Open Protocol: Multimodal MRI of myalgic encephalomyelitis/chronic fatigue syndrome: A cross-sectional neuroimaging study 2022 Shan et al

Andy

Andy

Senior Member (Voting rights)
Full title: Multimodal MRI of myalgic encephalomyelitis/chronic fatigue syndrome: A cross-sectional neuroimaging study toward its neuropathophysiology and diagnosis

Introduction: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), is a debilitating illness affecting up to 24 million people worldwide but concerningly there is no known mechanism for ME/CFS and no objective test for diagnosis. A series of our neuroimaging findings in ME/CFS, including functional MRI (fMRI) signal characteristics and structural changes in brain regions particularly sensitive to hypoxia, has informed the hypothesis that abnormal neurovascular coupling (NVC) may be the neurobiological origin of ME/CFS. NVC is a critical process for normal brain function, in which glutamate from an active neuron stimulates Ca2+ influx in adjacent neurons and astrocytes. In turn, increased Ca2+ concentrations in both astrocytes and neurons trigger the synthesis of vascular dilator factors to increase local blood flow assuring activated neurons are supplied with their energy needs.

This study investigates NVC using multimodal MRIs: (1) hemodynamic response function (HRF) that represents regional brain blood flow changes in response to neural activities and will be modeled from a cognitive task fMRI; (2) respiration response function (RRF) represents autoregulation of regional blood flow due to carbon dioxide and will be modeled from breath-holding fMRI; (3) neural activity associated glutamate changes will be modeled from a cognitive task functional magnetic resonance spectroscopy. We also aim to develop a neuromarker for ME/CFS diagnosis by integrating the multimodal MRIs with a deep machine learning framework.

Methods and analysis: This cross-sectional study will recruit 288 participants (91 ME/CFS, 61 individuals with chronic fatigue, 91 healthy controls with sedentary lifestyles, 45 fibromyalgia). The ME/CFS will be diagnosed by consensus diagnosis made by two clinicians using the Canadian Consensus Criteria 2003. Symptoms, vital signs, and activity measures will be collected alongside multimodal MRI.

The HRF, RRF, and glutamate changes will be compared among four groups using one-way analysis of covariance (ANCOVA). Equivalent non-parametric methods will be used for measures that do not exhibit a normal distribution. The activity measure, body mass index, sex, age, depression, and anxiety will be included as covariates for all statistical analyses with the false discovery rate used to correct for multiple comparisons.

Open access, https://www.frontiersin.org/articles/10.3389/fneur.2022.954142/full

The data will be randomly divided into a training (N = 188) and a validation (N = 100) group. Each MRI measure will be entered as input for a least absolute shrinkage and selection operator—regularized principal components regression to generate a brain pattern of distributed clusters that predict disease severity. The identified brain pattern will be integrated using multimodal deep Boltzmann machines as a neuromarker for predicting ME/CFS fatigue conditions. The receiver operating characteristic curve of the identified neuromarker will be determined using data from the validation group.

Ethics and study registry: This study was reviewed and approved by University of the Sunshine Coast University Ethics committee (A191288) and has been registered with The Australian New Zealand Clinical Trials Registry (ACTRN12622001095752).

Dissemination of results: The results will be disseminated through peer reviewed scientific manuscripts and conferences and to patients through social media and active engagement with ME/CFS associations.

See post #15 for information on how to join the study
 
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I’m not familiar with the authors, but this looks like a very impressive study. I don’t know how much evidence there is for their hypothesis beyond “well, that would explain a lot”.

It’s worth spelling out what they’ve done well t (and haven’t even done the study yet):
– published a protocol. This is important generally and particularly in MRI studies where there is a lot of scope for researcers to slice the data in different ways to get an interesting result.
– sedentary and disease controls.
– A training and a validation set. This is absolutely critical. It’s easy to get a positive results in a study (particularly if you’re flexible with analysis), it’s all together harder (and more impressive) to replicate that. Because they’re randomly dividing the sample into, they will have matched groups and identical methodologies.
– sample size . 91 is very big by the standards of MRI studies, though I gather hundreds is better (which can only happen with collaboration). So they will end up with two groups of 45 patients and because that is a fairly small sample, I think it increases the chance they won’t be able to validate any findings simply through lack of statistical power.

It’s still the best MRI study protocol I can remember seeing (Which might just mean better than the last two studies I’ve seen…).
 
This looks very thoughtful and useful on first read through. Once again, neuroimaging has the potential to unlock much that has been hidden.

