PET/CT Imaging

Accurate PSMA PET/CT interpretation is central to prostate cancer management, yet existing PET/CT AI models typically address isolated tasks. We propose a unified PSMA PET/CT vision-language model for report generation, visual question answering, and lesion segmentation. The framework adopts an LLaVA-style architecture, comprising a PET/CT vision encoder, an MLP-Mixer projection module, a LoRA-tuned large language model, and a 3D segmentation branch. Training followed a four-stage strategy: vision encoder pretraining, projection-layer alignment, VLM fine-tuning, and final multitask tuning. Language tasks used 5,747 PSMA PET/CT datasets with paired reports, while segmentation used the PSMA subset of AutoPET. The model outperformed PET2REP and a CT-based baseline across standard report-generation metrics, improved performance across VQA question types, and achieved higher Dice and lesion-level overlap F1 than SegAnyPET and nnUNet. These results support the feasibility of a unified framework for structured, interactive, interpretable PSMA PET/CT analysis with voxel-level grounding within a single multitask model architecture.

Computed tomography (CT) and positron emission tomography (PET) provide complementary anatomical and functional information for cancer diagnosis and treatment planning. However, the widespread use of PET is limited by high radiation exposure, elevated costs, and restricted availability. To address these limitations, deep learning-based CT-to-PET translation has emerged as a promising approach for synthesizing PET-like information directly from CT images, although accurately modeling the large cross-modal gap remains challenging. In this work, we propose a 3D CT-to-PET translation framework based on latent Brownian Bridge Diffusion (BBDM). The method consists of two stages. First, a Variational Autoencoder (VAE) is trained on paired CT-PET patches, integrating contrastive learning to improve latent alignment between anatomical and metabolic representations. Second, a BBDM is trained in the latent space to translate CT latent representations into their corresponding PET counterparts. The translated PET latents are then decoded and stitched to reconstruct the final 3D PET volume. We evaluate the proposed approach on two publicly available datasets. Quantitative results based on image fidelity and lesion-level PET-specific metrics demonstrate improved performance compared with competing methods. In particular, the proposed approach improves PET signal fidelity, better preserves clinically relevant uptake patterns, and shows improved performance in preserving small-lesion metabolic activation, paving the way for virtual imaging applications.

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.

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.

Interactive lesion segmentation in whole-body PET/CT requires a model to provide a strong initial prediction while also responding efficiently to sparse corrective scribbles during inference. This setting is particularly challenging because tracer distributions, physiological uptake patterns, lesion appearance, and acquisition characteristics differ substantially between FDG and PSMA studies. We present TRIAGE, Tracer-aware Refinement via Interactive Anatomy-Guided sEgmentation. The core backbone is a 3D STU-Net initialized through masked autoencoding pre-training with an asynchronous masking strategy, aiming to learn transferable anatomical and cross-modal representations before task-specific fine-tuning. In parallel, we train an auxiliary organ segmentation model whose predictions provide explicit anatomical context and help distinguish physiological uptake from malignant lesions. A dedicated tracer classifier first routes each study to an FDG- or PSMA-specific branch. Within each branch, a first-stage segmentation model consumes CT, PET, and organ context to generate an initial lesion mask. The initial prediction is then combined with cumulative foreground/background scribbles and refined by a second interactive segmentation network. The FDG and PSMA branches share the same overall processing pipeline but are trained independently to account for tracer-specific appearance and error modes. We additionally employ curriculum-style training and model ensembling to improve robustness across interaction steps and heterogeneous cohorts. Experiments are conducted using the official AutoPET V data and ten-fold split; quantitative results, ablations, and final test-set performance are left as placeholders to be completed after the challenge evaluation. Code: https://github.com/Liiiii2101/AUTOPET2026-MEDAI.

