ICC vs. Fukuda: Diffusion tensor imaging results differ based on diagnostic criteria (Thapaliya et al., 2021)

[Pyrrhus]

Diffusion tensor imaging reveals neuronal microstructural changes in ME/CFS (Thapaliya et al., 2021)
https://onlinelibrary.wiley.com/doi/10.1111/ejn.15413
From Dr. Kiran Thapaliya and Leighton Barnden, along with Donald Staines and Sonya Marshall-Gradisnik.

What is Diffusion Tensor Imaging (DTI)?

• Diffusion Tensor Imaging (DTI) is an MRI technique that uses the natural flow of water along nerves to approximately image the direction of neural pathways in the brain. Within cerebral white matter, water molecules tend to diffuse more freely along the direction of nerve bundles rather than across them. Such directional dependence of diffusivity is termed anisotropy. This direction of maximum diffusivity along the white-matter nerves is projected in the final image.

Main points of this study:

• This study looked at CFS patients diagnosed with the outdated Fukuda diagnostic criteria, ME patients diagnosed with the modern International Consensus Criteria (ICC), and a control group of healthy people.
• When comparing ME-ICC patients to healthy controls, significant abnormalities were seen in the brainstem.
• When comparing CFS-Fukuda patients to healthy controls, no significant abnormalities were seen.

Excerpt:

Myalgic Encephalomyelitis/Chronic fatigue syndrome (ME/CFS) patients suffer from a variety of physical and neurological complaints indicating the central nervous system plays a role in ME/CFS pathophysiology. Diffusion tensor imaging (DTI) has been used to study microstructural changes in neurodegenerative diseases.

In this study, we evaluated DTI parameters to investigate microstructural abnormalities in ME/CFS patients. We estimated DTI parameters in 25 ME/CFS patients who met Fukuda criteria (ME/CFSFukuda), 18 ME/CFS patients who met International Consent Criteria (ICC) (ME/CFSICC) only, and 26 healthy control subjects (HC). In addition to voxel-based DTI-parameter group comparisons, we performed voxel-based DTI-parameter interaction-with-group regressions with clinical and autonomic measures to test for abnormal regressions.

Group comparisons between ME/CFSICC and HC detected significant clusters (a) with decreased axial diffusivity (p=0.001) and mean diffusivity (p=0.01) in the descending cortico-cerebellar tract in the midbrain and pons, and (b) with increased transverse diffusivity in the medulla. The mode of anisotropy was significantly decreased (p=0.001) in a cluster in the superior longitudinal fasciculus region.

Voxel-based group comparisons between ME/CFSFukuda and HC did not detect significant clusters. For ME/CFSICC and HC, DTI parameter interaction-with-group regressions were abnormal for the clinical measures of information processing score, SF36 physical, sleep disturbance score, and respiration rate in both grey and white matter regions.

Our study demonstrated that DTI parameters are sensitive to microstructural changes in ME/CFSICC and could potentially act as an imaging biomarker of abnormal pathophysiology in ME/CFS. The study also shows that strict case definitions are essential in investigation of the pathophysiology of ME/CFS.

 

[Pyrrhus]

Related discussion on Diffusional Tensor Imaging (DTI) from different authors:

Brain abnormalities in myalgic encephalomyelitis/chronic fatigue syndrome: Evaluation by diffusional kurtosis imaging and neurite orientation dispersion and density imaging. (Kimura et al., 2018)
https://forums.phoenixrising.me/thr...gue-syndrome-evaluation-by-diffusional.62266/

 

[Rufous McKinney]

• When comparing ME-ICC patients to healthy controls, significant abnormalities were seen in the brainstem.
• When comparing CFS-Fukuda patients to healthy controls, no significant abnormalites were seen.

what might that all mean? wouldn't at least some percentage of the Fukuda criteria patients also meet ICC criteria?

 

[Rufous McKinney]

wouldn't at least some percentage of the Fukuda criteria patients also meet ICC criteria

answering my own dumb question: they did not overlap: from the paper..

"In the present exploratory study, those meeting the ME-ICC criteria were compared to those only meeting the Fukuda et al. (1994) criteria, referred to as the Fukuda CFS group throughout the paper. It was hypothesized that the ME-ICC case definition would identify individuals with more serious symptomatology and greater functional disability than those only meeting the Fukuda criteria."

so PEM, memory and concentration issues, are missing in Fukuda patients.

We need to seriously get past Fukuda.....

(editted, to wish I was a Fukuda only)

 

[Pyrrhus]

We need to seriously get past Fukuda.....

Yes, and we need to be honest about the decades of research that purported to study ME, but in fact used faulty diagnostic criteria from the CDC.