In response to @rvallee's question on using 3T vs 7T, higher field strength gives greater spatial resolution (or same SR with increased speed of acquisition if preferred). So 7T is going to be really valuable when looking at small complicated structures, like the brainstem (VanElzakker). I think this study is looking more at cerebral cortical blood flow, diffusion and spectroscopy and 3T will probably be ideal, as they want to sample contiguous small regions rather than little dots. Also, there's the practical matter that it's available where these researchers and patients are, and 7T ain't.

Their hardware is top notch: Siemens Skyra is the best clinical platform in my view (and what we use at ours). Importantly, they're using a 64 channel head coil which is best-in-class. It gives high bandwidth and high signal-to-noise over a large field-of-view, and I would expect their set-up will be ideal for this task.
 
SNT Gatchaman said:
I think this study is looking more at cerebral cortical blood flow, diffusion and spectroscopy and 3T will probably be ideal, as they want to sample contiguous small regions rather than little dots.
Click to expand...

Yes, since we don't know the field of view necessary to find ME's abnormalities, we might need studies at different scales. If a brain-wide scan shows abnormalities, they can probably get funding for a higher-resolution, smaller FOV study. Patients are likely to show abnormalities in different areas of their brain--producing an individual's set of symptoms--so you need the wide FOV to know where to focus on a particular patient.
 
World-first chronic fatigue study to help sufferers get answers
How a person’s brain controls its blood flow may hold the key to diagnosing and treating chronic fatigue syndrome and fibromyalgia, according to UniSC researchers.

UniSC’s Thompson Institute is seeking about 300 participants with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), fibromyalgia and others who are sedentary (tends to spend much time seated) but in good health for the cross-sectional study.

The “world’s first” study will use brain imaging to investigate the dynamics between blood supply, neuronal activity and energy needs.

Lead researcher Dr Zack Shan said the aim was to determine the neurobiological origin of ME/CFS.

There is currently no known underlying disease process and no objective diagnosis test for the debilitating syndrome which affects between 94,000 and 242,000 Australians and up to 24 million people worldwide.

Around 25 per cent of people with CFS cannot leave their house or bed.

“The study will allow us to investigate how healthy people differ from those with chronic fatigue syndrome to find better treatments,” Dr Shan said.

The study is also one of the first to attempts to develop a diagnostic tool by combining magnetic resonance imaging (MRI) and machine learning.
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https://www.sunshinecoastnews.com.a...tudy-seeks-answer-to-chronic-fatigue-mystery/

enough with the 'chronic fatigue' :arghh:
 
Can we find someone to hack into the internet and global replace all mention of 'chronic fatigue' with 'chronic fatigue-like-but-not-really-fatigue'?

Since I'm in favour of more studies on brain function, I'm not objecting to this study. I think it's a better use of resources than studying blood elsewhere in the body, or studying viral infection (if a virus 'pulled the trigger', you need to study the wound, or maybe the weapon, but not who pulled the trigger).
 
Creekside said:
Can we find someone to hack into the internet and global replace all mention of 'chronic fatigue' with 'chronic fatigue-like-but-not-really-fatigue'?

Since I'm in favour of more studies on brain function, I'm not objecting to this study. I think it's a better use of resources than studying blood elsewhere in the body, or studying viral infection (if a virus 'pulled the trigger', you need to study the wound, or maybe the weapon, but not who pulled the trigger).
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Then acknowledge all the subsequent effects the wound will also cause instead of saying MUS.
 
Merged thread

Sunshine Coast, Australia: Multimodal MRI of myalgic encephalomyelitis/chronic fatigue syndrome: a cross-sectional neuroimaging study

Multimodal MRI of myalgic encephalomyelitis/chronic fatigue syndrome: a cross-sectional neuroimaging study towards its neuropathophysiology and diagnosis
https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=384477&isReview=true

This cross-sectional study will recruit 288 participants (91 ME/CFS, 61 individuals with chronic fatigue, 91 healthy controls with sedentary lifestyles, 45 fibromyalgia). The ME/CFS will be diagnosed by an agreed diagnosis made by two clinicians using the Canadian Consensus Criteria. Symptoms, vital signs, and activity measures will be collected alongside multimodal MRI.

Register:
https://www.usc.edu.au/thompson-institute/research/chronic-fatigue-syndrome-me-cfs-study

Register your interest in being a volunteer research participant for our ME/CFS study. We appreciate your time and commitment to participate in the study. Thus, each participant will receive A$50 as reimbursement for travel costs per visit to the Thompson Institute for data collection purposes. Participants will also receive an image of their brain.

To facilitate sharing:
Click to expand...
 
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Novel brain imaging study seeks answers to chronic fatigue mystery
Vibrant, bubbly and full of energy, 24-year-old occupational rehabilitation consultant Nadia was living her best life. Then the fatigue took hold.