Errors in radiology reports can adversely affect patient treatment, yet automated report quality assurance remains challenging because errors are often subtle and require domain expertise to detect. Although large language models (LLMs) have recently been proposed for radiology report verification, their ability to detect clinically meaningful errors beyond chest X-ray datasets remains under-explored. To this end, we present the first systematic evaluation of language models for PET/CT report error detection, comparing compact domain-specific models with SOTA open-weight LLMs. We collected 30,633 oncology FDG PET/CT reports from 23 radiologists over 10 years. We trained domain-specific BERT models to detect clinically motivated synthetic reporting errors and evaluated alongside zero-/few-shot Qwen3-32B, Gemma-3-27B and Llama-3.3-70B on a held-out benchmark of 11,500 reports. A 15M-parameter model achieved 94.4% balanced accuracy with a 5.8% false-positive rate, compared with 84.0% for the strongest prompted LLM. Task-specific adaptation of Llama-3.3-70B closed this performance gap (94.4%) but retained substantially greater computational requirements. Our results suggest that domain-specific training matters more than model scale for PET/CT report error detection, supporting compact models as an accurate and computationally efficient approach to automated radiology report quality assurance.

Deep learning models that synthesize PET from CT or MRI can reduce patient dose and scanner demand, but are typically optimized with global losses such as L1 or mean squared error (MSE) that treat all voxels similarly. In whole-body PSMA-PET, tumor voxels occupy only a small fraction of the volume, yet carry the clinically relevant activity signal; as a result, models can achieve high structural similarity index measure (SSIM) and peak signal-to-noise ratio (PSNR) while still underestimating lesion activity or failing to preserve tumor-specific structure. Radiomics provides biologically meaningful descriptors of tumor intensity and texture, but direct radiomics conditioning is time-consuming because it requires feature extraction from delineated lesion regions. We propose LAFNO, a Lesion-Aware Adaptive Fourier Neural Operator for CT-to-PSMA-PET synthesis that replaces high-dimensional radiomics conditioning with two efficient CT-derived proxy channels. Motivated by radiomics analysis of PSMA-avid tumor core and peritumoral regions, LAFNO uses a contrast proxy for local density variation and a disorder proxy for local texture heterogeneity, both injected into the model bottleneck. LAFNO combines whole-volume reconstruction with lesion-level total lesion activity (TLA), tumor-core contrast, and peritumoral supervision. We evaluated LAFNO against four baseline architectures on the TCIA PSMA-PET-CT-Lesions dataset. LAFNO remained competitive on whole-volume image quality, achieving SSIM of 0.960 and 0.938 for 18F- and 68Ga-PSMA, respectively, while reducing per-patient TLA error to 48.3% and 64.0% for 18F- and 68Ga-PSMA, respectively, and achieving the highest tumor-core radiomics reproducibility across all feature classes for both tracers. Peritumoral reproducibility remained tracer-dependent, indicating that biological fidelity in synthetic PSMA-PET remains challenging.

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.

PET provides functional images relying on two-photon coincidences from positron-electron annihilation. In human tissue, about 40% of annihilations are preceded by Ps formation, of which o-Ps component partially decays into three photons, with the remainder annihilating via pick-off or spin-exchange into two photons. This three-photon channel carries additional information about the surrounding micro-environment, including the three-to-two-photon yield ratio as a potential diagnostic marker. We propose the TRIO algorithm, a novel three-photon event-by-event image reconstruction algorithm formulated as a Bayesian maximum a posteriori inference problem. TRIO unifies time-based trilateration, energy-based reconstruction and, for the first time, a physics-informed prior derived from the QED description of Ps decay within a single probabilistic framework. In contrast to positronium lifetime imaging, which requires a prompt photon and is therefore restricted to specific radionuclides, TRIO relies solely on the three photons and is fully compatible with standard radionuclides such as 18F. Monte Carlo simulation modelled after the Siemens Biograph Quadra scanner demonstrates a mean position error of 1.62~cm, improving by approximately a factor of two over the time-based trilateration (3.05 cm) and by about an order of magnitude over energy-based reconstruction alone (18 cm). More importantly, the proposed Bayesian approach is compatible with existing TOF-PET scanners that can register three-photon annihilation coincidences.

