Myocardial perfusion imaging using SPECT is widely utilized to diagnose coronary artery diseases, but image quality can be negatively affected in low-dose and few-view acquisition settings. Although various deep learning methods have been introduced to improve image quality from low-dose or few-view SPECT data, previous approaches often fail to generalize across different acquisition settings, limiting realistic applicability. This work introduced DiffSPECT-3D, a diffusion framework for 3D cardiac SPECT imaging that effectively adapts to different acquisition settings without requiring further network re-training or fine-tuning. Using both image and projection data, a consistency strategy is proposed to ensure that diffusion sampling at each step aligns with the low-dose/few-view projection measurements, the image data, and the scanner geometry, thus enabling generalization to different low-dose/few-view settings. Incorporating anatomical spatial information from CT and total variation constraint, we proposed a 2.5D conditional strategy to allow DiffSPECT-3D to observe 3D contextual information from the entire image volume, addressing the 3D memory/computational issues in diffusion model. We extensively evaluated the proposed method on 1,325 clinical 99mTc tetrofosmin stress/rest studies from 795 patients. Each study was reconstructed into 5 different low-count levels and 5 different projection few-view levels for model evaluations, ranging from 1% to 50% and from 1 view to 9 view, respectively. Validated against cardiac catheterization results and diagnostic review from nuclear cardiologists, the presented results show the potential to achieve low-dose and few-view SPECT imaging without compromising clinical performance. Additionally, DiffSPECT-3D could be directly applied to full-dose SPECT images to further improve image quality, especially in a low-dose stress-first cardiac SPECT imaging protocol.
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