Assessing Neuroinflammation in Gulf War Illness with Whole-Brain Magnetic Resonance Spectroscopy

Currently, there are no targeted treatments for Gulf War Illness (GWI). In order to solve that problem, it is essential that researchers discover the cause of GWI. It is similarly important that an objective test be developed that can clearly show why individuals suffer from GWI. While many attempts at developing such a test have been made, none of them have yielded a clinically-useful tool. Our central hypothesis is that GWI involves chronic neuroinflammation. The symptoms of GWI (e.g. fatigue, musculoskeletal pain, sleep disturbances, and cognitive dysfunction) overlap heavily with classic cytokine-induced sickness responses. In the case of GWI, microglial cells in the brain can be pushed into a hypersensitized state by toxins or abnormal immune challenges, leading to chronic overproduction of pro-inflammatory factors that result in the primary symptoms of GWI. To test the central hypothesis, it is necessary to measure neuroinflammation in humans in vivo. However, most techniques are too invasive for using in living individuals. To address that problem, we use an MRSI scan which provides metabolite concentrations in 4,000 separate voxels, giving whole-brain coverage. The scan yields measurements for: myo-inositol (a marker of glial cell proliferation), lactate (a product of anaerobic metabolism), choline (a sign of cellular breakdown), and N-acetylaspartate (a marker of neuronal health). The scan also provides absolute brain temperature, which is elevated with severe neuroinflammation.