We present HERMES (Hybrid Ensemble for Radiotherapy-target segmentation, Malignancy staging, and Event-free Survival), a single containerized algorithm for the three HECKTOR 2026 subtasks: segmentation of the primary tumor (GTVp) and pathological lymph nodes (GTVn), radiological T/N staging, and recurrence-free survival (RFS), computed from a paired FDG-PET/CT scan and an electronic health record. A 10-fold ensemble of STU-Net Small networks produces the segmentation; the predicted mask then drives two downstream tasks. Rather than pass a generic radiomics vector to the staging models, we derive from the predicted masks a compact set of geometry features aligned with the size and number axes of AJCC/UICC 7th-edition radiological N/T staging. On internal cross-validation these features raise N-stage balanced accuracy from 0.691 to 0.720 (+0.030), our largest single design gain, at lower feature dimensionality. For prognosis we combine complementary deep and clinical risk experts in an equal-weight ensemble, and train one deep expert with a concordance-tracking survival loss of our own, whose value approximates the concordance index during training. Every component was selected on honest out-of-fold predictions under a regularization-oriented protocol, with no tuning on the public validation set, and deployed as two decorrelated submissions. On the HECKTOR 2026 validation leaderboard, HERMES achieved a weighted score of 0.6454 (Mean Dice 0.641, T balanced accuracy 0.580, N balanced accuracy 0.642, RFS C-index 0.679) and qualified for the testing phase. Team: AMC_HNC.

The introduction of LAFOV PET scanners brings significant sensitivity gains but also a substantial increase in the background rate from accidental coincidences, phantom-scattered and detector-scattered photons. While machine learning methods have been applied to background reduction in PET imaging, they target specific background components in post-processing rather than event-by-event classification on the raw data. In this work, we formulate coincidence classification as a supervised multi-class problem and evaluate XGBoost, AdaBoost and Neural Network classifiers as pre-reconstruction filters, using Monte Carlo simulations of the Siemens Biograph Vision Quadra scanner with NEMA IEC and anthropomorphic XCAT phantoms. We investigate two feature sets: a 4-feature representation based on the Attenuation Factor, photon time difference, energy sum, and energy difference, and an extended 6-feature set that incorporates topology-based variables. A systematic robustness study via cross-phantom inference reveals that the 4-feature models generalise significantly better across different phantom geometries, with XGBoost suffering an accuracy loss of only 0.04 compared to 0.13 for the 6-feature variant. Our best models achieve accuracies of up to 0.74 and 0.69 for the NEMA IEC and XCAT phantoms, respectively, outperforming traditional geometry-based cuts. However, we show that this compact feature set not only provides limited suppression of in-phantom scattered coincidences, but it also can lead to non-trivial spatial patterns. With scattered coincidences being the dominant background component in clinical conditions, this suggests that while the method serves as an effective and geometry-agnostic replacement for traditional cut-based selection, meaningful further gains in image quality will require either larger input representations or dedicated treatment of the phantom-scattered component.

18F-FDG PET/CT plays a central role in staging, treatment planning, and response assessment for head and neck cancer by providing functional information that complements anatomical CT imaging. However, PET acquisition requires radiotracer administration, specialized infrastructure, and additional cost, limiting its availability for repeated imaging. We present a proof of concept deep learning framework for synthesizing PET like images directly from routine CT scans with the goal of providing complementary metabolic information that may support imaging triage and clinical decision support rather than replace diagnostic PET. Forty-four patients from the publicly available QIN-HEADNECK dataset were retrospectively analyzed using five fold cross-validation. We propose a fully three dimensional dual path architecture consisting of (i) a regression U-Net optimized for voxel-wise quantitative SUV estimation and (ii) a conditional generative adversarial network optimized for realistic PET texture. Their outputs are integrated using hotspot guided Laplacian pyramid blending, allowing quantitative information from the regression pathway to be preserved within metabolically active regions while leveraging adversarial texture synthesis elsewhere. The proposed framework achieved a mean absolute error of 0.00395, PSNR of 39.19 dB, and SSIM of 0.9634 on reconstructed three dimensional PET volumes. Qualitative evaluation demonstrated accurate localization of many FDG-avid lesions while producing anatomically realistic background texture. Consistent with previous CT to PET synthesis studies, the principal limitation was systematic underestimation of SUV within highly metabolically active tumor regions.

