DOI: 10.1007/s00259-018-3984-5Pages: 1432-1441

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

1. Imperial College London, Department of Medicine, Neurology Imaging Unit

2. Kings College London, Department of Neuroimaging, Institute of Psychiatry

3. Aarhus University, Department of Nuclear Medicine

4. University of Manchester, Wolfson Molecular Imaging Centre

Correspondence to:
Paul Edison
Tel: +44(0)20 3313 3725
Email: paul.edison@imperial.ac.uk

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Abstract

Purpose

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 11C–PBR28 PET, and compared these with compartmental and other kinetic models of quantification.

Methods

Thirteen 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.

Results

With 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.

Conclusions

This 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.

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  • Accepted: Feb 19, 2018
  • Online: Mar 9, 2018

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