Voxel-based analysis of 11C-PIB scans for diagnosing Alzheimer's disease

The positron emission tomography (PET) radioligand N-methyl-C-11-2-(4-methylaminophenyl)-6-hydroxybenzothiazole (also known as C-11-6-OH-BTA-1 or C-11-PIB) binds to amyloid-beta (A beta), which accumulates pathologically in Alzheimer's disease (AD). Although C-11-PIB accumulation is greater in patients with AD than in healthy controls at a group level, the optimal method for discriminating between these 2 groups has, to our knowledge, not been established. We assessed the use of data-determined standardized voxels of interest (VOIs) to improve the classification capability of C-11-PIB scans on patients with AD. Methods: A total of 16 controls and 14 AD age-matched patients were recruited. All subjects underwent a C-11-PIB scan and structural MRI. Binding potential (a measure of amyloid burden) was calculated for each voxel using the Logan graphical method with cerebellar gray matter as the reference region. Voxel maps were then partial-volume corrected and spatially normalized by MRI onto a standardized template. The subjects were divided into 2 cohorts. The first cohort (control, 12; AD, 9) was used for statistical parametric mapping analysis and delineation of data-based VOIs. These VOIs were tested in the second cohort (control, 4; AD, 5) of subjects. Results: Statistical parametric mapping analysis revealed significant differences between control and AD groups. The VOI map determined from the first cohort resulted in complete separation between the control and the AD subjects in the second cohort (P < 0.02). Binding potential values based on this VOI were in the same range as other reported individual and mean cortical VOI results. Conclusion: A standardized VOI template that is optimized for control or AD group discrimination provides excellent separation of control and AD subjects on the basis of C-11-PIB uptake. This VOI template can serve as a potential replacement for manual VOI delineation and can eventually be fully automated, facilitating potential use in a clinical setting. To facilitate independent analysis and validation with more and a broader variety of subjects, this VOI template and the software for processing will be made available through the Internet.