In order to improve tomographically reconstructed image quality, we have implemented a fully 3D reconstruction, using an ordered subsets expectation maximization (OSEM) algorithm for fan-beam collimator (FBC) SPECT, along with a volumetric system model-fan-volume system model (FVSM), a modified attenuation compensation, a 3D depth- and angle-dependent resolution and sensitivity correction, and a 3D total variation (TV) regularization. SPECT data were acquired in a 128×64 matrix, in 120 views with a circular orbit. The numerical Zubal brain phantom was used to simulate a FBC HMPAO Tc-99m brain SPECT scan, and a low noise and scatter-free projection dataset was obtained using the SimSET Monte Carlo package. A SPECT scan for a mini-Defrise phantom and brain HMPAO SPECT scans for five patients were acquired with a triple-head gamma camera (Triad 88) equipped with a low-energy high-resolution (LEHR) FBC. The reconstructed images, obtained using clinical filtered back projection (FBP), OSEM with a linelength system model (LLSM) and 3D TV regularization, and OSEM with FVSM and 3D TV regularization were quantitatively studied. Overall improvement in the image quality has been observed, including better axial and transaxial resolution, better integral uniformity, higher contrast-to-noise ration between the gray matter and the white matter, and better accuracy and lower bias in OSEM-FVSM, compared with OSEM-LLSM and clinical FBP.