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PLoS One. 2016 Mar 24;11(3):e0152082. doi: 10.1371/journal.pone.0152082. eCollection 2016.

Quantitative Amyloid Imaging in Autosomal Dominant Alzheimer's Disease: Results from the DIAN Study Group.

Author information

1
Department of Radiology, Washington University School of Medicine, Saint Louis, Missouri, United States of America.
2
Department of Neurology, Washington University School of Medicine, Saint Louis, Missouri, United States of America.
3
Department of Radiology, University of Michigan, Ann Arbor, Michigan, United States of America.
4
University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America.
5
University of California San Diego, La Jolla, California, United States of America.
6
Columbia University, New York, New York, United States of America.
7
Department of Neurology, Keck School of Medicine, University of Southern California, Los Angeles, California, United States of America.
8
Keck School of Medicine, University of Southern California, Los Angeles, California, United States of America.
9
Department of Radiology, Indiana University, Indianapolis, Indiana, United States of America.
10
Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States of America.
11
Butler Hospital and Brown University, Providence, Rhode Island, United States of America.
12
Neuroscience Research Australia and School of Medical Sciences, University of New South Wales, Sydney, New South Wales, Australia.
13
The Florey Institute and the University of Melbourne, Parkville, Victoria, Australia.
14
Dememtia Research Centre, Institute of Neurology, London, Great Britain.
15
Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE) München/Tübingen and Dept. of Nuclear Medicine, Technische Universität München, München, Germany.
16
Banner Alzheimer's Institute, Banner Health, 901 E. Willetta Street, Phoenix, Arizona, United States of America.
17
Division of Biostatistics, Washington University School of Medicine, Saint Louis, Missouri, United States of America.
18
Department of Radiology, University of California San Francisco, San Francisco, California, United States of America.

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.

PMID:
27010959
PMCID:
PMC4807073
DOI:
10.1371/journal.pone.0152082
[Indexed for MEDLINE]
Free PMC Article

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