Mitigating misalignment in MRI-to-CT synthesis for improved synthetic CT generation: an iterative refinement and knowledge distillation approach

Objective. Deep learning has shown promise in generating synthetic CT (sCT) from magnetic resonance imaging (MRI). However, the misalignment between MRIs and CTs has not been adequately addressed, leading to reduced prediction accuracy and potential harm to patients due to the generative adversarial network (GAN)hallucination phenomenon. This work proposes a novel approach to mitigate misalignment and improve sCT generation. Approach. Our approach has two stages: iterative refinement and knowledge distillation. First, we iteratively refine registration and synthesis by leveraging their complementary nature. In each iteration, we register CT to the sCT from the previous iteration, generating a more aligned deformed CT (dCT). We train a new model on the refined < dCT, MRI > pairs to enhance synthesis. Second, we distill knowledge by creating a target CT (tCT) that combines sCT and dCT images from the previous iterations. This further improves alignment beyond the individual sCT and dCT images. We train a new model with the < tCT, MRI > pairs to transfer insights from multiple models into this final knowledgeable model. Main results. Our method outperformed conditional GANs on 48 head and neck cancer patients. It reduced hallucinations and improved accuracy in geometry (3% up arrow Dice), intensity (16.7% down arrow MAE), and dosimetry (1% up arrow gamma(3%3mm)). It also achieved <1% relative dose difference for specific dose volume histogram points. Significance. This pioneering approach for addressing misalignment shows promising performance in MRI-to-CT synthesis for MRI-only planning. It could be applied to other modalities like cone beam computed tomography and tasks such as organ contouring.