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Diagnostics
  • Article
  • Open Access

29 July 2022

COVID-19 Diagnosis on Chest Radiographs with Enhanced Deep Neural Networks

and
Faculty of Information Science and Technology, Multimedia University, Melaka 75450, Malaysia
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Author to whom correspondence should be addressed.
This article belongs to the Section Machine Learning and Artificial Intelligence in Diagnostics

Abstract

The COVID-19 pandemic has caused a devastating impact on the social activity, economy and politics worldwide. Techniques to diagnose COVID-19 cases by examining anomalies in chest X-ray images are urgently needed. Inspired by the success of deep learning in various tasks, this paper evaluates the performance of four deep neural networks in detecting COVID-19 patients from their chest radiographs. The deep neural networks studied include VGG16, MobileNet, ResNet50 and DenseNet201. Preliminary experiments show that all deep neural networks perform promisingly, while DenseNet201 outshines other models. Nevertheless, the sensitivity rates of the models are below expectations, which can be attributed to several factors: limited publicly available COVID-19 images, imbalanced sample size for the COVID-19 class and non-COVID-19 class, overfitting or underfitting of the deep neural networks and that the feature extraction of pre-trained models does not adapt well to the COVID-19 detection task. To address these factors, several enhancements are proposed, including data augmentation, adjusted class weights, early stopping and fine-tuning, to improve the performance. Empirical results on DenseNet201 with these enhancements demonstrate outstanding performance with an accuracy of 0.999%, precision of 0.9899%, sensitivity of 0.98%, specificity of 0.9997% and F1-score of 0.9849% on the COVID-Xray-5k dataset.

1. Introduction

Since 2019, the SARS-CoV-2 virus has caused severe outbreaks of COVID-19 disease to the whole world. The virus is highly infectious; therefore, early detection of COVID-19 symptoms is of real significance to enable immediate isolation and prevention of the virus spreading to the healthy population. Due to the scarcity of publicly available chest radiographs (also known as chest X-rays) of COVID-19 patients, studies on COVID-19 detection from chest radiographs are still limited. Recently, a COVID-Xray-5k dataset with 5000 chest radiographs was compiled by Minaee et al. (2020) [1].
The dataset is challenging as it is highly imbalanced with 184 COVID-19 images and 5000 non-COVID-19 images. Not only that, the signs in the lungs that indicate the infection by the SARS-CoV-2 virus are hardly perceivable and diversified. Some sample COVID-19 and non-COVID-19 images are shown in Figure 1. In light of this, conventional machine-learning methods that require manual feature engineering to describe the images are ineffective. Therefore, the deep neural networks that are able to autonomously learn the prominent features and perform recognition are preferred in this COVID-19 diagnosis task.
Figure 1. Some sample COVID-19 and non-COVID-19 images from the COVID-Xray-5k dataset.
In this work, four deep neural networks are examined, including VGG16, MobileNetV2, ResNet50 and DenseNet201, for COVID-19 diagnosis. The performance of these models was evaluated on the COVID-Xray-5k dataset [1] for COVID-19 diagnosis. Since the COVID-19 chest radiographs are limited, the research faces the challenges of data scarcity and imbalanced class distribution.
Not only that, the mechanism to decide when to stop the training of deep neural networks is essential as it is a determining factor for the generalization capability of the model. Too many training epochs makes the model overfit the training data, while too few epochs lead to underfitting. Although the deep neural networks were pre-trained on the ImageNet, re-training the model on the COVID-19 chest radiograph dataset enables the model to better adapt to the downstream task, particularly COVID-19 diagnosis. In view of this, the following contributions are proposed to address the challenges:
  • Due to the limited number of COVID-19 chest radiographs, data augmentation is used to synthesize more samples for model learning. Different variations of COVID-19 chest radiographs, such as random cropping and intensity normalization, increase the number of samples of the COVID-19 chest radiographs. The random cropping and intensity normalization are appropriate as they are intuitively analogous to the different settings in radiography examinations.
  • As the sample distributions of COVID-19 and non-COVID-19 classes are highly imbalanced, the class weights are adjusted to be inversely proportional to the sample size in each class. The adjusted class weights reduce the bias and place more emphasis on the minority class, thus, mitigating the imbalanced class distribution issues.
  • To circumvent the overfitting and underfitting problems of the deep neural networks, the early stopping mechanism is implemented to terminate the training of deep neural networks after the validation accuracy stops improving for a certain number of epochs. The weights with the highest validation accuracy are then restored and used for testing.
  • Training the entire deep neural networks requires large datasets, while training only the final classification layer has the risk of inferior feature representation specific to the downstream task. In light of this, the fine-tuning is performed on the last few layers of deep neural networks to better represent the visual cues of chest radiographs. This is a trade-off between end-to-end training and training only the final classification layer.

