title: Quantitative Amyloid Imaging in Autosomal Dominant Alzheimer's Disease: Results from the DIAN Study Group.
abstract: Amyloid imaging plays an important role in the research and diagnosis of dementing disorders. Substantial variation in quantitative methods to measure brain amyloid burden exists in the field. The aim of this work is to investigate the impact of methodological variations to the quantification of amyloid burden using data from the Dominantly Inherited Alzheimer's Network (DIAN), an autosomal dominant Alzheimer's disease population. Cross-sectional and longitudinal [11C]-Pittsburgh Compound B (PiB) PET imaging data from the DIAN study were analyzed. Four candidate reference regions were investigated for estimation of brain amyloid burden. A regional spread function based technique was also investigated for the correction of partial volume effects. Cerebellar cortex, brain-stem, and white matter regions all had stable tracer retention during the course of disease. Partial volume correction consistently improves sensitivity to group differences and longitudinal changes over time. White matter referencing improved statistical power in the detecting longitudinal changes in relative tracer retention; however, the reason for this improvement is unclear and requires further investigation. Full dynamic acquisition and kinetic modeling improved statistical power although it may add cost and time. Several technical variations to amyloid burden quantification were examined in this study. Partial volume correction emerged as the strategy that most consistently improved statistical power for the detection of both longitudinal changes and across-group differences. For the autosomal dominant Alzheimer's disease population with PiB imaging, utilizing brainstem as a reference region with partial volume correction may be optimal for current interventional trials. Further investigation of technical issues in quantitative amyloid imaging in different study populations using different amyloid imaging tracers is warranted.
authors.affiliation: Department of Radiology, Washington University School of Medicine, Saint Louis, Missouri, United States of America.
authors.forename: Yi
authors.initials: Y
authors.lastname: Su
authors.affiliation: Department of Radiology, Washington University School of Medicine, Saint Louis, Missouri, United States of America.
authors.forename: Tyler M
authors.initials: TM
authors.lastname: Blazey
authors.affiliation: Department of Radiology, Washington University School of Medicine, Saint Louis, Missouri, United States of America.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Owen
authors.affiliation: Department of Radiology, Washington University School of Medicine, Saint Louis, Missouri, United States of America.
authors.forename: Jon J
authors.initials: JJ
authors.lastname: Christensen
authors.affiliation: Department of Radiology, Washington University School of Medicine, Saint Louis, Missouri, United States of America.
authors.forename: Karl
authors.initials: K
authors.lastname: Friedrichsen
authors.affiliation: Department of Radiology, Washington University School of Medicine, Saint Louis, Missouri, United States of America.
authors.forename: Nelly
authors.initials: N
authors.lastname: Joseph-Mathurin
authors.affiliation: Department of Radiology, Washington University School of Medicine, Saint Louis, Missouri, United States of America.
authors.forename: Qing
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Radiology, Washington University School of Medicine, Saint Louis, Missouri, United States of America.
authors.forename: Russ C
authors.initials: RC
authors.lastname: Hornbeck
authors.affiliation: Department of Neurology, Washington University School of Medicine, Saint Louis, Missouri, United States of America.
authors.forename: Beau M
authors.initials: BM
authors.lastname: Ances
authors.affiliation: Department of Radiology, Washington University School of Medicine, Saint Louis, Missouri, United States of America.|Department of Neurology, Washington University School of Medicine, Saint Louis, Missouri, United States of America.
authors.forename: Abraham Z
authors.initials: AZ
authors.lastname: Snyder
authors.affiliation: Department of Radiology, Washington University School of Medicine, Saint Louis, Missouri, United States of America.
