AI-assisted CT imaging analysis for COVID-19 screening: Building and deploying a medical AI system

2.1. Data acquisition

The very first step of building an AI-assisted diagnosis system for COVID-19 is image acquisition, in which Chest X-ray and CT images are most widely used. And there are more applications using CT images for COVID-19 diagnosis [11], [12], [13], [14], since the analysis and segmentation of CT images are always more precise and efficient than X-ray images.

Recently, there has been some progress on COVID-19 dataset construction. Zhao et al. [15] build a COVID-CT dataset which includes 288 CT slices of confirmed COVID-19 patients, collected from about 700 COVID-19 related publications on medRxiv and bioRxiv. The Coronacases Initiative releases some CT images of 10 confirmed COVID-19 patients on its website [16]. COVID-19 CT segmentation dataset [17] is also a publicly available dataset. It contains 100 axial CT slices of 60 confirmed COVID-19 patients, and all the CT slices are manually annotated with segmentation labels. Besides, Cohen et al. [18] collect 123 frontal view X-rays from some publications and websites and build the COVID-19 Image Data Collection.

Some efforts have been made on contactless data acquisition to reduce the risk of infection during COVID-19 pandemic [19], [20], [21]. For example, an automated scanning workflow equipped with mobile CT platform is built [19], in which the mobile CT platform has more flexible access to patients. During CT data acquisition, the positioning and scanning of patients are operated remotely by a technician.

2.2. Lung segmentation

The medical image segmentation and deep neural network [22], [23], [24], [25], [26], [27] plays an important role in AI-assisted COVID-19 analysis in many works. It highlights the regions of interest (ROIs) in CT or X-ray images for further examination. The segmentation tasks in COVID-19 applications can be divided into two groups: Lung region segmentation and lung lesion segmentation. During lung region segmentation, the whole lung region is separated from background, while in lung lesion segmentation tasks the lesion areas are distinguished from other lung areas. Lung region segmentation is often executed as a preprocessing step in CT segmentation tasks [28], [29], [30], in order to decrease the difficulty of lesion segmentation.

Several widely-used segmentation models are applied in COVID-19 diagnosis systems such as U-Net [31], V-Net [14] and U-Net++ [32]. Among them U-Net is a fully convolutional network in which skip connection is employed to fuse information of multi-resolution layers. V-Net adopts a volumetric, fully convolutional neural network and achieves 3D image segmentation. VB-Net [33] replaces the conventional convolutional layers inside down block and up block with the bottleneck, to achieve promising and efficient segmentation results. U-Net++ is composed of deeply-supervised encoder and decoder sub-networks. Nested skip connections are equipped to connect the two sub-networks, which could increase the segmentation performance.

In AI-assisted COVID-19 analysis applications, Li et al. [12] develop a U-Net based segmentation system to distinguish COVID-19 from community-acquired pneumonia on CT images. Qi et al. [34] also build a U-Net based segmentation model to separate lung lesions and extract the radiologic characteristics in order to predict the hospital stay of a patient. Shan et al. [35] propose a VB-Net based segmentation system to segment lung, lung lobes and lung lesion regions. And the segmentation results can also provide accurate quantification data for further study towards COVID-19. Chen et al. [36] train a U-Net++ based segmentation model to provide COVID-19 related lesions.

2.3. AI-assisted diagnosis

Medical imaging AI systems such as disease classification and segmentation are increasingly inspired and transformed from computer vision based AI systems. Morteza et al. [37] propose a data-driven model that recommends the necessary set of diagnostic procedures based on the patients’ most recent clinical record extracted from the Electronic Health Record (EHR). This has the potential to enable health systems expand timely access to initial medical specialty diagnostic workups for patients. Gu et al. [38] propose a series of collaborative techniques to engage human pathologists with AI given AI’s capabilities and limitations, based on which they prototype Impetus - a tool where an AI takes various degrees of initiatives to provide various forms of assistance to a pathologist in detecting tumors from histological slides. Samaniego et al. [39] propose a blockchain-based solution to enable distributed data access management in Computer-Aided Diagnosis (CAD) systems. This solution has been developed as a distributed application (DApp) using Ethereum in a consortium network. Li et al. [40] develop a visual analytics system that compares multiple models’ prediction criteria and evaluates their consistency. With this system, users can generate knowledge on different models’ inner criteria and how confidently we can rely on each model’s prediction for a certain patient.

AI-assisted COVID-19 diagnosis based on CT and X-ray images could accelerate the diagnosis and decrease the burden of radiologists, thus is highly desired in COVID-19 pandemic. And a series of models which can distinguish COVID-19 from other pneumonia and diseases have been widely explored.

