a b s t r a c tPartial volume effect is still considered one of the main limitations in brain PET imaging given the limited spatial resolution of current generation PET scanners. The accuracy of anatomically guided partial volume effect correction (PVC) algorithms in brain PET is largely dependent on the performance of MRI segmentation algorithms partitioning the brain into its main classes, namely gray matter (GM), white matter (WM), and cerebrospinal fluid (CSF). A comparative evaluation of four brain MRI segmentation algorithms bundled in the successive releases of Statistical Parametric Mapping (SPM) package (SPM99, SPM2, SPM5, SPM8) using clinical neurological examinations was performed. Subsequently, their impact on PVC in 18 F-FDG brain PET imaging was assessed. The principle of the different variants of the image segmentation algorithm is to spatially normalize the subject's MR images to a corresponding template. PET images were corrected for partial volume effect using GM volume segmented from coregistered MR images. The PVC approach aims to compensate for signal dilution in non-active tissues such as CSF, which becomes an important issue in the case of tissue atrophy to prevent a misinterpretation of decrease of metabolism owing to PVE. The study population consisted of 19 patients suffering from neurodegenerative dementia. Image segmentation performed using SPM5 was used as reference. The comparison showed that previous releases of SPM (SPM99 and SPM2) result in larger gray matter regions (∼20%) and smaller white matter regions (between −17% and −6%), thus introducing non-negligible bias in PVC PET activity estimates (between 30% and 90%). In contrary, the more recent release (SPM8) results in similar results (<1%). It was concluded that the choice of the segmentation algorithm for MRI-guided PVC in PET plays a crucial role for the accurate estimation of PET activity concentration. The segmentation algorithm embedded within the latest release of SPM satisfies the requirement of robust and accurate segmentation for MRI-guided PVC in brain PET imaging.Published by Elsevier Ltd.