Head Movement Was Minimized Using a Polyurethane Immobilizer Molded Around the Head. PET

Appendix e-1

PET Imaging

Head movement was minimized using a polyurethane immobilizer molded around the head. PET images were acquired on an ECAT EXACT HR+ (Siemens/CTI, Knoxville Tenn.). After a 10-minute transmission scan, mean 500.71 (SD 160.48) MBq of [11C]-PIB was administered intravenously as a bolus over 30 seconds. Emission data were collected in 3D mode for 90 minutes, binning over 18 frames of increasing duration (3 X 20 sec, 3 X 1 min, 3 X 2 min, 2 X 5 min, and 7 X 10 min). Images were reconstructed to 128 X 128 matrix (pixel size of 2.5 X 2.5 mm2). Reconstruction was performed with attenuation correction using the transmission data and scatter correction was done using a model-based approach.e1 The reconstruction filter and estimated image filter were Shepp 0.5 (2.5 full width half maximum (FWHM), Z filter was all pass 0.4 (2.0 FWHM), and the zoom factor was 4.0, leading to a final image resolution of 5.1 mm FWHM at the center of the field of view.e2

MR Imaging

Images were acquired on a GE Signa 3 Tesla whole body scanner with the following sequences. 3-Plane Localizer Repetition Time (TR) = 23.4 ms, Echo Time (TE) = 1.7 ms, Flip angle = 30°, Bandwidth = 31.3 MHz, field of view (FOV) = 24 x 24 cm, thickness = 5.0 mm, Spacing = 1.5 mm, 9 slices per volume (3 axials, 3 sagittals, 3 coronals), Matrix 256 x 128. 3D SPGR Anatomical Sequence TI 500 ms, TR 5 ms, TE Minimum (1.3 ms), Flip angle 11°, Band width 31.25 MHz, FOV 26 x 26, Slice thickness 1.1 mm, Spacing 0.0, 128 slices per volume, 1 NEX images x 2 (acquisitions averaged off line), Matrix 256 x 256. This sequence was acquired in the coronal orientation aligned to the long axis of the hippocampus, and these nearly isotropic images were easily reformatted into any plane for definition of ROI’s. T2 FLAIR: 2D IR axial images with TR=10,000 msec, TE=122 msec, TI=2000 msec, FOV=24, matrix = 320x256, NEX=1, Slice thickness=5 mm, 31 slices.

The four regions of interest (ROIs) examined were based on published studies of 11C-PIB PET. A trained, experienced technician drew the parahippocampus, cingulate, prefrontal and parietal cortex ROIs using atlas based approachese3 on MRI scans.e4,e5 In addition, total brain ROI, excluding cerebellum, was determined in an automated fashion by either Atropos (http://www.picsl.upenn.edu/ANTS/, Avants et al, 2010)e6 or Freesurfer (http://surfer.nmr.mgh.harvard.edu).e7 All ROIs were individually inspected for accuracy and transferred to each individual’s motion-corrected MRI coregistered PET images.

Image Analysis Platform

Image analysis was performed using Matlab 2006b (The Mathworks, MA) with calls to the following open source packages; Functional Magnetic Resonance Imaging of the Brain’s Linear Image Registration Tool (FLIRT) v5, Brain Extraction Tool (BET) v1.2, and University College of London’s Statistical Parametric Mapping (SPM5) normalization and segmentation routines. Partial volume correction was not done in this study.

PET Image Processing

To correct for subject motion, de-noising filter techniques were applied to all PET images starting at frame five (2.5 min). Frame 8 (5.0 min) was the reference to which all other frames were aligned using rigid body FLIRT. The mean of the motion corrected frames was registered, using FLIRT, to each subject's BET skull stripped MRI. The resultant transform was applied to the entire motion-corrected PET dataset.

e-References

e1. Watson CC ND, Casey ME. 1996. A single scatter simulation technique for scatter correction in 3D PET. Dordrecht.

e2. Mawlawi O, Martinez D, Slifstein M, et al. Imaging human mesolimbic dopamine transmission with positron emission tomography: I. Accuracy and precision of D(2) receptor parameter measurements in ventral striatum. J Cereb Blood Flow Metab 2001;21:1034-1057.

e3. Duvernoy H. 1991. The human brain. Surface, three-dimensional sectional anatomy and MRI. New York: Sringer-Verlag Wien.

e4. Mintun MA, Larossa GN, Sheline YI, et al. [11C]PIB in a nondemented population: potential antecedent marker of Alzheimer disease. Neurology 2006;67:446-452.

e5. Devanand DP, Mikhno A, Pelton GH, et al. Pittsburgh compound B (11C-PIB) and fluorodeoxyglucose (18 F-FDG) PET in patients with Alzheimer disease, mild cognitive impairment, and healthy controls. J Geriatr Psychiatry Neurol 2010;23:185-198.

e6. <http://www.picsl.upenn.edu/ANTS/ from Avants B, Klein A, Tustison N, et al. Evaluation of an Open-Access, Automated Brain Extraction Method on Multi-Site Multi-Disorder Data,Poster No:1388Human Brain Mapping 2010, Barcelona, Spain, June 2010

e7. http://surfer.nmr.mgh.harvard.edu/ from:Milak, M.S., DeLorenzo, C., Zanderigo, F. et al.In Vivo Quantification of Human Serotonin 1A Receptor Using 11C-CUMI-101, an Agonist PET Radiotracer. J Nucl Med 2010: 51(12):1892-1900.