Simulating the effect of cerebral blood flow changes on regional quantification of [18F]flutemetamol and [18F]florbetaben studies

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  • dc.contributor.author Heeman, Fiona
  • dc.contributor.author Yaqub, Maqsood
  • dc.contributor.author Lopes Alves, Isadora
  • dc.contributor.author Heurling, Kerstin
  • dc.contributor.author Bullich, Santiago
  • dc.contributor.author Gispert López, Juan Domingo
  • dc.contributor.author Boellaard, Ronald
  • dc.contributor.author Lammertsma, Adriaan A.
  • dc.contributor.author AMYPAD Consortium
  • dc.date.accessioned 2021-03-17T08:05:56Z
  • dc.date.available 2021-03-17T08:05:56Z
  • dc.date.issued 2021
  • dc.description.abstract Global and regional changes in cerebral blood flow (CBF) can result in biased quantitative estimates of amyloid load by PET imaging. Therefore, the current simulation study assessed effects of these changes on amyloid quantification using a reference tissue approach for [18F]flutemetamol and [18F]florbetaben. Previously validated pharmacokinetic rate constants were used to simulate time-activity curves (TACs) corresponding to full dynamic and dual-time-window acquisition protocols. CBF changes were simulated by varying the tracer delivery (K1) from +25 to -25%. The standardized uptake value ratio (SUVr) was computed and TACs were fitted using reference Logan (RLogan) and the simplified reference tissue model (SRTM) to obtain the relative delivery rate (R1) and volume of distribution ratio (DVR). RLogan was least affected by CBF changes (χ2 = 583 p < 0.001, χ2 = 81 p < 0.001, for [18F]flutemetamol and [18F]florbetaben, respectively) and the extent of CBF sensitivity generally increased for higher levels of amyloid. Further, SRTM-derived R1 changes correlated well with simulated CBF changes (R2 > 0.95) and SUVr's sensitivity to CBF changes improved for later uptake-times, with the exception of [18F]flutemetamol cortical changes. In conclusion, RLogan is the preferred method for amyloid quantification of [18F]flutemetamol and [18F]florbetaben studies and SRTM could be additionally used for obtaining a CBF proxy.
  • dc.description.sponsorship The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: the project leading to this application 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 http://www.imi.europa.eu. JDG holds a ‘Ramón y Cajal’ fellowship (RYC-2013-13054) from the Spanish Ministry of Science, Innovation and Universities.
  • dc.format.mimetype application/pdf
  • dc.identifier.citation Heeman F, Yaqub M, Lopes Alves I, Heurling K, Bullich S, Gispert JD, Boellaard R, Lammertsma AA; AMYPAD Consortium. Simulating the effect of cerebral blood flow changes on regional quantification of [18F]flutemetamol and [18F]florbetaben studies. J Cereb Blood Flow Metab. 2021; 41(3):579-89. DOI: 10.1177/0271678X20918029
  • dc.identifier.doi http://dx.doi.org/10.1177/0271678X20918029
  • dc.identifier.issn 0271-678X
  • dc.identifier.uri http://hdl.handle.net/10230/46811
  • dc.language.iso eng
  • dc.publisher SAGE Publications
  • dc.relation.ispartof J Cereb Blood Flow Metab. 2021; 41(3):579-89
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/115952
  • dc.rights The Author(s) 2020. This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage).
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri https://creativecommons.org/licenses/by-nc/4.0/
  • dc.subject.keyword Alzheimer’s disease
  • dc.subject.keyword Amyloid PET
  • dc.subject.keyword Cerebral blood flow
  • dc.subject.keyword Quantification
  • dc.subject.keyword Simulation study
  • dc.title Simulating the effect of cerebral blood flow changes on regional quantification of [18F]flutemetamol and [18F]florbetaben studies
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion

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