Medical segmentation uncertainty is often evaluated with calibration error or pixel-level error-detection scores, but these metrics do not show whether uncertainty improves downstream review decisions. We propose a decision-aware evaluation protocol that separates uncertainty estimation from deferral policy and evaluates their combination under fixed review budgets: which pixels, regions, or images should be accepted, and which should be reviewed. The protocol reports fixed-budget error reduction, risk-coverage behaviour, region-level review proxies, structural failure modes, probability-derived baselines, and sensitivity to review assumptions. We instantiate it across retinal vessel, skin lesion, and polyp segmentation with multiple backbones and uncertainty estimators. Under matched inference budgets and canonical multi-layer MC Dropout, test-time augmentation (TTA) gives a stronger error-detection signal across matched MC--TTA comparisons, including architecture and dropout-placement checks. However, estimator rankings are not universal. For example, probability-derived scores remain competitive, deep ensembles can outperform TTA, learned deferral helps mainly when the base estimator is weak, and rankings can change with review unit, uncertainty target, correction assumptions, and cost model. Structural and second-observer analyses further show that boundary and thin-structure failures are partly tied to annotation ambiguity. These findings support evaluating uncertainty as an estimator-policy-review configuration, not as a standalone score map. Code: https://anonymous.4open.science/r/Uncertainity-in-Medical-Image-Segmentation/README.md
Figures & tables
Figure 1: Decision-aware evaluation separates uncertainty estimation from the review decision . A trained segmentation backbone produces p^ and y^ ; an estimator, ensemble, or probability-derived baseline produces a score map u ; and a deferral policy ranks pixels or regions under budget β . ERR@ β , risk–coverage AURC, region error capture, and review-assumption sensitivity are measured after this decision, not from the uncertainty map alone.
Dataset
Train
Val / fit
Test
Split status
DRIVE
16
4
20
official test
FIVES
520
120
160
self-defined
ISIC 2018
1686
389
519
self-defined
Kvasir-SEG
650
150
200
self-defined
Table 1: Dataset splits and fitting data. DRIVE uses the official 20-image test set with a self-defined train/validation split. FIVES, ISIC, and Kvasir use fixed 65/15/20 splits. Learned heads and adaptive policies are fit only on validation images.
Comparison family
Positive
BH sig.
Mean Δ
Matched budget, anchor
24/24
24/24
+0.035
10 MC realizations
24/24
24/24
+0.033
Complementary backbone
24/24
24/24
+0.063
Dropout placement
72/72
72/72
+0.075
Dropout rate, DRIVE only
24/24
18/24
+0.015
Training seed, DRIVE only
15/18
10/18
+0.009
Table 2: Matched-budget MC–TTA robustness. Each row is a paired image-level comparison family with BH correction applied within that family. Positive cells favour TTA.
Dataset
Func.
MC-T6
MC-T50
TTA-T6
Ens.
ΔEns
DRIVE
Var
0.839
0.857
0.858
0.806
−0.052∗
DRIVE
MI
0.852
0.868
0.868
0.799
−0.069∗
FIVES
Var
0.852
0.878
0.858
0.881
+0.023∗
FIVES
MI
0.859
0.882
0.872
0.886
+0.014∗
ISIC
Var
0.803
0.840
0.867
0.896
+0.029∗
ISIC
MI
0.821
0.851
0.874
0.894
+0.019∗
Table 3: Estimator family changes the ranking. Mean image-level error-detection AUROC on the same held-out images. TTA uses six transforms. Δ values are paired differences against TTA-T6; positive means the competitor is better. Asterisks denote BH-corrected significance within the comparison family.
Figure 2: The score ranking is not the decision ranking. Per cell, TTA raw uncertainty and the probability baseline are compared under a score-level metric (left: error-detection AUROC) and a decision-level metric (right: fraction of all errors captured at a 20% review budget). Rankings can flip at the decision point.
Figure 3: Decision-layer sensitivity on the DRIVE anchor. Fraction of tested settings in which changing one review assumption changes the preferred estimator. Predictions are held fixed, so reversals isolate the decision layer. These are finite-grid sensitivity summaries, not population estimates.
Figure 4: DRIVE second-observer analysis. Uncertainty is near chance on pixels where the two observers disagree; changing the target definition changes the AUROC; and boundary conclusions depend on the morphological radius, while thin-structure effects are more stable.
Audit
Main result
Learned deferral
Capt.@20% improves in 16/18 cell–estimator settings; DRIVE uses only 4 validation images for fitting.
