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Cited by 50Dementia and Cognitive Impairment ResearchAlzheimer's disease research and treatmentsMedical Imaging Techniques and Applications

A multisite analysis of the concordance between visual image interpretation and quantitative analysis of [18F]flutemetamol amyloid PET images

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Bucci, Marco, Savitcheva, Irina, Farrar, Gill, Salvadó, Gemma, Collij, Lyduine, Doré, Vincent, Gispert, Juan Domingo, Gunn, Roger +10 more·2021·European Journal of Nuclear Medicine and Molecular Imaging
DOI 10.1007/s00259-021-05311-5PMC PMC8175298
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Abstract

Background: [18 F]flutemetamol PET scanning provides information on brain amyloid load and has been approved for routine clinical use based upon visual interpretation as either negative (equating to none or sparse amyloid plaques) or amyloid positive (equating to moderate or frequent plaques). Quantitation is however fundamental to the practice of nuclear medicine and hence can be used to supplement amyloid reading methodology especially in unclear cases. Methods: A total of 2770 [18 F]flutemetamol images were collected from 3 clinical studies and 6 research cohorts with available visual reading of [18 F]flutemetamol and quantitative analysis of images. These were assessed further to examine both the discordance and concordance between visual and quantitative imaging primarily using thresholds robustly established using pathology as the standard of truth. Scans covered a wide range of cases (i.e. from cognitively unimpaired subjects to patients attending the memory clinics). Methods of quantifying amyloid ranged from using CE/510K cleared marked software (e.g. CortexID, Brass), to other research-based methods (e.g. PMOD, CapAIBL). Additionally, the clinical follow-up of two types of discordance between visual and quantitation (V+Q- and V-Q+) was examined with competing risk regression analysis to assess possible differences in prediction for progression to Alzheimer’s disease (AD) and other diagnoses (OD). Results: Weighted mean concordance between visual and quantitation using the autopsy-derived threshold was 94% using pons as the reference region. Concordance from a sensitivity analysis which assessed the maximum agreement for each cohort using a range of cut-off values was also estimated at approximately 96% (weighted mean). Agreement was generally higher in clinical cases compared to research cases. V-Q+ discordant cases were 11% more likely to progress to AD than V+Q- for the SUVr with pons as reference region. Conclusions: Quantitation of amyloid PET shows a high agreement vs binary visual reading and also allows for a continuous measure that, in conjunction with possible discordant analysis, could be used in the future to identify possible earlier pathological deposition as well as monitor disease progression and treatment effectiveness.

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  • Aβ PET and tau PET are not perfectly accurate in detection of neuropathology.

    “Notably, Aβ PET and tau PET are not perfectly accurate in detection of neuropathology45,46”

    From Highly accurate blood test for Alzheimer's disease is similar or superior to clinical cerebrospinal fluid tests (2024) · cites this paper as [45]

    The Introduction (page unavailable) reports that [18F]flutemetamol amyloid PET was validated against pathology measures, with sensitivity and specificity over 90%—high, but not perfect. The paper does not address tau PET accuracy, so it supports only the amyloid PET part of the claim. (LLM, conf=0.90)

    Experimental — accuracy not yet measured

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Authors
Bucci, M., Savitcheva, I., Farrar, G., Salvadó, G., Collij, L., Doré, V., Gispert, J. D., Gunn, R., Hanseeuw, B., Hansson, O., Shekari, M., Lhommel, R., Molinuevo, J. L., Rowe, C., Sur, C., Whittington, A., Buckley, C., & Nordberg, A.
Affiliations
  • Karolinska Institutet (SE)
  • Karolinska University Hospital (SE)
  • General Electric (United Kingdom) (GB)
  • Pasqual Maragall Foundation (ES)
  • Amsterdam University Medical Centers (NL)
  • Commonwealth Scientific and Industrial Research Organisation (AU)
  • Universitat Pompeu Fabra (ES)
  • Invicro (United Kingdom) (GB)
  • Cliniques Universitaires Saint-Luc (BE)
  • Lund University (SE)
  • The University of Melbourne (AU)
  • Merck & Co., Inc., Rahway, NJ, USA (United States) (US)
Corresponding author
  • Bucci, Marco
  • Nordberg, Agneta
ORCID
Venue
European Journal of Nuclear Medicine and Molecular Imaging
Publisher
Springer Science and Business Media LLC
Published
2021-04-12
Volume
48
Issue
7
Pages
2183-2199
ISSN
  • 1619-7070 (ISSN-L)
  • 1619-7089
DOI
10.1007/s00259-021-05311-5
PMC
PMC8175298
OpenAlex
W3154120739
Cited by
50
References
38
Citations by year
2026: 9 · 2025: 13 · 2024: 9 · 2023: 10 · 2022: 8 · 2021: 1
FWCI
5.02
Type
journal article
Language
en
Open access
Licence
Locations
  • European Journal of Nuclear Medicine and Molecular Imaging (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Repositori digital de la UPF (Universitat Pompeu Fabra) (publishedVersion, cc-by)
  • Minerva Access (University of Melbourne) (submittedVersion, other-oa)
  • Digital Access to Libraries (submittedVersion, other-oa)
  • Lund University Publications (Lund University) (submittedVersion)
Funders
  • Stiftelsen för Strategisk Forskning (RB13-0192)
  • Center for Innovative Medicine, Karolinska institutet
  • Stockholms Läns Landsting (SE) KI
  • Hjärnfonden
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Medical Imaging Techniques and Applications
Keywords
18F-flutemetamol, amyloid PET, concordance, Alzheimer's disease progression, standardized uptake value ratio, memory clinic patients, competing risk regression
MeSH terms
Alzheimer Disease, Amyloid, Aniline Compounds, Brain, Humans, Amyloid beta-Peptides, Positron-Emission Tomography, Benzothiazoles

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