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This study utilized data from a recently published report that demonstrated the effects of peripheral endotoxin administration on neuroinflammation [6 (link)]. All procedures were carried out in accordance with the Animal Welfare Act, other federal regulations governing the care and responsible use of animals for research, and under the recommended principles set forth in the Guide for Care and Use of Laboratory Animals [13 ]. The protocol was approved by the Yale University Institutional Animal Care and Use Committee. Details regarding the prior study of six of the animals can be found in Hannestad et al. [6 (link)]. The present work also includes a baseline scan from a seventh baboon. Briefly, animals received a bolus injection of 172 ± 12.4 MBq of [¹¹C]PBR28, and dynamic data were acquired for 120 minutes on an ECAT EXACT HR+ (Siemens, Knoxville TN). Animals were scanned at baseline (n = 7), and at 1 hr (n = 4), 4 hr (n = 3), and 22 hr (n = 2) after IV administration of 0.1 mg/kg lipopolysaccharide (LPS). Arterial sampling was conducted during PET scanning for analysis of parent [¹¹C]PBR28 and radiolabeled metabolites. Image processing was as described previously [6 (link)]. A total of sixteen [¹¹C]PBR28 PET studies and results from the corresponding metabolite assays were available for this analysis.

PIB PET scans were performed at CUMC Kreitchman PET Center (n=45) on an ECAT EXACT HR+ (Siemens, Knoxville, TN) or Weill Cornell Medicine Citigroup Biomedical Imaging Center (n=32) on a Siemens Biograph mCT. Immediately following 30-second intravenous PIB injection, dynamic images were acquired in 3D mode at 3 × 20 sec, 3 × 1 min, 3 × 2 min, 2 × 5 min, and 7 × 10 min. Low-dose CT scan was performed for attenuation correction. A 3D SPGR T1 Sequence was performed on a GE Signa 3 Tesla MRI scanner. PET scans were performed within one year of UPSIT (mean interval = 93.9 ± 93.1 days), with the exception of one subject who had PET scan performed 16.5 months after UPSIT.
PET analysis was performed using PMOD 3.6. MR images were segmented using the PNEURO tool and the Hammers-N30R83–1MM atlas was used to define regions-of-interest (ROIs). ROIs were inspected and manually corrected if necessary. PET images 50–70 min post-injection were averaged, co-registered to the corresponding MR image, and individual subject ROIs were then applied. Mean uptake over 50–70 min from a composite gray matter ROI from frontal, parietal, and lateral temporal cortex (excluding sensorimotor cortex) was divided by mean uptake in cerebellar gray matter to create a global standardized uptake value ratio (SUVR). PIB SUVR > 1.5 was used to define amyloid-β positivity [22 (link), 23 (link)].

Imaging consisted of structural MRI and two different positron emission tomography (PET) imaging sessions: 1) amyloid imaging with [¹¹C]PIB and 2) quantitative cerebral blood flow imaging with [¹⁵O]water (with arterial blood sampling) under 3 conditions (counting task, list remembering task, rest task (eyes open, ears unplugged). All PET imaging was performed on a Siemens ECAT EXACT HR+ with transmission imaging ([⁶⁸Ge]) for attenuation correction performed prior to the injection of the radiotracers. MR imaging was performed on a 3.0T Siemens TIM Trio MRI Scanner or on a GE 750W 3T scanner. All image analyses were performed using the PMOD suite of tools (PVIEW, PFUSION, PNEURO, PXMOD, PKIN, PALZ, v. 3.7 and 3.8, PMOD Technologies, Ltd, Zurich, Switzerland).