Tohoku J. Exp. Med., 2014 November, 234(3)

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

AKIRA ARAI,¹ TOMOHIRO KANETA,¹ NOBUYUKI OKAMURA,² MANABU TASHIRO,³ REN IWATA,⁴ KENTARO TAKANAMI,¹ HIROSHI FUKUDA,⁵ SHOKI TAKAHASHI,¹ KAZUHIKO YANAI,² YUKITSUKA KUDO⁶ and HIROYUKI ARAI⁷

¹Department of Diagnostic Radiology, Tohoku University School of Medicine, Sendai, Miyagi, Japan
²Department of Pharmacology, Tohoku University School of Medicine, Sendai, Miyagi, Japan
³Cyclotron Nuclear Medicine, Cyclotron and Radioisotope Center, Tohoku University, Sendai, Miyagi, Japan
⁴Division of Radiopharmaceutical Chemistry, Cyclotron and Radioisotope Center, Tohoku University, Sendai, Miyagi, Japan
⁵Nuclear Medicine and Radiology, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Miyagi, Japan
⁶Innovation New Biomedical Engineering Center, Tohoku University, Sendai, Miyagi, Japan
⁷Department of Geriatrics and Gerontology, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Miyagi, Japan

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 ¹¹C-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.

keywords —— Alzheimer's; amyloid; 3-dimensional stereotactic surface projections; positron emission tomography; statistical parametric mapping

© 2014 Tohoku University Medical Press

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Tohoku J. Exp. Med., 2014, 234, 175-181

Correspondence: Akira Arai, M.D., Ph.D., Department of Diagnostic Radiology, Tohoku University School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8574, Japan.

e-mail: a-arai@rad.med.tohoku.ac.jp