Participants

Participants were included in the HABS cohort at baseline if their global CDR=0, performed within education-adjusted norms on the Logical Memory delayed recall score (16 years of education: >10; 8-15 years: >6; <8 years: >4), MMSE>25, and GDS<11.1,3,4 All participants underwent PiB-PET as well as MRI scanning within one year of their first neuropsychological session and were between the ages of 60-90 years old. All clinical, neuropsychological, and imaging assessments took place at the Athinoula A. Martinos Center for Biomedical Imaging at Massachusetts General Hospital in Boston, MA.

 

Structural MRI

ADNI Style MPRAGE

Magnetic resonance imaging (MRI) scanning was completed on a Siemens TIM Trio 3T System with a 12-channel head coil. Structural T1-weighted volumetric magnetization-prepared, rapid acquisition gradient echo (MPRAGE) scans were collected with one of two acquisitions:

  • ADNI1 MPRAGE: repetition time = 2300ms, echo time = 2.98ms, inversion time = 900ms, flip angle = 9°, 1x1x1.2mm resolution, 0 acceleration
  • ADNI2GO MPRAGE: repetition time = 2300ms, echo time = 2.95ms, inversion time = 900ms, flip angle = 9°, 1.1x1.1x1.2mm resolution, 2X GRAPPA acceleration

Note, these two acquisitions are considered interchangeable.

Region of interest (ROI) labeling was implemented using FreeSurfer v5.1 (http://surfer.nmr.mgh.harvard.edu/). Cortical region of interest measurements were made using the Desikan-Killiany atlas (https://surfer.nmr.mgh.harvard.edu/fswiki/CorticalParcellation). Subcortical region of interest measurements were made using the Freesurfer aseg atlas (https://surfer.nmr.mgh.harvard.edu/ftp/articles/fischl02-labeling.pdf)

Quality assurance (QA) of the ADNI style structural images involved manual assessment of the FS recons after running the full auto-recon process, and this assessment included examination of the white and pial surface segmentation using the brainmask.mgz file in the tkmedit tool. In cases where dura or skull influenced the segmentation result, voxels were either manually edited or corrected by adjusting the watershed threshold. In cases where the grey matter ribbon clearly included white matter or clearly excluded grey matter, control points were added to the recon and/or white matter edits were made to the wm.mgz file. Autorecon2 and autorecon3 processing steps were re-run on the edited files, and the process was repeated until the segmentation results were deemed either sufficient or irreparable. 

4X Accelerated MPRAGE

As above, MRI scanning was completed on a Siemens TIM Trio 3T System with a 12-channel head coil. Structural T1-weighted MPRAGE scans were collected (repetition time = 2200ms, echo time = 1.54ms/3.36ms/5.18ms/7ms, inversion time = 1100ms, flip angle = 7°, 1.2x1.2x1.2mm resolution) with a 4X GRAPPA acceleration factor. Data were processed with the same FreeSurfer pipeline, but were only QA’ed if the scan was later used for making ROI measurements in PET data.

 

Pittsburgh Compound-B PET

Acquisition

Deposition of beta-amyloid was measured with positron emission tomography (PET) using Pittsburgh Compound-B (PiB; N-methyl-[11C]-2(4-methylaminophenyl)-6-hydroxybenzothiazole). PiB was synthesized using a previously published protocol and imaging was performed using a Siemens ECAT EXACT HR+ PET scanner.2 Before injection, 10-minute transmission scans for attenuation correction were collected. After injection of 8.5-15 mCi PiB, 60-minutes of dynamic data were acquired in 3D acquisition mode. Data were then manually evaluated and corrected for motion. Following this, a mean image across the first 8 minutes of data acquisition was created and later used for co-registration purposes.

Processing - Harvard-Oxford ROIs

To obtain Harvard-Oxford ROIs, the mean image for each participant was normalized to the SPM O2-PET template. These normalization parameters where then applied to all PiB-PET frames to normalize that data to MNI space. Regions of interest were taken from the Harvard-Oxford atlas and distribution volume ratios (DVRs) were computed using the Logan plot method with cerebellar grey matter (as defined by the probabilistic cerebellar atlas: http://fsl.fmrib.ox.ac.uk/fsl/fslwiki/Atlases and http://www.icn.ucl.ac.uk/motorcontrol/imaging/propatlas.htm) as the reference region. Note that when computing ROI measurements no partial volume correction was used, and no smoothing of the data was performed prior to this measurement.

Processing - FreeSurfer Desikan-Killiany ROIs

To obtain FreeSurfer Desikan-Killiany ROIs, the mean PET image for each individual participant was coregistered to their FreeSurfer-processed, T1-structural image using a combination of bbregister and spm_coreg. After coregistration, FreeSurfer’s mri_label2vol was used to map the participant's aparc+aseg results into native PET space. The native space labels were then used to make ROI measurements computed using the Logan plot method using cerebellar grey matter (as determined by FreeSurfer) as the reference region. Again, no partial volume correction was used, and no smoothing of the data was performed prior to measurement.

 

Sources

  1. Folstein et al., "Mini-mental state". A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res. 1975;12(3):189-98.
  2. Johnson et al., Imaging of amyloid burden and distribution in cerebral amyloid angiopathy. Ann Neurol. 2007;62(3):229-34.
  3. Morris, The Clinical Dementia Rating (CDR): current version and scoring rules. Neurology. 1993;43(11):2412-4.
  4. Yesavage et al., Development and validation of a geriatric depression screening scale: a preliminary report. J Psychiatr Res. 1982-1983;17(1):37-49.