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

[C-11]Flumazenil ([C-11]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 [C-11]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 6 months 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 (BPND) were calculated from five reference tissue models and compared to BPND 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). BPND from all the reference tissue approaches correlated well with BPND 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 [C-11]FMZ PET in head-injured patients at 6 months following injury within both normal appearing and peri-lesional brain regions.