MetaStructAtlas: A Grounded 3D Vision-Language Dataset and Benchmark for Functional and Structural Reasoning in Whole-Body PET/CT

The joint interpretation of metabolic function and anatomical structure is essential for clinical diagnosis in whole-body PET/CT. Although recent advances in 3D medical vision-language models have demonstrated remarkable progress, current efforts are limited to regional CT imaging, leaving a critical void in comprehensive whole-body PET/CT analysis. In this work, we introduce MetaStructAtlas, a large-scale dataset for grounded whole-body PET/CT interpretation that synthesizes multimodal imaging with integrated anatomical, metabolic, and semantic annotations. MetaStructAtlas provides 490 co-registered 3D PET and CT volumes with 50,470 organ-level segmentation masks and grounded radiology reports. To facilitate interactive reasoning, we further developed MetaStructVQA, a standardized 3D grounded visual question-answering benchmark containing 100,565 QA pairs. This framework explicitly links diagnostic queries to visual evidence across modalities, encompassing anatomical, morphological, and metabolic characteristics. Finally, we evaluate state-of-the-art 3D medical VLMs on MetaStructVQA, establishing a robust foundation for multimodal representation learning and integrated whole-body reasoning in nuclear medicine.

Foundation Model-Enabled Efficient Data Sampling (FEEDS): A label-efficient training strategy for pan-cancer, multi-tracer PET/CT datasets

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.

PET/CT Radiogenomic Mutation Prediction in Non-Small Cell Lung Cancer Using Multi-Label Learning

Lung cancer remains one of the leading causes of cancer- related mortality worldwide. Although targeted therapies have improved outcomes for patients with non-small cell lung cancer (NSCLC), they rely on mutation profiling through tissue biopsy, an invasive procedure with several limitations. This study investigates PET/CT-based radio- genomic prediction of epidermal growth factor receptor (EGFR), tumour protein 53 (TP53), and Kirsten rat sarcoma viral oncogene (KRAS) mutations using deep learning. We further evaluate whether pairwise multi-label learning improves mutation prediction compared with conventional single-gene classification. To the best of our knowledge, this is among the first studies to systematically investigate multi-label learning for PET/CT radiogenomic mutation prediction in NSCLC. Experiments were conducted on a novel UK-based radiogenomics cohort. Joint pre- diction of KRAS and TP53 improved AUC from 0.58 to 0.64 for KRAS and from 0.69 to 0.71 for TP53. For the EGFR/KRAS pair, only EGFR benefited from joint learning, while no improvement was observed for the EGFR/TP53 pair. These findings demonstrate that the effectiveness of multi-label learning depends on the specific combination of gene mutations being modelled, suggesting that mutation-specific modelling strategies may be preferable for PET/CT radiogenomic prediction.

Time-Conditioned and Multi-Time Survival Prediction from 2D PET/CT Projections in Lung Cancer

Accurate prediction of overall survival (OS) from positron emission tomography/computed tomography (PET/CT) can support personalized treatment and follow-up strategies in oncology. However, the impact of temporal modeling on imaging-based survival prediction remains insufficiently explored. We investigate how different temporal formulations influence survival prediction by developing two complementary approaches: Attention-guided Time-Conditioned Survival (ATCS) and Multi-Time Survival (MTS). We retrospectively analyzed pre-treatment PET/CT images from 848 patients with non-small cell lung cancer (NSCLC), including 556 for model development and 292 for held-out testing. A previously proposed Time-Conditioned Survival (TCS) model was used as a baseline. Models were trained using 5-fold cross-validation and evaluated on the test set using time-dependent area under the curve (AUC) at 6-month intervals from 0.5 to 5 years. Both ATCS and MTS outperformed the baseline TCS model, achieving mean AUCs of 0.794 and 0.793, respectively, compared to 0.767. ATCS performed better at earlier time points (0.5-3 years), whereas MTS performed better at later intervals (3.5-5 years). Combining tumor-specific and tissue-wise PET/CT features improved performance over either input alone. Finer temporal discretization improved short-term prediction, while coarser intervals provided more stable long-term estimates. These findings demonstrate that temporal modeling and input design influence PET/CT-based survival prediction. The proposed approaches enable time-specific survival estimation from pre-treatment imaging and may support improved risk stratification and clinical decision-making.

Improving PET/CT-Based Whole-Body Lesion Segmentation Using Prediction Uncertainty-Augmented Models

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.