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Validation of a combined image derived input function and venous sampling approach for the quantification of [18F]GE-179 PET binding in the brain.

Accepted version
Peer-reviewed

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Authors

Galovic, Marian 
Erlandsson, Kjell 
Fryer, Tim D 
Hong, Young T 

Abstract

Blood-based kinetic analysis of PET data relies on an accurate estimate of the arterial plasma input function (PIF). An alternative to invasive measurements from arterial sampling is an image-derived input function (IDIF). However, an IDIF provides the whole blood radioactivity concentration, rather than the required free tracer radioactivity concentration in plasma. To estimate the tracer PIF, we corrected an IDIF from the carotid artery with estimates of plasma parent fraction (PF) and plasma-to-whole blood (PWB) ratio obtained from five venous samples. We compared the combined IDIF+venous approach to gold standard data from arterial sampling in 10 healthy volunteers undergoing [18F]GE-179 brain PET imaging of the NMDA receptor. Arterial and venous PF and PWB ratio estimates determined from 7 patients with traumatic brain injury (TBI) were also compared to assess the potential effect of medication. There was high agreement between areas under the curves of the estimates of PF (r = 0.99, p<0.001), PWB ratio (r = 0.93, p<0.001), and the PIF (r = 0.92, p<0.001) as well as total distribution volume (VT) in 11 regions across the brain (r = 0.95, p<0.001). IDIF+venous VT had a mean bias of -1.7% and a comparable regional coefficient of variation (arterial: 21.3 ± 2.5%, IDIF+venous: 21.5 ± 2.0%). Simplification of the IDIF+venous method to use only one venous sample provided less accurate VT estimates (mean bias 9.9%; r = 0.71, p<0.001). A version of the method that avoids the need for blood sampling by combining the IDIF with population-based PF and PWB ratio estimates systematically underestimated VT (mean bias -20.9%), and produced VT estimates with a poor correlation to those obtained using arterial data (r = 0.45, p<0.001). Arterial and venous blood data from 7 TBI patients showed high correlations for PF (r = 0.92, p = 0.003) and PWB ratio (r = 0.93, p = 0.003). In conclusion, the IDIF+venous method with five venous samples provides a viable alternative to arterial sampling for quantification of [18F]GE-179 VT.

Description

Keywords

Input function, NMDA receptor, Positron emission tomography, Adult, Brain Injuries, Traumatic, Female, Humans, Male, Middle Aged, Neuroimaging, Positron-Emission Tomography, Radiopharmaceuticals, Receptors, N-Methyl-D-Aspartate, Reproducibility of Results, Veins

Journal Title

Neuroimage

Conference Name

Journal ISSN

1053-8119
1095-9572

Volume Title

237

Publisher

Elsevier BV

Rights

All rights reserved
Sponsorship
Medical Research Council (MR/K02308X/1)
Medical Research Council (MR/L013215/1)
British Journal of Anaesthesia (BJA / RCoA grants NIAA 2015 R)
Cambridge University Hospitals NHS Foundation Trust (CUH) (unknown)
Medical Research Council (MR/M009041/1)
National Institute of Academic Anaesthesia/British Journal of Anaesthesia