 

[Rufous McKinney]

Yes, and we need to get real about the decades of research that purported to study ME, but in fact used faulty diagnostic criteria from the CDC.

this is a supremely valuable study in that regard! I'm impressed....

 

[SNT Gatchaman]

Thank you @Pyrrhus . I'll try and get the full article in the next few days (please let me know if it becomes easily available sooner).

This might be an interesting thing for me to try out on myself - I have access to advanced neuro-imaging and could try out some serial DTI MRs to see if there's any discernible changes that mirror my clinical state. Of course I don't want to repeat my wretched crash of two months ago - prefer to continue slowly improving - but the future is unknown.

Next: I wonder if I could persuade some of my neuro-imaging colleagues to take this any further with a local patient study - perhaps serially. It would be good to know if there is potential for discrimination regarding degree of observed brainstem effects vs simply normal / abnormal.

Would probably require sophisticated / reliable patient symptom assessment to have any meaning and that's clearly a tricky thing for researchers to achieve. Not something to just wade into I imagine. ("One does not simply walk into MEdor" ).

I would be pleased to get involved with useful research here and this is an area I could try and explore.

 

[Pyrrhus]

This might be an interesting thing for me to try out on myself - I have access to advanced neuro-imaging and could try out some serial DTI MRs to see if there's any discernible changes that mirror my clinical state.

That sounds like a truly fun experiment to try!

Next: I wonder if I could persuade some of my neuro-imaging colleagues to take this any further with a local patient study - perhaps serially. It would be good to know if there is potential for discrimination regarding degree of observed brainstem effects vs simply normal / abnormal.

Do any of your colleagues have experience with 19F MRI imaging?

Here's a proposed study I've been trying to get done for a number of years:

https://twitter.com/i/web/status/1385048561784557571

"One does not simply walk into MEdor"

LOL. That's a good one!

 

[SNT Gatchaman]

"One does not simply walk into MEdor"

LOL. That's a good one!

Well I couldn't resist making the meme image. Hope I've got the font right.

 

[SNT Gatchaman]

Do any of your colleagues have experience with 19F MRI imaging?

I don't think so - at least I haven't seen it used here. My characterisation of "advanced neuro-imaging" was in reference to my colleagues' skills in the clinical context - so I was probably overstating things in my enthusiasm . While there are high quality clinical magnets and software available, this doesn't extend to e.g. high field strength research magnets and more esoteric contrast agents - although there's certainly local interest and drive, so that may change. Much of the advances in NZ that I've seen over the last 20 years have been in the MR cardiac imaging space.

Gosh, if my eyes had been opened to this disease, but I hadn't been laid low and/or had recovered quickly (and there wasn't a global pandemic) I can imagine collaborating on all sorts of potentially useful imaging (MRI, PET). I'd been pressured to take a sabbatical for ages, too. Grrr. All the more incentive to slowly recover and be able to refocus my professional activities.

 

[Pyrrhus]

Here are two papers from Leonard Jason's group on the importance of diagnostic criteria:

Contrasting Case Definitions: ME International Consensus Criteria vs. the Fukuda et al. CFS Criteria (Brown et al., 2013)
https://forums.phoenixrising.me/thr...teria-vs-the-fukuda-et-al-cfs-criteria.24865/

The importance of a research case definition (Jason et al., 2017)
https://forums.phoenixrising.me/threads/the-importance-of-a-research-case-definition.55300/

 

[Pyrrhus]

And here are three previous, related studies by some of the same authors:

Hyperintense sensorimotor T1 spin echo MRI is associated with brainstem abnormality in chronic fatigue syndrome (Barnden et al., 2018)
https://forums.phoenixrising.me/thr...ated-with-brainstem-abnormality-in-cfs.62399/

Decreased connectivity and increased BOLD complexity in the default mode network in individuals with chronic fatigue syndrome (Shan et al., 2018)
https://forums.phoenixrising.me/thr...fault-mode-network-in-individuals-with.56258/

A systematic review of neurological impairments in ME/CFS using neuroimaging techniques (Maksoud et al., 2020)
https://forums.phoenixrising.me/thr...syndrome-using-neuroimaging-techniques.81884/

 

[Pyrrhus]

...Piping hot! Brand new research from the same authors!


Volumetric differences in hippocampal subfields and associations with clinical measures in ME/CFS (Thapaliya et al., 2022)
https://forums.phoenixrising.me/thr...easures-in-me-cfs-thapaliya-et-al-2022.87423/

 

[Pyrrhus]

The first author discusses this study in this interview:

Scientific Findings Distinguish Between Myalgic Encephalomyelitis and Chronic Fatigue Syndrome
https://phoenixrising.me/myalgic-encephalomyelitis-chronic-fatigue-syndrome/thapaliya-imaging/