Imaging Studies
1 Brain Imaging
Neuroimaging studies have documented structural, functional, and neuroinflammatory abnormalities in ME/CFS, though findings are heterogeneous across studies and methodologies: Structural MRI: Several studies report reduced white matter volume, cortical thinning, and altered white matter integrity (reduced fractional anisotropy on diffusion tensor imaging) in ME/CFS patients. Barnden et al. (2011) found white matter volume reductions correlating with fatigue severity. However, findings are inconsistent—some studies report no structural differences—possibly reflecting patient heterogeneity and small sample sizes. Functional MRI: The NIH deep phenotyping study (Section The NIH Deep Phenotyping Study (Walitt et al. 2024)) found reduced temporoparietal junction (TPJ) activity during motor tasks and abnormally sustained motor cortex activation despite declining force output (Walitt et al. 2024). Other fMRI studies have reported altered connectivity in the default mode network, salience network, and executive control network—patterns overlapping with those seen in chronic pain and neuroinflammatory conditions. PET imaging: Nakatomi et al. (2014) used 11C-PK11195 PET to demonstrate widespread neuroinflammation (activated microglia) in the cingulate cortex, hippocampus, amygdala, thalamus, midbrain, and pons of ME/CFS patients (Nakatomi et al. 2014). The degree of neuroinflammation correlated with cognitive impairment severity. Subsequent studies using more selective TSPO ligands have confirmed elevated neuroinflammatory markers, though the specificity of TSPO PET for microglial activation (versus astrocyte activation) remains debated. SPECT: Single-photon emission computed tomography studies have consistently shown reduced cerebral blood flow in ME/CFS, particularly in the brainstem, frontal, and temporal regions. Reduced perfusion correlates with cognitive symptoms and orthostatic intolerance. SPECT evidence predates and is consistent with the cerebral hypoperfusion documented by more recent techniques.
2 Cardiac Imaging
Cardiovascular imaging has revealed structural and functional cardiac abnormalities in ME/CFS that are distinct from deconditioning:
- Reduced blood volume: Studies using dual-label red blood cell volume testing have documented significant blood volume reductions in ME/CFS patients (average 10–15% below predicted). This hypovolemia contributes to reduced cardiac preload and orthostatic intolerance
- Cardiac MRI: Ponikowski et al. and subsequent studies found reduced left ventricular mass, reduced end-diastolic volume, and lower stroke volume in ME/CFS patients compared to healthy controls and deconditioned individuals. These reductions are disproportionate to the degree of inactivity, suggesting a disease-specific cardiac effect rather than pure deconditioning
- Invasive hemodynamic testing: Systrom et al. used invasive cardiopulmonary exercise testing with right heart catheterization to demonstrate reduced cardiac filling pressures (preload failure) and impaired peripheral oxygen extraction in ME/CFS, providing direct evidence of both central and peripheral circulatory dysfunction