Low-count Positron Emission Tomography (PET) reconstruction is severely hindered by the dissipative nature of prevailing generative models, where the inherent phase-space contraction leads to the numerical extinction (``wash-out'') of weak but diagnostically critical lesion signals. To overcome this geometric limitation, we propose \textbf{FlowPET}, a physics-informed framework that reformulates reconstruction as volume-preserving transport in a symplectic phase space. By parameterizing the posterior dynamics via a Separable Hamiltonian System, our approach guarantees a divergence-free vector field by construction, theoretically immunizing weak signals against probability mass collapse. To steer this conservative flow, we introduce conjugate boundary conditions based on the Range-Null space decomposition of the PET operator; this strictly enforces data consistency in the range space while confining stochastic uncertainty injection to the unobserved null space. We train the model via symplectic flow matching and perform inference using a symplectic leapfrog integrator. Extensive experiments on BrainWeb, clinical pediatric, and UDPET datasets demonstrate that \textbf{FlowPET} not only surpasses state-of-the-art deterministic and stochastic baselines in SSIM and PSNR but, more crucially, exhibits superior recovery of low-contrast lesions. The results confirm that imposing Hamiltonian structural constraints offers a robust geometric safeguard for medical inverse problems in high-noise regimes.

Whole-body fluorodeoxyglucose positron emission tomography combined with computed tomography is widely used in cancer care, but manual lesion delineation is slow, subjective, and difficult to scale. We present GLOW-FDG, an open-source artificial intelligence model for whole-body cancer lesion segmentation in fluorodeoxyglucose positron emission tomography and computed tomography. The model was trained on 1,563 scans spanning multiple cancer types and evaluated on 185 external scans from independent institutions. Across breast cancer, nonmetastatic and oligometastatic lung cancer, head and neck cancer, and metastatic melanoma, GLOW-FDG consistently outperformed publicly available benchmark models in lesion detection, while reducing false positives and maintaining strong segmentation accuracy. Quantification of total tumor burden and total lesion glycolysis was robust across cohorts, and performance approached the variability observed between expert radiation oncologists. These results support GLOW-FDG as a generalizable tool for automated cancer segmentation and quantitative imaging biomarker extraction in whole-body imaging.

Positron emission tomography (PET) provides essential functional information for disease assessment, however reducing injected activity or acquisition time produces low-dose (LD) PET with stronger count dependent noise and less reliable uptake quantification. Diffusion models offer a promising solution for PET denoising by progressively recovering high-dose (HD) PET images from LD inputs. However, LD-to-HD PET denoising is still challenging due to insufficient anatomical guidance, unstable multi-scale feature propagation, and uncertain frequency domain uptake recovery. We propose AnF-DiffPET, an anatomy- and frequency-guided diffusion framework for computed tomography (CT) conditioned LD PET denoising. The framework integrates Anatomical-Frequency Guidance (AFG), Multi-Scale Cross-Transformer Reconstruction (MSCTR), and Frequency-Contrastive Hard Mining (FCHM) to enhance anatomy aware feature modulation and frequency domain consistency during denoising. Experimental results across four PET/CT datasets show that the proposed method improves image fidelity, anatomical consistency, and quantitative fidelity over representative CNN-based, GAN-based, transformer-based, and diffusion-based methods. The code and trained models will be publicly released upon acceptance.

