Myocardial perfusion imaging (MPI) using single-photon emission computed tomography (SPECT) is a noninvasive imaging modality widely utilized... Show moreMyocardial perfusion imaging (MPI) using single-photon emission computed tomography (SPECT) is a noninvasive imaging modality widely utilized for diagnosis of coronary artery diseases (CAD) in nuclear medicine. Because of the concern of potential radiation risks, the imaging dose administered to patients is limited in SPECT-MPI. Due to the low count statistics in acquired data, SPECT images can suffer from high levels of noise. In this study, we investigate the potential benefit of applying deep learning (DL) techniques for denoising in SPECT-MPI studies. Owing to the lack of ground truth in clinical studies, we adopt a noise-to-noise (N2N) training approach for denoising in full-dose studies. Afterwards, we investigate the benefit of applying N2N DL on reduced-dose studies to improve the detection accuracy of perfusion defects. To address the great variability in noise level among different subjects, we propose a scheme to account for the inter-subject variabilities in training a DL denoising network to improve its generalizability. In addition, we propose a dose-blind training approach for denoising at multiple reduced-dose levels. Moreover, we investigate several training schemes to address the issue that defect and non-defect image regions are highly unbalanced in a data set, where the overwhelming majority by non-defect regions tends to have a more pronounced contribution to the conventional loss function. We investigate whether these training schemes can effectively improve preservation of perfusion defects and yield better defect detection accuracy. In the experiments we demonstrated the proposed approaches with a set of 895 clinical acquisitions. The results show promising performance in denoising and improving the detectability of perfusion-defects with the proposed approaches. Show less