The AI-assisted diagnosis systems can be grouped into two categories, i.e., X-ray based screening COVID-19 systems and CT based screening COVID-19 systems. Among X-ray based AI-assisted systems, Ghoshal et al. [41] develop a Bayesian Convolutional Neural network to measure the diagnosis uncertainty of COVID-19 prediction. Narin et al. [42] develop three widely-used models, i.e., ResNet-50 [43], Inception-V3 [44], and Inception-ResNet-V2 [45], to detect COVID-19 lesion in X-ray images and among them ResNet-50 achieves the best classification performance. And Zhang et al. [46] present a ResNet based model to detect COVID-19 lesions from X-ray images. This model can provide an anomaly score to help optimize the classification between COVID-19 and non-COVID-19.

As X-ray images are always the typical common-used imaging modality in pulmonary diseases diagnosis, they are usually not as sensitive as 3D CT images. Besides, the positive COVID-19 X-ray data in these studies is mainly from one online datasets [18] which only contains insufficient X-ray images from confirmed COVID-19 patients. And the lack of data could affect the generalization property of the diagnosis systems.

As for CT based AI-assisted diagnosis, a series of approaches with different frameworks are proposed. Some approaches employ a single model to determine the presence of COVID-19 disease or certain other diseases in CT images. Ying et al. [11] propose DeepPneumonia, which is a ResNet-50 based CT diagnosis system, to distinguish the COVID-19 patients from bacteria pneumonia patients and healthy people. Jin et al. [47] build a 2D CNN based model to segment the lung and then identify slices of COVID-19 cases. Li et al. [12] propose COVNet, which is a ResNet-50 based model employed on 2D slices with shared weights, to discriminate COVID-19 from community-acquired pneumonia and non-pneumonia. Shi et al. [13] apply VB-Net [33] to segment the CT images into the left or right lung, 5 lung lobes, and 18 pulmonary segments, then select hand-crafted features to train a random forest model to make diagnosis.

Some other works follow a segmentation and classification mechanism. Taking some approaches for instance, Xu et al. [48] build a deep learning model based on V-Net [14] and ResNet-18 to classify COVID-19 patients, Influenza-A patients, and healthy people. In this model, lung lesion region in CT image is extracted using V-Net first, then the type of lesion region is determined via ResNet-18. Zheng et al. [49] propose DeCoVNet, which is a combination of a U-Net [31] model and a 3D CNN model. The U-Net model is used for lung segmentation, then the segmentation results are input into the 3D CNN model for predicting the probability of existence of COVID-19.

3.1. Overview

As shown in Fig. 1, the construction of the AI model included four stages: (1) Data collection; (2) Data annotation; (3) Model training and evaluation, and (4) Model deployment. As we accumulated data, we iterated through the stages to continuously improve model performance.

3.2. Data collection

Our dataset was obtained from 5 hospitals (see Table 1). Most of the 877 positive cases were from hospitals in Wuhan, while half of the 541 negative cases were from hospitals in Beijing. Our positive samples were all collected from confirmed patients, following China’s national diagnostic and treatment guidelines at the time of the diagnosis, which required positive results in NAT. The positive cases offered a good sample of confirmed cases in Wuhan, covering different age and gender groups (see Fig. 4). We collect many CT images with other types of pneumonias, e.g. common pneumonia patients, viral pneumonia patients, fungal pneumonia patients, tumor patients, emphysema patients, lung lesions patients. To choose the reasonable negative cases, we employ several senior physicians to manually confirm each case. Based on the experiences of senior physicians, they choose the negative cases which have similar characteristics with COVID-19. Finally, we also had 450 cases with other known lung diseases with CT imaging features similar to COVID-19 to some extent (see Fig. 5).

The hospitals used different models of CT equipment from different manufacturers (see Table 2). Due to the shortage of CT scanners for hospitals in Wuhan, slice thicknesses varied from 0.625 mm to 10 mm, with a majority (81%) under 2 mm. We believed this variety helped to improve the generalizability of our model in real deployment. In addition, we removed the personally identifiable information (PII) from all CT scans for patients’ privacy. We randomly divided the whole dataset into a training set and a test set for each model training (see Table 4).

3.3. Data annotation

To train the models, a team of six data annotators annotated the lesion regions (if there are any), lung boundaries, and the parts of the lungs for transverse section layers in all CT samples.

