Evaluation of Reference Regions for (R)-[11C]PK11195 Studies in Alzheimer's Disease and Mild Cognitive Impairment

Abstract

Inflammation in Alzheimer's disease (AD) may be assessed using ( R)-[¹¹C]PK11195 and positron emission tomography. Data can be analyzed using the simplified reference tissue model, provided a suitable reference region is available. This study evaluates various reference regions for analyzing ( R)-[¹¹C]PK11195 scans in patients with mild cognitive impairment (MCI) and probable AD. Healthy subjects ( n = 10, 30 ± 10 years and n = 10, 70 ± 6 years) and patients with MCI ( n = 10, 74 ± 6 years) and probable AD ( n = 9, 71 ± 6 years) were included. Subjects underwent a dynamic three-dimensional ( R)-[¹¹C]PK11195 scan including arterial sampling. Gray matter, white matter, total cerebellum and cerebrum, and cluster analysis were evaluated as reference regions. Both plasma input binding potentials of these reference regions ( BP^PLASMA) and corresponding reference region input binding potentials of a target region ( BP^SRTM) were evaluated. Simulations were performed to assess cluster analysis performance at 5% to 15% coefficient of variation noise levels. Reasonable correlations for BP^PLASMA ( R² = 0.52 to 0.94) and BP^SRTM ( R² = 0.59 to 0.76) were observed between results using anatomic regions and cluster analysis. For cerebellum white matter, cerebrum white matter, and total cerebrum a considerable number of unrealistic BP^SRTM values were observed. Cluster analysis did not extract a valid reference region in 10% of the scans. Simulations showed that potentially cluster analysis suffers from negative bias in BP^PLASMA. Most anatomic regions outperformed cluster analysis in terms of absence of both scan rejection and bias. Total cerebellum is the optimal reference region in this patient category.