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

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Author(s)

    • Arai Akira
    • Department of Diagnostic Radiology, Tohoku University School of Medicine
    • Kudo Yukitsuka
    • Innovation New Biomedical Engineering Center, Tohoku University
    • Arai Hiroyuki
    • Department of Geriatrics and Gerontology, Institute of Development, Aging and Cancer, Tohoku University
    • Kaneta Tomohiro
    • Department of Diagnostic Radiology, Tohoku University School of Medicine
    • Tashiro Manabu
    • Cyclotron Nuclear Medicine, Cyclotron and Radioisotope Center, Tohoku University
    • Iwata Ren
    • Division of Radiopharmaceutical Chemistry, Cyclotron and Radioisotope Center, Tohoku University
    • Takanami Kentaro
    • Department of Diagnostic Radiology, Tohoku University School of Medicine
    • Fukuda Hiroshi
    • Nuclear Medicine and Radiology, Institute of Development, Aging and Cancer, Tohoku University
    • Takahashi Shoki
    • Department of Diagnostic Radiology, Tohoku University School of Medicine
    • Yanai Kazuhiko
    • Department of Pharmacology, Tohoku University School of Medicine

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 <sup>11</sup>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.

Journal

  • The Tohoku Journal of Experimental Medicine

    The Tohoku Journal of Experimental Medicine 234(3), 175-181, 2014

    Tohoku University Medical Press

Codes

  • NII Article ID (NAID)
    130004694506
  • Text Lang
    ENG
  • ISSN
    0040-8727
  • Data Source
    J-STAGE 
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