Abstract
PurposeNeuroinflammation 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 11C–PBR28 PET, and compared these with compartmental and other kinetic models of quantification.MethodsThirteen MCI and nine healthy controls were enrolled in this study. Subjects underwent 11C–PBR28 PET scans with arterial cannulation. Spectral analysis with an arterial plasma input function was used to generate 11C–PBR28 parametric maps. These maps were then compared with regional 11C–PBR28 VT (volume of distribution) using a two-tissue compartment model and Logan graphic analysis. Amyloid load was also assessed with 18F–Flutemetamol PET.ResultsWith SA, three component peaks were identified in addition to blood volume. The 11C–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 11C–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 11C–PBR28 binding in the thalamus of amyloid-positive MCI subjects, while Logan parametric maps did not perform well.ConclusionsThis study demonstrates for the first time that spectral analysis can be used to generate parametric maps of 11C–PBR28 uptake, and is able to detect microglial activation in amyloid-positive MCI subjects. IRF parametric maps of 11C–PBR28 uptake allow voxel-wise single-subject analysis and could be used to evaluate microglial activation in individual subjects.
Highlights
Electronic supplementary material The online version of this article contains supplementary material, which is available to authorized users.Amnestic mild cognitive impairment (MCI) is a transitional stage between preclinical Alzheimer’s disease and dementia
The MCI cohort demonstrated significantly lower neuropsychometric test scores compared to the age-matched healthy controls
We have demonstrated that spectral analysis can be used reliably to quantify 11C–PBR28 PET. 11C–PBR28 PET tracer has 80-fold higher affinity for translocator protein (TSPO) compared to previous tracers developed to evaluate microglial activation; different methodological approaches used in different studies have produced varying results [5, 14, 15, 33, 34]
Summary
Amnestic mild cognitive impairment (MCI) is a transitional stage between preclinical Alzheimer’s disease and dementia. Microglial activation plays a significant role in Alzheimer’s disease, along with amyloid and tau deposition [1,2,3]. Recent PET imaging studies have suggested that microglial activation correlates closely with the severity of dementia [1, 4, 5]. TSPO expression in normal brain is very low, but it increases significantly after trauma and inflammation [6,7,8]. The PET tracer 11C–RPK11195 PET has been used for over 20 years to assess the level of TSPO expression and microglial activation [9,10,11]
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