HDDPM: Heteroscedastic Denoising Diffusion Probabilistic Model for Quantitative Low-Count Brain PET Recovery

Raymond Confidence, Udunna C. Anazodo

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.