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

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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