Diffusion-weighted MR spectroscopy (DW-MRS) is sensitive to LPS-induced changes in human glial morphometry: A preliminary study.
Depression
Diffusion MRS
Inflammation
LPS
Microglia
Neuroinflammation
Journal
Brain, behavior, and immunity
ISSN: 1090-2139
Titre abrégé: Brain Behav Immun
Pays: Netherlands
ID NLM: 8800478
Informations de publication
Date de publication:
01 2022
01 2022
Historique:
received:
26
05
2021
revised:
17
09
2021
accepted:
11
10
2021
pubmed:
22
10
2021
medline:
15
3
2022
entrez:
21
10
2021
Statut:
ppublish
Résumé
Low-dose lipopolysaccharide (LPS) is a well-established experimental method for inducing systemic inflammation and shown by microscopy to activate microglia in rodents. Currently, techniques for in-vivo imaging of glia in humans are limited to TSPO (Translocator protein) PET, which is expensive, methodologically challenging, and has poor cellular specificity. Diffusion-weighted magnetic resonance spectroscopy (DW-MRS) sensitizes MR spectra to diffusion of intracellular metabolites, potentially providing cell-specific information about cellular morphology. In this preliminary study, we applied DW-MRS to measure changes in the apparent diffusion coefficients (ADC) of glial and neuronal metabolites to healthy participants who underwent an LPS administration protocol. We hypothesized that the ADC of glial metabolites will be selectively modulated by LPS-induced glial activation. Seven healthy male volunteers, (mean 25.3 ± 5.9 years) were each tested in two separate sessions once after LPS (1 ng/Kg intravenously) and once after placebo (saline). Physiological responses were monitored during each session and serial blood samples and Profile of Mood States (POMS) completed to quantify white blood cell (WBC), cytokine and mood responses. DW-MRS data were acquired 5-5½ hours after injection from two brain regions: grey matter in the left thalamus, and frontal white matter. Body temperature, heart rate, WBC and inflammatory cytokines were significantly higher in the LPS compared to the placebo condition (p < 0.001). The ADC of the glial metabolite choline (tCho) was also significantly increased after LPS administration compared to placebo (p = 0.008) in the thalamus which scaled with LPS-induced changes in POMS total and negative mood (Adj R DW-MRS may be a powerful new tool sensitive to glial cytomorphological changes in grey matter induced by systemic inflammation.
Sections du résumé
BACKGROUND
Low-dose lipopolysaccharide (LPS) is a well-established experimental method for inducing systemic inflammation and shown by microscopy to activate microglia in rodents. Currently, techniques for in-vivo imaging of glia in humans are limited to TSPO (Translocator protein) PET, which is expensive, methodologically challenging, and has poor cellular specificity. Diffusion-weighted magnetic resonance spectroscopy (DW-MRS) sensitizes MR spectra to diffusion of intracellular metabolites, potentially providing cell-specific information about cellular morphology. In this preliminary study, we applied DW-MRS to measure changes in the apparent diffusion coefficients (ADC) of glial and neuronal metabolites to healthy participants who underwent an LPS administration protocol. We hypothesized that the ADC of glial metabolites will be selectively modulated by LPS-induced glial activation.
METHODS
Seven healthy male volunteers, (mean 25.3 ± 5.9 years) were each tested in two separate sessions once after LPS (1 ng/Kg intravenously) and once after placebo (saline). Physiological responses were monitored during each session and serial blood samples and Profile of Mood States (POMS) completed to quantify white blood cell (WBC), cytokine and mood responses. DW-MRS data were acquired 5-5½ hours after injection from two brain regions: grey matter in the left thalamus, and frontal white matter.
RESULTS
Body temperature, heart rate, WBC and inflammatory cytokines were significantly higher in the LPS compared to the placebo condition (p < 0.001). The ADC of the glial metabolite choline (tCho) was also significantly increased after LPS administration compared to placebo (p = 0.008) in the thalamus which scaled with LPS-induced changes in POMS total and negative mood (Adj R
CONCLUSIONS
DW-MRS may be a powerful new tool sensitive to glial cytomorphological changes in grey matter induced by systemic inflammation.
Identifiants
pubmed: 34673176
pii: S0889-1591(21)00581-X
doi: 10.1016/j.bbi.2021.10.005
pii:
doi:
Substances chimiques
Lipopolysaccharides
0
Receptors, GABA
0
TSPO protein, human
0
Choline
N91BDP6H0X
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
256-265Informations de copyright
Copyright © 2021. Published by Elsevier Inc.