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Annals of Nuclear Medicine

, Volume 32, Issue 2, pp 75–86 | Cite as

Evaluation of amyloid status in a cohort of elderly individuals with memory complaints: validation of the method of quantification and determination of positivity thresholds

  • Marie-Odile HabertEmail author
  • Hugo Bertin
  • Mickael Labit
  • Mamadou Diallo
  • Sullivan Marie
  • Kelly Martineau
  • Aurélie Kas
  • Valérie Causse-Lemercier
  • Hovagim Bakardjian
  • Stéphane Epelbaum
  • Gael Chételat
  • Marion Houot
  • Harald Hampel
  • Bruno Dubois
  • Jean-François Mangin
  • INSIGHT-AD study group
Original Article

Abstract

Objective

Our aim is to validate the process steps implemented by the French CATI platform to assess amyloid status, obtained from 18F-Florbetapir PET scans, in a cohort of 318 cognitively normal subjects participating in the INSIGHT-preAD study. Our objective was to develop a method with partial volume effect correction (PVEC) on untransformed PET images, using an automated pipeline (“RACHEL”) adapted to large series of patients and including quality checks of results.

Methods

We compared RACHEL using different options (with and without PVEC, different sets of regions of interest), to two other methods validated in the literature, referred as the “AVID” and “CAEN” methods. A standard uptake value ratio (SUVR) was obtained with the different methods for participants to another French study, IMAP, including 26 normal elderly controls (NEC), 11 patients with mild cognitive impairment (MCI) and 16 patients with Alzheimer’s disease (AD). We determined two cutoffs for RACHEL method by linear correlation with the other methods and applied them to the INSIGHT-preAD subjects.

Results

RACHEL including PVEC and a combination of the whole cerebellum and the pons as a reference region allowed the best discrimination between NEC and AD participants. A strong linear correlation was found between RACHEL and the other two methods and yielded the two cutoffs of 0.79 and 0.88. According to the more conservative threshold, 19.8% of the INSIGHT-preAD subjects would be considered amyloid positive, and 27.7% according to the more liberal threshold.

Conclusions

With our method, we clearly discriminated between NEC with negative amyloid status and patients with clinical AD. Using a linear correlation with other validated cutoffs, we could infer our own positivity thresholds and apply them to an independent population. This method might be useful to the community, especially when the optimal cutoff could not be obtained from a population of healthy young adults or from correlation with post-mortem results.

Keywords

Brain PET 18F-Florbetapir Amyloid burden quantification Alzheimer’s disease 

Notes

Acknowledgements

We sincerely thank Alain Giron for helping with the statistical analyses and Anne Bertrand for her input on the manuscript. INSIGHT-AD study group Audrain C, Bakardjian H, Benali H, Bertin, H, Boukadida L, Cacciamani F, Causse-Lemercier V, Cavedo E, Chiesa P, Colliot O, Dos Santos A, Dubois B, Durrleman S, Epelbaum S, Gagliardi G, Genthon R, Habert M-O, Hampel H, Jungalee N, Kas A, Lehericy S, Lamari F, Letondor C, Levy M, Lista S, Mochel F, Nyasse F, Poisson C, Potier MC, Revillon M, Rojkova K, Roy P, Santos-Andrade K, Santos A, Simon V, Sole M, Tandetnik C, Thiebaud De Schotten M.

Compliance with ethical standards

Research involving human participants

A national ethics committee approved the INSIGHT study (ANSM 130134B-31), and all subjects gave written informed consent before their inclusion in the study. The IMAP study was approved by a regional ethics committee (Comité de Protection des Personnes Nord-Ouest III) and all participants gave written informed consent to the study prior to the investigation.

Funding

The INSIGHT-preAD study is supported by the IHU-A-ICM, Investissement d’Avenir from the French Ministry of Health, the French Foundation Plan-Alzheimer, Pfizer and AVID/Lilly companies. The French Foundation Plan-Alzheimer supports the CATI. Harald Hampel is supported by the AXA Research Fund, the Fondation Université Pierre et Marie Curie and the “Fondation pour la Recherche sur Alzheimer”, Paris, France. The research leading to these results has received funding from the program “Investissements d’avenir” ANR-10-IAIHU-06 (Agence Nationale de la Recherche-10-IA Institut Hospitalo-Universitaire-6).

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Copyright information

© The Japanese Society of Nuclear Medicine 2017

Authors and Affiliations

  • Marie-Odile Habert
    • 1
    • 2
    • 3
    Email author
  • Hugo Bertin
    • 1
  • Mickael Labit
    • 1
  • Mamadou Diallo
    • 1
  • Sullivan Marie
    • 1
  • Kelly Martineau
    • 1
  • Aurélie Kas
    • 1
    • 2
    • 3
  • Valérie Causse-Lemercier
    • 2
  • Hovagim Bakardjian
    • 4
    • 5
  • Stéphane Epelbaum
    • 4
    • 5
  • Gael Chételat
    • 6
    • 7
    • 8
    • 9
  • Marion Houot
    • 4
  • Harald Hampel
    • 4
    • 5
    • 10
  • Bruno Dubois
    • 4
    • 5
  • Jean-François Mangin
    • 1
    • 11
  • INSIGHT-AD study group
  1. 1.Centre pour l’Acquisition et le Traitement des ImagesSaclay, ParisFrance
  2. 2.Département de Médecine Nucléaire, Hôpital de la Pitié-SalpêtrièreAP-HPParisFrance
  3. 3.Laboratoire d’Imagerie Biomédicale, Inserm U 1146, CNRS UMR 7371Sorbonne Universités, UPMC Univ Paris 06ParisFrance
  4. 4.Département de Neurologie, Hôpital de la Pitié-Salpêtrière, Institut de la Mémoire et de la Maladie d’Alzheimer (IM2A) AP-HPParisFrance
  5. 5.Institut Cerveau Moelle (ICM) UMR S 1127, FrontlabParisFrance
  6. 6.INSERM U1077CaenFrance
  7. 7.Université de Caen Basse-Normandie UMR-S1077CaenFrance
  8. 8.Ecole Pratique des Hautes Etudes UMR-S1077CaenFrance
  9. 9.CHU de Caen, U1077CaenFrance
  10. 10.AXA Research Fund and UPMC ChairSorbonne Universities, Pierre and Marie Curie UniversityParis 06France
  11. 11.NeuroSpin, I2BM, Commissariat à l’Energie AtomiqueSaclayFrance

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