Abstract
BACKGROUND:
Accurate extraction of coronary arteries from invasive coronary angiography (ICA) images is essential for the diagnosis and risk stratification of coronary artery disease (CAD).
OBJECTIVE:
In this study, a novel deep learning (DL) method is proposed for automatically extracting coronary arteries from ICA images.
METHODS:
A convolutional neural network (CNN) was developed with full-scale skip connections and full-scale deep supervisions. The encoder architecture was based on the residual and inception modules to obtain multi-scale features from multiple convolutional layers with different window shapes. Transfer learning was utilized to improve both the initial performance and learning efficiency. A hybrid loss function was employed to further optimize the segmentation model.
RESULTS:
The model was tested on a data set of 616 ICAs obtained from 210 patients, composed of 437 images for training, 49 images for validation, and 130 images for testing. The segmentation model achieved a Dice score of 0.8942, a sensitivity of 0.8735, a specificity of 0.9954, and a Hausdorff distance of 6.0794 mm; it could predict arteries for a single ICA frame in 0.2114 seconds.
CONCLUSIONS:
The results showed that our model outperformed the state-of-the-art deep-learning models. Our new method has great potential for clinical use.
Keywords
Introduction
Coronary artery disease (CAD) is a prevalent cardiovascular condition that affects the coronary arteries, leading to symptoms such as angina and acute myocardial infarction [1, 2, 3]. It is recognized as one of the leading causes of mortality worldwide, particularly in developing countries. According to data from the World Health Organization, cardiovascular diseases claim the lives of around 17.9 million people annually, with CAD being one of the most common types [4].
Invasive coronary angiography (ICA), which provides assessments of artery stenosis and plaque characteristics, is an essential tool for CAD evaluation and treatment [5]. The utilization of ICA in CAD diagnosis necessitates manual segmentation by specialized physicians, which is time-consuming and labor-intensive. Automated extraction of coronary arteries from ICAs plays a key role in the clinical practice of interventional cardiology [6]. However, the accurate extraction of the coronary arteries from ICAs is a challenging task for the following reasons: 1) complex noise caused by the non-uniform illumination; 2) poor signal-to-noise ratio; 3) uneven intensity; 4) semantic information confusion. Automatic extraction techniques of blood vessels can be broadly classified into two main categories: traditional image processing and deep learning-based methods. The former includes Gaussian or Gabor filter-based, model-based, and line tracking-based methods [7, 8, 9], which focus primarily on the vascular extraction of low noise and high contrast. However, these methods cannot achieve satisfactory results when dealing with ICAs with extremely complex noise. The latter mainly contains convolution neural network-based methods (CNNs), which have shown excellent feature-extracting performance. Yang designed a method that applied correspondence matching and CNN for automatic coronary artery extraction, and a Dice score of 0.8007 was reported [10]. Nasr-Esfahani reported that using patches of pixels to evaluate the ICAs and a CNN was designed to determine the arteries and background [11]. To further improve the segmentation accuracy, E. Nasr et al. used two CNNs to a combination of primary and secondary features and achieved a Dice score of 0.8151 [12]. Image segmentation based on CNN methods, such as U-Net and U-Net
In this paper, we present a new method for coronary artery extraction from ICAs. Our method uses a network structure based on U-Net 3
Materials and methods
Patient data
Two hundred and ten patients (100 males and 110 females) who received ICA (616 images) were retrospectively analyzed. Institutional review board approval was obtained with no informed consent required for this HIPAA-compliant retrospective analysis. The acquired ICA images were 512
Artery extraction
The model developed in this study was used to extract the coronary artery from ICAs (Fig. 1). The ICAs were fed into the deep learning (DL) network, and the output was arterial contours.
Workflow of extracting coronary arteries from ICA images. (a) The input of ICA image. (b) Our deep learning models. (c) Predicted arterial contours.
Comparison of arterial extraction models of the (a) U-Net; (b) U-Net
The simplified overview of U-Net is illustrated in Fig. 2a. The low-level extracted feature maps from the encoder path are directly concatenated into the corresponding decoder path. The nodes
Where
U-Net
The decoding is not done directly from the encoding, and the number of layers in this convolution depends on the down-sampling layer corresponding to the coding direction [16].