4/18 significantly better, 9/18 significantly worse, 5/18 n.s.; refitting is usually safer.
DRIVE second observer
Global MC–TTA differences are n.s.; TTA gains concentrate on thin structures ( +0.072 variance, +0.075 MI).
Human-disagreement target
MI AUROC is 0.813 for MC and 0.817 for TTA, but all scores are near chance on disputed pixels.
Table 4: Policy, transfer, and annotation audits. Compact summary of decision-layer results. Learned-deferral counts use the deployable validation-fit protocol; transfer uses source-validation fitting and held-out target tests.
Coordinate
What should be reported
Estimator
MC/TTA/ensemble/probability score and uncertainty functional.
Compute
Number of passes or ensemble members; matched or deliberately swept.
Backbone
Segmentation checkpoint and whether the comparator changes it.
Policy
Raw ranking, adaptive threshold, learned head, or conformal rule.
Fitting data
Validation images used for policy fitting; no test-label fitting.
Review unit
Pixel, block, patch, connected component, region, or image.
Table 5: Minimum reporting checklist for decision-aware uncertainty evaluation. The estimator alone is insufficient; the reported result should identify the full configuration that turns uncertainty into a review decision.
Dataset
Architecture
Wave
Train
Val
Test
Split status
MC
TTA
Ens.
Head fit
Head eval
DRIVE
U-Net
canonical + Waves A/C/D/E/F
16
4
20
official test, self-defined train/val
20
20
20
4
20
DRIVE
MiT-B2 TransUNet
Wave B (complementary architecture)
16
4
20
official test, self-defined train/val
20
20
0
0
0
FIVES
MiT-B2 encoder + U-Net decoder
canonical + Waves A/C/D/E/F
520
120
160
self-defined
160
160
160
120
160
FIVES
U-Net
Wave B (complementary architecture)
520
120
160
self-defined
160
160
0
0
0
ISIC
U-Net
canonical + Waves A/C/D/E/F
1686
389
519
self-defined
519
519
519
389
519
ISIC
MiT-B2 TransUNet
Wave B (complementary architecture)
1686
389
519
self-defined
519
519
0
0
0
Table 6: Exact split and analysis counts. DRIVE uses the official 20-image test half but a self-defined 16/4 train/validation subdivision. FIVES, ISIC, and Kvasir use self-defined 65/15/20 splits (seed 42). Zero denotes an analysis not run for that architecture arm.
T=2
T=4
T=6
Dataset
Func.
MC
Δ
MC
Δ
MC
Δ
DRIVE
Var
0.805
+0.017 *
0.831
+0.019 *
0.839
+0.019 *
DRIVE
MI
0.807
+0.016 *
0.843
+0.017 *
0.852
+0.016 *
FIVES
Var
0.829
+0.004 *
0.844
+0.008 *
0.852
+0.007 *
FIVES
MI
0.837
+0.010 *
0.853
+0.014 *
0.859
+0.014 *
ISIC
Var
0.761
+0.056 *
0.793
+0.060 *
0.803
+0.064 *
Table 7: Matched inference budgets, canonical multi-layer MC Dropout. Mean image-level error-detection AUROC; MC and TTA draw the same T passes from the same checkpoint on the same images. Δ is the paired per-image mean TTA − MC; * marks q<0.05 after BH correction across this family of 24. TTA leads in all 24 and every bootstrap interval excludes zero.
Axis
TTA
BH
mean Δ
range Δ
Matched budget, anchor (4 ds)
24/24
24/24
+0.035
[+0.004, +0.065]
10 MC realizations (4 ds)
24/24
24/24
+0.033
[+0.003, +0.063]
Complementary backbone (4 ds)
24/24
24/24
+0.063
[+0.015, +0.133]
Dropout placement (4 ds)
72/72
72/72
+0.075
[+0.004, +0.250]
Dropout rate p (DRIVE)
24/24
18/24
+0.015
[+0.003, +0.038]
Training seed (DRIVE)
15/18
10/18
+0.009
[-0.004, +0.020]
Table 8: Robustness across every configuration axis raised in review. Each row is an independent family of paired image-level comparisons with its own BH correction; “TTA” counts positive point estimates and “BH” counts q<0.05 . The matched-budget, replication, architecture, and placement families are uniformly positive; the two DRIVE-only sweeps show smaller effects, non-significant cells, and three tiny seed reversals.
