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

Bucci, Marco ; Savitcheva, Irina ; Farrar, Gill ; Salvadó, Gemma ; Collij, Lyduine ; Doré, Vincent ; Gispert, Juan Domingo ; Gunn, Roger ; Hanseeuw, Bernard and Hansson, Oskar LU orcid , et al. (2021) In European Journal of Nuclear Medicine and Molecular Imaging 48(7). p.2183-2199
Abstract

Background: [18F]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 [18F]flutemetamol images were collected from 3 clinical studies and 6 research cohorts with available visual reading of [18F]flutemetamol and quantitative analysis of images. These were assessed further to examine both the... (More)

Background: [18F]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 [18F]flutemetamol images were collected from 3 clinical studies and 6 research cohorts with available visual reading of [18F]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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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Alzheimer’s disease, Amyloid PET, Image interpretation, Quantification, Visual inspection, [F]flutemetamol
in
European Journal of Nuclear Medicine and Molecular Imaging
volume
48
issue
7
pages
17 pages
publisher
Springer
external identifiers
  • scopus:85104507204
  • pmid:33844055
ISSN
1619-7070
DOI
10.1007/s00259-021-05311-5
language
English
LU publication?
yes
id
b1a0354f-75da-49a3-b2b8-d072aa6e6d37
date added to LUP
2021-05-04 09:40:07
date last changed
2024-06-16 13:21:49
@article{b1a0354f-75da-49a3-b2b8-d072aa6e6d37,
  abstract     = {{<p>Background: [<sup>18</sup>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 [<sup>18</sup>F]flutemetamol images were collected from 3 clinical studies and 6 research cohorts with available visual reading of [<sup>18</sup>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.</p>}},
  author       = {{Bucci, Marco and Savitcheva, Irina and Farrar, Gill and Salvadó, Gemma and Collij, Lyduine and Doré, Vincent and Gispert, Juan Domingo and Gunn, Roger and Hanseeuw, Bernard and Hansson, Oskar and Shekari, Mahnaz and Lhommel, Renaud and Molinuevo, José Luis and Rowe, Christopher and Sur, Cyrille and Whittington, Alex and Buckley, Christopher and Nordberg, Agneta}},
  issn         = {{1619-7070}},
  keywords     = {{Alzheimer’s disease; Amyloid PET; Image interpretation; Quantification; Visual inspection; [F]flutemetamol}},
  language     = {{eng}},
  month        = {{07}},
  number       = {{7}},
  pages        = {{2183--2199}},
  publisher    = {{Springer}},
  series       = {{European Journal of Nuclear Medicine and Molecular Imaging}},
  title        = {{A multisite analysis of the concordance between visual image interpretation and quantitative analysis of [<sup>18</sup>F]flutemetamol amyloid PET images}},
  url          = {{http://dx.doi.org/10.1007/s00259-021-05311-5}},
  doi          = {{10.1007/s00259-021-05311-5}},
  volume       = {{48}},
  year         = {{2021}},
}