The intestinal microbiota helps to maintain the integrity of the blood-brain barrier in fetal and adult mice.

Purpose Pathological studies suggest that neuroinflammation is exacerbated by increased beta-amyloid (Aβ) levels in the brain early in Alzheimer’s disease (AD). The time course and relationships between astrocytosis and Aβ deposition were examined using multitracer in vivo positron emission tomography (PET) imaging in an AD transgenic mouse model, followed by postmortem autoradiography and immunohistochemistry analysis. Methods PET imaging with the amyloid plaque tracer ¹¹C-AZD2184 and the astroglial tracer ¹¹C-deuterium-L-deprenyl (¹¹C-DED) was carried out in APPswe mice aged 6, 8–15 and 18–24 months (4–6 animals/group) and in wild-type (wt) mice aged 8–15 and 18–24 months (3–6 animals/group). Tracer uptake was quantified by region of interest analysis using PMOD software and a 3-D digital mouse brain atlas. Postmortem brain tissues from the same APPswe and wt mice in all age groups were analysed for Aβ deposition and astrocytosis by in vitro autoradiography using ³H-AZD2184, ³H-Pittsburgh compound B (PIB) and ³H-L-deprenyl and immunostaining performed with antibodies for Aβ₄₂ and glial fibrillary acidic protein (GFAP) in sagittal brain sections. Results ¹¹C-AZD2184 PET retention in the cerebral cortices of APPswe mice was significantly higher at 18–24 months than in age-matched wt mice. Cortical and hippocampal ¹¹C-DED PET binding was significantly higher at 6 months than at 8–15 months or 18–24 months in APPswe mice, and it was also higher than at 8–15 months in wt mice. In vitro autoradiography ³H-AZD2184 and ³H-PIB binding confirmed the in vivo findings with ¹¹C-AZD2184 and demonstrated age-dependent increases in Aβ deposition in APPswe cortex and hippocampus. There were no significant differences between APPswe and wt mice in ³H-L-deprenyl autoradiography binding across age groups. Immunohistochemical quantification demonstrated more Aβ₄₂ deposits in the cortex and hippocampus and more GFAP⁺ reactive astrocytes in the hippocampus at 18–24 months than at 6 months in APPswe mice. Conclusion The findings provide further in vivo evidence that astrocytosis occurs early in AD, preceding Aβ plaque deposition.

NanoScan is a high-resolution integrated system for consecutive PET and MR imaging of small laboratory animals. We evaluated the performance of the system, using the NEMA NU 4-2008 protocol for the PET component and the NEMA MS 1-2007, MS 2-2008, and MS 3-2007 standards for the MR imaging component. Methods: The imaging system uses magnetically shielded position-sensitive photomultiplier tubes and a compact 1-T permanent-magnet MR imaging platform. Spatial resolution, sensitivity, counting rate capabilities, and image quality parameters were evaluated in accordance with the aforementioned NEMA standards. Further in vivo evaluation experiments complement the physical validation results. Results: The spatial resolution of the PET system enabled the 0.8-mm rods of a Derenzo phantom to be resolved. With point source and 2-dimensional filtered backprojection reconstruction, the resolution varied from 1.50 to 2.01 mm in full width at half maximum in the radial direction and from 1.32 to 1.65 mm in the tangential direction within the radius of 25 mm. Peak absolute sensitivity was 8.41%. Scatter fraction was 17.3% and 34.0%, and maximum noise-equivalent counting rate was 406 and 119 kcps in the mouselike and ratlike phantom, respectively. The image quality test found a nonuniformity of 3.52% and a spillover ratio of 6.2% and 5.8% in water and air, respectively. In testing of the MR imaging component, artifact-free images with high signal-to-noise ratio were recorded. Geometric distortion was below 5%, and image uniformity was at least 94.5% and 96.6% for the 60- and 35-mm radiofrequency coils, respectively. Conclusion: The nanoScan integrated small-animal PET/MR imaging system has excellent spatial resolution and sensitivity. The performance characteristics of the PET and the MR imaging components are not compromised as a result of their integration onto a single platform. Because of its combination of features and performance parameters, the system provides crucial advantages for preclinical imaging studies over existing PET/CT systems, especially in neurologic and oncologic research.

¹⁸F-(E)-N-(3-iodoprop-2-enyl)-2β-carbofluoroethoxy-3β- (4′-methyl-phenyl)nortropane (¹⁸F-FE-PE2I) is a novel radioligand for dopamine transporter (DAT) PET. As compared with ¹¹C-N-(3-iodoprop-2E-enyl)-2β-carbomethoxy-3β-(4-methylphenyl)nortropane (¹¹C-PE2I), ¹⁸F-FE-PE2I shows faster kinetics and more favorable metabolism, with less production of a radiometabolite with intermediate lipophilicity (M1), which—in the case of ¹¹C-PE2I—has been shown to enter the rat brain. In this study, we compared DAT quantification with ¹¹C-PE2I and ¹⁸F-FE-PE2I in nonhuman primates, using kinetic and graphical analysis with the input function of both the parent and the radiometabolite, to assess the potential contribution of the radiometabolite. Methods: Three rhesus monkeys were examined with ¹¹C-PE2I and ¹⁸F-FE-PE2I using the HRRT system. Arterial input functions of the parent and radiometabolite M1 were measured. Kinetic and graphical analyses were applied using either the parent input (methods 1 and 3) or the parent plus radiometabolite input (methods 2 and 4). Outcome measures were distribution volumes (V_T and V_ND), specific-to-nondisplaceable tissue radioactivity ratio at equilibrium (BP_ND; parent input), and specific–to–nondisplaceable tissue radioactivity ratio at equilibrium in the presence of metabolites (R_T; parent plus radiometabolite input). Results: ¹¹C-PE2I showed higher distribution volumes than ¹⁸F-FE-PE2I calculated with methods 1 and 3 (striatal V_T, ∼300%; V_ND in cerebellum, ∼30%). With methods 2 and 4, V_T in the striatum was approximately 60% higher in the case of ¹¹C-PE2I, whereas no difference in V_ND was found in the cerebellum. For each radioligand, BP_ND estimated with methods 1 and 3 tended to be higher than R_T estimated with methods 2 and 4. However, the bias of BP_ND, compared with R_T, was much larger for ¹¹C-PE2I (40%–60% in the caudate and putamen) than for ¹⁸F-FE-PE2I (<10% in the caudate and putamen). Conclusion: The direct comparison between the radioligands confirmed that ¹⁸F-FE-PE2I shows faster kinetics and more favorable metabolism than ¹¹C-PE2I. The kinetic and graphical analyses with the input function of the parent and radiometabolite showed that the bias in BP_ND was much lower for ¹⁸F-FE-PE2I than for ¹¹C-PE2I and suggested that the lower production of the radiometabolite M1 would make ¹⁸F-FE-PE2I more suitable for the DAT quantification. Further studies in humans are necessary to confirm these findings.