title: Cerebral blood flow and glucose metabolism in healthy volunteers measured using a high-resolution PET scanner.
abstract: BACKGROUND
  Positron emission tomography (PET) allows for the measurement of cerebral blood flow (CBF; based on [15O]H2O) and cerebral metabolic rate of glucose utilization (CMRglu; based on [18 F]-2-fluoro-2-deoxy-d-glucose ([18 F]FDG)). By using kinetic modeling, quantitative CBF and CMRglu values can be obtained. However, hardware limitations led to the development of semiquantitive calculation schemes which are still widely used. In this paper, the analysis of CMRglu and CBF scans, acquired on a current state-of-the-art PET brain scanner, is presented. In particular, the correspondence between nonlinear as well as linearized methods for the determination of CBF and CMRglu is investigated. As a further step towards widespread clinical applicability, the use of an image-derived input function (IDIF) is investigated.
  
  
  METHODS
  Thirteen healthy male volunteers were included in this study. Each subject had one scanning session in the fasting state, consisting of a dynamic [15O]H2O scan and a dynamic [18 F]FDG PET scan, acquired at a high-resolution research tomograph. Time-activity curves (TACs) were generated for automatically delineated and for manually drawn gray matter (GM) and white matter regions. Input functions were derived using on-line arterial blood sampling (blood sampler derived input function (BSIF)). Additionally, the possibility of using carotid artery IDIFs was investigated. Data were analyzed using nonlinear regression (NLR) of regional TACs and parametric methods.
  
  
  RESULTS
  After quality control, 9 CMRglu and 11 CBF scans were available for analysis. Average GM CMRglu values were 0.33 ± 0.04 μmol/cm3 per minute, and average CBF values were 0.43 ± 0.09 mL/cm3 per minute. Good correlation between NLR and parametric CMRglu measurements was obtained as well as between NLR and parametric CBF values. For CMRglu Patlak linearization, BSIF and IDIF derived results were similar. The use of an IDIF, however, did not provide reliable CBF estimates.
  
  
  CONCLUSIONS
  Nonlinear regression analysis, allowing for the derivation of regional CBF and CMRglu values, can be applied to data acquired with high-spatial resolution current state-of-the-art PET brain scanners. Linearized models, applied to the voxel level, resulted in comparable values. CMRglu measurements do not require invasive arterial sampling to define the input function.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT00626080.
authors.affiliation: Diabetes Center/Department of Internal Medicine, VU University Medical Center, Amsterdam, 1081, HV, The Netherlands. L.vangolen@vumc.nl.
authors.forename: Marc C
authors.initials: MC
authors.lastname: Huisman
authors.forename: Larissa W
authors.initials: LW
authors.lastname: van Golen
authors.forename: Nikie J
authors.initials: NJ
authors.lastname: Hoetjes
authors.forename: Henri N
authors.initials: HN
authors.lastname: Greuter
authors.forename: Patrick
authors.initials: P
authors.lastname: Schober
authors.forename: Richard G
authors.initials: RG
authors.lastname: Ijzerman
authors.forename: Michaela
authors.initials: M
authors.lastname: Diamant
authors.forename: Adriaan A
authors.initials: AA
authors.lastname: Lammertsma