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. 2018 Dec 5;8(1):107.
doi: 10.1186/s13550-018-0456-7.

Centiloid scaling for quantification of brain amyloid with [18F]flutemetamol using multiple processing methods

Mark R Battle  1 , Lovena Chedumbarum Pillay  1 , Val J Lowe  2 , David Knopman  2 , Bradley Kemp  2 , Christopher C Rowe  3 , Vincent Doré  3 , Victor L Villemagne  3 , Christopher J Buckley  4
Affiliations

Centiloid scaling for quantification of brain amyloid with [18F]flutemetamol using multiple processing methods

Mark R Battle et al. EJNMMI Res. .

Abstract

Introduction: A standardised method for quantifying β-amyloid PET tracers would allow comparison across different tracers and different sites. The development of the Centiloid scale has aimed to achieve this, applying a common scale to better aid the diagnosis and prognosis of Alzheimer's disease (AD) and to monitor anti-amyloid therapeutic interventions. Here, we apply the Centiloid method to [18F]flutemetamol and [11C]PiB (PiB, Pittsburgh compound B) PET images and derive the scaling factor to express their binding in Centiloids.

Methods: Paired PiB and [18F]flutemetamol scans for 74 subjects, including 24 young healthy controls (37 ± 5 years), were analysed using the standard Centiloid method. The same subjects were also analysed using PMOD- and FSL-based pipelines as well as SPM8. Test-retest analysis of 10 AD subjects was also performed with each pipeline.

Results: The standard uptake value ratios (SUVR), determined using the standard SPM8 Centiloid process, showed a strong correlation between [18F]flutemetamol (Flute) and PiB binding (SUVR-Flute = 0.77 × SUVR-PiB + 0.22, R2 = 0.96). Application of the standard Centiloid process allowed the calculation of a direct conversion equation for SUVR-Flute to Centiloid units (CL) (CL = (121.42*SUVR-Flute) - 121.16). Analysis of the data via the two alternate Centiloid pipelines allowed us to derive standardised, SPM8-equivalent equations for both PMOD (CL = (115.24*SUVR-Flute) - 107.86) and FSL (CL = (120.32*SUVR-Flute) - 112.75) respectively. Test-retest analysis of 10 AD subjects showed an approximate 2% difference for each pipeline.

Conclusions: [18F]flutemetamol data can now be expressed in Centiloid units, enhancing its utility in clinical and research applications for β-amyloid imaging. The standard Centiloid method also demonstrates that [18F]flutemetamol has favourable performance compared with PiB and other β-amyloid tracers. Test-retest difference averaged 2%, with no difference between image processing pipelines. Centiloid scaling is robust and can be implemented on a number of platforms.

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Conflict of interest statement

Ethics approval and consent to participate

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all individual participants included in the study.

Consent for publication

Not applicable.

Competing interests

VJL is a consultant for Bayer Pharma, Piramal Imaging, and receives research support from GE Healthcare, AVID Radiopharmaceuticals, the NIH, the Dekelboum Family Foundation, and the Liston Family Foundation.

DK serves on a Data Safety Monitoring Board for Lundbeck Pharmaceuticals and for the DIAN study; is a clinical investigator for Biogen, TauRX Pharmaceuticals, Lilly Pharmaceuticals and the Alzheimer’s Disease Cooperative Study; and receives research support from the NIH.

CCR has received research grants for imaging in dementia from Bayer-Schering Pharma, Avid Radiopharmaceuticals, GE Healthcare, Piramal, Astra Zeneca, and Navidea. He has been a consultant or paid speaker at sponsored conference sessions for Bayer-Schering Pharma, Piramal, GE Healthcare, Astra Zeneca, Roche, and Janssen.

VLV has been a consultant or paid speaker at sponsored conference sessions for Bayer-Schering Pharma, Piramal, GE Healthcare, Astra Zeneca, and Novartis.

MRB, CJB and LCP are employees of GE Healthcare.

The remaining authors (BK and VD) have nothing to declare.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Process workflow for the standard SPM8 Centiloid methods, together with PMOD and FSL process methods
Fig. 2
Fig. 2
Correlation between SPM8-derived [18F]flutemetamol SUVR and [11C]PiB SUVR (a), PiB-Equivalent [18F]flutemetamol SUVR and PiB SUVR, further highlighting the wide spectrum of cognitive status comprising the ‘Other’ group (b) and [18F]flutemetamol Centiloids vs. [18F]flutemetamol SUVR’s (c). A total of 74 images (young healthy controls: n = 24, Other: n = 50) were processed
Fig. 3
Fig. 3
Correlation of PMOD-derived (a) and FSL-derived (b) [18F]flutemetamol SUVR vs. [11C]PiB
Fig. 4
Fig. 4
The correlation between the [18F]flutemetamol SUVRs and corresponding Centiloids for PMOD-processed (a) and FSL-processed (b) paired [11C]PiB and [18F]flutemetamol images
See this image and copyright information in PMC

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