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Purpose: An important issue in rodent imaging is the question whether a mixed population of male and female animals can be used rather than animals of a single sex. For this reason, the present study examined the test-retest stability of positron emission tomography (PET) with 2-deoxy-2-[ 18 F]fluoro-D-glucose ([ 18 F]FDG) in male rats and female rats at different phases of the estrous cycle., Procedures: Long-Evans rats (age 1 year) were divided into three groups: (1) males (n = 6), (2) females in metestrous (low estrogen levels, n = 9), and (3) females in proestrous (high estrogen levels, n = 7). Two standard [ 18 F]FDG scans with rapid arterial blood sampling were made at an interval of 10 days in subjects anesthetized with isoflurane and oxygen. Body temperature, heart rate, and blood oxygenation were continuously monitored. Regional cerebral metabolic rates of glucose were calculated using a Patlak plot with plasma radioactivity as input function., Results: Regional metabolic rate of glucose (rCMR glucose ) in male and female rats, or [ 18 F]FDG uptake in females at proestrous and metestrous, was not significantly different, but females showed significantly higher standardized uptake values (SUVs) and Patlak flux than males, particularly in the initial scan. The relative difference between the scans and the test-retest variability (TRV) were greater in females than in males. Intra-class correlation coefficients (ICCs) of rCMR glucose , SUV, normalized SUV, and glucose flux were good to excellent in males but poor to moderate in females., Conclusions: Based on these data for [ 18 F]FDG, the mixing of sexes in imaging studies of the rodent brain will result in an impaired test-retest stability of PET data and a need for larger group sizes to maintain statistical power in group comparisons. The observed differences between males and females do not indicate any specific gender difference in cerebral metabolism but are related to different levels of non-radioactive glucose in blood plasma during isoflurane anesthesia.

The name of the second author was incorrectly cited and is corrected now, as displayed here.

Purpose: This study evaluates the performance of several parametric methods for assessing [ 11 C]flumazenil binding distribution in the rat brain., Procedures: Dynamic (60 min) positron emission tomography data with metabolite-corrected plasma input function were retrospectively analyzed (male Wistar rats, n = 10). Distribution volume (V T ) images were generated from basis function method (BFM), Logan graphical analysis (Logan), and spectral analysis (SA). Using the pons as pseudo-reference tissue, binding potential (BP ND and DVR-1) images were obtained from receptor parametric imaging algorithms (RPM and SRTM2) and reference Logan (RLogan). Standardized uptake value images (SUV and SUVR) were also computed for different intervals post-injection. Next, regional averages were extracted from the parametric images, using pre-defined volumes of interest, which were also applied to the regional time-activity curves from the dynamic data. Parametric data were compared to their regional counterparts and to two-tissue compartment model (2TCM)-based values (previously defined as the model of choice for rats). Parameter agreement was assessed by linear regression analysis and Bland-Altman plots., Results: All parametric methods strongly correlated to their regional counterparts (R 2  > 0.97) and to the 2TCM values (R 2  ≥ 0.95). SA and RLogan underestimated V T and BP ND (slope of 0.93 and 0.86, respectively), while SUVR-1 overestimated BP ND (slope higher than 1.07 for all intervals). While BFM and SRTM2 had the smallest bias to 2TCM values (0.05 for both), ratio Bland-Altman plots showed Logan and RLogan displayed relative errors which were comparable between different regions, in contrast with the other methods. Although SUV consistently underestimated V T , the bias in this method was also constant across regions., Conclusions: All parametric methods performed well for the analysis of [ 11 C]flumazenil distribution and binding in the rat brain. However, Logan and RLogan slightly outperformed the other methods in terms of precision, providing robust parameter estimation and constant bias. Yet, other methods can be of interest, because they can provide tissue perfusion (i.e., K 1 with BFM and SA), relative flow (i.e., R 1 with RPM and SRTM2), and model order (SA) images.

Purpose: Small animal positron emission tomography (PET) can be used to detect small changes in neuroreceptor availability. This often requires rapid arterial blood sampling. However, current catheterization procedures do not allow repeated blood sampling. We have developed a procedure which allows arterial sampling on repeated occasions in the same animal., Procedures: Eleven male Wistar rats were two times catheterized via a superficial branch of a femoral artery and scanned with [(11)C]MPDX and blood sampling. PET images were co-registered to a magnetic resonance imaging (MRI) template. Regional tracer distribution volumes (V T) in the brain were calculated by the Logan analysis. The procedure was repeated after 1 week., Results: Surgery was successful in 90 % of the cases, and discomfort was minor. The V T data showed small differences between test and retest, low between subject variability, and a strong agreement between and within subjects., Conclusion: Repeated quantitative imaging with a high reproducibility is possible with this approach., Competing Interests: Compliance with Ethical Standards The study protocol was approved by the Institutional Animal Care and Use Committee of the University of Groningen. All experiments were performed by licensed investigators in compliance with the Law on Animal Experiments of The Netherlands. Conflict of Interest The authors declare that they have no conflict of interest.