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A pitfall of white matter reference regions used in [18F] florbetapir PET: a consideration of kinetics

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Abstract

Objective

Many studies have demonstrated the superiority of white matter (WM) reference regions (RR) in amyloid PET studies in comparison to cerebellar RR. However, the principle behind its improved measurement stability is yet to be elucidated. Our study aimed to determine the origin of WM stability; stability over cerebral blood flow and input function fluctuation or the greater statistical noise in the cerebellum due to its smaller size and its location in the axial periphery of the PET scanner bore.

Methods

We conducted simulations of [\({}^{18}\)F] florbetapir using in-house program varying \(K_1\) and input function, and adding statistical noise.

Results

Our simulations revealed that WM RR were more susceptible to CBF variation and input function fluctuation than cerebellar RR. WM RR did not gave superior measurement stability unless cerebellar statistical noise exceeded 4.55 times that in WM, a figure often surpassed in traditional amyloid PET studies. The greater statistical noise in cerebellum is likely the etiology for improved measurement stability of WM RR.

Conclusion

A longitudinal [\({}^{18}\)F] florbetapir PET study should be conducted with a long bore PET. It can also be hypothesized that a second scan with the cerebellum in the axial center of a 3D PET, using a cerebellar RR to calculate changes in tracer concentration may improve the measurement stability of longitudinal [\({}^{18}\)F] florbetapir studies.

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Acknowledgements

This study is partly supported by Grants-in-Aid for Scientific Research, Japan Society for the Promotion of Science (Grant No. 18K07488) for MK. The authors would like to thank Ms. Natalie Okawa for English language editing of this manuscript.

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Authors and Affiliations

  1. Department of Diagnostic Radiology, Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology, 35-2 Sakae-cho, Itabashi-ku, Tokyo, 173-0015, Japan

    Masashi Kameyama

  2. Research Team for Neuroimaging, Tokyo Metropolitan Institute of Gerontology, Tokyo, 173-0015, Japan

    Kenji Ishibash, Kei Wagatsuma, Jun Toyohara & Kenji Ishii

Authors
  1. Masashi Kameyama
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  2. Kenji Ishibash
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  3. Kei Wagatsuma
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  4. Jun Toyohara
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  5. Kenji Ishii
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Contributions

MK conceived the study, wrote the simulation coding for python and wrote the initial manuscript. KI analyzed dynamic PET data and advised on the project. KW and JT contributed to obtain input function data of [\({}^{18}\)F] florbetapir. KI supervised the project. All authors discussed and approved the final manuscript.

Corresponding author

Correspondence to Masashi Kameyama.

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Conflict of interest

MK received research fund from Fujifilm Toyama Chemical Co., Ltd., which supplies [\({}^{18}\)F] Florbetapir in Japan but played no role in this mamuscript, and Nihon Medi-Physics Co. Ltd.

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Kameyama, M., Ishibash, K., Wagatsuma, K. et al. A pitfall of white matter reference regions used in [18F] florbetapir PET: a consideration of kinetics. Ann Nucl Med 33, 848–854 (2019). https://doi.org/10.1007/s12149-019-01397-y

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  • DOI: https://doi.org/10.1007/s12149-019-01397-y

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