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Evidence of White Matter Neuroinflammation in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Diffusion‐Based Neuroinflammation Imaging Study
Journal article   Open access   Peer reviewed

Evidence of White Matter Neuroinflammation in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Diffusion‐Based Neuroinflammation Imaging Study

Qiang Yu, Kiana Justine Kothe, Richard A Kwiatek, Peter Del Fante, Anya Bonner, Vince D Calhoun and Zack Shan
Human Brain Mapping, Vol.47(4), pp.1-13
2026
DOI: https://doi.org/10.1002/hbm.70505
PMID: 41834684
Appears in  Thompson Institute Research Collection
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Abstract

diffusion tensor imaging diffusion‐based neuroinflammation imaging model myalgic encephalomyelitis/chronic fatigue syndrome neuroinflammation white matter microstructure Thompson Institute Special Collection Neuroimaging Chronic fatigue syndrome
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 abnormalities 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 fraction (NII‐RF), fibre fraction (NII‐FF), axial diffusivity (NII‐AD), radial diffusivity (NII‐RD), mean diffusivity (NII‐MD) and fractional 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 matter neuroinflammation in ME/CFS, characterised by cerebral edema (reduced NII‐HR), cellular infiltration (reduced NII‐RF) and axonal reorganisation (increased NII‐FF). This suggests NII‐derived indices may serve as sensitive biomarkers for neuroinflammation in ME/CFS. Diffusion‐based neuroinflammation imaging (NII) reveals widespread white matter abnormalities in ME/CFS patients, undetected by conventional DTI. NII metrics associate with mental health, disability and disease severity, providing novel evidence of neuroinflammation and highlighting NII's potential as a biomarker in ME/CFS.

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