title: Molecular imaging in the diagnosis of Alzheimer's disease: visual assessment of [11C]PIB and [18F]FDDNP PET images.
abstract: OBJECTIVE
  To evaluate visual assessment of [(11)C]PIB and [(18)F]FDDNP PET images as potential supportive diagnostic markers for Alzheimer's disease (AD).
  
  
  METHODS
  Twenty-one AD patients and 20 controls were included. Parametric [(11)C]PIB and [(18)F]FDDNP global binding potential (BP(ND)) images were visually rated as 'AD' or 'normal.' Data were compared with ratings of [(18)F]FDG PET images and MRI-derived medial temporal lobe atrophy (MTA) scores. Inter-rater agreement and agreement with clinical diagnosis were assessed for all imaging modalities. In addition, cut-off values for quantitative global [(11)C]PIB and [(18)F]FDDNP BP(ND) were determined. Visual ratings were compared with dichotomised quantitative values.
  
  
  RESULTS
  Agreement between readers was excellent for [(11)C]PIB, [(18)F]FDDNP and MTA (Cohen kappa kappa> or =0.85) and moderate for [(18)F]FDG (kappa=0.56). The highest sensitivity was found for [(11)C]PIB and [(18)F]FDG (both 1.0). The highest specificity was found for MTA (0.90) and [(11)C]PIB (0.85). [(18)F]FDDNP had the lowest sensitivity and specificity (0.67 and 0.53, respectively). The cut-off for quantitative [(11)C]PIB BP(ND) was 0.54 (sensitivity and specificity both 0.95) and for [(18)F]FDDNP BP(ND) 0.07 (sensitivity 0.80, specificity 0.73). Agreement between quantitative analyses and visual ratings was excellent for [(11)C]PIB (kappa=0.85) and fair for [(18)F]FDDNP (kappa=0.40).
  
  
  CONCLUSIONS
  Visual assessment of [(11)C]PIB images was straightforward and accurate, showing promise as a supportive diagnostic marker for AD. Moreover, [(11)C]PIB showed the best combination of sensitivity and specificity. Visual assessment of [(18)F]FDDNP images was insufficient. The quantitative analysis of [(18)F]FDDNP data showed a considerably higher diagnostic value than the visual analysis.
authors.affiliation: Department of Nuclear Medicine & PET Research, VU University Medical Centre, Amsterdam, The Netherlands. n.tolboom@vumc.nl
authors.forename: Nelleke
authors.initials: N
authors.lastname: Tolboom
authors.forename: Wiesje M
authors.initials: WM
authors.lastname: van der Flier
authors.forename: Jolanda
authors.initials: J
authors.lastname: Boverhoff
authors.forename: Maqsood
authors.initials: M
authors.lastname: Yaqub
authors.forename: Mike P
authors.initials: MP
authors.lastname: Wattjes
authors.forename: Pieter G
authors.initials: PG
authors.lastname: Raijmakers
authors.forename: Frederik
authors.initials: F
authors.lastname: Barkhof
authors.forename: Philip
authors.initials: P
authors.lastname: Scheltens
authors.forename: Karl
authors.initials: K
authors.lastname: Herholz
authors.forename: Adriaan A
authors.initials: AA
authors.lastname: Lammertsma
authors.forename: Bart N M
authors.initials: BN
authors.lastname: van Berckel
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000175:diagnosis* / Q000000981:diagnostic imaging*; D000814:Aniline Compounds; D001284:Atrophy; D052160:Benzothiazoles; D001923:Brain Chemistry; D005260:Female; D019788:Fluorodeoxyglucose F18; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007091:Image Processing, Computer-Assisted; D016013:Likelihood Functions; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009570:Nitriles; D015588:Observer Variation; D049268:Positron-Emission Tomography; D012372:ROC Curve; D019275:Radiopharmaceuticals; D013702:Temporal Lobe / Q000473:pathology; D013844:Thiazoles
chemical_list: C444520:2-(1-(6-((2-fluoroethyl)(methyl)amino)-2-naphthyl)ethylidene)malononitrile; C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; D000814:Aniline Compounds; D052160:Benzothiazoles; D009570:Nitriles; D019275:Radiopharmaceuticals; D013844:Thiazoles; D019788:Fluorodeoxyglucose F18; D005947:Glucose