Alzheimer's Disease

In our center, we acquire and analyze [11C] Pittsburgh compound-B (PIB) data for mild Alzheimer's disease (AD), Mild Cognitive Impairment (MCI) patients, and healthy volunteers (CTR). We are primarily interested early diagnosis of AD with PIB. This includes multivariate correlation models of PIB imaging data with clinical and chemical screening methods. We are also working on image derived methods, using PIB, for CTR and AD discrimination. Our objective there is derive an automatic screening method for different stages of AD. Our aim to is make our tools and ideas available to the general scientific community to facilitate validation, software and methodological improvements.

Voxel-Based Alzheimer's Diagnosis using PIB Imaging Data

We have developed and tested a standard space voxels of interest (VOI) atlas for calculating average cortical PIB binding in both healthy volunteers and Alzheimer's patients. This atlas is meant to establish areas to measure overall Amyloid-beta burdenwithout the need for traditional anatomical regions.

VOI Atlas Methods

• 12 CTR and 9 AD age-matched subjects were recruited. All subjects underwent a [11C]PIB scan and had a structural MRI.
• Using the Logan graphical method with cerebellar gray matter* as the reference region, BPND (a measure of amyloid burden) was calculated for each voxel.
• Voxel maps were then partial volume corrected and spatially normalized by MRI onto a standardized template (ICBM152).
• A two sample t-test was done between CTR and AD BPND normalized maps in SPM5 to create a statistical t-score map.
• The t-score map was thresholded at different t-scores and reapplied as a binary VOI to each subject BPND voxel map.
• Average gray matter BPND was calculated for each subject by taking the average within the gray matter masked binary VOI.
• The t-score that resulted in a VOI that produced the largest separation between CTR and AD subjects average gray matter BPND was selected. 
• For the resulting SPM map, the optimal t-score was 10.61.

The SPM map and the thresholded map will be made available for download. We are also making available a gray matter probability atlas of the cerebellum created from the 12 CTR subjects in this study. The cerebellar atlas may be transformed into a subjects MRI or PET space and used along with a gray matter segmentation mask to derive the gray matter cerebellar reference region need for Logan analysis.

-04/21/2008 

Accompanying Publication

Mikhno, A., Devanand D., Gunn R.N., Upton N., GH Pelton, K Cuasay, Lai R.Y.K., Libri V., Mann J.J., Parsey RV. Voxel-based analysis of [11C]PIB scans for diagnosing Alzheimer’s disease. Journal of Nuclear Medicine, August 2008, 2008.

Poster Presentations

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