Ensemble learning and personalized training for the improvement of unsupervised deep learning-based synthetic CT reconstruction

Background: The growing adoption of magnetic resonance imaging (MRI)-guided radiation therapy (RT) platforms and a focus on MRI-only RT workflows have brought the technical challenge of synthetic computed tomography (sCT) reconstruction to the forefront. Unpaired-data deep learning-based approaches to the problem offer the attractive characteristic of not requiring paired training data, but the gap between paired- and unpaired-data results can be limiting. Purpose: We present two distinct approaches aimed at improving unpaired-data sCT reconstruction results: a cascade ensemble that combines multiple models and a personalized training strategy originally designed for the paired-data setting. Methods: Comparisons are made between the following models: (1) the paired-data fully convolutional DenseNet (FCDN), (2) the FCDN with the Intentional Deep Overfit Learning (IDOL) personalized training strategy, (3) the unpaired-data CycleGAN, (4) the CycleGAN with the IDOL training strategy, and (5) the CycleGAN as an intermediate model in a cascade ensemble approach. Evaluation of the various models over 25 total patients is carried out using a five-fold cross-validation scheme, with the patient-specific IDOL models being trained for the five patients of fold 3, chosen at random. Results: In both the paired- and unpaired-data settings, adopting the IDOL training strategy led to improvements in the mean absolute error (MAE) between true CT images and sCT outputs within the body contour (mean improvement, paired- and unpaired-data approaches, respectively: 38%, 9%) and in regions of bone (52%, 5%), the peak signal-to-noise ratio (PSNR; 15%, 7%), and the structural similarity index (SSIM; 6%, <1%). The ensemble approach offered additional benefits over the IDOL approach in all three metrics (mean improvement over unpaired-data approach in fold 3; MAE: 20%; bone MAE: 16%; PSNR: 10%; SSIM: 2%), and differences in body MAE between the ensemble approach and the paired-data approach are statistically insignificant. Conclusions: We have demonstrated that both a cascade ensemble approach and a personalized training strategy designed initially for the paired-data setting offer significant improvements in image quality metrics for the unpaired-data sCT reconstruction task. Closing the gap between paired- and unpaired-data approaches is a step toward fully enabling these powerful and attractive unpaired-data frameworks.