Advanced Non-Invasive Analysis in ME/CFS Diagnosis and Treatment Decisions

A project summary as written by Jarred Younger:

In this project, we will test a magnetic resonance spectroscopic thermometry (MRSt) technique to assess absolute temperature across the entire brain. We will use the technique to investigate the pathophysiology of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), a condition of unknown etiology that is characterized by profound fatigue that is not alleviated by rest. The lack of information on ME/CFS pathophysiology has posed a substantial obstacle to the development of treatments that are specific and effective for the disorder. We hypothesize that ME/CFS is the result of low-level inflammation in the brain. Chronic activation of microglia and astrocytes provokes the release of proinflammatory agents that interact with neurons to cause symptoms of fatigue, pain sensitivity, and cognitive and mood disruption. MRSt may be able to detect that neuroinflammation by detecting the increased metabolic demand created by activated immune cells that overwhelm the cooling effect of the circulating blood. In such a case, neuroinflammation may be observed as a divergence between brain and core body temperatures. In this preliminary study, we will examine 20 women with ME/CFS and 20 age-matched healthy controls. Temperature will be assessed on a voxel-by-voxel basis throughout the entire brain, yielding approximately 500 assessments of brain temperature. We are testing 5 hypotheses. 1) The average whole-brain temperature of the ME/CFS group will be significantly higher than the control group. 2) The brain-body temperature dissociation (brain temperature minus core temperature) will be significantly greater in the ME/CFS group than in the control group. 3) Across the entire brain, ME/CFS individuals will show greater temperature variance from voxel to voxel than do controls, indicating areas of abnormal temperature elevation. 4) On whole-brain temperature maps, ME/CFS individuals will show discrete areas of temperature elevation in areas associated with fatigue and malaise (e.g., amygdala and rostral anterior cingulate cortex). 5) In the ME/CFS group, severity of fatigue will be correlated with higher whole-brain temperature. If the hypotheses are confirmed, we will have an objective test of ME/CFS pathology that will indicate the presence of neuroinflammation. This test would be the first completely non-invasive tool for detecting neuroinflammation, and will allow for safe and inexpensive longitudinal testing that cannot be accomplished with positron emission tomography (PET) approaches. Because we collect the entire available spectrum in each voxel, we will also have the first whole-brain metabolic data in ME/CFS. The MRS data can be used to quantify several putative markers of neuroinflammation, including myo-inositol, glutathione, lactate, and choline. We will therefore make the entire dataset available to other researchers for secondary analyses. Ultimately, we hope this non-invasive scanning technique will aid in ME/CFS diagnosis, treatment decisions, and the development of new treatments.