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Quantitative imaging of neuroinflammation in human white matter: A positron emission tomography study with translocator protein 18 kDa radioligand, [ 18 F]‐FEPPA
Author(s) -
Suridjan Ivonne,
Rusjan Pablo M.,
Kenk Miran,
Verhoeff Nicolaas Paul L.G.,
Voineskos Aristotle N.,
Rotenberg David,
Wilson Alan A.,
Meyer Jeffrey H.,
Houle Sylvain,
Mizrahi Romina
Publication year - 2014
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/syn.21765
Subject(s) - translocator protein , positron emission tomography , radioligand , white matter , nuclear medicine , fractional anisotropy , diffusion mri , binding potential , corpus callosum , internal capsule , magnetic resonance imaging , nuclear magnetic resonance , psychology , chemistry , neuroscience , medicine , pathology , neuroinflammation , physics , radiology , receptor , disease
ABSTRACT The ability to quantify translocator protein 18 kDa (TSPO) in white matter (WM) is important to understand the role of neuroinflammation in neurological disorders with WM involvement. This article aims to extend the utility of TSPO imaging in WM using a second‐generation radioligand, [ 18 F]‐FEPPA, and high‐resolution research tomograph (HRRT) positron emission tomography (PET) camera system. Four WM regions of interests (WM‐ROI), relevant to the study of aging and neuroinflammatory diseases, were examined. The corpus callosum, cingulum bundle, superior longitudinal fasciculus, and posterior limb of internal capsule were delineated automatically onto subject's T 1 ‐weighted magnetic resonance image using a diffusion tensor imaging‐based WM template. The TSPO polymorphism (rs6971) stratified individuals to three genetic groups: high‐affinity binders (HAB), mixed‐affinity binders (MAB), and low‐affinity binders. [ 18 F]‐FEPPA PET scans were acquired on 32 healthy subjects and analyzed using a full kinetic compartment analysis. The two‐tissue compartment model showed moderate identifiability (coefficient of variation 15–19%) for [ 18 F]‐FEPPA total volume distribution ( V T ) in WM‐ROIs. Noise affects V T variability, although its effect on bias was small (6%). In a worst‐case scenario, ≤6% of simulated data did not fit reliably. A simulation of increased TSPO density exposed minimal effect on variability and identifiability of [ 18 F]‐FEPPA V T in WM‐ROIs. We found no association between age and [ 18 F]‐FEPPA V T in WM‐ROIs. The V T values were 15% higher in HAB than in MAB, although the difference was not statistically significant. This study provides evidence for the utility and limitations of [ 18 F]‐FEPPA PET to measure TSPO expression in WM. Synapse 68:536–547, 2014 . © 2014 Wiley Periodicals, Inc.