Positron Emission Tomography (PET) reveals brain metabolism and is clinically central to neurodegenerative disease assessment, yet existing 3D brain foundation models treat PET as generic volumetric data, missing the structured regional metabolic information that distinguishes it from structural neuroimaging. To address these limitations, we propose ReMAP-PET, a framework that moves beyond visual encoding by supervising a partially-tuned MedicalNet 3D ResNet-50 with brain regional standardized uptake value ratio (SUVR) profiles through joint regression and contrastive objectives, enabling the encoder to learn the metabolic semantics underlying PET modality. On 1015 paired PET--SUVR samples, ReMAP-PET achieves 0.070 SUVR MAE and 77.8% PET SUVR Recall@1, substantially outperforming five frozen pretrained baselines. We further connect the metabolic embedding to clinical language via contrastive alignment with frozen BioClinicalBERT and demonstrate end-to-end PET-to-report generation through SUVR-constrained verbalization. Linear probing on diagnostic classification and cognitive regression tasks confirms that the embeddings retain clinically relevant information without task-specific fine-tuning. Our results show that grounding PET encoders in regional metabolic semantics -- rather than treating PET as generic volumetric data -- yields representations that are structured, interpretable, and language-compatible, pointing to a new direction for metabolic-aware PET understanding.

Positron emission tomography (PET) seeks to balance diagnostic quality with ra-diation dose. Low-count PET noise is non-Gaussian, non-stationary, and spatial-ly dependent. It scales directly with local activity and is shaped by iterative recon-struction and physical corrections. Standard denoising diffusion probabilistic models (DDPMs) ignore these PET properties. Their forward process adds iso-tropic, homoscedastic Gaussian noise to the target. Such an approach fails to cap-ture the realistic physical degradation generated by the imaging system. To ad-dress the above limitations, this study introduces a heteroscedastic residual diffu-sion model (HDDPM) for low-count brain PET recovery in which the forward corruption is itself intensity-aware. We designed a fixed, Poisson-based variance module to generate voxel-wise noise maps. These maps naturally place stronger noise perturbation on low-activity regions than high-activity ones, meanwhile the network predicts the low-to-standard-count residual under explicit dose-fraction conditioning. We evaluated our proposed model (HDDPM) alongside generative frameworks across three different scanners, using both internal and external da-tasets at various simulated dose levels (1% to 50%). HDDPM and isotropic DDPM showed comparable overall image quality, but HDDPM stood out in the lowest-dose (1%) external scans. It is highly reliable and significantly reduces measurement errors in both high- and low-activity regions, compared to the standard model. These results support that heteroscedastic noising with the pro-posed HDDPM is feasible, and it provides a physically motivated inductive bias for quantitative low-count PET recovery by reflecting the activity-dependent noise structure of PET.

Accurate lesion segmentation in PET/CT is critical for oncology, yet remains challenging because physiologic tracer uptake and artifacts can mimic malignant signal. We present RADIANT-PET, a reasoning-augmented framework that couples a high-sensitivity voxel-level segmentation model with lesion-level large language model (LLM) adjudication. Candidate uptake regions are generated with a deliberately permissive segmentation stage, then converted into structured textual descriptions that summarize uptake intensity, morphology, and regional and global anatomical context. An LLM classifies each candidate as true lesion vs. false positive, optionally leveraging the radiology report as additional clinical context. To strengthen lesion-level reasoning, we further optimize a local LLM via reinforcement learning using Group Relative Policy Optimization, rewarding correct lesion classification and anatomically concordant site assignment. Across AutoPET and an OSU test cohort, RADIANT-PET consistently outperforms strong image-only baselines, with the largest improvements observed when radiology reports are provided. Overall, these results demonstrate that LLM-based lesion-level reasoning adds a novel reasoning layer beyond conventional segmentation, suppressing physiologic false positives and aligning voxel-level predictions with clinical interpretation. The project repository is available at: https://github.com/jwang-580/RADIANT-PET.

