Inter-rater Variability of Visual Interpretation and Comparison with Quantitative Evaluation of C-PiB PET Amyloid Images of the Japanese Alzheimer's Disease Neuroimaging Initiative (J-ADNI) Multicenter Study

Overview

Journal Eur J Nucl Med Mol Imaging

Specialties Biophysics
Nuclear Medicine
Radiology

Date 2016 Dec 15

PMID 27966045

Citations 47

Authors

Tomohiko Yamane

Kenji Ishii

Muneyuki Sakata

Yasuhiko Ikari

Tomoyuki Nishio

Kazunari Ishii

Takashi Kato

Kengo Ito

Michio Senda

Affiliations

Soon will be listed here.

Abstract

Purpose: The aim of this study was to assess the inter-rater variability of the visual interpretation of C-PiB PET images regarding the positivity/negativity of amyloid deposition that were obtained in a multicenter clinical research project, Japanese Alzheimer's Disease Neuroimaging Initiative (J-ADNI). The results of visual interpretation were also compared with a semi-automatic quantitative analysis using mean cortical standardized uptake value ratio to the cerebellar cortex (mcSUVR).

Methods: A total of 162 C-PiB PET scans, including 45 mild Alzheimer's disease, 60 mild cognitive impairment, and 57 normal cognitive control cases that had been acquired as J-ADNI baseline scans were analyzed. Based on visual interpretation by three independent raters followed by consensus read, each case was classified into positive, equivocal, and negative deposition (ternary criteria) and further dichotomized by merging the former two (binary criteria).

Results: Complete agreement of visual interpretation by the three raters was observed for 91.3% of the cases (Cohen κ = 0.88 on average) in ternary criteria and for 92.3% (κ = 0.89) in binary criteria. Cases that were interpreted as visually positive in the consensus read showed significantly higher mcSUVR than those visually negative (2.21 ± 0.37 vs. 1.27 ± 0.09, p < 0.001), and positive or negative decision by visual interpretation was dichotomized by a cut-off value of mcSUVR = 1.5. Significant positive/negative associations were observed between mcSUVR and the number of raters who evaluated as positive (ρ = 0.87, p < 0.0001) and negative (ρ = -0.85, p < 0.0001) interpretation. Cases of disagreement among raters showed generally low mcSUVR.

Conclusions: Inter-rater agreement was almost perfect in C-PiB PET scans. Positive or negative decision by visual interpretation was dichotomized by a cut-off value of mcSUVR = 1.5. As some cases of disagreement among raters tended to show low mcSUVR, referring to quantitative method may facilitate correct diagnosis when evaluating images of low amyloid deposition.

Citing Articles

Automated quantification of brain PET in PET/CT using deep learning-based CT-to-MR translation: a feasibility study.

Kim D, Choo K, Lee S, Kang S, Yun M, Yang J Eur J Nucl Med Mol Imaging. 2025; .

PMID: 39964542 DOI: 10.1007/s00259-025-07132-2.

-Linked Parkinson Syndrome in Female Heterozygotes Is Associated With PET-Detectable Tau Pathology.

Yamamoto Y, Takahata K, Seki M, Okusa S, Tatebe H, Ueda R Neurol Genet. 2025; 11(1):e200235.

PMID: 39810750 PMC: 11731372. DOI: 10.1212/NXG.0000000000200235.

Clinical utility of plasma p-tau217 in identifying abnormal brain amyloid burden in an Asian cohort with high prevalence of concomitant cerebrovascular disease.

Chong J, Hilal S, Tan B, Venketasubramanian N, Scholl M, Zetterberg H Alzheimers Dement. 2025; 21(2):e14502.

PMID: 39807654 PMC: 11848187. DOI: 10.1002/alz.14502.

Subcortical tau deposition and plasma glial fibrillary acidic protein as predictors of cognitive decline in mild cognitive impairment and Alzheimer's disease.

Chang Y, Liu J, Xu X, Sun S, Zhang J, Zhang X Eur J Nucl Med Mol Imaging. 2024; 52(4):1496-1509.

PMID: 39690275 PMC: 11839848. DOI: 10.1007/s00259-024-07016-x.

Aβ status assessment in a hypothetical scenario prior to treatment with disease-modifying therapies: Evidence from 10-year real-world experience at university memory clinics.

Brendel M, Parvizi T, Gnorich J, Topfstedt C, Buerger K, Janowitz D Alzheimers Dement (Amst). 2024; 16(4):e70031.

PMID: 39583651 PMC: 11582924. DOI: 10.1002/dad2.70031.

References

Klunk W, Koeppe R, Price J, Benzinger T, Devous Sr M, Jagust W . The Centiloid Project: standardizing quantitative amyloid plaque estimation by PET. Alzheimers Dement. 2014; 11(1):1-15.e1-4. PMC: 4300247. DOI: 10.1016/j.jalz.2014.07.003. View

Ikari Y, Nishio T, Makishi Y, Miya Y, Ito K, Koeppe R . Head motion evaluation and correction for PET scans with 18F-FDG in the Japanese Alzheimer's disease neuroimaging initiative (J-ADNI) multi-center study. Ann Nucl Med. 2012; 26(7):535-44. DOI: 10.1007/s12149-012-0605-4. View

Tolboom N, van der Flier W, Yaqub M, Koene T, Boellaard R, Windhorst A . Differential association of [11C]PIB and [18F]FDDNP binding with cognitive impairment. Neurology. 2009; 73(24):2079-85. DOI: 10.1212/WNL.0b013e3181c679cc. View