Now, five years since her first symptoms of chronic fatigue appeared, she is taking part in a novel brain imaging study by the University of the Sunshine Coast seeking better, faster ways to diagnose and treat the debilitating syndrome that affects more than 24 million people worldwide.

"I find people do not understand how a twenty-something can be constantly fatigued," says Nadia, who believes an unknown virus was the trigger for her illness.

"After I recovered from that virus, I was never quite the same. I never regained my energy."

With no known cause, objective diagnostic test or cure, the study by UniSC's Thompson Institute could be the key to finally pinpointing the neurobiological origin of chronic fatigue syndrome (CFS), also known as myalgic encephalomyelitis (ME).

Lead researcher Dr. Zack Shan says the world-first research is using MRIs to track brain activity in around 300 study participants to determine how the brain controls its blood flow to match its energy needs, to better understand the disease process of fatigue-related illnesses.
Click to expand...
https://medicalxpress.com/news/2022-11-brain-imaging-chronic-fatigue-mystery.html
(yet more misuse of 'chronic fatigue')
 
Merged thread


https://www.usc.edu.au/thompson-ins...stitute/chronic-fatigue-syndrome-me-cfs-study


UniSC's Thompson Institute is seeking volunteer research participants who will help us understand the underlying illness process of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Participants will also help us develop imaging criteria that will aid the diagnosis of ME/CFS.

The study is the first to investigate brain function in ME/CFS in terms of energy supplies and chemical messengers. It is also the first significantly sized study to attempt to develop a diagnostic tool by combined advanced MRI and machine learning.

Eligibility
The study might be a good fit for you if you are:

  • aged 18-65 years old, and a healthy adult with an inactive lifestyle
    (NB: 'inactive lifestyle' means participating in vigorous physical activity for less than 160 minutes per week; such as running, gym, swimming etc. Walking is not considered vigorous activity unless it is push walking);

    or
  • aged 18-65 years old, and have:
    • an unexplained fatigue condition, or
    • ME/CFS, or
    • Fibromyalgia, or
    • Long COVID
The nature of the study's investigations also requires participants to:

  • Not be taking medication for high cholesterol, high blood pressure, or heart-related conditions
  • Have a body mass index (BMI) of 35 or below (this exclusion criterion is necessary because the brain and its functions can differ depending on BMI and thus is a potential confounding factor in our data collection. Please note that BMI is not related in any way to CFS risk or prevalence).
  • Meet safety requirements to participate in the study's Magnetic Resonance Imaging (MRI). This includes not having metal implants or facial tattoos.
thompson-institute-mri-scan-web.jpg

INTERESTED?
Register your interest in being a volunteer research participant for our ME/CFS study. We appreciate your time and commitment to participate in the study. Thus, each participant will receive A$50 as reimbursement for travel costs per visit to the Thompson Institute for data collection purposes. Participants will also receive an image of their brain.

REGISTER TO TAKE PART
Seeking adults with and without fatigue symptoms
What the study involves
As a research participant, you would take part in:

  • An online screening questionnaire;
  • At your own pace, ten questionnaires for assessing different aspects of mental and physical health status;
  • Blood pressure, pulse rate, height, weight, and oxygen saturation measurements and a joint hypermobility task;
  • Wearing an activity monitor wristwatch and chest strap to capture your physical activity, sleep/wake information and heart-rate for fourteen days. The wristwatch and chest strap need to be returned after fourteen days of usage;
  • One magnetic resonance imaging (MRI) scan (60 minutes’ scanning time plus preparation). If you are willing, a second scan may take place.
Participants with fatigue conditions will also take part in:

  • Two interviews with two specialists. Each interview will be scheduled for 30 – 45 minutes.
Research is conducted on the Sunshine Coast in Queensland.

Why this study is important
ME/CFS is a poorly understood, debilitating, complicated illness affecting 17 million people worldwide. There is no known underlying disease process for ME/CFS and no biological basis for diagnosis. Diagnoses are typically lengthy and occur by a process of elimination. Treatments are typically inadequate due to the unknown cause. Understanding the brain disease process of ME/CFS will allow the design of biologically-based therapeutic interventions and faster, more effective diagnosis methods.

Fibromyalgia is another common, debilitating and poorly understood condition, which frequently occurs together with ME/CFS, but can occur independently. This study therefore is also investigating individuals with Primary Fibromyalgia to try to understand this condition’s relationship with ME/CFS.

Contact us
Email: cfs@usc.edu.au
Tel: +61 7 5456 5445

Ethics Approval Number: A191288
This study is registered with the Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12622001095752
 
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