Cerebellum

PiB and florbetapir image data were analyzed using 2 processing streams. The PET-template analysis method was described in a separate study (10 (link)). This method was applied to the raw and unsmoothed datasets. Briefly, image data were spatially normalized to standard atlas coordinates in Talairach space using statistical parametric mapping software (11 ). Mean tracer retention was calculated for 6 predefined target cortical regions of interest (medial orbital frontal, temporal, parietal, anterior cingulate, posterior cingulate, and precuneus) that resulted from a statistical contrast of AD patients and cognitively normal subjects (1 (link)).
The Freesurfer method for quantifying cortical Aβ was applied to the unsmoothed and smoothed datasets. This method was described in detail elsewhere (2 (link),12 (link)) and online (13 ). Structural 1.5-T or 3-T MRI scans (T1-weighted images) were used to define cortical regions of interest and the cerebellar reference region. In general, 2 structural MRI scans were acquired at each visit across several years of follow-up, with the result that several MR images were available for each subject. For processing the PiB images, we chose the T1 scans acquired concurrently with (or closest in time to) the first PiB scan; and for the florbetapir processing, we chose the T1 scans acquired concurrently with (or closest in time to) the florbetapir scan. Structural MR images were segmented and parceled into individual cortical regions with Freesurfer (version 4.5.0; surfer.nmr.mgh.harvard.edu/) and subsequently used to extract mean PiB and florbetapir cortical retention ratios from gray matter within lateral and medial frontal, anterior and posterior cingulate, lateral parietal, and lateral temporal regions.
To examine several reference regions, the unscaled cortical means for each analysis method were divided by mean retention in the following 3 reference regions: brain stem–pons, whole cerebellum (white and gray matter), and cerebellar gray matter, yielding 3 cortical retention ratios for each preprocessing method. Because Freesurfer creates a brain stem, but not pons, region as part of its automated processing stream, the brain stem was used for the Free-surfer processing analysis method and the pons was used for the PET-template processing method.
To summarize, for each of 3 PET sessions (2 PiB scans and 1 florbetapir scan), every subject had cortical retention ratios for 2 levels of processing and 2 analysis methods (raw and unsmoothed for the PET-template method and unsmoothed and smoothed for the Freesurfer method), using 3 reference regions (brain stem–pons, whole cerebellum, cerebellar gray matter), resulting in 36 mean cortical retention ratios per subject that were compared in subsequent statistical analyses.