Probing the Pathophysiology of ME/CFS through Neuroimaging

The discovery of ME/CFS-specific biomarkers that can advance our understanding of the illness and its pathogenic mechanisms, differentiate the disorder from overlapping or comorbid diagnoses, and identify potential treatment targets is currently a pressing and unmet research and public health need.

We are working to fill this knowledge gap by using advanced neuroimaging techniques to test and then validate a pathophysiological model of ME/CFS which posits that oxidative stress and neuroinflammation are intertwined mechanisms in the etiopathogenesis of the disorder.

We have used proton magnetic resonance spectroscopy (1H MRS) to measure in vivo brain levels of glutathione (GSH)—the most abundant antioxidant in the central nervous system—as a marker of oxidative stress. The same method was used to measure in vivo brain levels of lactate and N-acetylaspartate (NAA) as markers of mitochondrial dysfunction.

To measure in vivo brain levels of ATP, creatine phosphate (PCr), and inorganic phosphate (Pi) as complementary indices of mitochondrial dysfunction, ³¹P MRS was used. In vivo brain ¹¹C-(R)-PK11195 positron emission tomography (PET) was used to measure the binding potential of the ligand as a marker of neuroinflammation. We examined the levels of circulating markers of neuroinflammation and oxidative stress to corroborate the proposed neuroimaging biomarkers.

Our analyses were performed before and following symptom provocation with cardiopulmonary exercise tests (CPET), known to trigger post-exertional malaise (PEM) in ME/CFS patients. This research has the potential to shed new light on the neurobiological mechanisms and underpinnings of ME/CFS; advance our understanding of the illness; and establish ME/CFS-specific biomarkers for differentiating the disorder from overlapping or comorbid diagnoses and identifying potential treatment targets.

Research Team

This NIH-funded project (U54NS105541) was led by Dr. Dikoma Shungu, an accomplished magnetic resonance spectroscopist, physicist, and computer programmer. In addition to prior work on ME/CFS, he has used neuroimaging methods to study fibromyalgia, Gulf War Illness, schizophrenia, major depression, anxiety and obsessive-compulsive disorders, Parkinson’s disease, ALS, primary mitochondrial disorders, and brain tumors.

Dr. Shungu was assisted by Xiangling Mao, a long-term associate and computer programmer skilled in the analysis of spectroscopy data.

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