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

作者：Zhen Fan, Melanie Dani, Grazia Daniela Femminella, Melanie Wood, Valeria Calsolaro, Mattia Veronese, Federico Turkheimer, Steve Gentleman, David J. Brooks, Rainer Hinz, Paul Edison · 发表于：European Journal of Nuclear Medicine and Molecular Imaging · 年份：2018 · DOI：10.1007/s00259-018-3984-5 · 被引用次数：26 · 研究领域：Alzheimer's disease research and treatments、S100 Proteins and Annexins、Neurological Disease Mechanisms and Treatments

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 11 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 11 C–PBR28 PET scans with arterial cannulation. Spectral analysis with an arterial plasma input function was used to generate 11 C–PBR28 parametric maps. These maps were then compared with regional 11 C–PBR28 V T (volume of distribution) using a two-tissue compartment model and Logan graphic analysis. Amyloid load was also assessed with 18 F–Flutemetamol PET. With SA, three component peaks were identified in addition to blood volume. The 11 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 11 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 11 C–PBR28 binding in the thalamus of amyloid-posit...