Saving time for radiologists was essential during the epidemic outbreak, so our data annotators performed most of the tasks, and we relied on a three-step quality inspection process to achieve reasonable accuracy for annotation. All of the annotators had radiology background, and we conducted a four-day hands-on training led by a senior radiologist with clinical experience of COVID-19 before they performed annotations.

Our three-step quality inspection process was the key to obtain high-quality annotations. We divided the six-annotator team into a group of four (Group A) and a group of two (Group B).

Step 1

Group A made all the initial annotations, and Group B performed a back-to-back quality check, i.e., each of the two members in Group B checked all the annotations independently and then compared their results. The pass rate for this initial inspection was 80%. The cases that failed to pass mainly had minor errors in small lesion region missing or the inexact boundary shape.

Step 2

Group A revised the annotations, and then Group B rechecked the annotations. This process continued until all of them passed the back-to-back quality test within the two-people group.

Step 3

When a batch of data was annotated and passed the first two steps, senior radiologists randomly checked 30% of the revised annotations for each batch. We observed a pass rate of 100% in this step, showing reasonable annotation quality.

Of course, there might still be errors remaining, and we relied on the model training process to tolerate these random errors.

3.4. Pre-processing

We performed the following preprocessing steps before we used them for training and testing. (1) Since different samples had different resolutions and slice thicknesses, we first normalized them to (1, 1, 2.5) mm using standard interpolation algorithms (e.g. nearest neighbor interpolation, bilinear interpolation and cubic interpolation [50], [51]). Note that we use cubic interpolation to obtain better image effect. (2) We adjusted the window width (WW) and window level (WL) for each model, generating three image sets, each with a specific window setting. For brevity, we used the [min, max] interval format in programming for WW and WL. Specifically, we set them to [−150, 350] for the lung region segmentation model, and [−1024, 350] for both of the lesion segmentation and classification models. (3) We first ran the lung segmentation model to extract areas of the lungs from each image and used only the extraction results in the subsequent steps. (4) We normalized all the values to the range of [0, 1]. (5) We applied typical data augmentation techniques [52], [53] to increase the diversity of data. For example, we randomly flipped, panned, and zoomed images for more variety, which had been shown to improve the generalization ability for the trained model.

3.5. Model library

Our model was a combination of a segmentation model and a classification model. Specifically, we used the segmentation model to obtain the lung lesion regions, and then the classification model to determine whether it was COVID-19-like for each lesion region. We selected both models empirically by training and testing all models in our previously-developed model library.

For the segmentation task, we considered several widely-used segmentation models such as fully convolutional networks (FCN-8s) [54], U-Net [31], V-Net [14] and 3D U-Net++ [32].

FCN-8s [54] was a “fully convolutional” network in which all the fully connected layers were replaced by convolution layers. Thus, the input of FCN-8s could have arbitrary size. FCN-8s introduced a novel skip architecture to fuse information of multi-resolution layers. Specifically, upsampled feature maps from higher layers were combined with feature maps skipped from the encoder, to improve the spatial precision of the segmentation details.

Similar to FCN-8s, U-Net [31] was a variant of encoder– decoder architecture and employed skip connection as well. The encoder of U-Net employed multi-stage convolutions to capture context features, and the decoder used multi-stage convolutions to fuse the features. Skip connection was applied in every decoder stage to help recover the full spatial resolution of the network output, making U-Net more precise, and thus suitable for biomedical image segmentation.

V-Net [14] was a 3D image segmentation approach, where volumetric convolutions were applied instead of processing the input volumes slice-wise. V-Net adopted a volumetric, fully convolutional neural network and could be trained end-to-end. Based on the Dice coefficient between the predicted segmentation and the ground truth annotation, a novel objective function was introduced to cope with the imbalance between the number of foregrounds and background voxels.

3D U-Net++ [32] was an effective segmentation architecture, composed of deeply-supervised encoder and decoder sub- networks. Concretely, a series of nested, dense re-designed skip pathways connected the two sub-networks, which could reduce the semantic gap between the feature maps of the encoder and the decoder. Integrate the multi-scale information, the 3D U-Net++ model could simultaneously utilize the semantic information and the texture information to make the correct predictions. Besides, deep supervision enabled more accurate segmentation, particularly for lesion regions. Both re-designed skip pathways and deep supervision distinguished U-Net++ from U-Net, and assisted U-Net++ to effectively recover the fine details of the target objects in biomedical images. Also, allowing 3D inputs could capture inter-slice features and generate dense volumetric segmentation.