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Cash
authors.affiliation: Department of Radiology, University of Michigan, Ann Arbor, Michigan, United States of America.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Koeppe
authors.affiliation: University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America.
authors.forename: William E
authors.initials: WE
authors.lastname: Klunk
authors.affiliation: University of California San Diego, La Jolla, California, United States of America.
authors.forename: Douglas
authors.initials: D
authors.lastname: Galasko
authors.affiliation: Columbia University, New York, New York, United States of America.
authors.forename: Adam M
authors.initials: AM
authors.lastname: Brickman
authors.affiliation: Department of Neurology, Washington University School of Medicine, Saint Louis, Missouri, United States of America.
authors.forename: Eric
authors.initials: E
authors.lastname: McDade
authors.affiliation: Department of Neurology, Keck School of Medicine, University of Southern California, Los Angeles, California, United States of America.
authors.forename: John M
authors.initials: JM
authors.lastname: Ringman
authors.affiliation: Keck School of Medicine, University of Southern California, Los Angeles, California, United States of America.
authors.forename: Paul M
authors.initials: PM
authors.lastname: Thompson
authors.affiliation: Department of Radiology, Indiana University, Indianapolis, Indiana, United States of America.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Saykin
authors.affiliation: Department of Radiology, Indiana University, Indianapolis, Indiana, United States of America.
authors.forename: Bernardino
authors.initials: B
authors.lastname: Ghetti
authors.affiliation: Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Reisa A
authors.initials: RA
authors.lastname: Sperling
authors.affiliation: Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Keith A
authors.initials: KA
authors.lastname: Johnson
authors.affiliation: Butler Hospital and Brown University, Providence, Rhode Island, United States of America.
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Salloway
authors.affiliation: Neuroscience Research Australia and School of Medical Sciences, University of New South Wales, Sydney, New South Wales, Australia.
authors.forename: Peter R
authors.initials: PR
authors.lastname: Schofield
authors.affiliation: The Florey Institute and the University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Colin L
authors.initials: CL
authors.lastname: Masters
authors.affiliation: The Florey Institute and the University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Victor L
authors.initials: VL
authors.lastname: Villemagne
authors.affiliation: Dememtia Research Centre, Institute of Neurology, London, Great Britain.
authors.forename: Nick C
authors.initials: NC
authors.lastname: Fox
authors.affiliation: Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE) München/Tübingen and Dept. of Nuclear Medicine, Technische Universität München, München, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Förster
authors.affiliation: Banner Alzheimer's Institute, Banner Health, 901 E. Willetta Street, Phoenix, Arizona, United States of America.
authors.forename: Kewei
authors.initials: K
authors.lastname: Chen
authors.affiliation: Banner Alzheimer's Institute, Banner Health, 901 E. Willetta Street, Phoenix, Arizona, United States of America.
authors.forename: Eric M
authors.initials: EM
authors.lastname: Reiman
authors.affiliation: Division of Biostatistics, Washington University School of Medicine, Saint Louis, Missouri, United States of America.
authors.forename: Chengjie
authors.initials: C
authors.lastname: Xiong
authors.affiliation: Department of Radiology, Washington University School of Medicine, Saint Louis, Missouri, United States of America.
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Marcus
authors.affiliation: Department of Radiology, University of California San Francisco, San Francisco, California, United States of America.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Weiner
authors.affiliation: Department of Neurology, Washington University School of Medicine, Saint Louis, Missouri, United States of America.
authors.forename: John C
authors.initials: JC
authors.lastname: Morris
authors.affiliation: Department of Neurology, Washington University School of Medicine, Saint Louis, Missouri, United States of America.
authors.forename: Randall J
authors.initials: RJ
authors.lastname: Bateman
authors.affiliation: Department of Radiology, Washington University School of Medicine, Saint Louis, Missouri, United States of America.
authors.forename: Tammie L S
authors.initials: TL
authors.lastname: Benzinger
mesh_terms: D000328:Adult; D000544:Alzheimer Disease / Q000000981:diagnostic imaging* / Q000235:genetics*; D000682:Amyloid / Q000378:metabolism*; D001921:Brain / Q000000981:diagnostic imaging*; D002247:Carbon Isotopes / Q000737:chemistry; D003430:Cross-Sectional Studies; D004252:DNA Mutational Analysis; D005192:Family Health; D005260:Female; D005799:Genes, Dominant; D006579:Heterozygote; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009154:Mutation; D049268:Positron-Emission Tomography; D012016:Reference Values
chemical_list: D000682:Amyloid; D002247:Carbon Isotopes