Toward MR-only proton therapy planning for pediatric brain tumors: Synthesis of relative proton stopping power images with multiple sequence MRI and development of an online quality assurance tool

Purpose To generate synthetic relative proton stopping power (sRPSP) images from magnetic resonance imaging (MRI) sequence(s) and develop an online quality assurance (QA) tool for sRPSP to facilitate safe integration of magnetic resonance (MR)-only proton planning into clinical practice. Materials and methods Planning computed tomography (CT) and MR images of 195 pediatric brain tumor patients were utilized (training: 150, testing: 45). Seventeen consistent-cycle generative adversarial network (ccGAN) models were trained separately using paired CT-converted RPSP and MRI datasets to transform a subject's MRI into sRPSP. T1-weighted (T1W), T2-weighted (T2W), and FLAIR MRI were permutated to form 17 combinations, with or without preprocessing, for determining the optimal training sequence(s). For evaluation, sRPSP images were converted to synthetic CT (sCT) and compared to the real CT in terms of mean absolute error (MAE) in Hounsfield units (HU). For QA, sCT was deformed and compared to a reference template built from training dataset to produce a flag map, highlighting pixels that deviate by >100 HU and fall outside the mean +/- standard deviation reference intensity. The gamma intensity analysis (10%/3 mm) of the deformed sCT against the QA template on the intensity difference was investigated as a surrogate of sCT accuracy. Results The sRPSP images generated from a single T1W or T2W sequence outperformed that generated from multi-MRI sequences in terms of MAE (all p < 0.05). Preprocessing with N4 bias and histogram matching reduced MAE of T2W MRI-based sCT (54 +/- 21 HU vs. 42 +/- 13 HU, p = 0.002). The gamma intensity analysis of sCT against the QA template was highly correlated with the MAE of sCT against the real CT in the testing cohort (r = -0.89 for T1W sCT; r = -0.93 for T2W sCT). Conclusion Accurate sRPSP images can be generated from T1W/T2W MRI for proton planning. A QA tool highlights regions of inaccuracy, flagging problematic cases unsuitable for clinical use.