Feasibility of Monte Carlo dropout-based uncertainty maps to evaluate deep learning-based synthetic CTs for adaptive proton therapy

BackgroundDeep learning has shown promising results to generate MRI-based synthetic CTs and to enable accurate proton dose calculations on MRIs. For clinical implementation of synthetic CTs, quality assurance tools that verify their quality and reliability are required but still lacking.PurposeThis study aims to evaluate the predictive value of uncertainty maps generated with Monte Carlo dropout (MCD) for verifying proton dose calculations on deep-learning-based synthetic CTs (sCTs) derived from MRIs in online adaptive proton therapy.MethodsTwo deep-learning models (DCNN and cycleGAN) were trained for CT image synthesis using 101 paired CT-MR images. sCT images were generated using MCD for each model by performing 10 inferences with activated dropout layers. The final sCT was obtained by averaging the inferred sCTs, while the uncertainty map was obtained from the HU variance corresponding to each voxel of 10 sCTs.The resulting uncertainty maps were compared to the observed HU-, range-, WET-, and dose-error maps between the sCT and planning CT. For range and WET errors, the generated uncertainty maps were projected along the 90-degree angle. To evaluate the dose distribution, a mask based on the 5%-isodose curve was applied to only include voxels along the beam paths. Pearson's correlation coefficients were calculated to determine the correlation between the uncertainty maps and HUs, range, WET, and dose errors. To evaluate the dosimetric accuracy of synthetic CTs, clinical proton treatment plans were recalculated and compared to the pCTsMethodsTwo deep-learning models (DCNN and cycleGAN) were trained for CT image synthesis using 101 paired CT-MR images. sCT images were generated using MCD for each model by performing 10 inferences with activated dropout layers. The final sCT was obtained by averaging the inferred sCTs, while the uncertainty map was obtained from the HU variance corresponding to each voxel of 10 sCTs.The resulting uncertainty maps were compared to the observed HU-, range-, WET-, and dose-error maps between the sCT and planning CT. For range and WET errors, the generated uncertainty maps were projected along the 90-degree angle. To evaluate the dose distribution, a mask based on the 5%-isodose curve was applied to only include voxels along the beam paths. Pearson's correlation coefficients were calculated to determine the correlation between the uncertainty maps and HUs, range, WET, and dose errors. To evaluate the dosimetric accuracy of synthetic CTs, clinical proton treatment plans were recalculated and compared to the pCTsResultsEvaluation of the correlation showed an average of r = 0.92 +/- 0.03 and r = 0.92 +/- 0.03 for errors between uncertainty-HU, r = 0.66 +/- 0.09 and r = 0.62 +/- 0.06 between uncertainty-range, r = 0.64 +/- 0.06 and r = 0.58 +/- 0.07 between uncertainty-WET, and r = 0.65 +/- 0.09 and r = 0.67 +/- 0.07 between uncertainty and dose difference for DCNN and cycleGAN model, respectively. Dosimetric comparison for target volumes showed an average 3%/3 mm gamma pass rate of 99.76 +/- 0.43 (DCNN) and 99.10 +/- 1.27 (cycleGAN).ConclusionThe observed correlations between uncertainty maps and the various metrics (HU, range, WET, and dose errors) demonstrated the potential of MCD-based uncertainty maps as a reliable QA tool to evaluate the accuracy of deep learning-based sCTs.