The reliable and efficient estimation of uncertainty in artificial intelligence (AI) models poses an ongoing challenge in many fields such as radiation therapy. AI models are intended to automate manual steps involved in the treatment planning workflow. We focus in this study on dose prediction models that predict an optimal dose trade-off for each new patient for a specific treatment modality. They can guide physicians in the optimization, be part of automatic treatment plan generation or support decision in treatmentindication. Most common uncertainty estimation methods are based on Bayesian approximations, like Monte Carlo dropout (MCDO) or Deep ensembling (DE). These two techniques, however, have a high inference time (i.e., require multiple inference passes) and might not work for detecting out-of-distribution (OOD) data (i.e., overlapping uncertainty estimate for in-distribution (ID) and OOD). In this study, we present a direct uncertainty estimation method and apply it for a dose prediction U-Net architecture. It can be used to flag OOD data and give information on the quality of the doseprediction. Our method consists in the addition of a branch decoding from the bottleneck which reconstructs the CT scan given as input. The input reconstruction error can be used as a surrogate of the model uncertainty. For the proof-of-concept, our method is applied to proton therapy dose prediction in head and neck cancer patients. A dataset of 60 oropharyngeal patients was used to train the network using a nested cross-validation approach with 11 folds (training: 50 patients, validation: 5 patients, test: 5 patients). For the OOD experiment, we used 10 extra patients with a different head and neck sub-location. Accuracy, time-gain, and OOD detection are analyzed for our method in this particular application and compared with the popular MCDO andDE. The additional branch did not reduce the accuracy of the dose prediction model. The median absolute error is close to zero for the target volumes and less than 1% of the dose prescription for organs at risk. Our input reconstruction method showed a higher Pearson correlation coefficient with the prediction error (0.620) than DE (0.447) and MCDO (between 0.599 and 0.612). Moreover, our method allows an easier identification of OOD (no overlap for ID and OOD data and a Z-score of 34.05). The uncertainty is estimated simultaneously to the regression task, therefore requires less time and computationalresources. This study shows that the error in the CT scan reconstruction can be used as a surrogate of the uncertainty of the model. The Pearson correlation coefficient with the dose prediction error is slightly higher than state-of-the-art techniques. OOD data can be more easily detected and the uncertainty metric is computed simultaneously to the regression task, therefore faster than MCDO or DE. The code and pretrained model are available on the gitlab repository: https://gitlab.com/ai4miro/ct-reconstruction-for-uncertainty-quatification-of-hdunet.
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