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Lutetium-based scintillators with high-performance electronics introduced time-of-flight (TOF) reconstruction in the clinical setting. Let G′ be the total signal to noise ratio gain in a reconstructed image using the TOF kernel compared with conventional reconstruction modes. G′ is then the product of G1 gain arising from the reconstruction process itself and (n−1) other gain factors (G2, G3, … Gn) arising from the inherent properties of the detector.We calculated G2 and G3 gains resulting from the optimization of the coincidence and energy window width for prompts and singles, respectively. Both quantitative and image-based validated Monte Carlo models of Lu2SiO5 (LSO) TOF-permitting and Bi4Ge3O12 (BGO) TOF-nonpermitting detectors were used for the calculations.G2 and G3 values were 1.05 and 1.08 for the BGO detector and G3 was 1.07 for the LSO. A value of almost unity for G2 of the LSO detector indicated a nonsignificant optimization by altering the energy window setting. G′ was found to be ∼1.4 times higher for the TOF-permitting detector after reconstruction and optimization of the coincidence and energy windows.The method described could potentially predict image noise variations by altering detector acquisition parameters. It could also further contribute toward a long-lasting debate related to cost-efficiency issues of TOF scanners versus the non-TOF ones. Some vendors re-engage nowadays to non-TOF product line designs in an effort to reduce crystal costs. Therefore, exploring the limits of image quality gain by altering the parameters of these detectors remains a topical issue.