Reducing radiation exposure in Positron Emission Tomography (PET) is important for patient safety; however, ultra-low-dose imaging suffers from severe noise, which may affect diagnostic interpretation without appropriate image enhancement. While current 3D deep generative models, particularly diffusion models, have shown strong reconstruction fidelity, their practical use can be limited by long inference times. In contrast, faster 2D-based alternatives may have difficulty maintaining volumetric consistency, an important consideration for whole-body PET imaging analysis. To bridge this gap, we propose a one-pass conditional 3D rectified flow (3D Flow) framework for whole-body PET image denoising that incorporates a novel optimized non-uniform sampling strategy. The model is trained with a one-pass linear-interpolant velocity-matching objective. This approach reconstructs a full 3D volume in approximately 30 seconds in our implementation, compared with multi-hour inference for the evaluated 3D DDPM baseline. Evaluations including zero-shot transfer to an independent clinical dataset show that our model achieves favorable global image quality and lesion conspicuity compared with the evaluated 3D DDPM and DDIM baselines, including on challenging short-acquisition data. Furthermore, the proposed method shows promising zero-shot transfer performance across the evaluated datasets and unseen dose levels (down to 1/100 of the standard dose), with artifact-focused visual comparisons supporting the need for further lesion-level validation. By balancing reconstruction fidelity and computational efficiency, this work presents a candidate approach for ultra-low-dose whole-body PET image denoising.
Accurate quantification and uptake measurement in PET are critical for assessing disease progression and supporting clinical decision-making. While high-count PET provides reliable image quality, the associated radiation dose and prolonged acquisition remain significant clinical concerns, motivating the adoption of low-count protocols. Diffusion-model-based methods have demonstrated strong potential for restoring low-count PET to near high-count quality, but their iterative sampling procedure becomes prohibitively expensive when applied to high-resolution 3D PET volumes, introducing substantial inference latency that limits practical clinical deployment. To address these challenges, we propose a training-free Global-Local Skipping Strategy that accelerates diffusion model-based 3D PET denoising while simultaneously improving reconstruction quality. The proposed method is plug-and-play and directly applicable to pre-trained diffusion models without retraining or architectural modification. Specifically, we introduce: (i) a global denoising step skipping strategy that initializes the reverse diffusion process from an intermediate denoising step using a noise-consistent transformation of the low-count input, substantially reducing the number of required denoising steps; and (ii) a local feature reuse shortcut that reuses slowly-varying high-level U-Net features across neighboring denoising steps, further reducing per-step computation while preserving image fidelity. We evaluate the proposed approach on multiple PET tracers from in-house and public datasets, including 18F-FDG PET, 68Ga-DOTATATE PET, and 18F-PSMA PET, demonstrating consistent acceleration of over an order of magnitude alongside improved or comparable reconstruction performance relative to the full-step baseline. Blinded reader studies further confirm enhanced clinical confidence and perceived diagnostic quality.
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.
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.