Diffusion-weighted MR Spectroscopy (DW-MRS) is sensitive to LPS-induced changes in human glial morphometry: a preliminary study

De Marco, Riccardo, Ronen, Itamar, Branzoli, Francesca, Amato, Marisa L, Asllani, Iris, Colasanti, Alessandro, Harrison, Neil A and Cercignani, Mara (2022) Diffusion-weighted MR Spectroscopy (DW-MRS) is sensitive to LPS-induced changes in human glial morphometry: a preliminary study. Brain, Behavior, and Immunity, 99. pp. 256-265. ISSN 0889-1591

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Abstract

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 R2 = 0.83; p = 0.004).

Conclusions
DW-MRS may be a powerful new tool sensitive to glial cytomorphological changes in grey matter induced by systemic inflammation.

Item Type: Article
Keywords: Depression, Inflammation, LPS, Microglia, Neuroinflammation, diffusion MRS
Schools and Departments: Brighton and Sussex Medical School > Brighton and Sussex Medical School
SWORD Depositor: Mx Elements Account
Depositing User: Mx Elements Account
Date Deposited: 04 Nov 2021 08:07
Last Modified: 04 Nov 2021 08:15
URI: http://sro.sussex.ac.uk/id/eprint/102675

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