TY - JOUR
T1 - Distribution of cholinergic nerve terminals in the aged human brain measured with [18F]FEOBV PET and its correlation with histological data
AU - Okkels, Niels
AU - Horsager, Jacob
AU - Labrador-Espinosa, Miguel A.
AU - Hansen, Frederik O.
AU - Andersen, Katrine B.
AU - Just, Mie Kristine
AU - Fedorova, Tatyana D.
AU - Skjærbæk, Casper
AU - Munk, Ole L.
AU - Hansen, Kim V.
AU - Gottrup, Hanne
AU - Hansen, Allan K.
AU - Grothe, Michel J.
AU - Borghammer, Per
N1 - Copyright © 2023. Published by Elsevier Inc.
PY - 2023/4
Y1 - 2023/4
N2 - INTRODUCTION: [18F]fluoroetoxybenzovesamicol ([18F]FEOBV) is a positron emission topography (PET) tracer for the vesicular acetylcholine transporter (VAChT), a protein located predominantly in synaptic vesicles in cholinergic nerve terminals. We aimed to use [18F]FEOBV PET to study the cholinergic topography of the healthy human brain.MATERIALS AND METHODS: [18F]FEOBV PET brain data volumes of healthy elderly humans were normalized to standard space and intensity-normalized to the white matter. Stereotactic atlases of regions of interest were superimposed to describe and quantify tracer distribution. The spatial distribution of [18F]FEOBV PET uptake was compared with histological and gene expression data.RESULTS: Twenty participants of both sexes and a mean age of 73.9 ± 6.0 years, age-range [64; 86], were recruited. Highest tracer binding was present in the striatum, some thalamic nuclei, and the basal forebrain. Intermediate binding was found in most nuclei of the brainstem, thalamus, and hypothalamus; the vermis and flocculonodular lobe; and the hippocampus, amygdala, insula, cingulate, olfactory cortex, and Heschl's gyrus. Lowest binding was present in most areas of the cerebral cortex, and in the cerebellar nuclei and hemispheres. The spatial distribution of tracer correlated with immunohistochemical post-mortem data, as well as with regional expression levels of SLC18A3, the VAChT coding gene.DISCUSSION: Our in vivo findings confirm the regional cholinergic distribution in specific brain structures as described post-mortem. A positive spatial correlation between tracer distribution and regional gene expression levels further corroborates [18F]FEOBV PET as a validated tool for in vivo cholinergic imaging. The study represents an advancement in the continued efforts to delineate the spatial topography of the human cholinergic system in vivo.
AB - INTRODUCTION: [18F]fluoroetoxybenzovesamicol ([18F]FEOBV) is a positron emission topography (PET) tracer for the vesicular acetylcholine transporter (VAChT), a protein located predominantly in synaptic vesicles in cholinergic nerve terminals. We aimed to use [18F]FEOBV PET to study the cholinergic topography of the healthy human brain.MATERIALS AND METHODS: [18F]FEOBV PET brain data volumes of healthy elderly humans were normalized to standard space and intensity-normalized to the white matter. Stereotactic atlases of regions of interest were superimposed to describe and quantify tracer distribution. The spatial distribution of [18F]FEOBV PET uptake was compared with histological and gene expression data.RESULTS: Twenty participants of both sexes and a mean age of 73.9 ± 6.0 years, age-range [64; 86], were recruited. Highest tracer binding was present in the striatum, some thalamic nuclei, and the basal forebrain. Intermediate binding was found in most nuclei of the brainstem, thalamus, and hypothalamus; the vermis and flocculonodular lobe; and the hippocampus, amygdala, insula, cingulate, olfactory cortex, and Heschl's gyrus. Lowest binding was present in most areas of the cerebral cortex, and in the cerebellar nuclei and hemispheres. The spatial distribution of tracer correlated with immunohistochemical post-mortem data, as well as with regional expression levels of SLC18A3, the VAChT coding gene.DISCUSSION: Our in vivo findings confirm the regional cholinergic distribution in specific brain structures as described post-mortem. A positive spatial correlation between tracer distribution and regional gene expression levels further corroborates [18F]FEOBV PET as a validated tool for in vivo cholinergic imaging. The study represents an advancement in the continued efforts to delineate the spatial topography of the human cholinergic system in vivo.
KW - Brain
KW - Cholinergic Neurons
KW - Healthy Volunteer
KW - PET-CT
KW - VAChT Proteins
KW - mRNA
UR - http://www.scopus.com/inward/record.url?scp=85149178525&partnerID=8YFLogxK
U2 - 10.1016/j.neuroimage.2023.119908
DO - 10.1016/j.neuroimage.2023.119908
M3 - Journal article
C2 - 36720436
SN - 1053-8119
VL - 269
JO - NeuroImage
JF - NeuroImage
M1 - 119908
ER -