PurposeTo create synthetic CTs and digital reconstructed radiographs (DRRs) from MR images that allow for fiducial visualization and accurate dose calculation for MR-only radiosurgery. MethodsWe developed a machine learning model to create synthetic CTs from pelvic MRs for prostate treatments. This model has been previously proven to generate synthetic CTs with accuracy on par or better than alternate methods, such as atlas-based registration. Our dataset consisted of 11 paired CT and conventional MR (T2) images used for previous CyberKnife (Accuray, Inc) radiotherapy treatments. The MR images were pre-processed to mimic the appearance of fiducial-enhancing images. Two models were trained for each parameter case, using a sub-set of the available image pairs, with the remaining images set aside for testing and validation of the model to identify the optimal patch size and number of image pairs used for training. Four models were then trained using the identified parameters and used to generate synthetic CTs, which in turn were used to generate DRRs at angles 45° and 315°, as would be used for a CyberKnife treatment. The synthetic CTs and DRRs were compared visually and using the mean squared error and peak signal-to-noise ratio against the ground-truth images to evaluate their similarity. ResultsThe synthetic CTs, as well as the DRRs generated from them, gave similar visualization of the fiducial markers in the prostate as the true counterparts. There was no significant difference found for the fiducial localization for the CTs and DRRs. Across the 8 DRRs analyzed, the mean MSE between the normalized true and synthetic DRRs was 0.66 ± 0.42% and the mean PSNR for this region was 22.9 ± 3.7 dB. For the full CTs, the mean MAE was 72.9 ± 88.1 HU and the mean PSNR was 31.2 ± 2.2 dB. ConclusionsOur machine learning-based method provides a proof of concept of a way to generate synthetic CTs and DRRs for accurate dose calculation and fiducial localization for use in radiation treatment of the prostate.