Leveraging deep transfer learning and explainable AI for accurate COVID-19 diagnosis: Insights from a multi-national chest CT scan study

The COVID-19 pandemic has emerged as a global health crisis, impacting millions worldwide. Although chest computed tomography (CT) scan images are pivotal in diagnosing COVID-19, their manual interpretation by radiologists is time-consuming and potentially subjective. Automated computer-aided diagnostic (CAD) frameworks offer efficient and objective solutions. However, machine or deep learning methods often face challenges in their reproducibility due to underlying biases and methodological flaws. To address these issues, we propose XCT-COVID, an explainable, transferable, and reproducible CAD framework based on deep transfer learning to predict COVID-19 infection from CT scan images accurately. This is the first study to develop three distinct models within a unified framework by leveraging a previously unexplored large dataset and two widely used smaller datasets. We employed five known convolutional neural network architectures, both with and without pretrained weights, on the larger dataset. We optimized hyperparameters through extensive grid search and 5-fold cross-validation (CV), significantly enhancing the model performance. Experimental results from the larger dataset showed that the VGG16 architecture (XCT-COVID-L) with pretrained weights consistently outperformed other architectures, achieving the best performance, on both 5-fold CV and independent test. When evaluated with the external datasets, XCT-COVID-L performed well with data with similar distributions, demonstrating its transferability. However, its performance significantly decreased on smaller datasets with lower-quality images. To address this, we developed other models, XCT-COVID-S1 and XCT-COVID-S2, specifically for the smaller datasets, outperforming existing methods. Moreover, eXplainable Artificial Intelligence (XAI) analyses were employed to interpret the models' functionalities. For prediction and reproducibility purposes, the implementation of XCT-COVID is publicly accessible at https://github.com/cbbl-skku-org/XCT-COVID/.