title: Voxelwise Relationships Between Distribution Volume Ratio and Cerebral Blood Flow: Implications for Analysis of β-Amyloid Images.
abstract: Quantification of β-amyloid (Aβ) in vivo is often accomplished using the distribution volume ratio (DVR), based on a simplified reference tissue model. We investigated the local relationships between DVR and cerebral blood flow (CBF), as well as relative CBF (R1), in nondemented older adults.
  
  
  METHODS
  Fifty-five nondemented participants (mean age, 78.5 y) in the Baltimore Longitudinal Study of Aging underwent (15)O-H2O PET CBF and dynamic (11)C-PiB PET. (15)O-H2O PET images were normalized and smoothed using SPM. A simplified reference tissue model with linear regression and spatial constraints was used to generate parametric DVR images. The DVR images were regressed on CBF images on a voxel-by-voxel basis using robust biologic parametric mapping, adjusting for age and sex (false discovery rate, P = 0.05; spatial extent, 50 voxels). DVR images were also regressed on R1 images, a measure of the transport rate constant from vascular space to tissue. All analyses were performed on the entire sample, and on high and low tertiles of mean cortical DVR.
  
  
  RESULTS
  Voxel-based analyses showed that increased DVR is associated with increased CBF in the frontal, parietal, temporal, and occipital cortices. However, this association appears to spare regions that typically show early Aβ deposition. A more robust relationship between DVR and CBF was observed in the lower tertile of DVR, that is, negligible cortical Aβ load, compared with the upper tertile of cortical DVR and Aβ load. The spatial distributions of the DVR-CBF and DVR-R1 correlations showed similar patterns. No reliable negative voxelwise relationships between DVR and CBF or R1 were observed.
  
  
  CONCLUSIONS
  Robust associations between DVR and CBF at negligible Aβ levels, together with similar spatial distributions of DVR-CBF and DVR-R1 correlations, suggest that regional distribution of DVR reflects blood flow and tracer influx rather than pattern of Aβ deposition in those with minimal Aβ load. DVR-CBF associations in individuals with a higher DVR are more likely to reflect true associations between patterns of Aβ deposition and CBF or neural activity. These findings have important implications for analysis and interpretation of voxelwise correlations with external variables in individuals with varying amounts of Aβ load.
authors.affiliation: Laboratory of Behavioral Neuroscience, National Institute on Aging, NIH, Bethesda, Maryland.
authors.forename: Jitka
authors.initials: J
authors.lastname: Sojkova
authors.affiliation: Laboratory of Behavioral Neuroscience, National Institute on Aging, NIH, Bethesda, Maryland National Taiwan University, Taipei, Taiwan.
authors.forename: Joshua
authors.initials: J
authors.lastname: Goh
authors.affiliation: Laboratory of Behavioral Neuroscience, National Institute on Aging, NIH, Bethesda, Maryland Department of Biomedical Engineering, Johns Hopkins University, Baltimore, Maryland.
authors.forename: Murat
authors.initials: M
authors.lastname: Bilgel
authors.affiliation: Department of Electrical Engineering, Vanderbilt University, Nashville, Tennessee.
authors.forename: Bennett
authors.initials: B
authors.lastname: Landman
authors.affiliation: Department of Electrical Engineering, Vanderbilt University, Nashville, Tennessee.
authors.forename: Xue
authors.initials: X
authors.lastname: Yang
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins University, Baltimore, Maryland.
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Laboratory of Behavioral Neuroscience, National Institute on Aging, NIH, Bethesda, Maryland.
authors.forename: Yang
authors.initials: Y
authors.lastname: An
authors.affiliation: Laboratory of Behavioral Neuroscience, National Institute on Aging, NIH, Bethesda, Maryland.
authors.forename: Lori L
authors.initials: LL
authors.lastname: Beason-Held
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins University, Baltimore, Maryland.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Kraut
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins University, Baltimore, Maryland Department of Psychiatry and Behavioral Sciences, Johns Hopkins University, Baltimore, Maryland Solomon Snyder Department of Neuroscience, Johns Hopkins University, Baltimore, Maryland; and Environmental Health Sciences, Johns Hopkins University, Baltimore, Maryland.
authors.forename: Dean F
authors.initials: DF
authors.lastname: Wong
authors.affiliation: Laboratory of Behavioral Neuroscience, National Institute on Aging, NIH, Bethesda, Maryland resnicks@mail.nih.gov.
authors.forename: Susan M
authors.initials: SM
authors.lastname: Resnick
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D016229:Amyloid beta-Peptides / Q000737:chemistry*; D000814:Aniline Compounds; D052160:Benzothiazoles / Q000737:chemistry; D002247:Carbon Isotopes / Q000737:chemistry; D002560:Cerebrovascular Circulation; D005189:False Positive Reactions; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D016014:Linear Models; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D010103:Oxygen Isotopes / Q000737:chemistry; D049268:Positron-Emission Tomography; D012016:Reference Values; D015203:Reproducibility of Results; D013844:Thiazoles; D014867:Water / Q000737:chemistry
chemical_list: C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; D016229:Amyloid beta-Peptides; D000814:Aniline Compounds; D052160:Benzothiazoles; D002247:Carbon Isotopes; D010103:Oxygen Isotopes; D013844:Thiazoles; D014867:Water
keywords: DVR; PiB; aging; amyloid; cerebral blood flow