Purpose: The authors are currently developing a dual-resolution multiple-pinhole microSPECT imaging system based on three large NaI(Tl) gamma cameras. Two multiple-pinhole tungsten collimator tubes will be used sequentially for whole-body "scout" imaging of a mouse, followed by high-resolution (hi-res) imaging of an organ of interest, such as the heart or brain. Ideally, the whole-body image will be reconstructed in real time such that data need only be acquired until the area of interest can be visualized well-enough to determine positioning for the hi-res scan. The authors investigated the utility of the origin ensemble (OE) algorithm for online and offline reconstructions of the scout data. This algorithm operates directly in image space, and can provide estimates of image uncertainty, along with reconstructed images. Techniques for accelerating the OE reconstruction were also introduced and evaluated. Methods: System matrices were calculated for our 39-pinhole scout collimator design. SPECT projections were simulated for a range of count levels using the MOBY digital mouse phantom. Simulated data were used for a comparison of OE and maximum-likelihood expectation maximization (MLEM) reconstructions. The OE algorithm convergence was evaluated by calculating the total-image entropy and by measuring the counts in a volume-of-interest (VOI) containing the heart. Total-image entropy was also calculated for simulated MOBY data reconstructed using OE with various levels of parallelization. Results: For VOI measurements in the heart, liver, bladder, and soft-tissue, MLEM and OE reconstructed images agreed within 6%. Image entropy converged after similar to 2000 iterations of OE, while the counts in the heart converged earlier at similar to 200 iterations of OE. An accelerated version of OE completed 1000 iterations in <9 min for a 6.8M count data set, with some loss of image entropy performance, whereas the same dataset required similar to 79 min to complete 1000 iterations of conventional OE. A combination of the two methods showed decreased reconstruction time and no loss of performance when compared to conventional OE alone. Conclusions: OE-reconstructed images were found to be quantitatively and qualitatively similar to MLEM, yet OE also provided estimates of image uncertainty. Some acceleration of the reconstruction can be gained through the use of parallel computing. The OE algorithm is useful for reconstructing multiple-pinhole SPECT data and can be easily modified for real-time reconstruction. (C) 2016 American Association of Physicists in Medicine.