Karran E, Mercken M, De Strooper B . The amyloid cascade hypothesis for Alzheimer's disease: an appraisal for the development of therapeutics. Nat Rev Drug Discov. 2011; 10(9):698-712. DOI: 10.1038/nrd3505. View

Sabri O, Seibyl J, Rowe C, Barthel H . Beta-amyloid imaging with florbetaben. Clin Transl Imaging. 2015; 3(1):13-26. PMC: 4339690. DOI: 10.1007/s40336-015-0102-6. View

Chen M . Ethnic or racial differences revisited: impact of dosage regimen and dosage form on pharmacokinetics and pharmacodynamics. Clin Pharmacokinet. 2006; 45(10):957-64. DOI: 10.2165/00003088-200645100-00001. View

Jack Jr C, Knopman D, Jagust W, Shaw L, Aisen P, Weiner M . Hypothetical model of dynamic biomarkers of the Alzheimer's pathological cascade. Lancet Neurol. 2010; 9(1):119-28. PMC: 2819840. DOI: 10.1016/S1474-4422(09)70299-6. View

Senda M, Sasaki M, Yamane T, Shimizu K, Patt M, Barthel H . Ethnic comparison of pharmacokinetics of (18)F-florbetaben, a PET tracer for beta-amyloid imaging, in healthy Caucasian and Japanese subjects. Eur J Nucl Med Mol Imaging. 2014; 42(1):89-96. PMC: 4244559. DOI: 10.1007/s00259-014-2890-8. View

Hatashita S, Yamasaki H, Suzuki Y, Tanaka K, Wakebe D, Hayakawa H . [18F]Flutemetamol amyloid-beta PET imaging compared with [11C]PIB across the spectrum of Alzheimer's disease. Eur J Nucl Med Mol Imaging. 2013; 41(2):290-300. DOI: 10.1007/s00259-013-2564-y. View

10.

Yamane T, Ikari Y, Nishio T, Ishii K, Kato T, Ito K . Visual-statistical interpretation of (18)F-FDG-PET images for characteristic Alzheimer patterns in a multicenter study: inter-rater concordance and relationship to automated quantitative evaluation. AJNR Am J Neuroradiol. 2013; 35(2):244-9. PMC: 7965770. DOI: 10.3174/ajnr.A3665. View

11.

Schreiber S, Landau S, Fero A, Schreiber F, Jagust W . Comparison of Visual and Quantitative Florbetapir F 18 Positron Emission Tomography Analysis in Predicting Mild Cognitive Impairment Outcomes. JAMA Neurol. 2015; 72(10):1183-90. DOI: 10.1001/jamaneurol.2015.1633. View

12.

Akamatsu G, Ikari Y, Ohnishi A, Nishida H, Aita K, Yamamoto Y . Automated PET-only quantification of amyloid deposition with adaptive template and empirically pre-defined ROI. Phys Med Biol. 2016; 61(15):5768-80. DOI: 10.1088/0031-9155/61/15/5768. View

13.

Tolboom N, van der Flier W, Boverhoff J, Yaqub M, Wattjes M, Raijmakers P . Molecular imaging in the diagnosis of Alzheimer's disease: visual assessment of [11C]PIB and [18F]FDDNP PET images. J Neurol Neurosurg Psychiatry. 2010; 81(8):882-4. DOI: 10.1136/jnnp.2009.194779. View

14.

Iwatsubo T . Japanese Alzheimer's Disease Neuroimaging Initiative: present status and future. Alzheimers Dement. 2010; 6(3):297-9. DOI: 10.1016/j.jalz.2010.03.011. View

15.

McKhann G, Knopman D, Chertkow H, Hyman B, Jack Jr C, Kawas C . The diagnosis of dementia due to Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement. 2011; 7(3):263-9. PMC: 3312024. DOI: 10.1016/j.jalz.2011.03.005. View

16.

Grimmer T, Wutz C, Alexopoulos P, Drzezga A, Forster S, Forstl H . Visual Versus Fully Automated Analyses of 18F-FDG and Amyloid PET for Prediction of Dementia Due to Alzheimer Disease in Mild Cognitive Impairment. J Nucl Med. 2015; 57(2):204-7. DOI: 10.2967/jnumed.115.163717. View

17.

Ng S, Villemagne V, Berlangieri S, Lee S, Cherk M, Gong S . Visual assessment versus quantitative assessment of 11C-PIB PET and 18F-FDG PET for detection of Alzheimer's disease. J Nucl Med. 2007; 48(4):547-52. DOI: 10.2967/jnumed.106.037762. View

18.

Senda M, Yamamoto Y, Sasaki M, Yamane T, Brooks D, Farrar G . An exploratory efficacy study of the amyloid imaging agent [(18)F]flutemetamol in Japanese Subjects. Ann Nucl Med. 2015; 29(5):391-9. DOI: 10.1007/s12149-015-0957-7. View

19.

Delacourte A, David J, Sergeant N, Buee L, WATTEZ A, Vermersch P . The biochemical pathway of neurofibrillary degeneration in aging and Alzheimer's disease. Neurology. 1999; 52(6):1158-65. DOI: 10.1212/wnl.52.6.1158. View

20.

Rosario B, Weissfeld L, Laymon C, Mathis C, Klunk W, Berginc M . Inter-rater reliability of manual and automated region-of-interest delineation for PiB PET. Neuroimage. 2011; 55(3):933-41. PMC: 3057323. DOI: 10.1016/j.neuroimage.2010.12.070. View