Visual assessment of [18F]flutemetamol PET images can detect early amyloid pathology and grade its extent

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• dc.contributor.author Collij, Lyduine E.
• dc.contributor.author Salvadó, Gemma
• dc.contributor.author Shekari, Mahnaz
• dc.contributor.author Lopes Alves, Isadora
• dc.contributor.author Reimand, Juhan
• dc.contributor.author Wink, Alle Meije
• dc.contributor.author Zwan, Marissa
• dc.contributor.author Niñerola-Baizán, Aida
• dc.contributor.author Perissinotti, Andrés
• dc.contributor.author Scheltens, Philip
• dc.contributor.author Ikonomovic, Milos D.
• dc.contributor.author Smith, Adrian P.L.
• dc.contributor.author Farrar, Gill
• dc.contributor.author Molinuevo, José Luis
• dc.contributor.author Barkhof, Frederik
• dc.contributor.author Buckley, Christopher, 1948-
• dc.contributor.author van Berckel, Bart N. M.
• dc.date.accessioned 2021-06-02T07:36:10Z
• dc.date.available 2021-06-02T07:36:10Z
• dc.date.issued 2021
• dc.description.abstract 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.
• dc.description.sponsorship 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). This work also received in kind sponsoring of the PET-tracer from GE Healthcare. 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.
• dc.format.mimetype application/pdf
• dc.identifier.citation Collij LE, Salvadó G, Shekari M, Lopes Alves I, Reimand J, Wink AM, Zwan M, Niñerola-Baizán A, Perissinotti A, Scheltens P, Ikonomovic MD, Smith APL, Farrar G, Molinuevo JL, Barkhof F, Buckley CJ, van Berckel BNM, Gispert JD; ALFA study; AMYPAD consortium. Visual assessment of [18F]flutemetamol PET images can detect early amyloid pathology and grade its extent. Eur J Nucl Med Mol Imaging. 2021;48(7):2169-82. DOI: 10.1007/s00259-020-05174-2
• dc.identifier.doi http://dx.doi.org/10.1007/s00259-020-05174-2
• dc.identifier.issn 1619-7070
• dc.identifier.uri http://hdl.handle.net/10230/47715
• dc.language.iso eng
• dc.publisher Springer
• dc.relation.ispartof Eur J Nucl Med Mol Imaging. 2021;48(7):2169-82
• dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/115952
• dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/666992
• dc.rights © The Author(s) 2021. 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/.
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• dc.subject.keyword Amyloid PET
• dc.subject.keyword Centiloid
• dc.subject.keyword Neuropathology
• dc.subject.keyword Regional visual read
• dc.subject.keyword Sensitivity
• dc.subject.keyword [18F]flutemetamol
• dc.title Visual assessment of [18F]flutemetamol PET images can detect early amyloid pathology and grade its extent
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion