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Research studies of artificial intelligence models in medical imaging have been hampered by poor generalization. This problem has been especially concerning over the last year with numerous applications of deep learning for COVID-19 diagnosis. Virtual imaging trials (VITs) could provide a solution for objective evaluation of these models. In this work utilizing the VITs, we created the CVIT-COVID dataset including 180 virtually imaged computed tomography (CT) images from simulated COVID-19 and normal phantom models under different COVID-19 morphology and imaging properties. We evaluated the performance of an open-source, deep-learning model from the University of Waterloo trained with multi-institutional data and an in-house model trained with the open clinical dataset called MosMed. We further validated the model's performance against open clinical data of 305 CT images to understand virtual vs. real clinical data performance. The open-source model was published with nearly perfect performance on the original Waterloo dataset but showed a consistent performance drop in external testing on another clinical dataset (AUC=0.77) and our simulated CVIT-COVID dataset (AUC=0.55). The in-house model achieved an AUC of 0.87 while testing on the internal test set (MosMed test set). However, performance dropped to an AUC of 0.65 and 0.69 when evaluated on clinical and our simulated CVIT-COVID dataset. The VIT framework offered control over imaging conditions, allowing us to show there was no change in performance as CT exposure was changed from 28.5 to 57 mAs. The VIT framework also provided voxel-level ground truth, revealing that performance of in-house model was much higher at AUC=0.87 for diffuse COVID-19 infection size <2.65% lung volume versus AUC=0.52 for focal disease with <2.65% volume. The virtual imaging framework enabled these uniquely rigorous analyses of model performance, which would be impracticable with real patients.
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