title: Optimization of Statistical Single Subject Analysis of Brain FDG PET for the Prognosis of Mild Cognitive Impairment-to-Alzheimer's Disease Conversion.
abstract: BACKGROUND
  Positron emission tomography (PET) with the glucose analog F-18-fluorodeoxyglucose (FDG) is widely used in the diagnosis of neurodegenerative diseases. Guidelines recommend voxel-based statistical testing to support visual evaluation of the PET images. However, the performance of voxel-based testing strongly depends on each single preprocessing step involved.
  
  
  OBJECTIVE
  To optimize the processing pipeline of voxel-based testing for the prognosis of dementia in subjects with amnestic mild cognitive impairment (MCI).
  
  
  METHODS
  The study included 108 ADNI MCI subjects grouped as 'stable MCI' (n = 77) or 'MCI-to-AD converter' according to their diagnostic trajectory over 3 years. Thirty-two ADNI normals served as controls. Voxel-based testing was performed with the statistical parametric mapping software (SPM8) starting with default settings. The following modifications were added step-by-step: (i) motion correction, (ii) custom-made FDG template, (iii) different reference regions for intensity scaling, and (iv) smoothing was varied between 8 and 18 mm. The t-sum score for hypometabolism within a predefined AD mask was compared between the different settings using receiver operating characteristic (ROC) analysis with respect to differentiation between 'stable MCI' and 'MCI-to-AD converter'. The area (AUC) under the ROC curve was used as performance measure.
  
  
  RESULTS
  The default setting provided an AUC of 0.728. The modifications of the processing pipeline improved the AUC up to 0.832 (p = 0.046). Improvement of the AUC was confirmed in an independent validation sample of 241 ADNI MCI subjects (p = 0.048).
  
  
  CONCLUSIONS
  The prognostic value of voxel-based single subject analysis of brain FDG PET in MCI subjects can be improved considerably by optimizing the processing pipeline.
authors.affiliation: Department of Nuclear Medicine, Charité - Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Catharina
authors.initials: C
authors.lastname: Lange
authors.affiliation: Department of Nuclear Medicine, Charité - Universitätsmedizin Berlin, Berlin, Germany.|jung diagnostics GmbH, Hamburg, Germany.
authors.forename: Per
authors.initials: P
authors.lastname: Suppa
authors.affiliation: Department of Nuclear Medicine, University of Freiburg, Freiburg, Germany.
authors.forename: Lars
authors.initials: L
authors.lastname: Frings
authors.affiliation: Department of Nuclear Medicine, Charité - Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Winfried
authors.initials: W
authors.lastname: Brenner
authors.affiliation: jung diagnostics GmbH, Hamburg, Germany.
authors.forename: Lothar
authors.initials: L
authors.lastname: Spies
authors.affiliation: Department of Nuclear Medicine, Charité - Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Ralph
authors.initials: R
authors.lastname: Buchert
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000175:diagnosis / Q000000981:diagnostic imaging* / Q000378:metabolism; D019540:Area Under Curve; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism; D060825:Cognitive Dysfunction / Q000175:diagnosis / Q000000981:diagnostic imaging* / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D019788:Fluorodeoxyglucose F18; D005500:Follow-Up Studies; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007090:Image Interpretation, Computer-Assisted / Q000379:methods; D008297:Male; D049268:Positron-Emission Tomography / Q000379:methods*; D011379:Prognosis; D012372:ROC Curve; D019275:Radiopharmaceuticals
chemical_list: D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; D005947:Glucose
keywords: Alzheimer’s Disease Neuroimaging Initiative; F-18-fluorodeoxyglucose; intensity scaling; mild cognitive impairment; positron emission tomography; processing pipeline; prognosis; single subject analysis; statistical parametric mapping; template