title: Image-derived input function for human brain using high resolution PET imaging with [C](R)-rolipram and [C]PBR28.
abstract: BACKGROUND
  The aim of this study was to test seven previously published image-input methods in state-of-the-art high resolution PET brain images. Images were obtained with a High Resolution Research Tomograph plus a resolution-recovery reconstruction algorithm using two different radioligands with different radiometabolite fractions. Three of the methods required arterial blood samples to scale the image-input, and four were blood-free methods.
  
  
  METHODS
  All seven methods were tested on twelve scans with [(11)C](R)-rolipram, which has a low radiometabolite fraction, and on nineteen scans with [(11)C]PBR28 (high radiometabolite fraction). Logan V(T) values for both blood and image inputs were calculated using the metabolite-corrected input functions. The agreement of image-derived Logan V(T) values with the reference blood-derived Logan V(T) values was quantified using a scoring system. Using the image input methods that gave the most accurate results with Logan analysis, we also performed kinetic modelling with a two-tissue compartment model.
  
  
  RESULTS
  For both radioligands the highest scores were obtained with two blood-based methods, while the blood-free methods generally performed poorly. All methods gave higher scores with [(11)C](R)-rolipram, which has a lower metabolite fraction. Compartment modeling gave less reliable results, especially for the estimation of individual rate constants.
  
  
  CONCLUSIONS
  OUR STUDY SHOWS THAT: 1) Image input methods that are validated for a specific tracer and a specific machine may not perform equally well in a different setting; 2) despite the use of high resolution PET images, blood samples are still necessary to obtain a reliable image input function; 3) the accuracy of image input may also vary between radioligands depending on the magnitude of the radiometabolite fraction: the higher the metabolite fraction of a given tracer (e.g., [(11)C]PBR28), the more difficult it is to obtain a reliable image-derived input function; and 4) in association with image inputs, graphical analyses should be preferred over compartmental modelling.
authors.affiliation: Molecular Imaging Branch, National Institute of Mental Health (NIMH), National Institutes of Health (NIH), Bethesda, Maryland, United States of America.
authors.forename: Paolo
authors.initials: P
authors.lastname: Zanotti-Fregonara
authors.forename: Jeih-San
authors.initials: JS
authors.lastname: Liow
authors.forename: Masahiro
authors.initials: M
authors.lastname: Fujita
authors.forename: Elodie
authors.initials: E
authors.lastname: Dusch
authors.forename: Sami S
authors.initials: SS
authors.lastname: Zoghbi
authors.forename: Elise
authors.initials: E
authors.lastname: Luong
authors.forename: Ronald
authors.initials: R
authors.lastname: Boellaard
authors.forename: Victor W
authors.initials: VW
authors.lastname: Pike
authors.forename: Claude
authors.initials: C
authors.lastname: Comtat
authors.forename: Robert B
authors.initials: RB
authors.lastname: Innis
mesh_terms: D000081:Acetamides / Q000737:chemistry / Q000493:pharmacokinetics; D000465:Algorithms; D002250:Carbon Radioisotopes / Q000737:chemistry / Q000493:pharmacokinetics; D003952:Diagnostic Imaging; D006801:Humans; D007090:Image Interpretation, Computer-Assisted / Q000379:methods; D007091:Image Processing, Computer-Assisted / Q000379:methods*; D008279:Magnetic Resonance Imaging / Q000379:methods; D019047:Phantoms, Imaging; D049268:Positron-Emission Tomography / Q000379:methods*; D011725:Pyridines / Q000737:chemistry / Q000493:pharmacokinetics; D020889:Rolipram / Q000737:chemistry / Q000493:pharmacokinetics
chemical_list: D000081:Acetamides; D002250:Carbon Radioisotopes; C526798:N-(2-methoxybenzyl)-N-(4-phenoxypyridin-3-yl)acetamide; D011725:Pyridines; D020889:Rolipram