ABSTRACT
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating disorder with suspected neuroinflammatory
pathophysiology. However, previous diffusion tensor imaging (DTI) studies have reported inconsistent white matter abnormali
ties in ME/CFS, and specific white matter inflammatory changes remain poorly characterised. This study employed an advanced
diffusion- based neuroinflammation imaging (NII) model to investigate white matter neuroinflammation in ME/CFS. Diffusion
MRI data from 67 ME/CFS patients (median age, 38; and 54 women) and 67 rigorously matched healthy controls (HCs) (median
age 38; and 52 women) were analysed. Seven NII- derived metrics were computed: hindered water ratio (NII- HR), restricted frac
tion (NII- RF), fibre fraction (NII- FF), axial diffusivity (NII- AD), radial diffusivity (NII- RD), mean diffusivity (NII- MD) and frac
tional anisotropy (NII- FA). Conventional DTI metrics were also calculated. Tract- based spatial statistics were used to perform
voxel- wise group comparisons, and multiple regression analysis was conducted to examine the relationship between NII/DTI
metrics and clinical measures of mental health, physical health, sleep quality, disability, disease severity and disease duration.
Compared to HCs, ME/CFS patients exhibited widespread white matter abnormalities, including significantly lower NII- HR and
NII- RF, and significantly higher NII- FF, NII- AD, NII- MD and NII- FA across association, commissural and projection fibres.
Additionally, some regions showed decreased NII- AD and NII- MD in ME/CFS. Lower NII- RF, NII- AD and NII- MD in ME/CFS
were significantly associated with worse mental health, while lower NII- RF was also associated with a higher level of disability.
Among ME/CFS patients, higher NII- FF was associated with lower disease severity. Conventional DTI showed minimal group
differences and no significant clinical associations. This study provides in vivo evidence of white …
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Evidence of White Matter Neuroinflammation in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Diffusion-Based Neuroinflammation Imaging Study
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