While longitudinal brain PET imaging is the gold standard for quantifying the spatiotemporal accumulation of Beta-amyloid, its widespread clinical utility is constrained by high operational costs and cumulative radiation risks. Recent deep generative models show promise in longitudinal image synthesis; however, they often fail to capture subtle pathological progression due to identity drift and a persistent bias toward trivially replicating baseline signal intensities rather than modeling temporal transition. To this end, we propose Delta-Diffusion, a novel progression-aware framework that redefines longitudinal PET synthesis as a conditional Poisson Diffusion Bridge (PDB) process. Unlike standard diffusion models that start from Gaussian noise, our PDB formulation is mathematically anchored to the subject's baseline PET, effectively transforming the generative task into a conditional distribution transition of the amyloid trajectory. To handle heteroscedastic nature of PET imaging, we introduce a physically-grounded Poisson perturbation within a Diffusion Transformer (DiT). This architecture uses adaptive scale-shift modulation to precisely calibrate the synthesis with the elapsed clinical interval and structural MRI context. A volume-of-interest balanced objective is designed to emphasize sparse, high-risk regions of amyloid accumulation. Validated on two cohorts with 542 subjects, Delta-Diffusion demonstrates superior performance in capturing longitudinal variations in amyloid deposition compared to state-of-the-art methods, offering a robust computational framework for tracking disease progression.

Head and neck cancers (HNC) represent a significant global health burden, with accurate tumor delineation being essential for effective radiotherapy planning. The complexity of the oropharyngeal anatomy, combined with the heterogeneous appearance of tumors on imaging, makes manual segmentation time-intensive and subject to inter-observer variability. Beyond segmentation, predicting long-term clinical outcomes, such as recurrence-free survival (RFS), and determining human papillomavirus (HPV) status from noninvasive imaging, remain challenging yet clinically valuable goals. The HECKTOR 2025 challenge addresses these needs by establishing a comprehensive benchmark for automated HNC analysis using multimodal PET/CT imaging and electronic health records. Building on previous editions (2020-2022), this challenge features an expanded multi-institutional dataset comprising over 1,100 patients from 10 centers worldwide. Participants were tasked with three complementary objectives: (1) segmenting primary gross tumor volumes (GTVp) and metastatic lymph nodes (GTVn), (2) predicting recurrence-free survival, and (3) classifying HPV status. The challenge attracted 35 registered teams, with 15 final submissions evaluated on a held-out test set. Top-performing algorithms achieved a mean Dice similarity coefficient of 0.75 for segmentation, a concordance index of 0.66 for survival prediction, and a balanced accuracy of 0.56 for HPV classification. This paper presents a comprehensive analysis of the submitted methodologies, evaluates their performance across different lesion characteristics, and discusses their implications for clinical translation in automated oncology workflows and decision support systems.

We present a Dual-Domain Equivariant Generative Adversarial Network (DDE-GAN) for multimodal CT-PET image synthesis. Traditional GAN-based approaches often operate solely in the spatial domain and ignore geometric consistency, resulting in limited structural fidelity. DDE-GAN addresses these challenges by jointly learning from both spatial and frequency (Fourier) domains, capturing complementary anatomical and spectral information. Furthermore, rotational equivariance embedded in the physics of the CT and PET measurements are integrated into the loss of both the generator and discriminator to ensure consistent responses under rotations, improving anatomical accuracy. A hierarchical dual-domain training strategy enforces intra- and inter-domain consistency through multi-stage loss functions. Evaluated on the HECKTOR 2022 CT-PET dataset, DDE-GAN achieves superior synthesis quality over baseline models for CT-PET image synthesis. The results demonstrate that combining dual-domain learning with geometric equivariance substantially enhances multimodal image synthesis accuracy and robustness, enabling practical applications in PET completion and data augmentation.