The proposed method for image segmentation, unlike U-Net and U-Net
(a) Architecture of the Inception A block. (b) Architecture of the Inception-ResNetA block. (c) Architecture of the Inception-ResNetB block. (d) Architecture of the Inception-ResNetC block.
Figure 3a shows the Inception A block, which consists of four branches. The first branch contains an average pooling layer followed by a convolutional layer. The other three branches consist of convolutional layers with different kernel size, such as 1
Figure 3c shows the structure of the Inception-ResNet-B block, which is divided into three branches. The first branch is directly output, the second branch is processed by a 2D convolution with a 1
The full-scale deep supervision in our method is employed to supervise each scale. The side outputs of the decoder are fed into a plain 3
A hybrid loss function is employed to control backpropagation. It contains Binary Cross Entropy loss (BCE_loss) [19], dice loss, and an L2 regularization term. Binary Cross Entropy is one of the most common evaluation methods in binary task, which can effectively handle the problem of convergence speed [20]. Coronary artery extraction is a single-label binary classification task whose purpose is to divide arterial targets from ICAs. For fast convergence and application to binary classification tasks, a BCE_loss is utilized in our study. The BCE_loss is defined in Eq. (3).
Where
The arterial contours are only a tiny fraction of the entire pixel in the ICAs. An ensemble similarity meter function, Dice, is introduced to alleviate the data sample discrepancy problem. It is usually used to calculate the similarity of two samples, and assign greater training weights to smaller samples in the dataset. The Dice score (DSC) is computed in Eq. (4).
Where
In the task of coronary artery extraction, there are many complex samples in the foreground class that are difficult to judge correctly, such as thinner blood vessel branches. To deal with the problem of the imbalanced distribution of difficulty in samples, it is necessary to make the model focus more attention on the learning of complex samples, which can be achieved by reducing the contribution of simple samples to the total loss and increasing the penalty weight of complex samples. Therefore, we utilize the overall loss defined as Eq. (5) as the loss function of the backbone network.
Due to the particularity caused by the low-contrast and high-noise of the ICAs of coronary artery extraction task, more attention should be paid to multi-scale information. The loss function should be used on each branch of deep supervision to control the training of the network. The deep supervised branching loss function is defined as Eq. (6)
The hybrid loss function is defined in Eq. (7) as the objective loss function.
The
Our method in this study was implemented in Python with a
The manually labeled 616 ICAs were still inadequate to train a 2D CNN. To address this issue and enhance the stability of the CNN model, data augmentation techniques based on geometric transformation and color transformation were applied. Geometric transformation such as flipping, rotating, shifting, and deforming were applied to geometrically transform the image. Color transformations such as Gaussian noise, Gaussian blur and luminance multiplication were applied to modify the content of the image. These techniques were used to make minor changes to the existing datasets randomly. The image obtained after data augmentation will be recognized as two different images by the deep learning model during the network training process, thus achieving the purpose of expanding the dataset. When images were fed into the model for training, a random sampling strategy was applied, and each type of data enhancement technique was executed randomly. Additionally, if an image performs data enhancement, the label performs the same data enhancement technique accordingly.
Metrics to evaluate the accuracy of artery extraction
Five metrics were used to evaluate the accuracy of coronary artery extraction. There are DSC, sensitivity (SN), specificity (SP), Hausdorff distance (HD) and average surface distance (ASD).
SN denotes the ratio of true positive (TP) samples to all actual positive sample pixels, and SP denotes the ratio of true negative (TN) samples to all actual negative sample pixels. The definitions of SN and SP are given in Eqs (8) and (9).
where FN and FP denote false negative sample pixels and false positive sample pixels, respectively.
Hausdorff distance represents the degree of similarity between two sets of points. Assume there are two sets of sets
The definitions of
The surface distance is a function describing the average variance in the surface between the prediction results and ground truth. Let
Where
Dataset
A total of 616 ICA images were used in our work, 405 of which were left coronary artery (LCA) images, and 211 were right coronary artery (RCA) images. All these images were manually annotated by well-trained operators and confirmed by experienced interventional cardiologists. Table 1 contains specific information on the ICA images used in this paper.
