Diffusion tensor imaging reveals neuronal microstructural changes in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome., 2021, Thapaliya et al

[Andy]

Abstract

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.

Paywall, https://onlinelibrary.wiley.com/doi/10.1111/ejn.15413

 

[cassava7]

While I have not read the study to check if the authors compared for multiple comparisons (i.e. whether the findings were truly statistically significant), it seems interesting that they found a difference between ICC and Fukuda patients.

With a sounder imaging technique, Raijmakers et al. could not replicate Nakatomi's PET scan study that found neuroinflammation, but in the former patients were diagnosed with Fukuda while they met both Fukuda and ICC in the latter.

Interestingly, another Japanese group had previously claimed that diffusion kurtosis imaging (an improvement on diffusion tensor imaging) revealed superior longitudinal fasciculus abnormalities in ME/CFS, which this study also found.

 

[Hutan]

DTI seems to be a type of MRI that quantifies the diffusion of water molecules in the brain.

An introduction to diffusion tensor image analysis

Unlike the diffusion1 in a glass of pure water, which would be the same in all directions (isotropic), the diffusion measured in tissue varies with direction (is anisotropic). The measured macroscopic diffusion anisotropy is due to microscopic tissue heterogeneity [6]. In the white matter of the brain, diffusion anisotropy is primarily caused by cellular membranes, with some contribution from myelination and the packing of the axons

 

[Hutan]

It looks like, as for other brain imaging, this is a technology where there is a lot of scope for bias.

Twenty-five pitfalls in the analysis of diffusion MRI data
Unfortunately, the pitfall article is paywalled, but it looks interesting

Obtaining reliable data and drawing meaningful and robust inferences from diffusion MRI can be challenging and is subject to many pitfalls. The process of quantifying diffusion indices and eventually comparing them between groups of subjects and/or correlating them with other parameters starts at the acquisition of the raw data, followed by a long pipeline of image processing steps. Each one of these steps is susceptible to sources of bias, which may not only limit the accuracy and precision, but can lead to substantial errors. This article provides a detailed review of the steps along the analysis pipeline and their associated pitfalls.

Knowing that, it made me want to check out the authors, to see if they had a track record of doing good diffusion MRI studies in other diseases.
The authors are:
Kiran Thapaliya, Sonya Marshall-Gradisnik, Don Staines, Leighton Barnden

Marshall-Gradisnik and Staines lead NCNED at Griffiths University. We have had qualms about their propensity to make big claims on the basis of small preliminary studies, and they are not brain imaging experts. Leighton Barnden though has a strong track record in brain imaging and has done a number of interesting solid studies in ME/CFS. So, without reading the paper, maybe there is something here worth watching.

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)

It's not clear to me from the abstract if the 18 patients who met the ICC criteria are a subset of the 25 patients who met the Fukuda criteria.

 

[FMMM1]

It looks like, as for other brain imaging, this is a technology where there is a lot of scope for bias.

Twenty-five pitfalls in the analysis of diffusion MRI data
Unfortunately, the pitfall article is paywalled, but it looks interesting


Knowing that, it made me want to check out the authors, to see if they had a track record of doing good diffusion MRI studies in other diseases.
The authors are:
Kiran Thapaliya, Sonya Marshall-Gradisnik, Don Staines, Leighton Barnden

Marshall-Gradisnik and Staines lead NCNED at Griffiths University. We have had qualms about their propensity to make big claims on the basis of small preliminary studies, and they are not brain imaging experts. Leighton Barnden though has a strong track record in brain imaging and has done a number of interesting solid studies in ME/CFS. So, without reading the paper, maybe there is something here worth watching.


It's not clear to me from the abstract if the 18 patients who met the ICC criteria are a subset of the 25 patients who met the Fukuda criteria.

Think MRI is considered to be more reliable than PET so anything based on MRI seems likely to be more reliable. With PET you basically artificially create a signal i.e. by using a ligand which attaches to what your interested in and produces the signal. With MRI the signal is a fundamental property of the compound. Having said that I know nothing about this derivative of MRI (or indeed MRI).

I wonder if there's a danger that the healthy controls could explain the differences? Also, did the Japanese study MRI study have healthy controls?

 

[ME/CFS Skeptic]

Sounds interesting but there seems to be quite a lot of degrees of freedom of how the authors could have influenced the results of their statistical tests.

The sample size and the decision to test for Fukuda and ICC group separately weren't pre-specified. The latter is a bit strange because this is (EDIT: one of the first) the first ME/CFS study that used this technique so I think most researchers would first look at the results for all ME/CFS patients (Fukuda and ICC group combined) versus healthy controls. That makes me think the analysis for the ICC group was a post-hoc decision.

It's strange that the results for all ME/CFS patients versus healthy controls aren't reported.

 

[ME/CFS Skeptic]

The authors write:

Correction for multiple regressions was performed similar to Barnden et al. (2015). The present analysis consisted of N = (1 + 9) * 2 * 7 = 140 regressions, where in brackets ‘1’ refers to the categorical (group) comparison of ME/CFS and HC and 9 refers to the autonomic and clinical regressors.

Shouldn't the 1 be turned into a 2 because they looked for differences in the Fukud and ICC group separately?

 

[ME/CFS Skeptic]

On Twitter, many interpret this study as showing a difference between Fukuda and ICC criteria but this would require a direct comparison between these groups, which isn't reported.

 

[Ravn]

Thapaliya (first link) and Barnden (second link) presentations related to this study.

https://www.facebook.com/111905763774120/videos/261497616086600?__so__=permalink

https://www.facebook.com/111905763774120/videos/326899692658292?__so__=permalink

 

[Dolphin]

The full text is now available free here
https://onlinelibrary.wiley.com/doi/pdf/10.1111/ejn.15413

 

[adambeyoncelowe]

The bit that says "18 ME/CFS patients who met International Consent Criteria (ICC) (ME/CFSICC) only" suggests they didn't also fulfil Fukuda, though?

So did some of the Fukuda group fulfil ICC criteria, whereas the second group only fulfilled ICC and not Fukuda?

Maybe it's poor wording.

 

[Ravn]

Anyone able to translate this paper into plain English?

Longitudinal studies should be per-formed to test progressive microstructural changes inME/CFS

What exactly are 'microstructural changes'?
Are they suggesting there could be something neurodegenerative going on in ME after all?

The bit that says "18 ME/CFS patients who met International Consent Criteria (ICC) (ME/CFSICC) only" suggests they didn't also fulfil Fukuda, though?

So did some of the Fukuda group fulfil ICC criteria, whereas the second group only fulfilled ICC and not Fukuda?

Maybe it's poor wording.

Poor wording would be my guess. Probably the 'only' was meant to refer to the Fukuda group but accidentally ended up in the wrong place.