Amyloid burden was measured with N-methyl-[11C]-2-(4-methylaminophenyl)-6-hydroxybenzothiazole (Pittsburgh Compound B; PiB), which binds to fibrillar amyloid, and was prepared at Massachusetts General Hospital as described previously (Klunk et al., 2004 (link); Mathis et al., 2003 (link)). Participants underwent PiB PET imaging as described previously (Gomperts et al., 2008 (link); Hedden et al., 2009 (link), 2012 (link); Sperling et al., 2009 (link)). Briefly, data were acquired using a Siemens/CTI ECAT HR+ scanner (3-D mode; 63 image planes; 15.2cm axial field of view; 5.6 mm transaxial resolution and 2.4mm slice interval; 39 frames: 8x15s, 4x60s, 27x120s). After a transmission scan, 8.5 to 15mCi [11C]-PiB was injected as a bolus and followed immediately by a 60-minute dynamic acquisition. PET data were reconstructed and attenuation corrected, and each frame was evaluated to verify adequate count statistics and absence of head motion (inter-frame head motion, if present, was corrected prior to further processing).
The dynamic PET data were reconstructed with scatter correction using commercially available routines for 3-D PET data. The average of the initial 0–8 minutes of dynamic PET data was spatially normalized to a PET MNI template using SPM8. PET data were parameterized by the distribution volume ratio (DVR) computed using the Logan graphical analysis technique (Logan et al., 1990 (link)) applied to the frame data acquired 40–60 minutes after injection; this method has been fully validated for PiB imaging (Price et al., 2005 (link)). Time-activity curves were measured in each brain region under analysis (region of interest or voxel) and in a reference region in cerebellar cortex known to contain low levels of fibrillar amyloid. This approach has been applied to numerous PiB studies (e.g., Fagan et al., 2006 (link); Johnson et al., 2007 (link); Lopresti et al., 2005 (link); Price et al., 2005 (link)) and yields data that are similar to arterial blood input methods (Lopresti et al., 2005 (link)).
For each subject an index of PiB binding in cortical regions was calculated using the dynamic data via Logan graphical modeling within a large aggregate cortical region of interest (ROI) consisting of frontal, lateral parietal and temporal, and retrosplenial cortices (the FLR region). PiB retention in the FLR region is substantial in patients with diagnosed AD and has been used as a summary measure of PiB retention in previous studies (Johnson et al., 2007 (link); Gomperts et al., 2008 (link); Hedden et al., 2009 (link), 2012 (link)). FLR DVR was log-transformed because of the non-normal distribution of PiB values and treated as a continuous variable in all analyses. Despite this transformation, non-normality of the distribution remains evident and individuals with very high values of PiB may have a disproportionate influence on the results.
The dynamic PET data were reconstructed with scatter correction using commercially available routines for 3-D PET data. The average of the initial 0–8 minutes of dynamic PET data was spatially normalized to a PET MNI template using SPM8. PET data were parameterized by the distribution volume ratio (DVR) computed using the Logan graphical analysis technique (Logan et al., 1990 (link)) applied to the frame data acquired 40–60 minutes after injection; this method has been fully validated for PiB imaging (Price et al., 2005 (link)). Time-activity curves were measured in each brain region under analysis (region of interest or voxel) and in a reference region in cerebellar cortex known to contain low levels of fibrillar amyloid. This approach has been applied to numerous PiB studies (e.g., Fagan et al., 2006 (link); Johnson et al., 2007 (link); Lopresti et al., 2005 (link); Price et al., 2005 (link)) and yields data that are similar to arterial blood input methods (Lopresti et al., 2005 (link)).
For each subject an index of PiB binding in cortical regions was calculated using the dynamic data via Logan graphical modeling within a large aggregate cortical region of interest (ROI) consisting of frontal, lateral parietal and temporal, and retrosplenial cortices (the FLR region). PiB retention in the FLR region is substantial in patients with diagnosed AD and has been used as a summary measure of PiB retention in previous studies (Johnson et al., 2007 (link); Gomperts et al., 2008 (link); Hedden et al., 2009 (link), 2012 (link)). FLR DVR was log-transformed because of the non-normal distribution of PiB values and treated as a continuous variable in all analyses. Despite this transformation, non-normality of the distribution remains evident and individuals with very high values of PiB may have a disproportionate influence on the results.
