Strategies for the generation of parametric images of [11C]PIB with plasma input functions considering discriminations and reproducibility

Pittsburgh compound B or [11C]PIB is an amyloid imaging agent which shows a clear differentiation between subjects with Alzheimer's disease (AD) and controls. However the observed signal difference in other forms of dementia such as dementia with Lewy bodies (DLB) is smaller, and mild cognitively impaired (MCI) subjects and some healthy elderly normals may show intermediate levels of [11C]PIB binding. The cerebellum, a commonly used reference region for non-specific tracer uptake in [11C]PIB studies in AD may not be valid in Prion disorders or monogenic forms of AD. The aim of this work was to: 1-compare methods for generating parametric maps of [11C]PIB retention in tissue using a plasma input function in respect of their ability to discriminate between AD subjects and controls and 2-estimate the test-retest reproducibility in AD subjects. 12  AD subjects (5 of which underwent a repeat scan within 6 weeks) and 10 control subjects had 90 minute [11C]PIB dynamic PET scans, and arterial plasma input functions were measured. Parametric maps were generated with graphical analysis of reversible binding (Logan plot), irreversible binding (Patlak plot), and spectral analysis. Between group differentiation was calculated using Student's t-test and comparisons between different methods were made using p values. Reproducibility was assessed by intraclass correlation coefficients (ICC). We found that the 75 min value of the impulse response function showed the best group differentiation and had a higher ICC than volume of distribution maps generated from Logan and spectral analysis. Patlak analysis of [11C]PIB binding was the least reproducible.