Figure 5: Complementary architecture audit. DRIVE, ISIC, and Kvasir are evaluated with a MiT-B2 TransUNet variant, while FIVES is evaluated with a U-Net variant. The paired TTA–MC effect remains positive in all budget–functional comparisons after the architecture swap.
Figure 6: Unequal compute changes the MC–TTA comparison. TTA is held at six passes while MC Dropout is increased to 10, 20, 30, and 50 stochastic passes. DRIVE approaches a tie, FIVES crosses to MC, and ISIC/Kvasir remain TTA-favourable in the tested settings.
Figure 7: Estimator family can change the winner. Five-member deterministic deep ensembles outperform TTA on FIVES and ISIC, underperform it on DRIVE, and are statistically indistinguishable from TTA on Kvasir after correction.
mean image AUROC
Δ vs TTA-T6
Dataset
Func.
MC T6
MC T50
TTA T6
Ens. 5
MC T50
Ens. 5
DRIVE
Var
0.839
0.857
0.858
0.806
-0.001
-0.052 *
DRIVE
MI
0.852
0.868
0.868
0.799
+0.000
-0.069 *
FIVES
Var
0.852
0.878
0.858
0.881
+0.019 *
+0.023 *
FIVES
MI
0.859
0.882
0.872
0.886
+0.010 *
+0.014 *
ISIC
Var
0.803
0.840
0.867
0.896
-0.028 *
+0.029 *
Table 9: No estimator family wins everywhere once budget is unconstrained. Mean image AUROC, same images and backbone throughout; TTA uses 6 passes. Δ columns are paired differences against TTA-T6 , so positive means the competitor is better; * is q<0.05 within each column’s family. At 8× the passes MC ties TTA on DRIVE and overtakes it on FIVES; deep ensembles beat TTA on FIVES and ISIC and lose on DRIVE.
Dataset
Train
Val / fit imgs
Test
Capt.@20 wins
DRIVE
16
4
20
2/2
FIVES
520
120
160
2/4
ISIC
1686
389
519
4/4
Kvasir
650
150
200
8/8
Total
–
–
–
16/18
Table 10: Learned-deferral accounting. The deployable head is fitted on the held-out validation split and evaluated on test. The separate five-fold test-distribution cross-fit is retained only as a diagnostic upper bound.
Cell
Arm
Fit imgs
Eval imgs
Learned
Plain u
Δ
95% CI
q
drive/unet
MC
4
20
0.796
0.623
+0.173 ∗
[+0.133,+0.218]
<.001
drive/unet
TTA
4
20
0.830
0.817
+0.013 ∗
[+0.010,+0.015]
<.001
fives/unet
MC
120
160
0.861
0.790
+0.071 ∗
[+0.059,+0.084]
<.001
fives/unet
TTA
120
160
0.924
0.928
-0.004 ∗
[-0.004,-0.003]
<.001
fives/unetpp
MC
120
160
0.838
0.778
+0.061 ∗
[+0.053,+0.069]
<.001
fives/unetpp
TTA
120
160
0.908
0.909
-0.001
[-0.002,+0.001]
0.337
Table 11: Deployable validation-fitted learned deferral at Capt.@20%. The head is fitted only on each cell’s validation split and evaluated on test. Δ= learned minus plain uncertainty; ∗ denotes BH q<.05 within the corresponding estimator family.
Arm
Source
Target
n
Transfer
Reference
Δ
95% CI
q
Verdict
A cross domain
kvasir/unetpp
fives/unetpp
160
0.0023
0.0022
+0.0002 ∗
[+0.0001,+0.0002]
<.001
Reference
A cross domain
fives/unetpp
kvasir/unetpp
200
0.0236
0.0082
+0.0154 ∗
[+0.0102,+0.0212]
<.001
Reference
A cross domain
kvasir/deeplabv3plus
isic/deeplabv3plus
519
0.0074
0.0081
-0.0008 ∗
[-0.0011,-0.0004]
<.001
Transfer
A cross domain
isic/deeplabv3plus
kvasir/deeplabv3plus
200
0.0083
0.0084
-0.0001
[-0.0002,+0.0000]
0.086
n.s.
A cross domain
drive/unet
fives/unet
160
0.0019
0.0018
+0.0001 ∗
[+0.0000,+0.0001]
<.001
Reference
A cross domain
fives/unet
drive/unet
20
0.0173
0.0151
+0.0021 ∗
[+0.0019,+0.0024]
<.001
Reference
Table 12: Clean TTA policy transfer versus raw target uncertainty (AURC, 18 pairs). Source policies are fitted on source validation data and evaluated on the full target test set. AURC is lower-is-better, so negative Δ= transfer minus reference favours transfer. ∗ denotes BH q<.05 across the 18-pair family.
