Dr. Zack Shan is director of the neuroimaging program at the University of the Sunshine Coast (Australia), where he specializes in developing new ways to visualize how ME/CFS affects brain tissues. His research team just published an article in Scientific Reports about using a method called “diffusion tensor imaging” (or “diffusion MRI”) to see how ME/CFS affects brain white matter. White matter connects different regions of the brain and helps coordinate brain signals and activities.
The research team used diffusion MRI to compare white matter in people whose ME/CFS developed soon after infectious triggers (the “post-infectious group”); people whose ME/CFS developed slowly with no clear infectious triggers (“gradual onset group”); and sedentary but otherwise healthy people.
The team found people in these groups differed in white matter “axial diffusivity,” which measures how freely water flows along brain fibers, reflecting neuronal health. Axial diffusivity in the post-infectious group was significantly higher than in healthy people for white matter regions that participate in cognition, that control movement, and that process emotions.
In these cases, people with higher axial diffusivity had worse physical health. On the other hand, axial diffusivity in the gradual onset group was significantly lower than in healthy people for regions that coordinate information from distinct parts of the brain. Here, the people with lower axial diffusivity had worse mental health. In other diseases, higher and lower axial diffusivity can reflect serious neuronal damage. For example, higher axial diffusivity is associated with neuroinflammation in patients with COVID-19, traumatic brain injury, or multiple concussions. And lower axial diffusivity is associated with nerve degeneration in patients with bipolar disorder, major depressive disorder, obsessive-compulsive disorder, or schizophrenia.
These results are important because they suggest that distinct changes in brain white matter are associated with distinct subgroups of ME/CFS (post-infectious, or gradual onset with no infectious trigger) and drive distinct symptoms (physical or mental). Changes in white matter usually affect physical health in people with post-infectious ME/CFS; but usually affect mental health in people with gradual onset ME/CFS with no infectious trigger.
Considering similar white matter changes in patients with other diseases, the researchers suspect that the immune response drives physical symptoms in people with post-infectious ME/CFS, while long-term problems with brain tissue (for example, chronic oxidative stress or mitochondrial dysfunction) drive cognitive symptoms in people with gradual onset ME/CFS. This suggests that different treatments may be appropriate for the two subgroups of patients.
On the one hand, treatments targeting the immune system and reducing neuroinflammation may improve physical functioning in those patients with post-infectious ME/CFS with higher white matter axial diffusivity. On the other hand, cognitive rehabilitation and treatments protecting brain tissue may improve mental functioning in patients with gradual onset ME/CFS with lower white matter axial diffusivity.
These results also suggest we may use diffusion MRI to measure imaging biomarkers associated with the two patient subgroups. Diffusion MRI is not invasive, and doctors already use it to monitor white matter in patients with various neurological conditions.
Moving forward with developing diffusion MRI to study ME/CFS subgroups and symptoms, the research team stressed the need for more standardized protocols to collect and analyze images. Also, future studies should include more patients to determine whether changes in white matter correlate with symptom severity; and should also collect biological samples from patients to understand whether imaging biomarkers correlate with specific molecular biomarkers.
Why This Study Matters to the Patient Community:
- Lays the Groundwork for Targeted Treatments: Describes instances where treatments addressing physical symptoms of ME/CFS might be appropriate; and instances where treatments addressing cognitive symptoms might be appropriate.
- Advances Diagnostic Tools: Shows how a noninvasive imaging technique (diffusion MRI) and an imaging biomarker (white matter axial diffusivity) can help understand ME/CFS disease pathology and classify patients into useful subgroups.
- Validates key symptoms of ME/CFS: Correlates physical and cognitive symptoms of ME/CFS with distinct changes in brain tissues.
- Centers Patient Experience: Shows how patients’ histories of infection can influence ME/CFS symptoms.