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Quantitative Amyloid imaging in autosomal Dominant Alzheimer's disease: Results from the DIAN study group

Su, Y and Blazey, TM and Owen, CJ and Christensen, JJ and Friedrichsen, K and Joseph-Mathurin, N and Wang, Q and Hornbeck, RC and Ances, BM and Snyder, AZ and Cash, LA and Koeppe, RA and Klunk, WE and Galasko, D and Brickman, AM and McDade, E and Ringman, JM and Thompson, PM and Saykin, AJ and Ghetti, B and Sperling, RA and Johnson, KA and Salloway, SP and Schofield, PR and Masters, CL and Villemagne, VL and Fox, NC and Förster, S and Chen, K and Reiman, EM and Xiong, C and Marcus, DS and Weiner, MW and Morris, JC and Bateman, RJ and Benzinger, TLS (2016) Quantitative Amyloid imaging in autosomal Dominant Alzheimer's disease: Results from the DIAN study group. PLoS ONE, 11 (3).

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Abstract

© 2016 Su et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 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 [ 11 C]-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.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Su, Y
Blazey, TM
Owen, CJ
Christensen, JJ
Friedrichsen, K
Joseph-Mathurin, N
Wang, Q
Hornbeck, RC
Ances, BM
Snyder, AZ
Cash, LA
Koeppe, RA
Klunk, WEwek1@pitt.eduWEK1
Galasko, D
Brickman, AM
McDade, E
Ringman, JM
Thompson, PM
Saykin, AJ
Ghetti, B
Sperling, RA
Johnson, KA
Salloway, SP
Schofield, PR
Masters, CL
Villemagne, VL
Fox, NC
Förster, S
Chen, K
Reiman, EM
Xiong, C
Marcus, DS
Weiner, MW
Morris, JC
Bateman, RJ
Benzinger, TLS
Contributors:
ContributionContributors NameEmailPitt UsernameORCID
EditorHerholz, KarlUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Date: 1 March 2016
Date Type: Publication
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Journal or Publication Title: PLoS ONE
Volume: 11
Number: 3
DOI or Unique Handle: 10.1371/journal.pone.0152082
Institution: University of Pittsburgh
Schools and Programs: School of Medicine > Medicine
Refereed: Yes
Date Deposited: 25 Aug 2016 15:58
Last Modified: 13 Apr 2019 22:55
URI: http://d-scholarship.pitt.edu/id/eprint/28278

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