Evaluation of Uncertainty-Aware Multi-Software Ensembles for Hippocampal Segmentation

In this study, we explore in depth a few under-studied topics at the intersection of uncertainty estimation and segmentation. Prior work has shown that the quality of uncertainty estimates can be very sensitive to a range of variables. As one of the main uses of uncertainty estimation is to help identify and deal with prediction errors in practical scenarios, any factors that affect this must be clearly identified. For example, do more challenging domains or different datasets and architectures result in worse performance when using uncertainty estimates? Can prior frames in a video sequence in fact provide useful uncertainty estimates comparable to other approaches? Is it possible to combine uncertainty estimation approaches, taking advantage of sample diversity, to get better estimates? Finally, when might it make sense to use an ensemble-based uncertainty estimate over a deterministic network? We address these questions by creating a framework for and executing a large scale study across many variables such as datasets, backbones, and downstream tasks, for both semantic and panoptic segmentation. We find that a) the more challenging task of panoptic segmentation usually results in worse performance while high performance variance between datasets and backbones indicates that generalization is not guaranteed, b) time series samples can be useful for specific configurations, but in many cases are not worth the cost, c) sample diversity shows the most promise in the downstream task of calibration, but otherwise fails to beat simpler alternatives, d) a deterministic approach is adequate for some downstream tasks, but ensembles allow for significant improvements if the right conditions can be achieved in deployment.

Ensemble disagreement is widely used as a proxy for epistemic uncertainty in medical image segmentation. In practice, many studies form ensembles via K-fold cross-validation (CV), yet refer to them as ``deep ensembles'' (DE). Because CV members are trained on different data subsets, their disagreement mixes seed-driven variability with data-exposure effects, which can change how uncertainty should be interpreted. We audit recent segmentation uncertainty studies and find that terminology--implementation mismatches are common. We then compare a standard 5-fold CV ensemble to a 5-member DE (fixed training set, different random seeds) under otherwise identical configurations on three multi-rater segmentation datasets spanning three modalities. We evaluate uncertainty for calibration, failure detection, ambiguity modeling, and robustness under distribution shift. DE match segmentation accuracy while improving calibration and failure detection, whereas CV ensembles sometimes correlate more strongly with inter-rater variability on the studied datasets. Thus, ensemble construction should be chosen to match the research question: DE for reliability-oriented use (e.g., selective referral/failure detection) and CV ensembles as a proxy for ambiguity. We provide a lightweight nnU-Net modification enabling DE training within the default pipeline.

In medical image segmentation, uncertainty estimates are often reported but rarely used to guide decisions. We study the missing step: how uncertainty maps are converted into actionable policies such as accepting, flagging, or deferring predictions. We formulate segmentation as a two-stage pipeline, estimation followed by decision, and show that optimizing uncertainty alone fails to capture most of the achievable safety gains. Using retinal vessel segmentation benchmarks (DRIVE, STARE, CHASE_DB1), we evaluate two uncertainty sources (Monte Carlo Dropout and Test-Time Augmentation) combined with three deferral strategies, and introduce a simple confidence-aware deferral rule that prioritizes uncertain and low-confidence predictions. Our results show that the best method and policy combination removes up to 80 percent of segmentation errors at only 25 percent pixel deferral, while achieving strong cross-dataset robustness. We further show that calibration improvements do not translate to better decision quality, highlighting a disconnect between standard uncertainty metrics and real-world utility. These findings suggest that uncertainty should be evaluated based on the decisions it enables, rather than in isolation.