What is MTR?

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What is MRI? is one of the most read educational pieces on the blog. MRI lets us look in the brain, but the problem is no one really knows what the images mean. They corelate with this and they correlate with that, which means it has a woolly relationship with anything. MTR (magnetization transfer ratio) is going to be an important one because it is being used to assess the sucess of remyelination trials. So in a week you will hear the good bad or indiffrent news of the remyelination trial from Cambridge that will be based on MTR.

What is the patholoigal correlate. for example gadolinium T 1 lesions measure fluid molement from the blood into the brains and is believed to be a correlate of cells moving from the blood into the brain. What about MTR

Pathological correlates of the magnetization transfer ratio in multiple sclerosis.Moccia M, van de Pavert S, Eshaghi A, Haider L, Pichat J, Yiannakas M, Ourselin S, Wang Y, Wheeler-Kingshott C, Thompson A, Barkhof F, Ciccarelli O.Neurology. 2020 Sep 16:10.1212/WNL.0000000000010909. doi: 10.1212/WNL.0000000000010909.

Objective: To identify pathological correlate(s) of magnetization transfer ratio (MTR) in multiple sclerosis (MS) in a MRI-pathology study.

Methods: We acquired MTR maps at 3T from 16 fixed MS brains and four controls, and immunostained 100 tissue blocks for neuronal neurofilaments, myelin (SMI94), tissue macrophages (CD68), microglia (IBA1), B-lymphocytes, T-lymphocytes, cytotoxic T-lymphocytes, astrocytes (GFAP), and mitochondrial damage (COX4, VDAC). We defined regions-of-interest in lesions, normal-appearing white matter (NAWM) and cortical normal-appearing grey matter (NAGM). Associations between MTR and immunostaining intensities were explored

Results: MTR was the lowest in WM lesions (23.4±9.4%), and the highest in NAWM (38.1±8.7%). In MS brains, lower MTR was associated with lower immunostaining intensity for myelin (Coeff=0.31; 95% confidence interval (CI)=0.07,0.55), macrophages (Coeff=0.03; 95%CI=0.01,0.07), and astrocytes (Coeff=0.51; 95%CI=0.02,1.00), and with greater mitochondrial damage (Coeff=0.31; 95%CI=0.07,0.55). Based on interaction terms, MTR was more strongly associated with myelin in WM (Coeff=1.58; 95%CI=1.09,2.08) and GM lesions (Coeff=0.66; 95%CI=0.13,1.20), and with macrophages (Coeff=1.40; 95%CI=0.56,2.25), astrocytes (Coeff=2.66; 95%CI=1.31,4.01), and mitochondrial damage (Coeff=-12.59; 95%CI=-23.16,-2.02) in MS brains than controls. In the multivariate model, myelin immunostaining intensity was the best correlate of MTR (Coeff=0.31; 95%CI=0.09,0.52; p=0.004).

Conclusions: Myelin was the strongest correlate of MTR, especially in WM and cortical GM lesions, but additional correlates should be kept in mind when designing and interpreting MTR observational and experimental studies in MS

So as you can see there is a suggestion that myelination is being picked up but it may be something else….but the trials are being done so what are they seeing? Surely this should be done before you use the outcome in trials. I am sure ProfK may want to add to this. The trials are only as good as the read-out, is MTR the way to go?….We find out next week

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MouseDoctor

9 comments

  • Mouse,

    Try and be supportive of your colleagues in Cambridge. They are trying to do something which all MSers want – to develop therapies which provide some degree of neuro protection and repair. The chances of success are no doubt low, but they are at least trying.

    When the results are announced, go for the humble response. If it’s successful, say well done, if it’s not successful, acknowledge the effort. I don’t want to see the usual “I knew it wouldn’t work…. blah, blah, blah”. The lack of collaboration between MS research team is a shocker to me. The childish rivalry, silo mentality, and focus on the number of papers published and grants awarded does MSers no favours. If MS research teams had worked more collaboratively and openly over the last 50 years we would be much further advanced in really addressing this disease.

    Best wishes Cambridge team – whatever the outcome of the Bexarotene trial, you were willing to do something different.

    • Sid, I think we are very collaborative. For example, I have just dropped Cambridge an invite to participate in the ADIOS trial design and submission. I have always give Cambridge credit for their perseverance and resilience when it came to testing and getting alemtuzumab developed. And they reciprocate, for example, I am presenting on cladribine at their grand round this Tuesday.

      • You need to resit your English Language gcse as I have no idea what you are trying to say (or have you just staggered back after a couple of pints at the Sarecens Head?).

    • I will be excited to hear the results and this paper is very relevant to this. As a coauthor of a paper with Franklin Coles a few times and one in press done over the past two years you are so wrong about the lack of collaboration.The UK is more collaborative than anywhere I know. We haven’t done remyelination so there is no competition.

      • Also ProfC is being part of the chariot MS team with ProfK.
        Robin Franklinstein has been one of the essential.innovators in the remyelination studies I don’t understand why you would think I want the trial to fail or would take any pleasure in this.

        • I’m really saddened by the negativity of some of the respondents to these blogposts. Even before I read the replies by Prof G and MouseDr, I’m thinking, ‘where does this assumption of this person come from? What proof do they have that MS researchers are not collaborative?’ That’s the point: they are just that; assumptions; baseless ones usually. And as for MouseDr’s dyslexia..MDr has explained all that eloquently before. It all takes us away from the research and these fantastically useful blogs. I’ve seen these people at conferences and they are always networking and collaborating on behalf of PwMS.

          • Altmann DR, Button T, Schmierer K (profK), D J Tozer, C A Wheeler-Kingshott, A Coles (ProfC), D H Miller . Sample sizes for lesion magnetisation transfer ratio outcomes in remyelination trials for multiple sclerosis. Mult Scler Relat Disord. 2014;3(2):237-243.

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