# Improving PET/CT-Based Whole-Body Lesion Segmentation Using Prediction Uncertainty-Augmented Models

arXiv: https://arxiv.org/abs/2606.10115 · HTML: https://mlsanity.com/paper/2606.10115/

## Key facts

- No citing papers in the map yet (data through 14 Oct 2026).
- Builds on 24 of its 58 references that are in the map.
- First posted on arXiv 8 Jun 2026.

## Builds on (most cited first, 24 of 24)

- [U-Net: Convolutional Networks for Biomedical Image Segmentation](https://mlsanity.com/paper/1505.04597/) (2015)
- [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)
- [What Uncertainties Do We Need in Bayesian Deep Learning for Computer Vision?](https://mlsanity.com/paper/1703.04977/) (2017)
- [V-Net: Fully Convolutional Neural Networks for Volumetric Medical Image Segmentation](https://mlsanity.com/paper/1606.04797/) (2016)
- [On Large-Batch Training for Deep Learning: Generalization Gap and Sharp Minima](https://mlsanity.com/paper/1609.04836/) (2016)
- [A Review of Uncertainty Quantification in Deep Learning: Techniques, Applications and Challenges](https://mlsanity.com/paper/2011.06225/) (2020)
- [Evidential Deep Learning to Quantify Classification Uncertainty](https://mlsanity.com/paper/1806.01768/) (2018)
- [Predictive Uncertainty Estimation via Prior Networks](https://mlsanity.com/paper/1802.10501/) (2018)
- [Aleatoric uncertainty estimation with test-time augmentation for medical image segmentation with convolutional neural networks](https://mlsanity.com/paper/1807.07356/) (2018)
- [Shape-aware Meta-learning for Generalizing Prostate MRI Segmentation to Unseen Domains](https://mlsanity.com/paper/2007.02035/) (2020)
- [Assessing Reliability and Challenges of Uncertainty Estimations for Medical Image Segmentation](https://mlsanity.com/paper/1907.03338/) (2019)
- [Domain Generalization for Medical Image Analysis: A Review](https://mlsanity.com/paper/2310.08598/) (2023)
- [MaxStyle: Adversarial Style Composition for Robust Medical Image Segmentation](https://mlsanity.com/paper/2206.01737/) (2022)
- [From Denoising Training to Test-Time Adaptation: Enhancing Domain Generalization for Medical Image Segmentation](https://mlsanity.com/paper/2310.20271/) (2023)
- [Efficient Bayesian Uncertainty Estimation for nnU-Net](https://mlsanity.com/paper/2212.06278/) (2022)
- [From FDG to PSMA: A Hitchhiker's Guide to Multitracer, Multicenter Lesion Segmentation in PET/CT Imaging](https://mlsanity.com/paper/2409.09478/) (2024)
- [Bayesian U-Net for Segmenting Glaciers in SAR Imagery](https://mlsanity.com/paper/2101.03249/) (2021)
- [Autopet III challenge: Incorporating anatomical knowledge into nnUNet for lesion segmentation in PET/CT](https://mlsanity.com/paper/2409.12155/) (2024)
- [Accurate Esophageal Gross Tumor Volume Segmentation in PET/CT using Two-Stream Chained 3D Deep Network Fusion](https://mlsanity.com/paper/1909.01524/) (2019)
- [The autoPET3 Challenge: Automated Lesion Segmentation in Whole-Body PET/CT unicodex2013 Multitracer Multicenter Generalization](https://mlsanity.com/paper/2605.05775/) (2026)
- [Dual channel CW nnU-Net for 3D PET-CT Lesion Segmentation in 2024 autoPET III Challenge](https://mlsanity.com/paper/2409.07144/) (2024)
- [AutoPET Challenge: Tumour Synthesis for Data Augmentation](https://mlsanity.com/paper/2409.08068/) (2024)
- [Data-Centric Strategies for Overcoming PET/CT Heterogeneity: Insights from the AutoPET III Lesion Segmentation Challenge](https://mlsanity.com/paper/2409.10120/) (2024)

## Abstract (arXiv)

Accurate lesion segmentation from whole-body Positron Emission Tomography (PET)/Computed Tomography (CT) scans is essential for cancer staging and treatment planning. PET provides functional metabolic information with different radiotracers, while CT offers anatomical localization. Lesion delineation from PET/CT imaging is clinically challenging due to subtle imaging features, confounders, and inter-reader variability. Existing deep learning approaches suffer from training-related stochasticity, inconsistent predictions, missed lesions in high tumor-burden cases, and lack uncertainty quantification, limiting their clinical reliability. Using nnU-Net as a baseline, we propose an uncertainty-aware framework for whole-body PET/CT lesion segmentation that integrates (1) Bayesian ensembling to reduce training stochasticity, (2) voxel-wise uncertainty quantification with epistemic and aleatoric decomposition, and (3) epistemic uncertainty-augmented training to improve lesion detection. Two public datasets, AutoPET-III (1,611 scans) and Deep-PSMA (200 scans), comprising FDG and PSMA studies across multiple cancer types, are used for training and evaluation. Bayesian ensembling improves robustness and performance over deterministic nnU-Net models on the unseen AutoPET-III test set. Uncertainty maps highlight regions of model disagreement and correlate with misclassifications, particularly false positives. Uncertainty-augmented training improves lesion recovery at the cost of increased FPVol, reflecting a precision-recall trade-off. A case-adaptive routing strategy further improves Dice by selecting between the base and augmented models. To our knowledge, this is the first study to systematically investigate uncertainty quantification in multi-tracer, pan-cancer PET/CT segmentation and to combine Bayesian ensembling with uncertainty-aware modeling for this task.