title: Pitfalls of voxel-based amyloid PET analyses for diagnosis of Alzheimer's disease: artifacts due to non-specific uptake in the white matter and the skull.
abstract: Two methods are commonly used in brain image voxel-based analyses widely used for dementia work-ups: 3-dimensional stereotactic surface projections (3D-SSP) and statistical parametric mapping (SPM). The methods calculate the Z-scores of the cortical voxels that represent the significance of differences compared to a database of brain images with normal findings, and visualize them as surface brain maps. The methods are considered useful in amyloid positron emission tomography (PET) analyses to detect small amounts of amyloid-β deposits in early-stage Alzheimer's disease (AD), but are not fully validated. We analyzed the (11)C-labeled 2-(2-[2-dimethylaminothiazol-5-yl]ethenyl)-6-(2-[fluoro]ethoxy)benzoxazole (BF-227) amyloid PET imaging of 56 subjects (20 individuals with mild cognitive impairment [MCI], 19 AD patients, and 17 non-demented [ND] volunteers) with 3D-SSP and the easy Z-score imaging system (eZIS) that is an SPM-based method. To clarify these methods' limitations, we visually compared Z-score maps output from the two methods and investigated the causes of discrepancies between them. Discrepancies were found in 27 subjects (9 MCI, 13 AD, and 5 ND). Relatively high white matter uptake was considered to cause higher Z-scores on 3D-SSP in 4 subjects (1 MCI and 3 ND). Meanwhile, in 17 subjects (6 MCI, 9 AD, and 2 ND), Z-score overestimation on eZIS corresponded with high skull uptake and disappeared after removing the skull uptake ("scalping"). Our results suggest that non-specific uptakes in the white matter and skull account for errors in voxel-based amyloid PET analyses. Thus, diagnoses based on 3D-SSP data require checking white matter uptake, and "scalping" is recommended before eZIS analysis.
authors.affiliation: Department of Diagnostic Radiology, Tohoku University School of Medicine.
authors.forename: Akira
authors.initials: A
authors.lastname: Arai
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Kaneta
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Okamura
authors.forename: Manabu
authors.initials: M
authors.lastname: Tashiro
authors.forename: Ren
authors.initials: R
authors.lastname: Iwata
authors.forename: Kentaro
authors.initials: K
authors.lastname: Takanami
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Fukuda
authors.forename: Shoki
authors.initials: S
authors.lastname: Takahashi
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Yanai
authors.forename: Yukitsuka
authors.initials: Y
authors.lastname: Kudo
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Arai
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000000981:diagnostic imaging* / Q000473:pathology; D000682:Amyloid; D016477:Artifacts; D001583:Benzoxazoles; D060825:Cognitive Dysfunction / Q000000981:diagnostic imaging; D003704:Dementia / Q000000981:diagnostic imaging; D003710:Demography; D005260:Female; D006801:Humans; D008297:Male; D049268:Positron-Emission Tomography; D012886:Skull / Q000000981:diagnostic imaging*; D013844:Thiazoles; D066127:White Matter / Q000000981:diagnostic imaging* / Q000473:pathology
chemical_list: C516779:2-(2-(2-dimethylaminothiazol-5-yl)ethenyl)-6-(2-(fluoro)ethoxy)benzoxazole; D000682:Amyloid; D001583:Benzoxazoles; D013844:Thiazoles