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 in | European journal of nuclear medicine and molecular imaging Vol. 48; no. 7; pp. 2183 - 2199 |
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Main Authors | , , , , , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Berlin/Heidelberg
Springer Berlin Heidelberg
01.07.2021
Springer Nature B.V |
Subjects | |
Online Access | Get full text |
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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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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 Strategic research areas (SRA) Clinical Memory Research Klinisk minnesforskning Medicinska fakulteten Profilområden och andra starka forskningsmiljöer Institutionen för kliniska vetenskaper, Malmö |
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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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FarrarGMolinuevoJLZanetteMIs there a difference in regional read [18 F] flutemetamol amyloid patterns between end-of-life subjects and those with amnestic mild cognitive impairment?Eur J Nucl Med Mol Imaging201946129913081:CAS:528:DC%2BC1MXntFKgsLg%3D10.1007/s00259-019-04282-y PontecorvoMJAroraAKDevineMLuMGalanteNSiderowfAQuantitation of PET signal as an adjunct to visual interpretation of florbetapir imagingEur J Nucl O Hansson (5311_CR23) 2018; 14 CJ Buckley (5311_CR8) 2017; 38 R Sperling (5311_CR38) 2014; 84 5311_CR25 MO Habert (5311_CR42) 2018; 32 5311_CR26 A Chincarini (5311_CR14) 2019; 23 S Salloway (5311_CR6) 2017; 9 ME Schmidt (5311_CR40) 2015; 11 JL Molinuevo (5311_CR27) 2016; 2 L Thurfjell (5311_CR17) 2014; 55 A Whittington (5311_CR24) 2019; 60 P Bourgeat (5311_CR29) 2015; 36 R Vandenberghe (5311_CR7) 2010; 68 G Chételat (5311_CR3) 2020; 19 5311_CR9 SS Mirra (5311_CR4) 1991; 41 5311_CR1 A Leuzy (5311_CR18) 2019; 46 5311_CR2 D Fakhry-Darian (5311_CR16) 2019; 92 DA Wolk (5311_CR48) 2018; 75 ER Fantoni (5311_CR11) 2018; 63 5311_CR20 WE Klunk (5311_CR41) 2007; 27 5311_CR33 MJ Pontecorvo (5311_CR15) 2017; 44 5311_CR34 5311_CR13 5311_CR35 R La Joie (5311_CR44) 2019; 15 SL Leal (5311_CR47) 2018; 38 5311_CR37 R Vandenberghe (5311_CR45) 2013; 64 H Barthel (5311_CR12) 2017; 58 5311_CR19 JP Kim (5311_CR46) 2020; 47 G Farrar (5311_CR10) 2019; 46 G Salvadó (5311_CR22) 2019; 11 MD Ikonomovic (5311_CR5) 2016; 4 WE Klunk (5311_CR43) 2015; 11 MD Zwan (5311_CR21) 2017; 9 KA Ellis (5311_CR28) 2009; 21 MW Donoghoe (5311_CR36) 2017; 17 5311_CR30 A Chincarini (5311_CR39) 2016; 54 5311_CR31 5311_CR32 |
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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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Title | A multisite analysis of the concordance between visual image interpretation and quantitative analysis of [18F]flutemetamol amyloid PET images |
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