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