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.
This paper proposes a novel approach for uncertainty quantification in dense Conditional Random Fields (CRFs). The presented approach, called Perturb-and-MPM, enables efficient, approximate sampling from dense multi-label CRFs via random perturbations. An analytic error analysis was performed which identified the main cause of approximation error as well as showed that the error is bounded. Spatial uncertainty maps can be derived from the Perturb-and-MPM model, which can be used to visualize uncertainty in image segmentation results. The method is validated on synthetic and clinical Magnetic Resonance Imaging data. The effectiveness of the approach is demonstrated on the challenging problem of segmenting the tumor core in glioblastoma. We found that areas of high uncertainty correspond well to wrongly segmented image regions. Furthermore, we demonstrate the potential use of uncertainty maps to refine imaging biomarkers in the case of extent of resection and residual tumor volume in brain tumor patients.