Budget-Aware Uncertainty for Radiotherapy Segmentation QA Using nnU-Net
Authors: Ricardo Coimbra Brioso, Lorenzo Mondo, Damiano Dei, Nicola Lambri, Pietro Mancosu, Marta Scorsetti, Daniele Loiacono
Organizations: Dipartimento di Elettronica, Informazione e Bioingegneria, Politecnico di Milano, Milan, Italy · Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy · Radiotherapy and Radiosurgery Department, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy
Accurate delineation of the Clinical Target Volume (CTV) is essential for radiotherapy planning, yet remains time-consuming and difficult to assess, especially for complex treatments such as Total Marrow and Lymph Node Irradiation (TMLI). While deep learning-based auto-segmentation can reduce workload, safe clinical deployment requires reliable cues indicating where models may be wrong. In this work, we propose a budget-aware uncertainty-driven quality assurance (QA) framework built on nnU-Net, combining uncertainty quantification and post-hoc calibration to produce voxel-wise uncertainty maps (based on predictive entropy) that can guide targeted manual review. We compare temperature scaling (TS), deep ensembles (DE), checkpoint ensembles (CE), and test-time augmentation (TTA), evaluated both individually and in combination on TMLI as a representative use case. Reliability is assessed through ROI-masked calibration metrics and uncertainty--error alignment under realistic revision constraints, summarized as AUC over the top 0-5% most uncertain voxels. Across configurations, segmentation accuracy remains stable, whereas TS substantially improves calibration. Uncertainty-error alignment improves most with calibrated checkpoint-based inference, leading to uncertainty maps that highlight more consistently regions requiring manual edits. Overall, integrating calibration with efficient ensembling seems a promising strategy to implement a budget-aware QA workflow for radiotherapy segmentation.
Figures & tables
Method
DSC ↑
ECE ↓
BS ↓
BASE
0.838 ± 0.046 *
0.062 ± 0.015 *
0.068 ± 0.014 *
BASE+TS
0.838 ± 0.046 *
0.031 ± 0.006
0.059 ± 0.011 *
BASE+TTA
0.837 ± 0.045 *
0.042 ± 0.015 *
0.063 ± 0.013 *
BASE+TS+TTA
0.837 ± 0.045 *
0.034 ± 0.009
0.059 ± 0.010 *
DE
0.843 ± 0.044
0.058 ± 0.015 *
0.065 ± 0.014 *
DE+TS
0.843 ± 0.044
0.031 ± 0.008
0.056 ± 0.011
TABLE I: Summary of DSC and ROI-masked calibration metrics (mean ± std); bold indicates the best method per metric; a global Friedman test across the 12 methods showed significant differences for all metrics ( p<0.0001 ); * denotes results significantly different from the best method after FDR correction ( α=0.05 ).
Method
UEOAUC
(FP−TP)AUC
(FN−TN)AUC
BASE
0.154 ± 0.037 *
0.057 ± 0.023 *
0.674 ± 0.092 *
BASE+TS
0.170 ± 0.040
0.067 ± 0.027 *
0.876 ± 0.043 *
BASE+TTA
0.169 ± 0.039 *
0.078 ± 0.031 *
0.886 ± 0.040 *
BASE+TS+TTA
0.170 ± 0.039
0.072 ± 0.029 *
0.888 ± 0.038 *
DE
0.152 ± 0.038 *
0.059 ± 0.026 *
0.701 ± 0.081 *
DE+TS
0.167 ± 0.042 *
0.078 ± 0.032 *
0.894 ± 0.029 *
TABLE II: Summary of AUC metrics (mean ± std); bold indicates the best method per metric; a global Friedman test across the 12 methods showed significant differences for all metrics ( p<0.0001 ); * denotes results significantly different from the best method after FDR correction ( α=0.05 ).
UEO
FPcoverage
FNcoverage
Method
0.5%
1%
2%
5%
0.5%
1%
2%
5%
0.5%
1%
2%
5%
BASE
0.374 *
0.240 *
0.131 *
0.056
0.887 *
0.991
1.000
1.000
0.687 *
0.718 *
0.721 *
0.729 *
BASE+TS
0.383
0.266
0.154
0.066
0.897 *
0.995
1.000
1.000
0.716 *
0.881 *
0.969 *
0.978 *
BASE+TTA
0.379 *
0.268
0.155
0.066
0.867 *
0.992 *
1.000
1.000
0.731 *
0.896 *
0.977 *
0.986 *
BASE+TS+TTA
0.386
0.267
0.155
0.066
0.890 *
0.995
1.000
1.000
0.739 *
0.895 *
0.979 *
0.988 *
DE
0.374 *
0.236 *
0.129 *
0.055
0.906
0.994
1.000
1.000
0.715 *
0.747 *
0.749 *
0.757 *
TABLE III: Point-wise summary of UEO , FPcoverage , and FNcoverage at 0.5%, 1%, 2%, and 5% uncertain-volume budgets; bold indicates the best value per metric–percentage column; ∗ denotes results significantly different from the best one after FDR correction ( α=0.05 ).
