Advanced Tumor Segmentation in PET/CT Imaging: A Training Strategy Study with nnU-Net for AutoPET III

We report the design and results of the third autoPET challenge (MICCAI 2024), which benchmarked automated lesion segmentation in whole-body PET/CT under a compositional generalization setting. Training data comprised 1,014 [18F]-FDG PET/CT studies from the University Hospital Tübingen and 597 [18F]/[68Ga]-PSMA PET/CT studies from the LMU University Hospital Munich, constituting the largest publicly available annotated PSMA PET/CT dataset to date. The held-out test set of 200 studies covered four tracer-center combinations, two of which represented unseen compositional pairings. A complementary data-centric award category isolated the contribution of data handling strategies by restricting participants to a fixed baseline model. Seventeen teams submitted 27 algorithms, predominantly nnU-Net-based 3D networks with PET/CT channel concatenation. The top-ranked algorithm achieved a mean DSC of 0.66, FNV of 3.18 mL, and FPV of 2.78 mL across all four test conditions, improving DSC by 8% and reducing the false-negative volume by 5 mL relative to the provided baseline. Ranking was stable across bootstrap resampling and alternative ranking schemes for the top tier. Beyond the benchmark, we provide an in-depth analysis of segmentation performance at the patient and lesion level. Three main conclusions can be drawn: (1) in-domain multitracer PET/CT segmentation is sufficient and probably approaching reader agreement; (2) compositional generalization to unseen tracer-center combinations remains an open problem mainly driven by systematic volume overestimation; (3) heterogeneity and case difficulty drive performance variation substantially more than the choice of algorithm among top-ranked teams.

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.

Automated lesion segmentation in whole-body PET/CT is complicated by the variety of physiological tracer uptake patterns and by the differing appearance of lesions across tracers. The autoPET/CT V challenge addresses this by making segmentation interactive: user scribbles marking foreground and background are supplied alongside the image, and the algorithm is expected to exploit them. We present our submission, a scribble-conditioned residual encoder U-Net operating on four input channels: CT, PET, and a sparse scribble map for each of foreground and background. The network is initialised from the autoPET-III winning weights and extended from two to four input channels, with the two scribble channels zero-initialised so that the pretrained representation is preserved exactly at initialisation. Every model is fine-tuned per fold from the corresponding autoPET-III fold checkpoint, so that no validation case is seen during pretraining. PET intensities are normalised against a per-scan aorta blood-pool reference derived from a CT segmentation, which removes tracer- and centre-specific scaling without requiring lesion labels. At inference the five fold models are ensembled by averaging their softmax outputs per sliding-window patch, before Gaussian-weighted stitching. On the challenge's five-fold split, with each fold evaluated on its own validation cases, mean Dice is 0.554 and mean lesion-level F1 is 0.528 without scribbles, rising to 0.751 and 0.733 after five correction rounds. About 85% of that gain follows the first scribble, and the spread between fold models narrows five-fold over the same rounds, so interaction largely compensates for how well or badly a given model segments unaided.