title: The influence of biological and technical factors on quantitative analysis of amyloid PET: Points to consider and recommendations for controlling variability in longitudinal data.
abstract: In vivo imaging of amyloid burden with positron emission tomography (PET) provides a means for studying the pathophysiology of Alzheimer's and related diseases. Measurement of subtle changes in amyloid burden requires quantitative analysis of image data. Reliable quantitative analysis of amyloid PET scans acquired at multiple sites and over time requires rigorous standardization of acquisition protocols, subject management, tracer administration, image quality control, and image processing and analysis methods. We review critical points in the acquisition and analysis of amyloid PET, identify ways in which technical factors can contribute to measurement variability, and suggest methods for mitigating these sources of noise. Improved quantitative accuracy could reduce the sample size necessary to detect intervention effects when amyloid PET is used as a treatment end point and allow more reliable interpretation of change in amyloid burden and its relationship to clinical course.
authors.affiliation: Janssen Pharmaceutica, Beerse, Belgium. Electronic address: mschmid4@its.jnj.com.
authors.forename: Mark E
authors.initials: ME
authors.lastname: Schmidt
authors.affiliation: Biogen IDEC, Cambridge, MA, USA.
authors.forename: Ping
authors.initials: P
authors.lastname: Chiao
authors.affiliation: Synarc, Newark, CA, USA.
authors.forename: Gregory
authors.initials: G
authors.lastname: Klein
authors.affiliation: ADM Diagnostics LLC, Chicago, IL, USA.
authors.forename: Dawn
authors.initials: D
authors.lastname: Matthews
authors.affiliation: GE Healthcare, Uppsala, Sweden.
authors.forename: Lennart
authors.initials: L
authors.lastname: Thurfjell
authors.affiliation: Takeda Pharmaceuticals, Deerfield, IL, USA.
authors.forename: Patricia E
authors.initials: PE
authors.lastname: Cole
authors.affiliation: CereSpir, Inc., New York, NY, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Margolin
authors.affiliation: Helen Wills Neuroscience Institute, University of California, Berkeley, Berkeley, CA, USA.
authors.forename: Susan
authors.initials: S
authors.lastname: Landau
authors.affiliation: Division of Cognitive Neurology, University of Utah, Salt Lake City, UT, USA.
authors.forename: Norman L
authors.initials: NL
authors.lastname: Foster
authors.affiliation: Department of Radiology, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: N Scott
authors.initials: NS
authors.lastname: Mason
authors.affiliation: Piramal Imaging, Boston, MA, USA.
authors.forename: Susan
authors.initials: S
authors.lastname: De Santi
authors.affiliation: Synarc, Newark, CA, USA.
authors.forename: Joyce
authors.initials: J
authors.lastname: Suhy
authors.affiliation: Division of Nuclear Medicine, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Koeppe
authors.affiliation: Helen Wills Neuroscience Institute, University of California, Berkeley, Berkeley, CA, USA.
authors.forename: William
authors.initials: W
authors.lastname: Jagust
mesh_terms: D000682:Amyloid / Q000378:metabolism*; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism*; D006801:Humans; D049268:Positron-Emission Tomography / Q000295:instrumentation / Q000379:methods*; D019275:Radiopharmaceuticals
chemical_list: D000682:Amyloid; D019275:Radiopharmaceuticals
keywords: ADNI; Alzheimer's disease; Amyloid; Multi-site trials; Positron emission tomography; Quantitative analysis; Within subject variability