Computed tomography (CT)-based attenuation and scatter correction improves quantitative PET but adds radiation exposure that is particularly undesirable in pediatric imaging. Existing CT-free methods are commonly trained in homogeneous settings and often degrade under scanner or radiotracer shifts, which limits their clinical utility. We propose the Generalizable PET Correction Network (GPCN), a dual-domain network for domain-robust CT-free PET attenuation and scatter correction. GPCN combines a multi-band contextual refinement module, which models pediatric anatomical variability through wavelet-based multiscale decomposition and long-range spatial context modeling, with a frequency-aware spectral decoupling module, which performs coordinate-conditioned amplitude/phase refinement in the Fourier domain. By synergizing multi-band spatial contextual modeling with asymmetric frequency-spectrum decoupling, the network explicitly separates invariant topological structures from domain-specific noise, thereby achieving precise quantitative recovery of both anatomical organs and focal lesions. This design aims to separate anatomy-dominant structures from domain-sensitive spectral residuals and to improve robustness across heterogeneous imaging conditions. We train and evaluate the method on 1085 pediatric whole-body PET scans acquired with two scanners and five radiotracers. In both joint training and zero-shot cross-domain evaluation, GPCN outperforms representative baselines and maintains stable quantitative accuracy on unseen scanner-tracer combinations. The method is further supported by ablation, region-wise quantitative analysis, and downstream segmentation experiments. In our cohort, the CT component of the conventional protocol corresponded to an average effective dose of 10.8 mSv, indicating the potential clinical value of reliable CT-free correction for pediatric PET.
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.
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.
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.