Arm
Source
Target
n
Transfer
Reference
Δ
95% CI
q
Verdict
A cross domain
kvasir/unetpp
fives/unetpp
160
0.0023
0.0021
+0.0002 ∗
[+0.0002,+0.0003]
<.001
Reference
A cross domain
fives/unetpp
kvasir/unetpp
200
0.0236
0.0082
+0.0153 ∗
[+0.0102,+0.0211]
<.001
Reference
A cross domain
kvasir/deeplabv3plus
isic/deeplabv3plus
519
0.0074
0.0059
+0.0015 ∗
[+0.0007,+0.0023]
<.001
Reference
A cross domain
isic/deeplabv3plus
kvasir/deeplabv3plus
200
0.0083
0.0082
+0.0001
[-0.0000,+0.0002]
0.100
n.s.
A cross domain
drive/unet
fives/unet
160
0.0019
0.0020
-0.0001 ∗
[-0.0002,-0.0001]
<.001
Transfer
A cross domain
fives/unet
drive/unet
20
0.0173
0.0126
+0.0047 ∗
[+0.0039,+0.0056]
<.001
Reference
Table 13: Clean TTA policy transfer versus an in-domain refit (AURC, 18 pairs). Negative Δ= transfer minus reference favours transfer. The mixed result shows that target-domain refitting is usually safer than transferring the source policy. ∗ denotes BH q<.05 across the 18-pair family.
Figure 8: Decision-layer reversal rates on the DRIVE anchor. Predictions are held fixed while one review assumption is varied. These are finite-grid sensitivity summaries, not population rates.
Table 14: CPU decision-assumption campaign. All analyses reuse stored prediction artifacts. PASS_WITH_LIMITATION is retained rather than collapsed into PASS; the separately planned cross-domain EXP14 is blocked because comparable non-DRIVE validation maps were not retained and is not treated as a null result.
Figure 9: DRIVE second-observer audit. Disagreement is the XOR of the two manual annotations inside the DRIVE field of view. Human disagreement is concentrated near vessel boundaries, while uncertainty is near chance on the disputed pixels themselves.
Score
Region
MC
TTA
Δ
95% CI
q
variance
Global
0.857
0.859
+0.001
[-0.005,+0.009]
0.862
variance
DisAgree
0.474
0.473
-0.001
[-0.008,+0.006]
0.971
variance
Agree
0.922
0.924
+0.002
[-0.001,+0.006]
0.444
variance
Boundary r=2
0.714
0.717
+0.003
[-0.000,+0.005]
0.164
variance
Thin r=1
0.514
0.585
+0.072 ∗
[+0.061,+0.084]
<.001
MI
Global
0.868
0.868
+0.000
[-0.005,+0.007]
0.971
Table 15: DRIVE second-observer MC–TTA audit ( n=20 ). Scores detect model error with respect to observer 2. Δ= TTA − MC. Global MC/TTA differences are negligible; the robust positive difference is concentrated on thin structures. Second-observer evidence is DRIVE-only.
Dataset
Region
r
n
Region frac.
MC
TTA
Δ
95% CI
DRIVE
Boundary
1
20
0.154
0.621
0.625
+0.005
[+0.002,+0.007]
DRIVE
Boundary
2
20
0.267
0.714
0.717
+0.003
[-0.000,+0.005]
DRIVE
Boundary
3
20
0.356
0.761
0.760
-0.001
[-0.004,+0.002]
DRIVE
Boundary
4
20
0.429
0.786
0.783
-0.003
[-0.007,+0.000]
DRIVE
Thin
1
20
0.071
0.514
0.585
+0.072
[+0.061,+0.084]
DRIVE
Thin
2
20
0.107
0.624
0.694
+0.070
[+0.059,+0.082]
Table 16: Boundary/thin-region radius sweep (variance AUROC). Δ= TTA − MC. The DRIVE boundary sign changes at radii 3–4, whereas the thin-structure advantage remains positive. Other datasets are included to expose radius sensitivity rather than canonize one radius.
Figure 10: Representative qualitative examples across domains. Examples make the ranking problem concrete rather than supporting a new quantitative claim. High uncertainty tends to concentrate around difficult boundaries, small structures, and local segmentation failures, while different estimators allocate review mass differently.
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.
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
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