Journal article
Evidence of White Matter Neuroinflammation in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Diffusion‐Based Neuroinflammation Imaging Study
Human Brain Mapping, Vol.47(4), pp.1-13
2026
PMID: 41834684
Appears in Thompson Institute Research Collection
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 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.
Details
- Title
- Evidence of White Matter Neuroinflammation in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Diffusion‐Based Neuroinflammation Imaging Study
- Authors
- Qiang Yu (Corresponding Author) - University of the Sunshine CoastKiana Justine Kothe - University of the Sunshine CoastRichard A Kwiatek - University of the Sunshine CoastPeter Del Fante - University of the Sunshine CoastAnya Bonner - University of the Sunshine CoastVince D Calhoun - Center for Translational Research in Neuroimaging and Data ScienceZack Shan - University of the Sunshine Coast
- Publication details
- Human Brain Mapping, Vol.47(4), pp.1-13
- Publisher
- John Wiley & Sons, Inc.
- Date published
- 2026
- DOI
- 10.1002/hbm.70505
- ISSN
- 1097-0193
- PMID
- 41834684
- Copyright note
- © 2026 The Author(s). Human Brain Mapping published by Wiley Periodicals LLC. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
- Data Availability
- The demographics, symptom scores, and preprocessed NII- (NII-HR, NII-RF, NII-FF, NII-AD, NII-RD, NII-MD and NII-FA) and DTI- (DTI-FA, DTI-MD, DTI-AD and DTI-RD) derived metrics of each participant that support the findings of this study are openly available in the Zenodo repository at http://doi.org/10.5281/zenodo.16916830.
- Grants
- Dynamic Monitoring the Central Parasympathetic Modulation to Elucidate Neurological Underpinnings of Post-Exertional Malaise and Non-restorative Sleep, 0980027998, The Mason Foundation
- Organisation Unit
- Healthy Ageing Research Cluster; Thompson Institute; School of Health - Paramedicine
- Language
- English
- Record Identifier
- 991216247202621
- Output Type
- Journal article
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