Diffusion models have recently enabled state-of-the-art reconstruction of positron emission tomography (PET) images while requiring only image training data. However, domain shift remains a key concern for clinical adoption: priors trained on images from one anatomy, acquisition protocol or pathology may produce artefacts on out-of-distribution data. We propose integrating steerable conditional diffusion (SCD) with our previously-introduced likelihood-scheduled diffusion (PET-LiSch) framework to improve the alignment of the diffusion model's prior to the target subject. At reconstruction time, for each diffusion step, we use low-rank adaptation (LoRA) to align the diffusion model prior with the target domain on the fly. Experiments on realistic synthetic 2D brain phantoms demonstrate that our approach suppresses hallucinated artefacts under domain shift, i.e. when our diffusion model is trained on perturbed images and tested on normal anatomy, our approach suppresses the hallucinated structure, outperforming both OSEM and diffusion model baselines qualitatively and quantitatively. These results provide a proof-of-concept that steerable priors can mitigate domain shift in diffusion-based PET reconstruction and motivate future evaluation on real data.

Medical image reconstruction with pre-trained score-based generative models (SGMs) has advantages over other existing state-of-the-art deep-learned reconstruction methods, including improved resilience to different scanner setups and advanced image distribution modeling. SGM-based reconstruction has recently been applied to simulated positron emission tomography (PET) datasets, showing improved contrast recovery for out-of-distribution lesions relative to the state-of-the-art. However, existing methods for SGM-based reconstruction from PET data suffer from slow reconstruction, burdensome hyperparameter tuning and slice inconsistency effects (in 3D). In this work, we propose a practical methodology for fully 3D reconstruction that accelerates reconstruction and reduces the number of critical hyperparameters by matching the likelihood of an SGM's reverse diffusion process to a current iterate of the maximum-likelihood expectation maximization algorithm. Using the example of low-count reconstruction from simulated $[^{18}$F]DPA-714 datasets, we show our methodology can match or improve on the NRMSE and SSIM of existing state-of-the-art SGM-based PET reconstruction while reducing reconstruction time and the need for hyperparameter tuning. We evaluate our methodology against state-of-the-art supervised and conventional reconstruction algorithms. Finally, we demonstrate a first-ever implementation of SGM-based reconstruction for real 3D PET data, specifically $[^{18}$F]DPA-714 data, where we integrate perpendicular pre-trained SGMs to eliminate slice inconsistency issues.

Low-dose PET offers a valuable means of minimizing radiation exposure in PET imaging. However, the prevalent practice of employing additional CT scans for generating attenuation maps (u-map) for PET attenuation correction significantly elevates radiation doses. To address this concern and further mitigate radiation exposure in low-dose PET exams, we propose POUR-Net - an innovative population-prior-aided over-under-representation network that aims for high-quality attenuation map generation from low-dose PET. First, POUR-Net incorporates an over-under-representation network (OUR-Net) to facilitate efficient feature extraction, encompassing both low-resolution abstracted and fine-detail features, for assisting deep generation on the full-resolution level. Second, complementing OUR-Net, a population prior generation machine (PPGM) utilizing a comprehensive CT-derived u-map dataset, provides additional prior information to aid OUR-Net generation. The integration of OUR-Net and PPGM within a cascade framework enables iterative refinement of $\mu$-map generation, resulting in the production of high-quality $\mu$-maps. Experimental results underscore the effectiveness of POUR-Net, showing it as a promising solution for accurate CT-free low-count PET attenuation correction, which also surpasses the performance of previous baseline methods.

Score-based generative models have demonstrated highly promising results for medical image reconstruction tasks in magnetic resonance imaging or computed tomography. However, their application to Positron Emission Tomography (PET) is still largely unexplored. PET image reconstruction involves a variety of challenges, including Poisson noise with high variance and a wide dynamic range. To address these challenges, we propose several PET-specific adaptations of score-based generative models. The proposed framework is developed for both 2D and 3D PET. In addition, we provide an extension to guided reconstruction using magnetic resonance images. We validate the approach through extensive 2D and 3D $\textit{in-silico}$ experiments with a model trained on patient-realistic data without lesions, and evaluate on data without lesions as well as out-of-distribution data with lesions. This demonstrates the proposed method's robustness and significant potential for improved PET reconstruction.