# Explaining Uncertainty in Multiple Sclerosis Cortical Lesion Segmentation Beyond Prediction Errors

arXiv: https://arxiv.org/abs/2504.04814 · HTML: https://mlsanity.com/paper/2504.04814/

## Key facts

- No citing papers in the map yet (data through 14 Oct 2026).
- Builds on 33 of its 76 references that are in the map.
- First posted on arXiv 7 Apr 2025.

## Builds on (most cited first, 30 of 33)

- [U-Net: Convolutional Networks for Biomedical Image Segmentation](https://mlsanity.com/paper/1505.04597/) (2015)
- [On Calibration of Modern Neural Networks](https://mlsanity.com/paper/1706.04599/) (2017)
- [Dropout as a Bayesian Approximation: Representing Model Uncertainty in Deep Learning](https://mlsanity.com/paper/1506.02142/) (2015)
- [Simple and Scalable Predictive Uncertainty Estimation using Deep Ensembles](https://mlsanity.com/paper/1612.01474/) (2016)
- [3D U-Net: Learning Dense Volumetric Segmentation from Sparse Annotation](https://mlsanity.com/paper/1606.06650/) (2016)
- [Can You Trust Your Model's Uncertainty? Evaluating Predictive Uncertainty Under Dataset Shift](https://mlsanity.com/paper/1906.02530/) (2019)
- [Aleatoric and Epistemic Uncertainty in Machine Learning: An Introduction to Concepts and Methods](https://mlsanity.com/paper/1910.09457/) (2019)
- [A Survey of Uncertainty in Deep Neural Networks](https://mlsanity.com/paper/2107.03342/) (2021)
- [A Probabilistic U-Net for Segmentation of Ambiguous Images](https://mlsanity.com/paper/1806.05034/) (2018)
- [Effect of Confidence and Explanation on Accuracy and Trust Calibration in AI-Assisted Decision Making](https://mlsanity.com/paper/2001.02114/) (2020)
- [Aleatoric uncertainty estimation with test-time augmentation for medical image segmentation with convolutional neural networks](https://mlsanity.com/paper/1807.07356/) (2018)
- [SynthSeg: Segmentation of brain MRI scans of any contrast and resolution without retraining](https://mlsanity.com/paper/2107.09559/) (2021)
- [Trustworthy AI: From Principles to Practices](https://mlsanity.com/paper/2110.01167/) (2021)
- [Exploring Uncertainty Measures in Deep Networks for Multiple Sclerosis Lesion Detection and Segmentation](https://mlsanity.com/paper/1808.01200/) (2018)
- [Evaluating Bayesian Deep Learning Methods for Semantic Segmentation](https://mlsanity.com/paper/1811.12709/) (2018)
- [PHiSeg: Capturing Uncertainty in Medical Image Segmentation](https://mlsanity.com/paper/1906.04045/) (2019)
- [Shifts: A Dataset of Real Distributional Shift Across Multiple Large-Scale Tasks](https://mlsanity.com/paper/2107.07455/) (2021)
- [A Deeper Look into Aleatoric and Epistemic Uncertainty Disentanglement](https://mlsanity.com/paper/2204.09308/) (2022)
- [Trustworthy clinical AI solutions: a unified review of uncertainty quantification in deep learning models for medical image analysis](https://mlsanity.com/paper/2210.03736/) (2022)
- [FUTURE-AI: International consensus guideline for trustworthy and deployable artificial intelligence in healthcare](https://mlsanity.com/paper/2309.12325/) (2023)
- [A Review of Uncertainty Estimation and its Application in Medical Imaging](https://mlsanity.com/paper/2302.08119/) (2023)
- [Prediction Error Meta Classification in Semantic Segmentation: Detection via Aggregated Dispersion Measures of Softmax Probabilities](https://mlsanity.com/paper/1811.00648/) (2018)
- [Bayesian QuickNAT: Model Uncertainty in Deep Whole-Brain Segmentation for Structure-wise Quality Control](https://mlsanity.com/paper/1811.09800/) (2018)
- [A review of uncertainty quantification in medical image analysis: probabilistic and non-probabilistic methods](https://mlsanity.com/paper/2310.06873/) (2023)
- [Explanation and Use of Uncertainty Quantified by Bayesian Neural Network Classifiers for Breast Histopathology Images](https://mlsanity.com/paper/2010.12575/) (2020)
- [Annotator Consensus Prediction for Medical Image Segmentation with Diffusion Models](https://mlsanity.com/paper/2306.09004/) (2023)
- [Novel structural-scale uncertainty measures and error retention curves: application to multiple sclerosis](https://mlsanity.com/paper/2211.04825/) (2022)
- [Structural-Based Uncertainty in Deep Learning Across Anatomical Scales: Analysis in White Matter Lesion Segmentation](https://mlsanity.com/paper/2311.08931/) (2023)
- [Beyond Voxel Prediction Uncertainty: Identifying brain lesions you can trust](https://mlsanity.com/paper/2209.10877/) (2022)
- [Boundary-weighted logit consistency improves calibration of segmentation networks](https://mlsanity.com/paper/2307.08163/) (2023)

## Abstract (arXiv)

Trustworthy artificial intelligence (AI) is essential in healthcare, particularly for high-stakes tasks like medical image segmentation. Explainable AI and uncertainty quantification significantly enhance AI reliability by addressing key attributes such as robustness, usability, and explainability. Despite extensive technical advances in uncertainty quantification for medical imaging, understanding the clinical informativeness and interpretability of uncertainty remains limited. This study presents an interpretability framework for analyzing lesion-scale predictive uncertainty in cortical lesion segmentation in multiple sclerosis using deep ensembles. The analysis shifts the focus from the uncertainty--error relationship towards clinically relevant medical and engineering factors. Our findings reveal that instance-wise uncertainty is strongly related to lesion size, shape, and cortical involvement. Expert rater feedback confirms that similar factors impede annotator confidence. Evaluations conducted on two datasets (206 patients, almost 2000 lesions) under both in-domain and distribution-shift conditions highlight the utility of the framework in different scenarios.