Abstract
Original language | English |
---|---|
Pages (from-to) | 2169-2182 |
Number of pages | 14 |
Journal | European journal of nuclear medicine and molecular imaging |
Volume | 48 |
Issue number | 7 |
Early online date | 2021 |
DOIs | |
Publication status | Published - Jul 2021 |
Keywords
- Amyloid PET
- Centiloid
- Neuropathology
- Regional visual read
- Sensitivity
- [F-18]flutemetamol
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In: European journal of nuclear medicine and molecular imaging, Vol. 48, No. 7, 07.2021, p. 2169-2182.
Research output: Contribution to journal › Article › Academic › peer-review
TY - JOUR
T1 - Visual assessment of [18F]flutemetamol PET images can detect early amyloid pathology and grade its extent
AU - Collij, Lyduine E.
AU - Salvado, Gemma
AU - Shekari, Mahnaz
AU - Alves, Isadora Lopes
AU - Reimand, Juhan
AU - Wink, Alle Meije
AU - Zwan, Marissa
AU - Ninerola-Baizan, Aida
AU - Perissinotti, Andres
AU - Scheltens, Philip
AU - Ikonomovic, Milos D.
AU - Smith, Adrian P. L.
AU - Farrar, Gill
AU - Molinuevo, Jose Luis
AU - Barkhof, Frederik
AU - Buckley, Christopher J.
AU - van Berckel, Bart N. M.
AU - Gispert, Juan Domingo
N1 - Funding Information: This project has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 115952. This Joint Undertaking receives support from the European Union’s Horizon 2020 research and innovation programme and EFPIA. The ALFA Study is funded by “la Caixa” Foundation (LCF/PR/GN17/10300004) and the Alzheimer’s Association and an international anonymous charity foundation through the the TriBEKa Imaging Platform project (TriBEKa-17-519007). Additional funding has been obtained by Project RTI2018-102261-B-I00, funded by European Regional Development Fund (EDRF) / Ministry of Science and Innovation - State Research Agency (Spain). Funding Information: Research of the Alzheimer Center Amsterdam is part of the neurodegeneration research program of Amsterdam Neuroscience. The clinical database structure was developed with funding from Stichting Dioraphte. Alzheimer Center Amsterdam is supported by Alzheimer Nederland and Stichting VUmc fonds. Funding Information: Prof. Frederik Barkhof received payment and honoraria from Bayer-Schering Pharma, Sanofi-Aventis, Genzyme, Biogen-Idec, TEVA, Merck-Serono, Novartis, Roche, Jansen Research, IXICO Ltd., GeNeuro, and Apitope Ltd. for consulting; payment from the Serono Symposia Foundation, IXICOLtd, and MedScape for educational presentations; research support via grants from EU/EFPIA Innovative Medicines Initiative Joint Undertaking (AMYPAD consortium), EuroPOND (H2020), UK MS Society, Dutch MS Society, PICTURE (IMDI-NWO), NIHR UCLH Biomedical Research Centre (BRC), ECTRIMS-MAGNIMS. Funding Information: The project leading to this paper has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 115952. This Joint Undertaking receives the support from the European Union’s Horizon 2020 research and innovation programme and EFPIA. This communication reflects the views of the authors and neither IMI nor the European Union and EFPIA are liable for any use that may be made of the information contained herein Funding Information: Dr. J.D. Gispert has received speaker’s fees from Biogen and Philips. In addition he holds a ‘Ramón y Cajal’ fellowship (RYC-2013-13054) from the Spanish Ministry of Economy and Competitiveness, has received research support from the EU/EFPIA Innovative Medicines Initiative Joint Undertaking AMYPAD grant agreement n° 115952, and from Ministerio de Ciencia y Universidades (grant agreement RTI2018-102261). Funding Information: FB is supported by the NIHR UCLH biomedical research centre. FB and AMW are supported by the European Union’s Horizon 2020 research and innovation programme under grant agreement No. 666992. Funding Information: The project leading to these results has received funding from “la Caixa” Foundation (ID 100010434), under agreement LCF/PR/GN17/50300004 and the Alzheimer’s Association and an international anonymous charity foundation through the TriBEKa Imaging Platform project (TriBEKa-17-519007). Funding Information: Prof. J. L. Molinuevo is currently a full-time employee of Lundbeck and priory has served as a consultant or at advisory boards for the following for-profit companies, or has given lectures in symposia sponsored by the following for-profit companies: Roche Diagnostics, Genentech, Novartis, Lundbeck, Oryzon, Biogen, Lilly, Janssen, Green Valley, MSD, Eisai, Alector, BioCross, GE Healthcare, ProMIS Neurosciences. He also received research support from the EU/EFPIA Innovative Medicines Initiative Joint Undertaking AMYPAD grant agreement n° 115952; the EU/EFPIA Innovative Medicines Initiative Joint Undertaking EPAD grant agreement n° 115736; the EU/EFPIA Innovative Medicines Initiative Joint Undertaking AETIONOMY grant n° 115568; and ‘la Caixa’ Foundation. Publisher Copyright: © 2021, The Author(s). Copyright: Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/7
