Impact of partial volume correction on the regional correspondence between in vivo [C-11]PiB PET and postmortem measures of Aß load.

ABSTRACT

The positron emission tomography (PET) radiotracer Pittsburgh Compound B ([C-11]PiB) demonstrates a high affinity for fibrillary amyloid-beta (Aß) aggregates. However, [C-11]PiB's in vivo sensitivity and specificity is an ongoing area of investigation in correlation studies with postmortem measures of Aß pathology. One potential confound in PET-to-postmortem correlation studies is the limited spatial resolution of PET and resulting partial volume effects (PVEs). In this work, we evaluated the impact of three partial volume correction (PVC) techniques - the Meltzer, the modified Müller-Gärtner, and the Region-Based Voxel-Wise - on correlations between region-matched in vivo [C-11]PiB standardized uptake value ratios (SUVRs) and postmortem measures of Aß pathology in a unique cohort of nine subjects. Postmortem Aß pathology was assessed histologically as percent area coverage of 6-CN-PiB positive and Aß immunoreactive (4G8 antibody) deposits. The application of all three PVC techniques resulted in minimally reduced PET-to-postmortem correlations relative to no PVC. However, correlations to both 6-CN-PiB and 4G8 percent area across all PVC techniques and no PVC were statistically significant at p < 0.01, suggesting that PVC is of minimal importance in understanding the relationship between Aß PET and neuropathologically assessed Aß. Thus, the utility of PVC in Aß PET imaging should continue to be examined on an application-specific basis.