Participants were imaged at 23 sites using clinical PET and PET/computed tomographic scanners. Each participant underwent a 10-minute PET scan, which began 50 minutes after receiving an intravenous bolus of 370 MBq (10 mCi) florbetapir F 18. Images were acquired with a 128 × 128 matrix (zoom × 2) and were reconstructed using iterative or row action maximization likelihood algorithms.
Florbetapir-PET images were assessed visually using a semiquantitative score ranging from 0 (no amyloid) to 4 (high levels of cortical amyloid) by 3 board-certified nuclear medicine physicians who were not involved in any other aspects of the study. The only experience these physicians had with florbetapir-PET imaging occurred during a half-day training session. The median rating of the readers served as a primary outcome variable. Readers were blinded to clinical, demographic, and neuropathological information and viewed and rated images under the supervision and at the facility of the imaging core laboratory (ImageMetrix, a division of the American College of Radiology, Philadelphia, Pennsylvania). The initial 6 postmortem evaluations were rated by 4 readers and the median rating of the 4 raters served as the primary outcome variable for these 6 participants.
For the younger control cohort, the PET images were mixed in random order with 40 images from the autopsy cohort that had a median visual read score between 2 and 4 (inclusive). To remove image recognition bias, these images were rated as amyloid positive or negative at ImageMetrix by a different group of 3 external readers. The majority rating was used as the primary outcome variable for this analysis.
A semiautomated quantitative analysis of the ratio of cortical to cerebellar signal (SUVr) also was performed for florbetapir-PET images from all study participants. The images were first normalized to a standard template in the Talairach space and then the SUVrs were calculated for the 6 predefined cortical regions of interest (frontal, temporal, parietal, anterior cingulate, posterior cingulate, and precuneus). The whole cerebellum was used as the reference region.
Florbetapir-PET images were assessed visually using a semiquantitative score ranging from 0 (no amyloid) to 4 (high levels of cortical amyloid) by 3 board-certified nuclear medicine physicians who were not involved in any other aspects of the study. The only experience these physicians had with florbetapir-PET imaging occurred during a half-day training session. The median rating of the readers served as a primary outcome variable. Readers were blinded to clinical, demographic, and neuropathological information and viewed and rated images under the supervision and at the facility of the imaging core laboratory (ImageMetrix, a division of the American College of Radiology, Philadelphia, Pennsylvania). The initial 6 postmortem evaluations were rated by 4 readers and the median rating of the 4 raters served as the primary outcome variable for these 6 participants.
For the younger control cohort, the PET images were mixed in random order with 40 images from the autopsy cohort that had a median visual read score between 2 and 4 (inclusive). To remove image recognition bias, these images were rated as amyloid positive or negative at ImageMetrix by a different group of 3 external readers. The majority rating was used as the primary outcome variable for this analysis.
A semiautomated quantitative analysis of the ratio of cortical to cerebellar signal (SUVr) also was performed for florbetapir-PET images from all study participants. The images were first normalized to a standard template in the Talairach space and then the SUVrs were calculated for the 6 predefined cortical regions of interest (frontal, temporal, parietal, anterior cingulate, posterior cingulate, and precuneus). The whole cerebellum was used as the reference region.
