Mapping Neuroinflammation With Diffusion-Weighted Magnetic Resonance Imaging: A Randomized Crossover Study

Abstract

Background

The pathophysiology of neuroinflammation in psychiatric conditions remains poorly understood, highlighting the need for noninvasive tools that can measure neuroinflammation in vivo. We explored advanced diffusion-weighted magnetic resonance imaging (MRI) techniques for detection of low-level neuroinflammation induced by typhoid vaccine, with potential applications to psychiatric disorders.

Methods

Twenty healthy volunteers (10 males; median age 34, range 18–44 years) participated in a randomized, placebo-controlled, crossover design study. Participants underwent MRI before and after receiving placebo or vaccine in alternating sessions, separated by a washout period. Diffusion tensor (multishell and single shell), diffusion kurtosis, and neurite orientation dispersion and density imaging parameter maps were generated. Probabilistic tractography investigated differences in tract volume, fractional anisotropy, and mean diffusivity (MD) of the tracts. Thirteen tracts and 15 regions were analyzed using a region-of-interest (ROI) approach entered into linear mixed models to evaluate treatment effects.

Results

A treatment effect was observed on white matter tracts derived from XTRACT, with a global reduction in MD (p = .040). White matter tracts of interest showed increased axial kurtosis (p < .001) while gray matter ROIs demonstrated increased mean and radial kurtosis (both ps = .038). Additionally, several correlations were found between the inflammatory marker interleukin 6 and diffusion parameters.

Conclusions

Our findings demonstrate that diffusion-weighted MRI may be sensitive to inflammation-induced microstructural changes in the brain. Future studies should integrate complementary techniques and clinical assessments to deepen our understanding of inflammatory pathophysiology and its implications for health outcomes in clinical populations.