MAP-Diff: Multi-Anchor Guided Diffusion for Progressive 3D Whole-Body Low-Dose PET Denoising

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.

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.

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.