3. Pre-Trained Convolutional Neural Networks

Generally, the deep neural networks require extremely huge training datasets for the model learning so that the model can perform classification or prediction tasks acceptably. As the training on huge dataset involves high computational resources, researchers turn to adopting pre-trained deep neural networks. For image classification tasks, the pre-trained CNNs are mostly used. Pre-trained CNNs are the CNNs that have been trained on a large image dataset with annotations, such as ImageNet.
The model architecture and weights are then saved to be used for other downstream tasks. The downstream tasks first load the architecture and weights of the pre-trained CNNs. As the downstream tasks usually have different target classes than the dataset that the model was trained on, the final classification layer of the pre-trained model will then be replaced and re-trained with the new target classes of the downstream tasks.
In this study, four pre-trained CNNs are explored for COVID-19 detection using chest radiographs. The pre-trained CNNs include VGG16 [19], MobileNetV2 [20], ResNet50V2 [21] and DenseNet201 [22]. To adapt to the COVID-19 diagnosis task, the final classification layer of the pre-trained model is substituted with a new classification layer and re-trained on the classes in COVID-Xray-5k dataset, i.e., COVID-19 and non-COVID-19. A quick overview of each deep neural network is given below:
  • VGG16 comprises multiple blocks of convolutional and max pooling layers. The VGG16 replaces the large size kernels in convolutional layers with smaller 3 × 3 kernels one after another. The max pooling layer uses 2 × 2 kernel size.
  • MobileNetV2 is an enhancement on MobileNetV1 with a depthwise convolution layer that applies a single convolutional kernel for each input channel. The depthwise convolution dramatically reduces the complexity and computation cost of convolutional neural networks.
  • ResNet152 introduced the concept of residual connections where the original input is added to the output of the convolution block as the shortcut path. Adding this connection for gradient flow mitigates the problem of vanishing gradient. ResNet50 is a smaller version of ResNet152 that is frequently used as the starting point for transfer learning.
  • DenseNet201 comprises multiple dense blocks. Each layer in the dense block concatenates the inputs from the preceding layers with its own feature maps and passes on to the subsequent layers. This characteristic gives the features richer patterns and varying complexity levels.
Prior to the new final classification layer, a global average pooling layer and a dropout layer are added after the pre-trained model. The global average pooling layer flattens the features from the preceding layers and produces a feature map for each class. As deep neural networks are prone to overfitting, the dropout layer added for regularization purposes to improve the generalization capability. The overall architecture of the deep neural network is depicted in Figure 2.
Figure 2. The architecture of the deep neural network for COVID-19 diagnosis.
The performance of these pre-trained models is evaluated on COVID-Xray-5k dataset. The COVID-Xray-5k dataset is divided into 2084 training and 3100 test images. Out of 2084 training samples, 84 are COVID-19 images, and 2000 are non-COVID-19 images. On the other hand, there are 100 COVID-19 images and 3000 non-COVID-19 images in the test set. The distributions of the training and testing sets are presented in Table 2.
Table 2. The number of training and testing samples in the COVID-Xray-5k dataset.
All chest radiographs are resized to 224 × 224 as the input to the deep neural networks. The last layer of each model is fine-tuned and trained for 100 epochs, and the batch size is 16. The learning rate is set to 0.0001, and the Adaptive Moment Estimation (Adam) optimizer was adopted to optimize the model training. The cross-entropy loss function was adopted for the training, which is defined as:
L C E = i = 1 N p i log q i
where p i and q i denote the true and predicted probabilities for each sample, respectively. The hyperparameter settings of the deep neural networks are presented in Table 3.
Table 3. The hyperparameter settings of the deep neural networks.
Several metrics are used in the performance evaluation of the deep neural networks—namely, the accuracy, precision, sensitivity (also known as recall), specificity and F1-score. The evaluation metrics are based on the True Positive (TP), True Negative (TN), False Positive (FP) and False Negative (FN) as depicted in Figure 3. The evaluation metrics are defined as:
Accuracy = TP + TN TP + FP + TN + FN
Precision = TP TP + FP
Sensitivity = TP TP + FN
Specificity = TN FP + TN
F 1 - score = 2 × Precision × Sensitivity Precision + Sensitivity
Figure 3. True Positive (TP), True Negative (TN), False Positive (FP) and False Negative (FN).
In this work, the Python programming language is engaged for the development of deep neural networks. Python contains many frameworks, libraries and extensions that facilitate the implementation of deep-learning models. The main libraries used are Tensorflow, Keras and Scikit-Learn.
TensorFlow is an open-source deep learning library developed by Google that is widely adopted in classification and regression tasks. Tensorflow is built in a modular manner, making it flexible and easily scalable. Another important library is Keras, where it provides the fundamental abstractions and building elements for designing and constructing the machine learning systems. As for the performance evaluation, various metric modules provided by Scikit-Learn, such as the accuracy, precision, recall, F1-score and confusion matrix are leveraged. The experiments were executed on Google Colaboratory with GPU enabled.
Table 4 demonstrates that all pre-trained deep neural networks achieved promising results. DenseNet201 yielded the highest accuracy where the model correctly labeled 98.58% of the COVID-19 and non-COVID-19 images. MobileNetV2 recorded the highest precision where 100% of the predicted COVID-19 images were correctly labeled. DenseNet201 achieved the highest sensitivity rate of 0.58. The sensitivity indicates the ability of the model in identifying the actual COVID-19 chest radiographs and is important in COVID-19 screening. MobileNetV2 achieved the highest specificity where it correctly labeled all non-COVID-19 test images.
Table 4. The performance of the pre-trained deep neural networks on the COVID-Xray-5k dataset.
DenseNet201 recorded the highest F1-score at 0.725 with a good balance between precision and sensitivity. The training and testing times of the pre-trained models are also presented in the table. Figure 4 shows the receiver operating characteristics curve of the pre-trained models. The DenseNet201 has the highest area under the curve, which indicates that the model had relatively higher discriminating capability among the models. The confusion matrices of the pre-trained deep neural networks are presented in Figure 5.
Figure 4. The receiver operating characteristics curve of the pre-trained models.
Figure 5. The confusion matrices of the pre-trained models: (a) VGG16, (b) MobileNetV2, (c) ResNet50V2 and (d) DenseNet201.
Among the models in comparison, DenseNet201 generally outshined other models in comparison. Nevertheless, the models recorded sensitivity rates that are considered low in COVID-19 detection tasks. In view of this, some enhancements are proposed with the aim to improve the performance of the DenseNet201 model for COVID-19 diagnosis.

