Optimization of Statistical Single Subject Analysis of Brain FDG PET for the Prognosis of Mild Cognitive Impairment-to-Alzheimer's Disease Conversion

J Alzheimers Dis. 2016;49(4):945-959. doi: 10.3233/JAD-150814.


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).

Conclusion: 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.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Validation Study

MeSH terms

  • Aged
  • Alzheimer Disease / diagnosis
  • Alzheimer Disease / diagnostic imaging*
  • Alzheimer Disease / metabolism
  • Area Under Curve
  • Brain / diagnostic imaging*
  • Brain / metabolism
  • Cognitive Dysfunction / diagnosis
  • Cognitive Dysfunction / diagnostic imaging*
  • Cognitive Dysfunction / metabolism
  • Disease Progression
  • Female
  • Fluorodeoxyglucose F18*
  • Follow-Up Studies
  • Glucose / metabolism
  • Humans
  • Image Interpretation, Computer-Assisted / methods
  • Male
  • Positron-Emission Tomography / methods*
  • Prognosis
  • ROC Curve
  • Radiopharmaceuticals*


  • Radiopharmaceuticals
  • Fluorodeoxyglucose F18
  • Glucose