PET: 18F T807 (AV1451) was prepared at MGH with a radiochemical yield of 14±3% and specific activity of 216±60 GBq/µmol at the end of synthesis (60min), and validated for human use.21 11C Pittsburgh Compound B was prepared and PET data were acquired as described previously.16 (link) All PET data were acquired using a Siemens/CTI (Knoxville, TN) ECAT HR+ scanner (3D mode; 63 image planes; 15.2cm axial field of view; 5.6mm transaxial resolution and 2.4mm slice interval. 11C PiB PET was acquired with a 8.5 to 15 mCi bolus injection followed immediately by a 60-minute dynamic acquisition in 69 frames (12×15 seconds, 57×60 seconds). 18F T807 was acquired from 80–100 minutes after a 9.0 to 11.0 mCi bolus injection in 4 × 5-minute frames. PET data were reconstructed and attenuation corrected, and each frame was evaluated to verify adequate count statistics and absence of head motion. The mean ± standard deviation (SD) lag time between 18F T807 and MMSE and CDR ratings was 4.9 ± 3.5 months, and between 18F T807 and 11C PiB PET imaging, 3.5 ± 2.6 months.
MRI was performed on a 3T Tim Trio (Siemens) and included a magnetization-prepared rapid gradient-echo (MPRAGE) processed with Freesurfer (FS) as described previously to identify grey-white and pial surfaces to permit ROI parcellation as follows: cerebellar grey, hippocampus, and the following Braak Stage related cortices: entorhinal (ER), parahippocampal (PH), inferior temporal (IT), fusiform (FF), posterior cingulate (PC), as described previously.16 (link), 22 –25 (link)To evaluate the anatomy of cortical T807 binding, each individual PET data set was rigidly co-registered to the subject’s MPRAGE data using SPM8 (Wellcome Department of Cognitive Neurology, Function Imaging Laboratory, London). The cortical ribbon and subcortical ROIs defined by MR as described above were transformed into the PET native space; PET data were sampled within each right-left ROI pair. SUVR values were represented graphically on vertices at the pial surface. PET data were not partial volume corrected.
18F T807 specific binding was expressed in FS ROIs as the standardized uptake value ratio (SUVR) to cerebellum, similar to a previous report, using the FS cerebellar grey ROI as reference. For voxel-wise analyses, each subject’s MPRAGE was registered to the template MR in SPM8 (SPM), and the spatially transformed SUVR PET data was smoothed with a 8 mm Gaussian kernel to account for individual anatomic differences.7 (link)11C PiB PET data were expressed as the distribution volume ratio (DVR) with cerebellar grey as reference tissue; regional time-activity curves (TAC) were used to compute regional DVRs for each ROI using the Logan graphical method applied to data from 40 to 60 minutes after injection.16 (link), 26 (link)11C PiB retention was assessed using a large cortical ROI aggregate that included frontal, lateral temporal and retrosplenial cortices (FLR) as described previously.17 (link), 27
MRI was performed on a 3T Tim Trio (Siemens) and included a magnetization-prepared rapid gradient-echo (MPRAGE) processed with Freesurfer (FS) as described previously to identify grey-white and pial surfaces to permit ROI parcellation as follows: cerebellar grey, hippocampus, and the following Braak Stage related cortices: entorhinal (ER), parahippocampal (PH), inferior temporal (IT), fusiform (FF), posterior cingulate (PC), as described previously.16 (link), 22 –25 (link)To evaluate the anatomy of cortical T807 binding, each individual PET data set was rigidly co-registered to the subject’s MPRAGE data using SPM8 (Wellcome Department of Cognitive Neurology, Function Imaging Laboratory, London). The cortical ribbon and subcortical ROIs defined by MR as described above were transformed into the PET native space; PET data were sampled within each right-left ROI pair. SUVR values were represented graphically on vertices at the pial surface. PET data were not partial volume corrected.
18F T807 specific binding was expressed in FS ROIs as the standardized uptake value ratio (SUVR) to cerebellum, similar to a previous report, using the FS cerebellar grey ROI as reference. For voxel-wise analyses, each subject’s MPRAGE was registered to the template MR in SPM8 (SPM), and the spatially transformed SUVR PET data was smoothed with a 8 mm Gaussian kernel to account for individual anatomic differences.7 (link)11C PiB PET data were expressed as the distribution volume ratio (DVR) with cerebellar grey as reference tissue; regional time-activity curves (TAC) were used to compute regional DVRs for each ROI using the Logan graphical method applied to data from 40 to 60 minutes after injection.16 (link), 26 (link)11C PiB retention was assessed using a large cortical ROI aggregate that included frontal, lateral temporal and retrosplenial cortices (FLR) as described previously.17 (link), 27