Indicators of the number of different angles of LCA and RCA. Note that LCA and RCA represents the left coronary artery and right coronary artery. LAO and RAO represent the left anterior oblique and right anterior oblique
Indicators of the number of different angles of LCA and RCA. Note that LCA and RCA represents the left coronary artery and right coronary artery. LAO and RAO represent the left anterior oblique and right anterior oblique
We divided the dataset into the training set, validation set, and test set according to what ratios of 70%, 10%, and 20%. 210 patients had 616 ICA images, of which 437 images were used for the training set, 49 images were used for the validation set, and 130 images were used for the test set.
DSC was used to evaluate the vessel extraction ability of the deep learning models applied in our paper on an external test set and used 10-fold cross-validation for the final evaluation.
There different methods are compared with our proposed method including U-Net, U-Net
As shown in Fig. 4, examples of extracting arteries from ICAs by different deep learning models are delineated in red. We can observe that our proposed algorithm yields the best arteries extraction with the closest visual appearance to the reference ground truth among all the methods.
Quantitative results associated with different methods for the images in the testing dataset. Note that HD and ASD represents the Hausdorff distance and average surface distance. DSC, SN and SP represents Dice similarity coefficient, sensitivity and specificity, respectively
Quantitative results associated with different methods for the images in the testing dataset. Note that HD and ASD represents the Hausdorff distance and average surface distance. DSC, SN and SP represents Dice similarity coefficient, sensitivity and specificity, respectively
Comparison among the state-of-the-art methods. Note that DSC, SN and SP represents Dice similarity coefficient, sensitivity and specificity, respectively
The raw ICAs and ground truth are shown in (a) and (b), respectively. Arterial segmentation results of the left coronary artery and the right coronary artery illustrated by (c) CGNet, (d) PSPNet, (e) DeepLabV3, (f) DeepLabV3+, (g) U-Net, (h) U-Net
In Table 2, the HD, DSC, SN, SP, and ASD indexes are given in terms of average scores for the 10-fold cross-validation results of the test dataset. The quantitatively compared results of the model performance of CGNet, PSPNet, DeepLabV3, DeepLabV3
Results of the 10-fold cross-validation experiment. (a) DSC (b) SN (C) SP.
As shown in Fig. 5, 10-fold cross-validation was employed to ensure the stability of the experimental results. The DSC, SP and SN of each experiment was almost on the same level (DSC: 0.8941; 0.8980; 0.8960; 0.8916; 0.8913; 0.8937; 0.8926; 0.8955; 0.8955; 0.8934), so it could be concluded that our experimental results have good reliability and stability.
Performance analysis
Various methods based on machine learning techniques have been introduced in healthcare to assist doctors in diagnosis and improve medical efficiency [28, 29, 30]. They have demonstrated extensive applications in the field of cardiology [31]. Deep learning models have been developed and achieved remarkable results on image segmentation tasks [13, 14, 15].
U-Net has been widely used for the segmentation of medical images since it was proposed. However, the plain skip connections in U-Net require the fusion of equal amounts of feature maps from the encoder and decoder networks, even though they may not be semantically identical. This limitation can affect the performance of feature repair in the decoder path, leading to reduced quality and efficiency in coronary segmentation [32].
U-Net
PSPNet, which takes advantage of the pyramid parsing module and can aggregate contextual information from different regions. CGNet learn both local and global features by obtaining contextual texture features. DeepLabV3, which takes advantage of spatial pyramidal pooling based on atrous convolution to augment image-level features.
To improve the accuracy of image segmentation, the U-Net 3
In this study, we propose a novel deep learning model for accurate coronary artery extraction. The full-scale skip connections allow for exploring more semantic information and capturing more detailed features, leading to improved segmentation accuracy. Deep-supervised methods have demonstrated an effective approach for addressing the vanishing gradient and exploding gradient problems that are common in CNNs [34, 35]. The full-scale deep supervision not only avoids over fitting, enables the CNN to learn a more comprehensive representation of arterial information, which is beneficial for segmenting arterial details. In addition, the inception module downscales matrices with larger sizes and concatenates visual information from different scales for feature extraction. The Residual module accelerates neural network training and also improves neural network performance. The Inception and Residual modules in the encoder structure can improve segmentation accuracy by enlarging the receptive field and reducing the feature loss during convolution. Our proposed model can learn arterial semantic information from aggregated feature maps at different scales and enhance the extraction of arterial boundary information, thus improving the performance of coronary artery extraction.
