Validation of reference tissue modelling for [11C]flumazenil positron emission tomography following head injury

Abstract

[(11)C]Flumazenil ([(11)C]FMZ) positron emission tomography (PET) can be used as a measure of neuronal loss. The purpose of this study was to validate reference tissue kinetic modelling of [(11)C]FMZ PET within a group of patients with head injury. Following earlier studies, the pons was used as the reference region. PET scans were performed on 16 controls and 11 patients at least 6months following injury, each of whom also had arterial blood sampling to provide whole blood and metabolite-corrected plasma input functions. Regional non-displaceable binding potentials (BP(ND)) were calculated from five reference tissue models and compared to BP(ND) from arterial input models. For the patients, the regions included a peri-lesional region of interest (ROI). Total distribution volume of the pons was not significantly different between control and patient groups (P=0.24). BP(ND) from all the reference tissue approaches correlated well with BP(ND) from the plasma input models for both controls (r (2)=0.98-1.00; P<0.001) and patients (r (2)=0.99-1.00; P<0.001). For the peri-lesional regions (n=11 ROI values), the correlation was also high (r (2)=0.91). These results indicate that reference tissue modelling with the pons as the reference region is valid for [(11)C]FMZ PET in head-injured patients at 6months following injury within both normal appearing and peri-lesional brain regions.