Parametric mapping using spectral analysis for 11 C-PBR28 PET reveals neuroinflammation in mild cognitive impairment subjects

Neuroinflammation and microglial activation play an important role in amnestic mild cognitive impairment (MCI) and Alzheimer's disease. In this study, we investigated the spatial distribution of neuroinflammation in MCI subjects, using spectral analysis (SA) to generate parametric maps and quantify C-PBR28 PET, and compared these with compartmental and other kinetic models of quantification. Thirteen MCI and nine healthy controls were enrolled in this study. Subjects underwent C-PBR28 PET scans with arterial cannulation. Spectral analysis with an arterial plasma input function was used to generate C-PBR28 parametric maps. These maps were then compared with regional C-PBR28 V (volume of distribution) using a two-tissue compartment model and Logan graphic analysis. Amyloid load was also assessed with F-Flutemetamol PET. With SA, three component peaks were identified in addition to blood volume. The C-PBR28 impulse response function (IRF) at 90 min produced the lowest coefficient of variation. Single-subject analysis using this IRF demonstrated microglial activation in five out of seven amyloid-positive MCI subjects. IRF parametric maps of C-PBR28 uptake revealed a group-wise significant increase in neuroinflammation in amyloid-positive MCI subjects versus HC in multiple cortical association areas, and particularly in the temporal lobe. Interestingly, compartmental analysis detected group-wise increase in C-PBR28 binding in the thalamus of amyloid-positive MCI subjects, while Logan parametric maps did not perform well. This study demonstrates for the first time that spectral analysis can be used to generate parametric maps of C-PBR28 uptake, and is able to detect microglial activation in amyloid-positive MCI subjects. IRF parametric maps of C-PBR28 uptake allow voxel-wise single-subject analysis and could be used to evaluate microglial activation in individual subjects.