Distribution of cholinergic nerve terminals in the aged human brain measured with [18F]FEOBV PET and its correlation with histological data
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 t...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-04-01
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| Series: | NeuroImage |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1053811923000563 |
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| author | Niels Okkels Jacob Horsager Miguel A. Labrador-Espinosa Frederik O. Hansen Katrine B. Andersen Mie Kristine Just Tatyana D. Fedorova Casper Skjærbæk Ole L. Munk Kim V. Hansen Hanne Gottrup Allan K. Hansen Michel J. Grothe Per Borghammer |
| author_facet | Niels Okkels Jacob Horsager Miguel A. Labrador-Espinosa Frederik O. Hansen Katrine B. Andersen Mie Kristine Just Tatyana D. Fedorova Casper Skjærbæk Ole L. Munk Kim V. Hansen Hanne Gottrup Allan K. Hansen Michel J. Grothe Per Borghammer |
| author_sort | Niels Okkels |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-10T17:26:21Z |
| format | Article |
| id | doaj.art-caac9405089a4f35a1aa5b913d872eba |
| institution | Directory Open Access Journal |
| issn | 1095-9572 |
| language | English |
| last_indexed | 2024-04-10T17:26:21Z |
| publishDate | 2023-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | NeuroImage |
| spelling | doaj.art-caac9405089a4f35a1aa5b913d872eba2023-02-04T04:17:29ZengElsevierNeuroImage1095-95722023-04-01269119908Distribution of cholinergic nerve terminals in the aged human brain measured with [18F]FEOBV PET and its correlation with histological dataNiels Okkels0Jacob Horsager1Miguel A. Labrador-Espinosa2Frederik O. Hansen3Katrine B. Andersen4Mie Kristine Just5Tatyana D. Fedorova6Casper Skjærbæk7Ole L. Munk8Kim V. Hansen9Hanne Gottrup10Allan K. Hansen11Michel J. Grothe12Per Borghammer13Department of Nuclear Medicine and PET, Aarhus University Hospital, Aarhus, Denmark; Department of Clinical Medicine, Aarhus University, Aarhus, Denmark; Department of Neurology, Aarhus University Hospital, Aarhus, Denmark; Corresponding author at: Department of Nuclear Medicine and PET, Aarhus University Hospital, Palle Juul-Jensens Boulevard 165, J220, Aarhus N 8200, DenmarkDepartment of Nuclear Medicine and PET, Aarhus University Hospital, Aarhus, DenmarkUnidad de Trastornos del Movimiento, Servicio de Neurología y Neurofisiología Clínica, Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Seville, Spain; Centro de Investigación Biomédica en Red Sobre Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III, Madrid, SpainDepartment of Nuclear Medicine and PET, Aarhus University Hospital, Aarhus, Denmark; Department of Clinical Medicine, Aarhus University, Aarhus, DenmarkDepartment of Nuclear Medicine and PET, Aarhus University Hospital, Aarhus, Denmark; Department of Clinical Medicine, Aarhus University, Aarhus, DenmarkDepartment of Nuclear Medicine and PET, Aarhus University Hospital, Aarhus, Denmark; Department of Clinical Medicine, Aarhus University, Aarhus, DenmarkDepartment of Nuclear Medicine and PET, Aarhus University Hospital, Aarhus, Denmark; Department of Clinical Medicine, Aarhus University, Aarhus, DenmarkDepartment of Nuclear Medicine and PET, Aarhus University Hospital, Aarhus, Denmark; Department of Clinical Medicine, Aarhus University, Aarhus, DenmarkDepartment of Nuclear Medicine and PET, Aarhus University Hospital, Aarhus, Denmark; Department of Clinical Medicine, Aarhus University, Aarhus, DenmarkDepartment of Nuclear Medicine and PET, Aarhus University Hospital, Aarhus, DenmarkDepartment of Neurology, Aarhus University Hospital, Aarhus, DenmarkDepartment of Nuclear Medicine and PET, Aarhus University Hospital, Aarhus, Denmark; Department of Nuclear Medicine, Aalborg University Hospital, Aalborg, DenmarkUnidad de Trastornos del Movimiento, Servicio de Neurología y Neurofisiología Clínica, Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Seville, Spain; Centro de Investigación Biomédica en Red Sobre Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III, Madrid, SpainDepartment of Nuclear Medicine and PET, Aarhus University Hospital, Aarhus, DenmarkIntroduction: [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.http://www.sciencedirect.com/science/article/pii/S1053811923000563BrainCholinergic NeuronsVAChT ProteinsPET-CTmRNAHealthy Volunteer |
| spellingShingle | Niels Okkels Jacob Horsager Miguel A. Labrador-Espinosa Frederik O. Hansen Katrine B. Andersen Mie Kristine Just Tatyana D. Fedorova Casper Skjærbæk Ole L. Munk Kim V. Hansen Hanne Gottrup Allan K. Hansen Michel J. Grothe Per Borghammer Distribution of cholinergic nerve terminals in the aged human brain measured with [18F]FEOBV PET and its correlation with histological data NeuroImage Brain Cholinergic Neurons VAChT Proteins PET-CT mRNA Healthy Volunteer |
| title | Distribution of cholinergic nerve terminals in the aged human brain measured with [18F]FEOBV PET and its correlation with histological data |
| title_full | Distribution of cholinergic nerve terminals in the aged human brain measured with [18F]FEOBV PET and its correlation with histological data |
| title_fullStr | Distribution of cholinergic nerve terminals in the aged human brain measured with [18F]FEOBV PET and its correlation with histological data |
| title_full_unstemmed | Distribution of cholinergic nerve terminals in the aged human brain measured with [18F]FEOBV PET and its correlation with histological data |
| title_short | Distribution of cholinergic nerve terminals in the aged human brain measured with [18F]FEOBV PET and its correlation with histological data |
| title_sort | distribution of cholinergic nerve terminals in the aged human brain measured with 18f feobv pet and its correlation with histological data |
| topic | Brain Cholinergic Neurons VAChT Proteins PET-CT mRNA Healthy Volunteer |
| url | http://www.sciencedirect.com/science/article/pii/S1053811923000563 |
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