ABSTRACT: BACKGROUND:Two novel methods of image reconstruction, xSPECT Quant (xQ) and xSPECT Bone (xB), that use an ordered subset conjugate gradient minimizer (OSCGM) for SPECT/CT reconstruction have been proposed. The present study compares the performance characteristics of xQ, xB, and conventional Flash3D (F3D) reconstruction using images derived from phantoms and patients. METHODS:A custom-designed body phantom for bone SPECT was scanned using a Symbia Intevo (Siemens Healthineers), and reconstructed xSPECT images were evaluated. The phantom experiments proceeded twice with different activity concentrations and sphere sizes. A phantom with 28-mm spheres containing a 99mTc-background and tumor-to-normal bone ratios (TBR) of 1, 2, 4, and 10 were generated, and convergence property against various TBR was evaluated across 96 iterations. A phantom with four spheres (13-, 17-, 22-, and 28-mm diameters), containing a 99mTc-background at TBR4, was also generated. The full width at half maximum of an imaged spinous process (10?mm), coefficients of variance (CV), contrast-to-noise ratio (CNR), and recovery coefficients (RC) were evaluated after reconstructing images of a spine using Flash 3D (F3D), xQ, and xB. We retrospectively analyzed images from 20 patients with suspected bone metastases (male, n = 13) which were acquired using [99mTc]Tc-(H)MDP SPECT/CT, then CV and standardized uptake values (SUV) at the 4th vertebral body (L4) were compared after xQ and xB reconstruction in a clinical setup. RESULTS:Mean activity concentrations with various TBR converged according to increasing numbers of iterations. The spatial resolution of xB was considerably superior to xQ and F3D, and it approached almost the actual size regardless of the iteration numbers during reconstruction. The CV and RC were better for xQ and xB than for F3D. The CNR peaked at 24 iterations for xQ and 48 iterations for F3D and xB, respectively. The RC between xQ and xB significantly differed at lower numbers of iterations but were almost equivalent at higher numbers of iterations. The reconstructed xQ and xB images of the clinical patients showed a significant difference in the SUVmax and SUVpeak. CONCLUSIONS:The reconstructed xQ and xB images were more accurate than those reconstructed conventionally using F3D. The xB for bone SPECT imaging offered essentially unchanged spatial resolution even when the numbers of iterations did not converge. The xB reconstruction further enhanced SPECT image quality using CT data. Our findings provide important information for understanding the performance characteristics of the novel xQ and xB algorithms.