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.

Most existing deep learning-based PET image denoising methods assume a fixed and known dose reduction factor (DRF) for low-dose PET images. However, these methods encounter significant performance degradation when the DRF varies beyond the assumed one in practical applications. To address the challenge posed by varied DRFs, several preliminary studies focus on the task of universal PET image denoising, aiming to train a universal model over low-dose data across DRFs. Nonetheless, these vanilla universal models often struggle with misaligned styles present in different DRF data, leading to the \textit{style elimination issue} with a significant over-smoothing effect. To deal with this issue, we innovatively introduce domain generalization to PET image denoising and propose a universal PET image denoising network (UniPET) to achieve high-quality PET image denoising across diverse DRFs. UniPET comprises two primary innovations: a style alignment network (SAN) and a region-aware learning strategy (RALS). Specifically, SAN utilizes style alignment techniques derived from domain generalization to align and recover styles across different DRFs, ensuring the model's generalizability across various DRFs while effectively preserving styles. Furthermore, to enhance style recovery, RALS distinguishes between flat and stylized regions, exclusively conducting adversarial learning on the latter, thereby more effectively guiding the model's focus towards learning stylized regions. It is demonstrated that our proposed UniPET can adaptively recover different DRF styles and achieve high-quality PET image denoising across DRFs. Comprehensive experiments show that UniPET exhibits comparable performance to individual DRF-specific models at specific DRFs and realizes state-of-the-art performance in universal PET image denoising quantitatively, perceptually, and clinically.

Existing deep learning models for Positron Emission Tomography (PET) image denoising often suffer from severe performance degradation under distribution shifts, fundamentally restricting their robust clinical deployment. This lack of generalization stems from the conventional paradigm of fixed-parameter models that cannot adapt to variations in test data (e.g., dose levels or scanner types) after training. To overcome this limitation and achieve robust generalization, we introduce U-TTT, a novel U-shaped model that integrates Test-Time Training (TTT) layers to dynamically adjust model parameters during inference through self-supervision, thereby adapting to the specific characteristics of each test instance. Furthermore, to comprehensively capture the complex degradations of 3D PET data, U-TTT features a dual-domain adaptation mechanism comprising a Spatial Test-Time Training (S-TTT) layer and a Frequency Test-Time Training (F-TTT) layer. The S-TTT layer captures and corrects spatial structural degradations, while the F-TTT layer suppresses global noise spectra and restores delicate high-frequency details. Extensive experiments demonstrate that U-TTT achieves state-of-the-art PET denoising performance and exhibits superior generalization under challenging distribution shifts, including both unseen dose levels and unseen scanners. Our code will be available at https://github.com/Yaziwel/U-TTT.

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.

The synergistic interpretation of anatomical information from computed tomography (CT) and metabolic information from positron emission tomography (PET) is important to oncologic imaging. However, existing deep learning methods for PET/CT remain largely task-specific, are often trained on single-center cohorts, or adopt dual-branch fusion schemes that delay cross-modal interaction and underutilize early spatial correspondence between PET and CT. To address these limitations, we present an open-source, multi-center, whole-body FDG PET/CT foundation model utilizing 4,997 harmonized scans from four public datasets. Our framework employs hierarchical UNet-shaped backbones with early channel-wise concatenation, enabling anatomical and metabolic features to interact from the first embedding layer onward. We further introduce a masked autoencoding objective based on zero-mean imputation, combined with a weighted global reconstruction loss. This design avoids non-physical intensity discontinuities at masked-region boundaries that arise from learnable mask tokens. On downstream AutoPET lesion segmentation, the proposed models demonstrate strong label efficiency: with only 10% of the labeled training data, they achieve performance comparable to models trained from scratch on the full dataset. Under extreme 5-shot linear probing, joint PET/CT pretraining also achieves higher Dice scores than separated-modality pretraining. This multi-center foundation model demonstrates label efficiency and cross-modality representation learning for PET/CT tumor segmentation. It provides a robust, open-source basis for advancing automated oncologic imaging, significantly reducing the need for large-scale manual annotations in clinical practice.

