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J Nucl Med. 2015 Aug;56(8):1199-205. doi: 10.2967/jnumed.114.152405. Epub 2015 Jun 4.

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

Author information

1
Department of Radiology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
2
Department of Biostatistics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
3
Department of Neurology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania; and.
4
Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
5
Department of Radiology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania pricejc@upmc.edu.

Abstract

The primary goal of this study was to assess the suitability of (11)C-Pittsburgh compound B ((11)C-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 (11)C-PiB retention (amyloid-β 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, (15)O-water PET, and (11)C-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 (15)O-water and (11)C-PiB measures of delivery and (11)C-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., (15)O-water K1 and (11)C-PiB K1, relative K1 normalized to cerebellum [Rel-K1-Water and Rel-K1-PiB], and (11)C-PiB SRTM2-R1) and between delivery measures and (11)C-PiB retention, using the Bonferroni method for multiple-comparison correction.

RESULTS:

Primary analysis showed positive correlations (ρ ≈0.2-0.5) between (15)O-water K1 and (11)C-PiB K1 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 (11)C-PiB SRTM2-R1 (ρ ≈0.5-0.8, P < 0.0036) across primary cortical regions. Secondary analysis showed few significant correlations between (11)C-PiB retention and relative (11)C-PiB delivery measures (but not (15)O-water delivery measures) in primary cortical areas that arose only after accounting for cerebrospinal fluid dilution.

CONCLUSION:

(11)C-PiB SRTM2-R1 is highly correlated with regional relative CBF, as measured by (15)O-water K1 normalized to cerebellum, and cross-sectional (11)C-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-β load and relative CBF) through dynamic (11)C-PiB imaging.

KEYWORDS:

Alzheimer’s disease; PiB PET; amyloid; blood flow; kinetic modeling

PMID:
26045309
PMCID:
PMC4730871
DOI:
10.2967/jnumed.114.152405
[Indexed for MEDLINE]
Free PMC Article

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