It can be concluded that the method we applied achieved the highest DSC on the ICA dataset (Table 2). The average Dice score of our proposed model was 1.43%, 1.28% and 0.74% higher than that of U-Net, U-Net
Comparison between the segmentation results and the ground truth. Green and red colors indicate the pixels with segmentation errors. (a) ICA, (b) ground truth, (c) CGNet, (d)PSPNet, (e) DeepLabV3, (f) DeepLabV3+, (g) U-Net, (h) U-Net
As shown in Fig. 6, the green indicates false negative segmentation, where the artery is incorrectly predicted as background. The red color indicates false positive segmentation where the background is incorrectly predicted as an artery. The yellow color indicates the artery that has been accurately extracted. The segmentation model proposed in this paper predicts fewer erroneous pixel regions than other models.
The advantage of the proposed network includes the following: it can achieve excellent DSC when applied to ICAs and the significance of boosting modules in our method was demonstrated by ablation experiments.
There are the following limitations on automatic coronary artery extraction by our proposed model. 1) The sample size is still limited. More ICA images with manual annotation will further improve the performance of our method. 2) Automatic extraction of coronary arteries in this study is based on the contour of single-view single-frame ICA. New methods that incorporate adjacent frames in the ICA videos will improve the segmentation performance of our method, particularly for missing and overlapped vessels.
Clinical overview and application
At present, ICA is still the reference gold standard imaging technique for the evaluation of clinically significant CAD. The fundamental task required for the interpretation of ICA is to identify and quantify the severity of coronary stenosis [36]. However, manual estimation of coronary stenosis is time-consuming and determination of the degree of stenosis depends on training and visual estimation. In recent years, automatic detection of coronary stenosis in ICA has become an important factor in assisting physicians with clinical diagnosis, so improving the accuracy of automatic stenosis detection is a necessity for computer-aided diagnostic systems.
The general scheme for automated or semi-automated quantitative stenosis assessment in ICA is artery extraction, geometry calculation, and stenosis analysis [37]. Accurate coronary artery extraction is an important step in the stenosis detection task. We propose an automated coronary artery extraction model, which will enhance the accuracy of coronary stenosis assessment. Especially in those patients with diffuse stenosis or continuous angiography, where accurate automated coronary artery extraction is extremely important.
In the assessment of eccentric lesions, relying on accurate coronary artery auto-extraction models, such as the proposed algorithm, can enhance the accuracy of coronary artery auto-extraction, which will facilitate the assessment of coronary stenosis and thus improve the identification of similar complex lesions.
3D arterial anatomy can also be reconstructed from two-dimensional ICAs to aid in clinical diagnosis of CAD. Automated extraction of coronary from ICA is essential for 3D vessel reconstruction [38, 39]. The automatic extraction of coronary arteries in this study will be used with our 3D vessel revascularization for clinical decision-making of CAD diagnosis and treatment.
Conclusion
In this paper, we present a deep learning-based method for automatic extraction of coronary arteries from ICA. Several important techniques were designed to improve the performance of our model, including full-scale skip connections, full-scale deep supervisions, and the incorporation of inception and residual modules in the encoder. Our model achieved a Dice score of 0.8942, which outperformed the state-of-the-art deep-learning models. It has great promise for clinical applications.
Footnotes
Acknowledgments
We sincerely thank Zhihui Xu, MD, at the Department of Cardiology in The First Affiliated Hospital of Nanjing Medical University, for providing the ICA images for this research.
Conflict of interest
The authors declare no conflict of interest.
Funding
This research was supported by the Key Science Research Project of Colleges and Universities in Henan Province of China (No. 22A520046) and the Key Science and Technology Program of Henan Province (232102211003).
