Advance scanner

Dynamic [¹¹C]PiB PET studies (33 time frames over 70 minutes) were performed in 3D mode on a GE Advance scanner at the Johns Hopkins University PET facility. Details of image acquisition and processing, including quantification of distribution volume ratio (DVR), are described elsewhere [2 (link), 9 (link)]. Mean cortical DVR was calculated as the average of DVR values from the cingulate, frontal, parietal (including precuneus), lateral temporal, and lateral occipital cortices, excluding the sensorimotor strip. PiB+/− status was determined using a previously defined mean cortical DVR cutoff of 1.066 [9 (link)]. Those with a mean cortical DVR greater than 1.066 are more likely to accumulate greater amyloid burden over time compared to those with mean cortical DVR less than 1.066. In addition to PiB+/−, we were also interested in amyloid burden in motor-related cortical and subcortical regions, including primary motor cortex, putamen, and caudate.

For each subject, a baseline scan was acquired first, followed by a ‘tariquidar scan’ on a later date (> two weeks) both with full arterial blood sampling. After a bolus injection of ¹⁸F-FCWAY (376 ± 8 MBq), a PET scan was acquired on a GE advance scanner for two hours with increasing frame duration of 30 seconds to five minutes. For the tariquidar scan, the potent and selective P-gp inhibitor tariquidar was administered at 2 mg/kg (two subjects) or 4 mg/kg (six subjects) via constant infusion during the PET scan. Infusion began 30 minutes before radioligand injection and continued at a rate of 2 mg/kg/h, ending 30 minutes and 90 minutes after radioligand injection, respectively. The infusion rate was kept constant to avoid adverse effects (Kreisl et al., 2010 (link)). Images were reconstructed using 3D filtered backprojection with scatter, attenuation, and frame-based motion correction.

CT and MRI from the neck to the pelvis were carried out in all patients. Most of the patients underwent PET or PET/CT scanning using 2 different radiopharmaceuticals and/or [^123/131I]-MIBG scintigraphy. CT scans of the neck, chest, abdomen, and pelvis were performed using initially single-channel or multichannel spiral CT machines (GE Healthcare Technologies, Chicago, IL), and since early 2003 exclusively multichannel helical CT equipment (General Electric Healthcare Technologies; Philips Medical Systems, Amsterdam, the Netherlands; Siemens Medical Solutions, Munich, Germany). MRI scans of the neck, chest, abdomen, and pelvis were obtained with 1.5- or 3- Tesla scanners (General Electric Healthcare Technologies and Philips Medical Systems). For PET and PET/CT scanning, the patients fasted for at least 4 hours before intravenous (i.v.) injection of [¹⁸F]-fluorodopamine ([¹⁸F]-FDA) (1 mCi) or [¹⁸F]-fluorodeoxyglucose ([¹⁸F]-FDG) (15 mCi). [¹⁸F]-FDA PET scans performed before March 2005 used an Advance Scanner (General Electric Medical Systems) with a 15-cm axial field of view. Subsequent [¹⁸F]-FDA and all [¹⁸F]-FDG scans were done using a PET/CT scanner (Siemens) with a 15 cm axial field of view. For [^123/131I]-MIBG scanning, patients were imaged at 24 h (and 48 h in some cases) following i.v. administration of 10 mCi (370 MBq) of [¹²³I]-MIBG or 0.5 mCi (18.5 MBq) of [¹³¹I]-MIBG.

Dynamic ¹¹C-PiB PET scans were obtained on 3D mode from a GE Advance scanner, started immediately after intravenous bolus injection of ¹¹C-PiB. Distribution volume ratio (DVR) images were computed using a simplified reference tissue model [34 (link)] with cerebellar gray matter as the reference region. Mean cortical amyloid-β (Aβ) burden was calculated as the average of the DVR values in anterior, middle, and posterior cingulate regions, superior, middle and inferior frontal and orbitofrontal, superior parietal, supramarginal and angular gyrus regions, superior, middle and inferior temporal, pre-cuneus, superior, middle and inferior occipital, excluding the sensorimotor strip. All analyses were run using PiB cortical DVR (cDVR) both as a continuous variable and a dichotomized variable based on PiB positivity (defined as cDVR > 1.061 based on 2-class Gaussian mixture modeling [35 (link)]).

PET scans were conducted on a GE Advance scanner. Subjects were fitted with a thermoplastic mask in order to reduce motion artifacts. Dynamic [¹¹C]-PiB PET data acquisition was performed in 3D mode immediately following an intravenous bolus injection of [¹¹C]-PiB with an acquisition protocol of 4×0.25 minutes, 8×0.5 minutes, 9×1 minutes, 2×3 minutes, 10×5 minutes (total 70 minutes, 33 frames). All PET images were corrected for attenuation using ⁶⁸Ge transmission scans, and were reconstructed to have 2×2 mm pixel size and 4.25 mm slice thickness.