An Open Multi-Center Whole-Body FDG PET/CT Foundation Model for Tumor Segmentation

Organ segmentation from PET/CT is critical for quantitative analysis and radiotherapy planning in oncology. To ease the high annotation cost of PET/CT segmentation, semi-supervised learning (SSL) provides a practical and effective solution for developing deep models with limited labeled data. Recent developments in visual foundation models have demonstrated remarkable adaptability with improved efficiency. In this work, we propose a mutual distillation framework that seamlessly exploits both structural and functional foundation models, which act as modality-specific generalists for distilling knowledge from structural CT and metabolic PET imaging. By bridging the gap between the task-specific precision of student models and the segmentation priors of generalist foundation models, we propose \textbf{MuDuo}, a mutual distillation framework that synergistically leverages SAM-Med3D for CT and SegAnyPET for PET to distill their knowledge into a lightweight student network. Our approach eliminates the need for manual prompts while maximizing the utility of unlabeled data for automatic segmentation, achieving state-of-the-art performance on the AutoPET dataset with only 5 labeled cases. Our source code is available at https://github.com/Wu-beining/MuDuo.

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 imaging can assist clinicians with cancer detection, staging, and treatment planning across radiotracers and cancer types. However, training lesion segmentation models that capture variations in lesion size, distribution, and appearance requires large annotated datasets, whose creation is both time- and expertise-intensive. As a result, models trained on limited labeled PET/CT data often lack the accuracy and generalizability needed for clinical use. We present FEEDS (Foundation model-Enabled Efficient Data Sampling), a label- and compute-efficient learning strategy that uses vision foundation model embeddings to select the most informative and diverse unlabeled cases for expert annotation. Unlike unsupervised, semi-supervised, and active learning approaches, FEEDS is a one-step training paradigm requiring only a limited, representative training set, making it label- and compute-efficient. We train and validate FEEDS using the AutoPET-III dataset. We test its accuracy and generalizability on three held-out sets: AutoPET-III, DeepPSMA, and an internal Dartmouth-Hitchcock Medical Center dataset. We evaluate clinical utility at the voxel, lesion, and anatomic region level to assess performance in high-risk areas and treatment planning utility. FEEDS outperforms random-sampling-based labeling, pseudolabel-based semi-supervised learning, and training with limited labeled data alone. It generalizes across all three test sets, FDG and PSMA tracers, and multiple diseases, matching fully-labeled (100%) training performance with 70% less annotation burden. FEEDS addresses the challenge of label scarcity in an automatic lesion segmentation framework by providing a practical approach for constructing representative and diverse annotation queues from large, unannotated clinical repositories.