3.1. Data Augmentation

As COVID-19 is a relatively new disease, the current COVID-19 dataset suffers from image scarcity and class imbalance problems. In this work, data augmentation is leveraged to increase the number of training images by producing transformed variations of the images. Two data augmentation techniques—namely, random cropping and intensity normalization—were implemented to increase the size of the training set.
Random cropping produces synthetic images of smaller sizes ( r 5 , c 5 ) and ( r 10 , c 10 ) , where ( r , c ) is the original image size. The small distortions produce more COVID-19 samples while preserving the prominent region of the chest radiographs. The output of random cropping is homogeneous to images with different distances between the focal spot and patient surface in radiography examinations. Figure 6 illustrates the sample chest X-ray images before and after random cropping.
Figure 6. Sample chest X-ray images: (a) original, (b) random cropping ( r 5 , c 5 ) and (c) random cropping ( r 10 , c 10 ) .
Intensity normalization adjusts the intensity values of the original image I ( x , y ) into I ( x , y ) , as below:
I ( x , y ) = I ( x , y ) m e a n v a r i a n c e
Three pairs of mean and variance values are used: ( m e a n = 0.485 , v a r i a n c e = 0.229 ) , ( m e a n = 0.456 and v a r i a n c e = 0.224 ) and ( m e a n = 0.406 and v a r i a n c e = 0.225 ) [1]. The output of the intensity normalization is analogous to images with slight illumination variations. Figure 7 depicts the sample chest X-ray images before and after intensity normalization.
Figure 7. Sample chest X-ray images: (a) original, (b) intensity normalization ( m e a n = 0.485 and v a r i a n c e = 0.229 ) , (c) intensity normalization ( m e a n = 0.456 and v a r i a n c e = 0.224 ) and (d) intensity normalization ( m e a n = 0.406 , v a r i a n c e = 0.225 ) .
The data augmentation procedures increase the training set by a factor of 5, which means the number of COVID-19 chest radiographs increased from 84 to 420.

