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

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). Quant...

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Published inEuropean journal of nuclear medicine and molecular imaging Vol. 48; no. 7; pp. 2183 - 2199
Main Authors Bucci, Marco, Savitcheva, Irina, Farrar, Gill, Salvadó, Gemma, Collij, Lyduine, Doré, Vincent, Gispert, Juan Domingo, Gunn, Roger, Hanseeuw, Bernard, Hansson, Oskar, Shekari, Mahnaz, Lhommel, Renaud, Molinuevo, José Luis, Rowe, Christopher, Sur, Cyrille, Whittington, Alex, Buckley, Christopher, Nordberg, Agneta
Format Journal Article
LanguageEnglish
Published Berlin/Heidelberg Springer Berlin Heidelberg 01.07.2021
Springer Nature B.V
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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.
AbstractList 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 rangedfrom 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.
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.MethodsA 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).ResultsWeighted 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.ConclusionsQuantitation 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.
[ 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. A total of 2770 [ F]flutemetamol images were collected from 3 clinical studies and 6 research cohorts with available visual reading of [ 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). 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. 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.
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.
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.
Author Shekari, Mahnaz
Buckley, Christopher
Bucci, Marco
Doré, Vincent
Whittington, Alex
Salvadó, Gemma
Savitcheva, Irina
Nordberg, Agneta
Rowe, Christopher
Hansson, Oskar
Gispert, Juan Domingo
Molinuevo, José Luis
Lhommel, Renaud
Farrar, Gill
Gunn, Roger
Collij, Lyduine
Sur, Cyrille
Hanseeuw, Bernard
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CorporateAuthor MultiPark: Multidisciplinary research focused on Parkinson's disease
Lunds universitet
Profile areas and other strong research environments
Department of Clinical Sciences, Malmö
Lund University
Strategiska forskningsområden (SFO)
Faculty of Medicine
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Clinical Memory Research
Klinisk minnesforskning
Medicinska fakulteten
Profilområden och andra starka forskningsmiljöer
Institutionen för kliniska vetenskaper, Malmö
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Issue 7
Keywords F]flutemetamol
Quantification
Alzheimer’s disease
Amyloid PET
Image interpretation
[
Visual inspection
[18F]flutemetamol
Language English
License Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
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PublicationTitle European journal of nuclear medicine and molecular imaging
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References_xml – reference: Peira E, Grazzini M, Bauckneht M, Sensi F, Bosco P, Arnaldi D, et al. Probing the role of a regional quantitative assessment of amyloid PET. J Alzheimers Dis. 2021. https://doi.org/10.3233/JAD-201156.
– reference: GE Healthcare. Vizamyl™ flutemetamol 18F injection electronic training programme. Arlington Heights, IL: GE Healthcare; 2020. https://www.readvizamyl.com/en-gb. Accessed 14 Aug 2020.
– reference: HanssonOSeibylJStomrudEZetterbergHTrojanowskiJQBittnerTCSF biomarkers of Alzheimer’s disease concord with amyloid-β PET and predict clinical progression: a study of fully automated immunoassays in BioFINDER and ADNI cohortsAlzheimers Dement2018141470148110.1016/j.jalz.2018.01.010294991716119541
– reference: ZwanMDBouwmanFHKonijnenbergEVan Der FlierWMLammertsmaAAVerheyFRDiagnostic impact of [18 F] flutemetamol PET in early-onset dementiaAlzheimers Res Ther20179210.1186/s13195-016-0228-4
– reference: WolkDASadowskyCSafirsteinBRinneJODuaraRPerryRUse of flutemetamol F 18-labeled positron emission tomography and other biomarkers to assess risk of clinical progression in patients with amnestic mild cognitive impairmentJAMA Neurol2018751114112310.1001/jamaneurol.2018.0894297999846143120
– reference: EllisKABushAIDarbyDDe FazioDFosterJHudsonPThe Australian Imaging, Biomarkers and Lifestyle (AIBL) study of aging: methodology and baseline characteristics of 1112 individuals recruited for a longitudinal study of Alzheimer’s diseaseInt Psychogeriatr20092167268710.1017/S104161020900940519470201
– reference: PontecorvoMJAroraAKDevineMLuMGalanteNSiderowfAQuantitation of PET signal as an adjunct to visual interpretation of florbetapir imagingEur J Nucl Med Mol Imaging20174482583710.1007/s00259-016-3601-428064343
– reference: SalvadóGMolinuevoJLBrugulat-SerratAFalconCGrau-RiveraOSuárez-CalvetMCentiloid cut-off values for optimal agreement between PET and CSF core AD biomarkersAlzheimers Res Ther2019112710.1186/s13195-019-0478-z309020906429814
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Snippet Background [ 18 F]flutemetamol PET scanning provides information on brain amyloid load and has been approved for routine clinical use based upon visual...
[ F]flutemetamol PET scanning provides information on brain amyloid load and has been approved for routine clinical use based upon visual interpretation as...
Background[18F]flutemetamol PET scanning provides information on brain amyloid load and has been approved for routine clinical use based upon visual...
Background: [18F]flutemetamol PET scanning provides information on brain amyloid load and has been approved for routine clinical use based upon visual...
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StartPage 2183
SubjectTerms [F]flutemetamol
Alzheimer's disease
Amyloid PET
Autopsies
Autopsy
Cardiology
Clinical Medicine
Discordance
Fluorine isotopes
Image interpretation
Image processing
Imaging
Klinisk medicin
Language
Medical and Health Sciences
Medical imaging
Medicin och hälsovetenskap
Medicine
Medicine & Public Health
Neurodegenerative diseases
Neuroimaging
Neurology – Dementia
Nuclear Medicine
Oncology
Original
Original Article
Orthopedics
Pons
Positron emission
Positron emission tomography
Quantification
Quantitation
Quantitative analysis
Radiologi och bildbehandling
Radiology
Radiology and Medical Imaging
Radiology, Nuclear Medicine and Medical Imaging
Regression analysis
Risk analysis
Senile plaques
Sensitivity analysis
Tomography
Visual inspection
Visual thresholds
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Title A multisite analysis of the concordance between visual image interpretation and quantitative analysis of [18F]flutemetamol amyloid PET images
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