The high-resolution research tomograph (HRRT) is a dedicated human brain PET scanner. The purpose of this study was to compare the quantitative accuracy of the HRRT with that of the clinical HR1 PET scanner and to assess effects of differences in spatial resolution between both scanners (;2.7 mm and ;7.0 mm for HRRT and HR1, respectively). Methods: Paired 11 Cflumazenil scans of 7 healthy volunteers were assessed. For each volunteer, dynamic scans (including arterial sampling) were acquired on both scanners on the same day, thereby minimizing intersubject variability. Volume of distribution was generated using Logan plot analysis with plasma input. In addition, other plasma input, reference tissue (with pons as the reference tissue input), and parametric methods were included in the interscanner comparison. Results: Logan volume-of-distribution analysis of HRRT data showed higher values than that of HR1 data (slope with the intercept fixed at the origin of 1.14 6 0.10 to 1.19 6 0.10, depending on the HRRT reconstruction method used). Smoothing HRRT reconstructions with a 6-mm full width at half maximum gaussian kernel reduced this slope toward the line of identity (1.04 6 0.11 to 1.07 6 0.11), retaining good correlation between HR1 and HRRT data (r, ;0.98). Similar trends were observed for other plasma input, reference tissue, and parametric methods. However, after reference matching the reference tissue models showed lower HRRT kinetic parameter values than HR1 values (slope with fixed intercept, 0.90 6 0.10 to 0.94 6 0.13). Conclusion: Higher values of pharmacokinetic parameter values, obtained from HRRT versus HR1 PET studies, indicate improved HRRT PET quantification primarily due to a reduction in partial-volume effects. The availability of lutetium oxyorthosilicate/lutetiumyttrium oxyorthosilicate (LSO/LYSO) crystals has generated interest in new PET scanners that have higher spatial image resolution. The ECAT High-Resolution Research Tomograph (HRRT) (CTI/Siemens) is a dedicated human brain scanner with design features that enable high spatial image resolution combined with high sensitivity (1). The HRRT is the first commercially available PET scanner that uses a double layer of LSO/LYSO crystals to achieve photon detection with depth-of-interaction information.To date, only a limited number of human brain studies have been performed using the HRRT (2-7). Most human brain studies have been acquired with clinical (whole-body) PET scanners, such as the ECAT EXACT HR1 (CTI/Siemens). Therefore, it is worthwhile to compare the accuracy of quantitative human HRRT studies with that of HR1 studies. The HR1 scanner has a single layer of bismuth germinate crystals. Over the years, its quantitative accuracy has been studied extensively (8)(9)(10).A direct quantitative comparison between HRRT and HR1 has been performed in a limited way, using only phantoms (11). Recently, Leroy et al. (3) performed a comparative study between similar patient groups, matched in age, acquired on either an HR1 or an HRRT. Although this ...