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True three dimensional (3-D) volume reconstruction from fully 3-D data in positron emission tomography (PET) has only a limited clinical use because of its large computational burden. Fourier rebinning (FORE) of the fully 3-D data into a set of 2-D sinogram data decomposes the 3-D reconstruction process into multiple 2-D reconstructions of decoupled 2-D image slices, thus substantially decreasing the computational burden even in the case when the 2-D reconstructions are performed by an iterative reconstruction algorithm. On the other hand, the approximations involved in the rebinning combined with the decoupling of the image slices cause a certain reduction of image quality, especially when the signal-to-noise ratio of the data is low. The authors propose a 2.5-D Simultaneous Multislice Reconstruction approach, based on the series expansion principle, where the volume is represented by the superposition of 3-D spherically symmetric bell-shaped basis functions. It takes advantage of the time reduction due to the use of the FORE (2-D) data, instead of the original fully 3-D data, but at the same time uses a 3-D iterative reconstruction approach with 3-D basis functions. The same general approach can be applied to any reconstruction algorithm belonging to the class of series expansion methods (iterative or noniterative) using 3-D basis functions that span multiple slices, and can be used for any multislice sinogram or list mode data whether obtained by a special rebinning scheme or acquired directly by a PET scanner in the 2-D mode using septa. The authors' studies confirm that the proposed 2.5-D approach provides a considerable improvement in reconstruction quality, as compared to the standard 2-D reconstruction approach, while the reconstruction time is of the same order as that of the 2-D approach and is clinically practical even on a general-purpose computer.