title: Optimizing PiB-PET SUVR change-over-time measurement by a large-scale analysis of longitudinal reliability, plausibility, separability, and correlation with MMSE.
abstract: Quantitative measurements of change in β-amyloid load from Positron Emission Tomography (PET) images play a critical role in clinical trials and longitudinal observational studies of Alzheimer's disease. These measurements are strongly affected by methodological differences between implementations, including choice of reference region and use of partial volume correction, but there is a lack of consensus for an optimal method. Previous works have examined some relevant variables under varying criteria, but interactions between them prevent choosing a method via combined meta-analysis. In this work, we present a thorough comparison of methods to measure change in β-amyloid over time using Pittsburgh Compound B (PiB) PET imaging.
  
  
  
  We compare 1,024 different automated software pipeline implementations with varying methodological choices according to four quality metrics calculated over three-timepoint longitudinal trajectories of 129 subjects: reliability (straightness/variance); plausibility (lack of negative slopes); ability to predict accumulator/non-accumulator status from baseline value; and correlation between change in β-amyloid and change in Mini Mental State Exam (MMSE) scores.
  
  
  
  From this analysis, we show that an optimal longitudinal measure of β-amyloid from PiB should use a reference region that includes a combination of voxels in the supratentorial white matter and those in the whole cerebellum, measured using two-class partial volume correction in the voxel space of each subject's corresponding anatomical MR image.
authors: Department of Radiology, Mayo Clinic and Foundation, Rochester, MN, United States. Electronic address: schwarz.christopher@mayo.edu.
authors: Christopher G
authors: CG
authors: Schwarz
authors: Department of Radiology, Mayo Clinic and Foundation, Rochester, MN, United States; Department of Information Technology, Mayo Clinic and Foundation, Rochester, MN, United States.
authors: Matthew L
authors: ML
authors: Senjem
authors: Department of Radiology, Mayo Clinic and Foundation, Rochester, MN, United States; Department of Information Technology, Mayo Clinic and Foundation, Rochester, MN, United States.
authors: Jeffrey L
authors: JL
authors: Gunter
authors: Department of Health Sciences Research, Division of Biostatistics, Mayo Clinic and Foundation, Rochester, MN, United States.
authors: Nirubol
authors: N
authors: Tosakulwong
authors: Department of Health Sciences Research, Division of Biostatistics, Mayo Clinic and Foundation, Rochester, MN, United States.
authors: Stephen D
authors: SD
authors: Weigand
authors: Department of Radiology, Mayo Clinic and Foundation, Rochester, MN, United States.
authors: Bradley J
authors: BJ
authors: Kemp
authors: Department of Radiology, Mayo Clinic and Foundation, Rochester, MN, United States.
authors: Anthony J
authors: AJ
authors: Spychalla
authors: Department of Radiology, Mayo Clinic and Foundation, Rochester, MN, United States.
authors: Prashanthi
authors: P
authors: Vemuri
authors: Department of Neurology, Mayo Clinic and Foundation, Rochester, MN, United States.
authors: Ronald C
authors: RC
authors: Petersen
authors: Department of Radiology, Mayo Clinic and Foundation, Rochester, MN, United States.
authors: Val J
authors: VJ
authors: Lowe
authors: Department of Radiology, Mayo Clinic and Foundation, Rochester, MN, United States.
authors: Clifford R
authors: CR
authors: Jack
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000814:Aniline Compounds; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism*; D060825:Cognitive Dysfunction / Q000000981:diagnostic imaging; D003704:Dementia / Q000000981:diagnostic imaging; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography / Q000379:methods* / Q000592:standards; D015203:Reproducibility of Results; D013844:Thiazoles
chemical_list: C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; D016229:Amyloid beta-Peptides; D000814:Aniline Compounds; D013844:Thiazoles