title: Relative 11C-PiB Delivery as a Proxy of Relative CBF: Quantitative Evaluation Using Single-Session 15O-Water and 11C-PiB PET.
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.
  
  
  CONCLUSIONS
  (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.
authors.affiliation: Department of Radiology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
authors.forename: Yin J
authors.initials: YJ
authors.lastname: Chen
authors.affiliation: Department of Biostatistics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
authors.forename: Bedda L
authors.initials: BL
authors.lastname: Rosario
authors.affiliation: Department of Biostatistics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
authors.forename: Wenzhu
authors.initials: W
authors.lastname: Mowrey
authors.affiliation: Department of Radiology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
authors.forename: Charles M
authors.initials: CM
authors.lastname: Laymon
authors.affiliation: Department of Radiology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
authors.forename: Xueling
authors.initials: X
authors.lastname: Lu
authors.affiliation: Department of Neurology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania; and.
authors.forename: Oscar L
authors.initials: OL
authors.lastname: Lopez
authors.affiliation: Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
authors.forename: William E
authors.initials: WE
authors.lastname: Klunk
authors.affiliation: Department of Radiology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Lopresti
authors.affiliation: Department of Radiology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
authors.forename: Chester A
authors.initials: CA
authors.lastname: Mathis
authors.affiliation: Department of Radiology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania pricejc@upmc.edu.
authors.forename: Julie C
authors.initials: JC
authors.lastname: Price
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000000981:diagnostic imaging; D000814:Aniline Compounds; D052160:Benzothiazoles / Q000737:chemistry*; D001812:Blood-Brain Barrier / Q000737:chemistry; D001921:Brain / Q000000981:diagnostic imaging; D002247:Carbon Isotopes / Q000737:chemistry; D002560:Cerebrovascular Circulation; D015331:Cohort Studies; D016503:Drug Delivery Systems; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D059906:Neuroimaging; D010103:Oxygen Isotopes / Q000737:chemistry; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals / Q000737:chemistry; D015203:Reproducibility of Results; D013844:Thiazoles; D014867:Water / Q000737:chemistry*
chemical_list: C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; D000814:Aniline Compounds; D052160:Benzothiazoles; D002247:Carbon Isotopes; D010103:Oxygen Isotopes; D019275:Radiopharmaceuticals; D013844:Thiazoles; D014867:Water
keywords: Alzheimer’s disease; PiB PET; amyloid; blood flow; kinetic modeling