Y1 - 2021/7
N2 - Purpose: To investigate the sensitivity of visual read (VR) to detect early amyloid pathology and the overall utility of regional VR. Methods: [18F]Flutemetamol PET images of 497 subjects (ALFA+ N = 352; ADC N = 145) were included. Scans were visually assessed according to product guidelines, recording the number of positive regions (0–5) and a final negative/positive classification. Scans were quantified using the standard and regional Centiloid (CL) method. The agreement between VR-based classification and published CL-based cut-offs for early (CL = 12) and established (CL = 30) pathology was determined. An optimal CL cut-off maximizing Youden’s index was derived. Global and regional CL quantification was compared to VR. Finally, 28 post-mortem cases from the [18F]flutemetamol phase III trial were included to assess the percentage agreement between VR and neuropathological classification of neuritic plaque density. Results: VR showed excellent agreement against CL = 12 (κ =.89, 95.2%) and CL = 30 (κ =.88, 95.4%) cut-offs. ROC analysis resulted in an optimal CL = 17 cut-off against VR (sensitivity = 97.9%, specificity = 97.8%). Each additional positive VR region corresponded to a clear increase in global CL. Regional VR was also associated with regional CL quantification. Compared to mCERADSOT-based classification (i.e., any region mCERADSOT > 1.5), VR was in agreement in 89.3% of cases, with 13 true negatives, 12 true positives, and 3 false positives (FP). Regional sparse-to-moderate neuritic and substantial diffuse Aβ plaque was observed in all FP cases. Regional VR was also associated with regional plaque density. Conclusion: VR is an appropriate method for assessing early amyloid pathology and that grading the extent of visual amyloid positivity could present clinical value.
AB - Purpose: To investigate the sensitivity of visual read (VR) to detect early amyloid pathology and the overall utility of regional VR. Methods: [18F]Flutemetamol PET images of 497 subjects (ALFA+ N = 352; ADC N = 145) were included. Scans were visually assessed according to product guidelines, recording the number of positive regions (0–5) and a final negative/positive classification. Scans were quantified using the standard and regional Centiloid (CL) method. The agreement between VR-based classification and published CL-based cut-offs for early (CL = 12) and established (CL = 30) pathology was determined. An optimal CL cut-off maximizing Youden’s index was derived. Global and regional CL quantification was compared to VR. Finally, 28 post-mortem cases from the [18F]flutemetamol phase III trial were included to assess the percentage agreement between VR and neuropathological classification of neuritic plaque density. Results: VR showed excellent agreement against CL = 12 (κ =.89, 95.2%) and CL = 30 (κ =.88, 95.4%) cut-offs. ROC analysis resulted in an optimal CL = 17 cut-off against VR (sensitivity = 97.9%, specificity = 97.8%). Each additional positive VR region corresponded to a clear increase in global CL. Regional VR was also associated with regional CL quantification. Compared to mCERADSOT-based classification (i.e., any region mCERADSOT > 1.5), VR was in agreement in 89.3% of cases, with 13 true negatives, 12 true positives, and 3 false positives (FP). Regional sparse-to-moderate neuritic and substantial diffuse Aβ plaque was observed in all FP cases. Regional VR was also associated with regional plaque density. Conclusion: VR is an appropriate method for assessing early amyloid pathology and that grading the extent of visual amyloid positivity could present clinical value.
KW - Amyloid PET
KW - Centiloid
KW - Neuropathology
KW - Regional visual read
KW - Sensitivity
KW - [F-18]flutemetamol
UR - http://www.scopus.com/inward/record.url?scp=85101270143&partnerID=8YFLogxK
U2 - https://doi.org/10.1007/s00259-020-05174-2
DO - https://doi.org/10.1007/s00259-020-05174-2
M3 - Article
C2 - 33615397
SN - 1619-7070
VL - 48
SP - 2169
EP - 2182
JO - European journal of nuclear medicine and molecular imaging
JF - European journal of nuclear medicine and molecular imaging
IS - 7
ER -