Fig. 1: Budget-aware uncertainty visualization on three axial slices from a representative case (AUTOMI_0007), comparing DE and CE+TS+TTA. The first and fourth rows overlay the filled ground truth (green) and prediction (red). Subsequent rows show entropy-based uncertainty maps thresholded by uncertain-volume budgets (top-0.5%, 1%, and 2% most uncertain voxels), displayed with the ground-truth contour (green). DE at 2% is omitted since not informative, i.e., <1% of voxels have non-zero uncertainty.
Medical image segmentation models often report high benchmark accuracy under ideal imaging conditions, yet their failures under clinical degradation can be quiet: sensor noise, patient motion, low- resolution acquisition, and contrast variability may all alter model behavior without producing an obvious warning. We present a reproducible framework for evaluating uncertainty-aware segmentation under con- trolled clinical degradation. Our experiments use a synthetic multimodal brain tumor MRI cohort generated with a biophysical phantom simulator that follows the BraTS protocol. We train U-Net and Attention U-Net baselines for multi-class tumor sub-region segmentation and augment both models with Monte Carlo dropout to estimate per-voxel uncertainty. Across eight clinically motivated corruption types at five severity levels, we measure segmentation accuracy, calibration, failure detection, and selective prediction coverage. On clean data, Attention U-Net achieves a whole-tumor Dice of 0.990; under severe Gaussian noise, its performance falls to 0.089. Predictive uncertainty rises with degradation and tracks segmentation error (Pearson r = 0.53 under severity-3 Gaussian noise), allowing us to flag failures with an AUROC of 0.843. These results argue for uncertainty-aware inference as a practical safety layer in physician-in-the-loop radiology workflows. We release the code, trained models, and evaluation protocol to support direct reproduction.
Pranav Kaliaperumal, Manisha Kaliaperumal
Department of Computer Science University of Colorado Denver Aurora, CO, USA · Department of Biology (Pre-Medical) Creighton University Omaha, NE, USA
Glioma segmentation in multiparametric MRI is a critical component of treatment planning. A segmentation model that fails silently on treatment-critical sub-regions represents a patient safety risk that overlap-based metrics such as Dice scores cannot expose. We ask whether voxel-level uncertainty estimation via Monte Carlo (MC) Dropout can reliably identify segmentation errors in clinically critical sub-regions, and whether calibration failure modes are detectable from standard reporting metrics alone. In an empirical two-model case study on 126 BraTS21 patients, we evaluate a high-performance pretrained SegResNet and a locally trained UNet with residual units (UNet-Res). MC dropout preserved segmentation accuracy (∣ΔDice∣<0.01) while achieving strong uncertainty-error alignment (AUROC for entropy (H) ≈0.97), indicating uncertainty correctly ranks erroneous voxels above correct ones. Entropy-based patient stratification identified a high-uncertainty subgroup with substantially lower segmentation performance (median whole-tumour Dice 0.835 vs. 0.925), supporting uncertainty as a practical triage signal. However, global alignment can mask important region-specific differences. Despite similar AUROC, UNet-Res exhibited near-zero enhancing tumour entropy (0.054) and Expected Calibration Error (ECE) of 0.915, with a Dice of only 0.714, indicating severely miscalibrated confidence on the most clinically critical sub-region, a failure mode invisible to standard Dice and AUROC reporting. These findings demonstrate that strong uncertainty-error alignment is necessary but insufficient for clinical safety: sub-region-specific calibration assessment must accompany AUROC evaluation when selecting models for clinical deployment.
Xin Ci Wong, Duygu Sarikaya, Kieran Zucker +2
Centre for Doctoral Training in AI for Medical Diagnosis and Care, School of Computing, University of Leeds · School of Computer Science, University of Leeds · Leeds Cancer Centre, St James’s University Hospital, Leeds, UK
Reliable uncertainty estimation is critical for medical image segmentation, where automated contours feed downstream quantification and clinical decision support. Many strong uncertainty methods require repeated inference, while efficient single-forward-pass alternatives often provide weaker failure ranking or rely on restrictive feature-space assumptions. We present SegWithU, a post-hoc framework that augments a frozen pretrained segmentation backbone with a lightweight uncertainty head. SegWithU taps intermediate backbone features and models uncertainty as perturbation energy in a compact probe space using rank-1 posterior probes. It produces two voxel-wise uncertainty maps: a calibration-oriented map for probability tempering and a ranking-oriented map for error detection and selective prediction. Across ACDC, BraTS2024, and LiTS, SegWithU is the strongest and most consistent single-forward-pass baseline, achieving AUROC/AURC of 0.9838/2.4885, 0.9946/0.2660, and 0.9925/0.8193, respectively, while preserving segmentation quality. These results suggest that perturbation-based uncertainty modeling is an effective and practical route to reliability-aware medical segmentation. Source code is available at https://github.com/ProjectNeura/SegWithU.
Tianhao Fu, Austin Wang, Charles Chen +2
University of Toronto, Toronto, ON, Canada · Vector Institute, Toronto, ON, Canada · Project Neura, Toronto, ON, Canada +4