3.2. Class Weights

The dataset of COVID-Xray-5k dataset is highly imbalanced as there are 184 COVID-19 images and 5000 non-COVID-19 images. In order to solve class imbalance problems, several works [23,24] proposed sampling methods, either undersampling or oversampling. Undersampling reduces the samples from the majority class. In contrast, oversampling attempts to generate new samples for the minority class. However, sampling methods have their own drawbacks. Undersampling may cause the loss of representative samples, while oversampling may cause overfitting. In view of this, class weight is proposed to mitigate the class imbalance problem. The class weights are adjusted by placing more emphasis on the minority class, enabling the classifier to learn equally from all classes. The class weight is calculated as:
w j = n s a m p l e s n c l a s s × n s a m p l e s j
where
  • w j denotes the weight for class j,
  • n s a m p l e s is the total number of samples,
  • n c l a s s represents the number of class and
  • n s a m p l e s j denotes the number of samples in class j.
In doing so, the weights are adjusted to be inversely proportional to the data size of each class, thus, mitigating the class imbalance problem.

3.3. Early Stopping

Another challenge of deep neural networks lies in the choice of the number of training epochs. The number of epochs affects the generalization capability and the performance of the deep neural networks. Too many epochs may result in the model overfitting the training dataset. On the other hand, too few epochs may lead to an underfitted model.
Both overfitting and underfitting impact the generalization capability and decay the performance of the model. In view of this, an early stopping strategy is adopted to halt the training once the model stops improving on the validation accuracy for a certain number of epochs. Subsequently, the model weights from the epoch with the highest validation accuracy will be restored.

3.4. Fine-Tuning

In transfer learning, the pre-trained model weights are redeployed to another smaller dataset by some modifications. In this work, the last five layers of DenseNet201 are unfrozen, and a new final classification layer is appended. These layers are subsequently trained on the COVID-Xray-5k dataset to fine-tune the higher-order feature representations, thus, tailoring the representations for COVID-19 detection.
With these enhancements, the overall process flow of model training and testing is illustrated in Figure 8.
Figure 8. The process flow of the proposed COVID-19 diagnosis with enhanced DenseNet201.

4. Experimental Results

The performance of DenseNet201 with enhancements was evaluated on the COVID-Xray-5k dataset. The last five layers of DenseNet201 were fine-tuned for 100 epochs, and the batch size was set to 16. In the training process, the data augmentation was deployed on the training set to increase the data size by a factor of 5. The training process was terminated once the validation accuracy stops improving for 15 epochs, and the weights with the highest validation accuracy were used. Not only that, the class weights were adjusted to be inversely proportional to the sample size of the COVID-19 and non-COVID-19 classes to compensate for the imbalanced class distribution. The confusion matrices of DenseNet201 with enhancements are presented in Figure 9.
Figure 9. The confusion matrices of DensetNet201 with enhancements: (a) DenseNet201 with data augmentation, (b) DenseNet201 with data augmentation and adjusted class weights, (c) DenseNet201 with data augmentation, adjusted class weights and early stopping and (d) DenseNet201 with data augmentation, adjusted class weights, early stopping and fine-tuning.
As observed in Table 5, data augmentation slightly improved the performance of DenseNet201 in terms of the accuracy, sensitivity and F1-score. This is attributable to better discriminating power when more COVID-19 samples are generated for training. Although the accuracy slightly dropped when the adjusted class weights were added, the sensitivity improved tremendously. It is worth mentioning that the model sensitivity is crucial to ensure the early diagnosis of COVID-19 where the model is able to correctly identify COVID-19 samples.
Table 5. The performance of DenseNet201 with different enhancements (DA = data augmentation, CW = adjusted class weights, ES = early stopping and FT = finetuning).
The sensitivity of the model greatly increased from 0.69 to 0.91 when the class weights were adjusted to give more emphasis on the minority class. The improvement corroborates that adjusted class weights are effective in alleviating the bias caused by the skewed class distributions.
We also observed that incorporating early stopping avoids the overfitting problem and improves the overall performance of the model. To further improve the model for COVID-19 screening, fine-tuning the last few layers of DenseNet201 makes the learned feature maps more representative towards COVID-19 chest radiographs. The DenseNet201 model with data augmentation, adjusted class weights, early stopping and fine-tuning demonstrated outstanding classification accuracy, precision and F1-score despite the fact that limited COVID-19 samples were available.
The experimental results also exhibited high sensitivity and specificity rates, which are essential in COVID-19 screening. To further evaluate the performance of the enhanced DenseNet201 method, comparison with several state-of-the-art deep neural network methods was conducted as presented in Table 6.
Table 6. Comparison with the state-of-the-art deep neural network methods.
Since the COVID-Xray-5k dataset is highly imbalanced, sensitivity and specificity are two important metrics for the comparison. Noticeably, the proposed method outperformed the state-of-the-art deep neural network methods. This is mainly due to the enhancements of data augmentation, class weights, early stopping and fine-tuning to the proposed method. Data augmentation increased the training samples and provided better representation to the model. In addition, the adjusted class weights help to mitigate the class imbalance problem. Furthermore, early stopping determined the best performing model and reduced the overfitting. Moreover, fine-tuning allowed the model to learn more robust representation towards the dataset.

