AbstractPurposeThis work was set out to investigate the feasibility of dose reduction in SPECT myocardial perfusion imaging (MPI) without sacrificing diagnostic accuracy. A deep learning approach was proposed to synthesize full-dose images from the corresponding low-dose images at different dose reduction levels in the projection space.MethodsClinical SPECT-MPI images of 345 patients acquired on a dedicated cardiac SPECT camera in list-mode format were retrospectively employed to predict standard-dose from low-dose images at half-, quarter-, and one-eighth-dose levels. To simulate realistic low-dose projections, 50%, 25%, and 12.5% of the events were randomly selected from the list-mode data through applying binomial subsampling. A generative adversarial network was implemented to predict non-gated standard-dose SPECT images in the projection space at the different dose reduction levels. Well-established metrics, including peak signal-to-noise ratio (PSNR), root mean square error (RMSE), and structural similarity index metrics (SSIM) in addition to Pearson correlation coefficient analysis and clinical parameters derived from Cedars-Sinai software were used to quantitatively assess the predicted standard-dose images. For clinical evaluation, the quality of the predicted standard-dose images was evaluated by a nuclear medicine specialist using a seven-point (− 3 to + 3) grading scheme.ResultsThe highest PSNR (42.49 ± 2.37) and SSIM (0.99 ± 0.01) and the lowest RMSE (1.99 ± 0.63) were achieved at a half-dose level. Pearson correlation coefficients were 0.997 ± 0.001, 0.994 ± 0.003, and 0.987 ± 0.004 for the predicted standard-dose images at half-, quarter-, and one-eighth-dose levels, respectively. Using the standard-dose images as reference, the Bland–Altman plots sketched for the Cedars-Sinai selected parameters exhibited remarkably less bias and variance in the predicted standard-dose images compared with the low-dose images at all reduced dose levels. Overall, considering the clinical assessment performed by a nuclear medicine specialist, 100%, 80%, and 11% of the predicted standard-dose images were clinically acceptable at half-, quarter-, and one-eighth-dose levels, respectively.ConclusionThe noise was effectively suppressed by the proposed network, and the predicted standard-dose images were comparable to reference standard-dose images at half- and quarter-dose levels. However, recovery of the underlying signals/information in low-dose images beyond a quarter of the standard dose would not be feasible (due to very poor signal-to-noise ratio) which will adversely affect the clinical interpretation of the resulting images.