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.
Diffusion models have demonstrated superior fidelity for medical image-to-image translation, but their extension to high-resolution 3D volumes is severely constrained by prohibitive computational cost and GPU memory requirements. Existing memory-efficient strategies often compromise global volumetric consistency or fine anatomical detail. In this work, we propose the Pixel Puzzling Diffusion Model (PPDM), a simple and effective framework for memory- and speed-efficient 3D medical image translation. PPDM introduces a reversible pixel puzzle-unpuzzle operator that trades spatial resolution for channel dimensionality, substantially reducing activation memory while preserving global context. To further improve efficiency and stability, we adopt a direct bridge diffusion formulation that starts from the conditional input rather than pure noise, enabling the model to focus on task-relevant residuals. In addition, a puzzle-gradient loss is incorporated to enforce spatial coherence and suppress grid-like artifacts introduced by spatial rearrangement. We evaluate PPDM on multiple challenging 3D medical image translation tasks, including low-count PET denoising, joint PET denoising and attenuation correction, and cross-modal MRI translation. Across all tasks, PPDM consistently matches or outperforms full 3D diffusion models while reducing training GPU memory usage by up to an order of magnitude and significantly accelerating inference, and it outperforms existing memory-efficient diffusion approaches based on latent compression or frequency decomposition. These results demonstrate that PPDM provides a practical and scalable solution for high-fidelity 3D diffusion-based medical image translation under limited computational resources.
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.