Evidence of White Matter Neuroinflammation in [ME/CFS]: A Diffusion-Based Neuroinflammation Imaging Study 2026 Yu et al

Andy

Andy

Senior Member (Voting rights)

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.

Open access
 
Andy said:

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.

Open access
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This sounds like it could be absolutely massive, so I assume someone is going to be along to point out how deeply flawed it is any minute :rofl:
 
ME/CFS patients were interviewed by two clinicians to confirm a Canadian Consensus Criteria (CCC)-consistent (Carruthers et al. 2003) diagnosis of ME/CFS. A consensus diagnosis approach was employed to minimise the risk of an ill-defined disease cohort. The study intentionally recruited HCs with sedentary lifestyles (< 60 min in moderate or high-intensity activity [i.e., exercise] per week) to reduce the confounding effects of disease deconditioning (Nijs et al. 2011).
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sedentary lifestyles (< 60 min in moderate or high-intensity activity [i.e., exercise] per week)
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Up to 60 min moderate activity doesn't sound very intensely sedentary to me. But the study is probably better with this condition than without, anyway.
 
One of those studies that will need replication by multiple teams. It would be great to see that sooner rather than later. As far as I understand, this technique is also not fully established/standardized yet. I was involved in funding a more “standard DTI” MRI study in the past, but I am obviously not an expert. Certainly curious to learn more about this.

It's not a technique that requires a special MRI machine I think, it's more a software/normative datasetd issue, I believe?
 
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Liie said:
How does this relate to the work of other researchers who talk about "neuroinflammation" and "microglia activation" and similar things?
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Inasmuch as I can follow the paper they are suggesting a change in water content in white matter, which is a characteristic feature of most inflammation. If it is real it would be a good indicator of very low level inflammation (anything more in terms of water change in brain tends to lead to coma).

They are also suggesting a change in cellularity although I doubt they can pin that down to microglia, which would be the inflammatory cell. They cite NAkatomi but the signal in Nakatomi's study was not in white matter particularly. It was mostly down in midbrain and brainstem I think. And it was not replicated.

It might be that this is finally going to give us evidence of structural change in brain of a low-grade inflammatory type. However, (1) they point out the inconsistency of previous studies and this one may be no different and (2) it may be better to analyse this in terms of the raw data - water, cell and fibre changes, without premature labelling as inflammatory.
 
Liie said:
How does this relate to the work of other researchers who talk about "neuroinflammation" and "microglia activation" and similar things?
Click to expand...
It certainly is a shame that Dr. Younger is teaching at the moment because of the NIH funding situation. It’ll be exciting to see what his PET and MRI imaging combo reveals.



He seemed pretty confident he had something in his last update. Has to be substantiated of course.
 
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