Synthetic PET images are valuable for quantitative imaging workflow development, scalable virtual imaging trials, and deep learning model training, but conventional physics-based simulation approaches are computationally intensive, limited in anatomical variability, and often fail to capture heterogeneous PET uptake. This study developed a pretrained domain-adapted diffusion (PAD) model for anatomy-conditioned PET synthesis from uniform organ activity maps. PAD adopts a natural-image pretrained text-to-image decoder with an upstream conditioning encoder and a downstream PET-domain adapter. A two-phase training strategy was used, with the first phase learning coarse uptake distributions and the second refining local image details. Uniform organ activity maps were generated from CT-based segmentations by assigning each organ its mean uptake from the paired PET image. Evaluation included quantitative accuracy, noise assessment, radiomic analysis, tumor segmentation performance, and a human observer study. PAD-generated images achieved high quantitative accuracy, with concordance correlation coefficients above 0.92 between organ mean SUVs and assigned activity values. The synthesized images showed noise levels and texture characteristics similar to target PET images and produced comparable tumor segmentation performance. In a two-alternative forced-choice observer study, four readers achieved approximately 50% accuracy, indicating visual indistinguishability between synthesized and target images. PAD also generated realistic PET images from XCAT-derived activity maps, demonstrating compatibility with phantom-based anatomical priors. Overall, PAD provides a diffusion-based framework for generating clinically relevant heterogeneous PET images from uniform organ activity maps derived from clinical segmentations or digital phantoms, supporting data augmentation and downstream imaging studies.

Early and accurate diagnosis and lesion localization of bone infections are crucial for clinical treatment. PET-CT integrates anatomical information from CT with metabolic information from PET, making it an important imaging modality for diagnosing bone infections. However, accurate lesion segmentation remains challenging due to indistinct lesion boundaries and inconsistencies in annotations generated by different experts or automated systems. In this work, we investigate multimodal segmentation of bone infections under annotation discrepancy. We develop a bimodal end-to-end segmentation framework that integrates PET metabolic signals and CT bone-window anatomy through an early-fusion multimodal representation.To mitigate performance inflation caused by inter-slice correlation in small datasets, this study discards traditional two-dimensional evaluation methods and implements a rigorous patient-level 3D volumetric evaluation and cross-validation. Furthermore, instead of forcing a singular consensus, we propose a decoupled dual-source learning framework where parallel models are trained on independent expert annotations driven by high-sensitivity and high-specificity clinical intents. Experimental results objectively report performance variations at the patient level (Mean + SD and Mean - SD), demonstrating the effectiveness of multimodal PET-CT fusion. The cross-evaluation matrix quantitatively reveals how models successfully internalize distinct expert diagnostic philosophies, providing a robust, diversity-preserving paradigm for clinical AI deployment in bone infection segmentation.

Positron Emission Tomography (PET) image reconstruction is inherently challenged by Poisson noise and physical degradation factors, which are further exacerbated in limited-angle acquisitions. While deep learning methods demonstrate promising performance, their generalization to unseen clinical data distributions remains limited without extensive retraining. We propose PET-Adapter, a test-time domain adaptation framework for generative PET reconstruction models pretrained solely on phantom data. Our method enables adaptation to clinical datasets with varying anatomies, tracers, and scanner configurations without requiring paired ground truth. PET-Adapter introduces layer-wise low-rank anatomical conditioning during adaptation and Ordered Subset Expectation Maximization-based warm-starting that initializes the generation from physics-informed reconstructions, reducing diffusion steps from 50 to 2 without compromising quality. Experiments across multiple clinical datasets demonstrate superior 3D reconstruction performance in both full-angle and limited-angle settings, highlighting the clinical feasibility and computational efficiency of the proposed approach.

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.