Despite the recent improvements in overall accuracy, deep learning systems still exhibit low levels of robustness. Detecting possible failures is critical for a successful clinical integration of these systems, where each data point corresponds to an individual patient. Uncertainty measures are a promising direction to improve failure detection since they provide a measure of a system's confidence. Although many uncertainty estimation methods have been proposed for deep learning, little is known on their benefits and current challenges for medical image segmentation. Therefore, we report results of evaluating common voxel-wise uncertainty measures with respect to their reliability, and limitations on two medical image segmentation datasets. Results show that current uncertainty methods perform similarly and although they are well-calibrated at the dataset level, they tend to be miscalibrated at subject-level. Therefore, the reliability of uncertainty estimates is compromised, highlighting the importance of developing subject-wise uncertainty estimations. Additionally, among the benchmarked methods, we found auxiliary networks to be a valid alternative to common uncertainty methods since they can be applied to any previously trained segmentation model.

Uncertainty estimation methods are expected to improve the understanding and quality of computer-assisted methods used in medical applications (e.g., neurosurgical interventions, radiotherapy planning), where automated medical image segmentation is crucial. In supervised machine learning, a common practice to generate ground truth label data is to merge observer annotations. However, as many medical image tasks show a high inter-observer variability resulting from factors such as image quality, different levels of user expertise and domain knowledge, little is known as to how inter-observer variability and commonly used fusion methods affect the estimation of uncertainty of automated image segmentation. In this paper we analyze the effect of common image label fusion techniques on uncertainty estimation, and propose to learn the uncertainty among observers. The results highlight the negative effect of fusion methods applied in deep learning, to obtain reliable estimates of segmentation uncertainty. Additionally, we show that the learned observers' uncertainty can be combined with current standard Monte Carlo dropout Bayesian neural networks to characterize uncertainty of model's parameters.

Background: Automated brain tumor segmentation methods are computational algorithms that yield tumor delineation from, in this case, multimodal magnetic resonance imaging (MRI). We present an automated segmentation method and its results for resection cavity (RC) in glioblastoma multiforme (GBM) patients using deep learning (DL) technologies. Methods: Post-operative, T1w with and without contrast, T2w and fluid attenuated inversion recovery MRI studies of 30 GBM patients were included. Three radiation oncologists manually delineated the RC to obtain a reference segmentation. We developed a DL cavity segmentation method, which utilizes all four MRI sequences and the reference segmentation to learn to perform RC delineations. We evaluated the segmentation method in terms of Dice coefficient (DC) and estimated volume measurements. Results: Median DC of the three radiation oncologist were 0.85 (interquartile range [IQR]: 0.08), 0.84 (IQR: 0.07), and 0.86 (IQR: 0.07). The results of the automatic segmentation compared to the three different raters were 0.83 (IQR: 0.14), 0.81 (IQR: 0.12), and 0.81 (IQR: 0.13) which was significantly lower compared to the DC among raters (chisquare = 11.63, p = 0.04). We did not detect a statistically significant difference of the measured RC volumes for the different raters and the automated method (Kruskal-Wallis test: chi-square = 1.46, p = 0.69). The main sources of error were due to signal inhomogeneity and similar intensity patterns between cavity and brain tissues. Conclusions: The proposed DL approach yields promising results for automated RC segmentation in this proof of concept study. Compared to human experts, the DC are still subpar.

Automatic segmentation of brain tumors has the potential to enable volumetric measures and high-throughput analysis in the clinical setting. Reaching this potential seems almost achieved, considering the steady increase in segmentation accuracy. However, despite segmentation accuracy, the current methods still do not meet the robustness levels required for patient-centered clinical use. In this regard, uncertainty estimates are a promising direction to improve the robustness of automated segmentation systems. Different uncertainty estimation methods have been proposed, but little is known about their usefulness and limitations for brain tumor segmentation. In this study, we present an analysis of the most commonly used uncertainty estimation methods in regards to benefits and challenges for brain tumor segmentation. We evaluated their quality in terms of calibration, segmentation error localization, and segmentation failure detection. Our results show that the uncertainty methods are typically well-calibrated when evaluated at the dataset level. Evaluated at the subject level, we found notable miscalibrations and limited segmentation error localization (e.g., for correcting segmentations), which hinder the direct use of the voxel-wise uncertainties. Nevertheless, voxel-wise uncertainty showed value to detect failed segmentations when uncertainty estimates are aggregated at the subject level. Therefore, we suggest a careful usage of voxel-wise uncertainty measures and highlight the importance of developing solutions that address the subject-level requirements on calibration and segmentation error localization.

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