Due to high noise levels in the voxel kinetics, development of reliable parametric imaging algorithms remains one of most active areas in dynamic brain PET imaging, which in the vast majority of cases involves receptor/transporter studies with reversibly binding tracers. As such, the focus of this work has been to develop a novel direct 4D parametric image reconstruction scheme for such tracers. Based on a relative equilibrium (RE) graphical analysis formulation (Zhou et al 2009b Neuroimage 44

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... 61-70), we developed a closed-form 4D EM algorithm to directly reconstruct distribution volume (DV) parametric images within a plasma input model, as well as DV ratio (DVR) images within a reference tissue model scheme (wherein an initial reconstruction was used to estimate the reference tissue time-activity curves). A particular challenge with the direct 4D EM formulation is that the intercept parameters in graphical (linearized) analysis of reversible tracers (e.g. Logan or RE analysis) are commonly negative (unlike for irreversible tracers, e.g. using Patlak analysis). Subsequently, we focused our attention on the AB-EM algorithm, derived by Byrne (1998, Inverse Problems 14 1455-67) to allow inclusion of prior information about the lower (A) and upper (B) bounds for image values. We then generalized this algorithm to the 4D EM framework, thus allowing negative intercept parameters. Furthermore, our 4D AB-EM algorithm incorporated and emphasized the use of spatially varying lower bounds to achieve enhanced performance. As validation, the means of parameters estimated from 55 human 11 C-raclopride dynamic PET studies were 0031-9155/12/030733+23$33.00