Abstract

Accurate hippocampal segmentation can be a useful tool for diagnosing and monitoring neurological conditions such as Alzheimer’s disease and epilepsy. While numerous automated segmentation methods exist, their clinical adoption remains limited. Reliable uncertainty assessment can enhance trust and facilitate clinical translation. This study evaluates ensembles of five heterogeneous hippocampal segmentation methods — InnerEye, ASHS, FastSurfer, HippoSeg, and FreeSurfer — across two dementia datasets and one epilepsy dataset. The sub-ensemble containing InnerEye, FastSurfer, and HippoSeg emerged as both accurate and efficient, highlighting the feasibility of balancing computational cost and performance. Additionally, ensemble-derived uncertainty quantification with sample variance, mutual information, and predictive entropy is shown to reduce inaccurate segmentations by flagging low-confidence cases, potentially providing a mechanism for automatically escalating ambiguous cases for expert assessment. Lastly, this study explores the downstream clinical utility of ensemble-derived uncertainty, finding a significant correlation with motion artefact severity and a modest contribution to Alzheimer’s disease classification.