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Diffusion-weighted MR spectroscopy (DW-MRS) is sensitive to LPS-induced changes in human glial morphometry: A
Riccardo De Marco1, Itamar Ronen2, Francesca Branzoli3
1Department of Neuroscience, Brighton and Sussex Medical School, Brighton, UK.
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.
Insights
Low-dose lipopolysaccharide (LPS) induced systemic inflammation, increasing glial metabolite diffusion in the thalamus. Diffusion-weighted magnetic resonance spectroscopy (DW-MRS) shows potential for imaging glial changes in vivo.
Area of Science:
- Neuroscience
- Medical Imaging
- Inflammation Research
Background:
- Low-dose lipopolysaccharide (LPS) is a standard method for inducing systemic inflammation and microglial activation in animal models.
- Current in-vivo glial imaging in humans, such as TSPO-PET, faces limitations in cost, complexity, and cellular specificity.
- Diffusion-weighted magnetic resonance spectroscopy (DW-MRS) offers a potential non-invasive method to assess cellular morphology by measuring metabolite diffusion.
Purpose of the Study:
- To investigate the utility of DW-MRS in detecting changes in glial and neuronal metabolites following LPS-induced systemic inflammation in healthy human participants.
- To test the hypothesis that DW-MRS can selectively detect alterations in the apparent diffusion coefficients (ADC) of glial metabolites due to LPS administration.
Main Methods:
- Seven healthy male volunteers received either LPS (1 ng/Kg IV) or placebo in a crossover design.
- Physiological responses, blood markers (WBC, cytokines), and mood (POMS) were monitored.
- DW-MRS data were acquired from the thalamus and frontal white matter 5-5.5 hours post-injection.
Main Results:
- LPS administration significantly increased body temperature, heart rate, WBC, and inflammatory cytokines compared to placebo (p < 0.001).
- The apparent diffusion coefficient (ADC) of the glial metabolite choline (tCho) was significantly elevated in the thalamus after LPS administration (p = 0.008).
- Increased tCho ADC in the thalamus correlated with LPS-induced changes in total and negative mood scores (Adj R² = 0.83; p = 0.004).
Conclusions:
- DW-MRS is sensitive to LPS-induced glial cytomorphological changes in the grey matter of the thalamus.
- This preliminary study suggests DW-MRS is a promising tool for in-vivo imaging of glial responses during systemic inflammation.
