proposed SMEARNET model, used 10-fold cross-validation and evaluated with benchmark datasets. The number of training samples should be increased to attain better classification. The overall comparisons of the various methods are as shown in the Table 4.
Table 3 Confusion Matrix
Superficial squamous epithelial Intermediate squamous epithelial Columnar squamous epithelial Mild squamous non-keratinizing dysplasia Moderate squamous Severe squamous Squamous cell carcinoma
Superficial squamous epithelial 98.64 2.78 1.58 0 0 0 0
Intermediate squamous epithelial 2.58 96.87 1.55 0 0 0 0
Columnar squamous epithelial 5.05 2.04 93.48 0.49 3.94 0 0
Mild squamous non-keratinizing dysplasia 0 0 0 95.05 0 4.95 0
Moderate squamous 0 0 2.47 0 92.25 0 6.28
Severe squamous 0 0 0.68 3.48 0 92.52 1.32
Squamous cell carcinoma 2.98 0 0 0 1.75 0 97.27
Table 4 Performance comparison of the proposed method
Classifiers Accuracy (%) Error (%)
Normal smear cells Abnormal smear cells Normal Abnormal
Principal component analysis (PCA) 87 81 13 19
Discrete Wavelet Transform Kernel Principal component analysis (DWT-KPCA) 90 85 10 15
Support vector machine (SVM) 92 90 8 10
probabilistic neural network (PNN) 97 93 3 7
Convolutional neural network (CNN) 99.34 98.7 0.7 1.23
Proposed SMEARNET 99.57 99.21 0.41 0.81
Table 5 shows that the overall performance measures of the smear cell segmentation. The parameters of the accuracy, sensitivity and specificity are calculated. The proposed method improved the accuracy, sensitivity and specificity in the classification of smear cells.
Table 5 Overall performance measures
Methods Accuracy Sensitivity Specificity
Semi automatic morphology approach[8] 92.68 92.23 93.22
Contour property-based approach[33] 96.8 92.43 93.63
B spline based method[38] 98.65 94.65 96.71
Geodisc segmentation[7] 98.85 96.32 95.23
Multi thresholding clustering[35] 99.39 96.32 95.53
Clustering based Methods[32] 98.96 97.32 94.32
Fuzzy Based Techniques[36] 98.81 96.11 94.91
Histogram-based Techniques[40] 97.12 94.91 93.67
Proposed method 99.57 98.57 97.30

4 Conclusion

In this paper novel Smear-net model is discussed for the analysis of pap-smear cells. The proposed method achieved 95.39 percentage of sensitivity, 90.18 specificity and 96.89 accuracy for P-cell segmentation. The proposed method achieved 99.9 percentage of sensitivity, 98.30 in specificity and 98.65 accuracy for S-cell segmentation. The classification accuracy of smear-net model is 99.87 for normal cells and for abnormal cells segmentation accuracy of 99.41. The smear-net model provides the classification accuracy of 99.57 for normal cells and for abnormal cells segmentation accuracy of 99.21.

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