For all the segmentation models, we used patch size (i.e., the input image size to the model) of (256, 256, 128). The positive data for the segmentation models were those images with arbitrary lung lesion regions, regardless of whether the lesions were COVID-19 or not. Then the model made per-pixel predictions of whether the pixel was within the lung lesion region.

In the classification task, we evaluated some state-of-the-art classification models such as ResNet-50 [43], Inception networks [44], [45], [55], DPN-92 [56], and Attention ResNet-50 [57].

Residual network (ResNet) [43] was a widely-used deep learning model that introduced a deep residual learning framework. ResNet was composed of a number of residual blocks, the shortcut connections element-wisely combined the input features with the output of the same block. These connections could assist the higher layers to access information from distant bottom layers and effectively alleviated the gradient vanishing problem, since they backpropagated the gradient to the bottom gradient without diminishing magnitude. For this reason, ResNet was able to be deeper and more accurate. Here, we used a 50-layer model ResNet-50.

Inception families [44], [45], [55] had evolved a lot over time, while there was an inherent property among them, which was a split-transform-merge strategy. The input of the inception model was split into a few lower-dimensional embeddings, transformed by a set of specialized filters, and merged by concatenation. This split-transform-merge behavior of inception module was expected to approach the representational power of large and dense layers but at a considerably lower computational complexity.

Dual path network (DPN-92) [56] was a modularized classification network that presented a new topology of connections internally. Specifically, DPN-92 shared common features and maintained the flexibility of exploring new features via dual path architectures, and realized effective feature reuse and exploration. Compared with some other advanced classification models such as ResNet-50, DPN-92 had higher parameter efficiency and was easy to optimize.

Residual attention network (Attention ResNet) [57] was a classification model which adopted attention mechanism. Attention ResNet could generate adaptive attention-aware features by stacking attention modules. In order to extract valuable features, the attention-aware features from different attention modules change adaptively when layers going deeper. In that way, the meaningful areas in the images could be enhanced while the invalid information could be suppressed. We used Attention ResNet-50 in the residual attention network.

All the classification models took the input of dual-channel information, i.e., the lesion regions and their corresponding segmentation masks (obtained from the previous segmentation models) were simultaneously sent into the classification models, then gave the classification results (positive or negative).

3.6. Model training

For neural network training, we trained all models from scratch with random initial parameters. Table 4 described the training and test data distribution of both segmentation and classification tasks. We trained the models on a server with eight NVIDIA TITAN RTX GPUs using the PyTorch [58] framework. We used Adam optimizer with an initial learning rate of $1{\mathrm{e}}^{-4}$ and learning rate decay of $5{\mathrm{e}}^{-4}$.

3.7. Deployment

We deployed the trained models on workstations that we deployed on premise of the hospitals. A typical workstation contained an Intel Xeon E5-2680 CPU, an Intel I210 NIC, two TITAN X GPUs, and 64GB RAM (see Fig. 6). The server imported images from the hospital’s Picture Archiving and Communication Systems (PACS), and displayed the results iteratively. The server automatically checked for model/software updates and installed them so we could update the models remotely.

3.8. Evaluation metrics

We used the Dice coefficient to evaluate the performance of the segmentation tasks and the area under the curve (AUC) to evaluate the performance of the classification tasks. Besides, we also analyzed the selected best classification model with sensitivity and specificity.

Concretely, the Dice coefficient was the double area of overlap divided by the total number of pixels in both images, which was widely used to measure the ability of the segmentation algorithm in medical image segmentation tasks. AUC denoted “area under the ROC curve”, in which ROC stood for “receiver operating characteristic”. ROC curve was drawn by plotting the true positive rate versus the false positive rate under different classification thresholds. Then AUC calculated the two-dimensional area under the entire ROC curve from (0, 0) to (1, 1), which could provide an aggregate measure of the classifier performance across varied discrimination thresholds. Sensitivity/specificity was also known as the true positive/negative rate, measured the fraction of positives/negatives that were correctly identified as positive/negative.

3.9. Reader study

Five qualified physicians (three from hospitals in Wuhan, two from hospitals in Beijing) participated in this reader study. Four of them were attending physicians with average working years of five, while the last one was an associate chief physician with working years of eighteen. For this reader study, we generated a new dataset consisting of 170 cases. Among them, 89 were positive cases provided by The Seventh Hospital of Wuhan and Wuhan Leishenshan Hospital. The other 81 negative cases were chest CT scans with other lung diseases provided by Xi’an Gaoxin Hospital and The Seventh Hospital of Wuhan. Both the physicians and the AI system performed the diagnosis purely based on CT images.