5. Conclusions

Early diagnosis of the SARS-CoV-2 virus has become a challenge for scientists. The Polymerase Chain Reaction (PCR) test was introduced to detect the COVID-19 [25] patients. However, the PRC test is time-consuming, and it has an increased risk of false positives due to its lower specificity compared to culturing and staining [26]. In view of this, this paper evaluated four pre-trained deep neural networks—namely, VGG16, MobileNetV2, ResNet50 and DenseNet201—for COVID-19 diagnosis based on chest radiographs. The classification layer of the pre-trained models was replaced and trained on the COVID-Xray-5k dataset. DenseNet201 outshined the other models in comparison; however, the sensitivity rate was still moderate. To improve the robustness in early detection of COVID-19 cases, a high sensitivity rate is prominent. The sensitivity rate reflects how well the model can correctly recognize the COVID-19 samples. To this end, some enhancements on DenseNet201 are proposed.
The DenseNet201 model encourages feature reuse via dense connections among the layers within a dense block. The dense connections enhance the gradient flow and enable strong feature propagation through the layers. Furthermore, DenseNet201 uses much fewer trainable parameters, thus, improving the computational efficiency. In addition to that, some enhancements were incorporated into the DenseNet201 model. First, data augmentation was performed to address data scarcity problems due to the limited COVID-19 samples.
Secondly, the class weights were adjusted proportionally to alleviate the bias and skewness caused by the imbalanced class distribution. Thirdly, early stopping was leveraged to mitigate the overfitting problem while preserving the generalization capability of deep neural networks. Fourthly, fine-tuning was performed on the last few layers of DenseNet201 to better adapt the learned high-level features for the COVID-19 detection task. The empirical results demonstrate that DenseNet201 with these enhancements performed outstandingly despite the challenges posed by the dataset and deep neural network architecture.
Inspired by the promising performance of the attention-based models, such as Transformers, future works in COVID-19 diagnosis on chest X-rays could be done using attention-based models. As the regions in the chest X-rays that show the infections of COVID-19 are hardly perceivable, attention-based models are needed to assign higher significance to the infected regions, thus, improving the representation learning and classification of the model.

Author Contributions

Conceptualization, C.P.L. and K.M.L.; methodology, C.P.L. and K.M.L.; software, C.P.L. and K.M.L.; validation, C.P.L. and K.M.L.; formal analysis, C.P.L. and K.M.L.; investigation, C.P.L. and K.M.L.; resources, C.P.L. and K.M.L.; data curation, C.P.L. and K.M.L.; writing—original draft preparation, C.P.L. and K.M.L.; writing—review and editing, C.P.L. and K.M.L.; visualization, C.P.L. and K.M.L.; supervision, C.P.L. and K.M.L.; project administration, C.P.L.; funding acquisition, C.P.L. All authors have read and agreed to the published version of the manuscript.

Funding

The research in this work was supported by the Fundamental Research Grant Scheme of the Ministry of Higher Education under award number FRGS/1/2021/ICT02/MMU/02/4 and Multimedia University Internal Research Grant with award number MMUI/220021.

Institutional Review Board Statement

Not applicable.

Data Availability Statement

Not applicable.

Conflicts of Interest

The authors declare no conflict of interest.

Abbreviations

The following abbreviations are used in this manuscript:
AdamAdaptive Moment Estimation
TPTrue Positive
TNTrue Negative
FPFalse Positive
FNFalse Negative

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