Diffusion-weighted MR spectroscopy (DW-MRS) is sensitive to LPS-induced changes in human glial morphometry: A...

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.