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

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

doi:10.1186/s13550-018-0456-7

Abstract

IntroductionA 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.MethodsPaired 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.ResultsThe 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.

Highlights

A standardised method for quantifying β-amyloid PET tracers would allow comparison across different tracers and different sites
‘Gold-Standard’ amyloid PET tracer for research studies, its use is limited by the short half-life (20 min) of 11C, requiring an on-site cyclotron when imaging with this tracer
The Centiloid process Klunk et al provide details of the standard SPM8-based processing system (Statistical Parametric Mapping, version 8, Wellcome Trust Centre for Neuroimaging, http://www.fil.ion.ucl.ac.uk) and downloadable volumes of interest, Pittsburgh compound B (PiB) and T1 3D MRI image data sets and standard uptake values ratios (SUVR) results that should be obtained with this data if the method is executed correctly [10]

Summary

Introduction

A standardised method for quantifying β-amyloid PET tracers would allow comparison across different tracers and different sites. The use of imaging biomarkers to visualise and measure the β-amyloid plaque load in individuals was introduced by Klunk et al, where a 11C-labelled Thioflavin-T-based molecule was developed to visualise amyloid plaque ‘Gold-Standard’ amyloid PET tracer for research studies, its use is limited by the short half-life (20 min) of 11C, requiring an on-site cyclotron when imaging with this tracer. This prompted the generation and clinical approval of 18F-labelled tracers (110 min half-life), allowing greater distribution and utilisation in PET centres [5]. Another tracer, [18F]NAV4694, has been studied in a limited setting

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