Image-Conditioned Diffusion Models for Quality Assurance of Organ-at-Risk Segmentations in Radiotherapy

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.

Diffusion models can synthesise contrast-enhanced CT (CECT) from non-contrast CT (NCCT), avoiding contrast administration and its environmental and patient-access costs. However, visually realistic images are not necessarily anatomically correct, and the pixel-intensity and feature-space similarity metrics used to assess generation quality do not directly measure anatomical correctness. In this work, we investigate whether uncertainty can serve as a proxy for semantic correctness in diffusion-based medical image synthesis. We study NCCT-to-CECT synthesis using AortaDiff, a multitask diffusion framework that jointly generates CECT images and lumen segmentations. The segmentation output provides an explicit representation of the generated vascular anatomy, enabling segmentation-derived errors to be used as a quantitative measure of generation correctness. Six methods spanning weight (Ensemble, HyperDiff, BayesDiff), architecture-perturbation (MCDropout), generative-stochasticity (RDS) and input-perturbation (TTA) uncertainty are compared at the pixel, region and image levels, and for detection of clinically relevant out-of-distribution (OOD) cases. Uncertainty proves informative at all three spatial scales, remains informative on an external multi-centre dataset under distribution shift, and supports OOD detection. MCDropout stands out among the six: it ranks among the leading methods at every scale, generalizes well on the external dataset, and can be enabled at inference on any model already trained with dropout, so reliable uncertainty comes at no extra training cost. Uncertainty reliably flags severe failures but discriminates poorly among already high-quality images. These findings support uncertainty as a practical and computationally economical signal for quality filtering, reliability assessment and OOD detection in NCCT-to CECT synthesis.

Distribution-free risk control adds organ-specific recall guarantees to frozen segmentation. We calibrate per-organ thresholds for an AMOS-trained nnU-Net, audit transfer to RAOS, and estimate local re-certification cost using case-level voxel false-negative rate (FNR). The AMOS control passes, but $7/12$ organs exceed $α{=}0.10$ after transfer; smaller calibration sets can mask exceedances with conservative or vacuous thresholds. Risk-Controlling Prediction Sets (RCPS) give high-probability control of population-mean risk, whereas Conformal Risk Control (CRC) gives weaker expectation control. Both require exchangeability; fixed and global thresholds give no per-organ guarantee. The Waudby--Smith--Ramdas (WSR) betting bound re-certifies six Tier-1 organs with 25 local cases, versus 30--40 for Hoeffding--Bentkus (HB). CRC needs 10--15 but has a heavier individual-case tail. No Tier-2 organ meets our illustrative precision criterion with 25 cases.