Relative 11C-PiB Delivery as a Proxy of Relative CBF: Quantitative Evaluation Using Single-Session 15O-Water and 11C-PiB PET

The primary goal of this study was to assess the suitability of C-11-Pittsburgh compound B (C-11-PiB) blood-brain barrier delivery (K-1) and relative delivery (R-1) parameters as surrogate indices of cerebral blood flow (CBF), with a secondary goal of directly examining the extent to which simplified uptake measures of C-11-PiB retention (amyloid-beta load) may be influenced by CBF, in a cohort of controls and patients with mild cognitive impairment (MCI) and Alzheimer disease (AD). Methods: Nineteen participants (6 controls, 5 AD, 8 MCI) underwent MR imaging, O-15-water PET, and C-11-PiB PET in a single session. Fourteen regions of interest (including cerebellar reference region) were defined on MR imaging and applied to dynamic coregistered PET to generate time-activity curves. Multiple analysis approaches provided regional O-15-water and C-11-PiB measures of delivery and C-11-PiB retention that included compartmental modeling distribution volume ratio (DVR), arterial- and reference-based Logan DVR, simplified reference tissue modeling 2 (SRTM2) DVR, and standardized uptake value ratios. Spearman correlation was performed among delivery measures (i.e., O-15-water K-1 and C-11-PiB K-1, relative K-1 normalized to cerebellum [Rel-K1-Water and Rel-K1-PiB], and C-11-PiB SRTM2-R-1) and between delivery measures and C-11-PiB retention, using the Bonferroni method for multiple-comparison correction. Results: Primary analysis showed positive correlations (rho approximate to 0.2-0.5) between O-15-water K-1 and C-11-PiB K-1 that did not survive Bonferroni adjustment. Significant positive correlations were found between Rel-K1-Water and Rel-K1-PiB and between Rel-K1-Water and C-11-PiB SRTM2-R-1 (rho approximate to 0.5-0.8, P < 0.0036) across primary cortical regions. Secondary analysis showed few significant correlations between C-11-PiB retention and relative C-11-PiB delivery measures (but not O-15-water delivery measures) in primary cortical areas that arose only after accounting for cerebrospinal fluid dilution. Conclusion: C-11-PiB SRTM2-R-1 is highly correlated with regional relative CBF, as measured by O-15-water K-1 normalized to cerebellum, and cross-sectional C-11-PiB retention did not strongly depend on CBF across primary cortical regions. These results provide further support for potential dual-imaging assessments of regional brain status (i.e., amyloid-beta load and relative CBF) through dynamic C-11-PiB imaging.