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 ¹¹CPittsburgh compound B (¹¹C-PiB) blood.brain barrier delivery (K₁) and relative delivery (R1) parameters as surrogate indices of cerebral blood flow (CBF), with a secondary goal of directly examining the extent to which simplified uptake measures of ¹¹C-PiB retention (amyloid-b 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, 15O-water PET, and ¹¹C-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 15O-water and ¹¹C-PiB measures of delivery and ¹¹C-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., 15O-water K1 and ¹¹C-PiB K1, relative K1 normalized to cerebellum [Rel-K1-Water and Rel-K1-PiB], and ¹¹C-PiB SRTM2-R1) and between delivery measures and ¹¹C-PiB retention, using the Bonferroni method for multiple-comparison correction. Results: Primary analysis showed positive correlations (r.0.2.0.5) between 15O-water K1 and ¹¹C-PiB K1 that did not survive Bonferroni adjustment. Significant positive correlations were found between Rel-K1-Water and Rel-K1-PiB and between Rel-K_1-Water and ¹¹C-PiB SRTM2-R₁ (ρ.0.5.0.8, P < 0.0036) across primary cortical regions. Secondary analysis showed few significant correlations between ¹¹C-PiB retention and relative ¹¹C-PiB delivery measures (but not 15O-water delivery measures) in primary cortical areas that arose only after accounting for cerebrospinal fluid dilution. Conclusion: ¹¹C-PiB SRTM2-R1 is highly correlated with regional relative CBF, as measured by 15O-water K1 normalized to cerebellum, and cross-sectional ¹¹C-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-b load and relative CBF) through dynamic ¹¹C-PiB imaging.