Quick MRI Method May Reliably Detect Myelin Repair in People
SyMRI may be useful to test myelin-repairing therapies in clinical trials
A quick MRI-based method called SyMRI may be useful in future clinical trials to test experimental myelin-repairing therapies in diseases like multiple sclerosis (MS), a new study shows.
The study, “Quantification of individual remyelination during short-term disease course by synthetic magnetic resonance imaging,” was published in Brain Communications.
MS is caused by inflammation in the central nervous system (CNS) — consisting of the brain and spinal cord. This inflammation initially causes damage to the myelin sheath, a fatty coating around nerve fibers (axons), ultimately leading to neuronal dysfunction and disease symptoms.
As the disease progresses, however, the myelin loss (demyelination) is followed by actual damage to nerve cells, which is much harder to reverse.
Disease-modifying therapies currently available for MS work by reducing the inflammatory attack that causes myelin damage. There aren’t any medications that have been proven to promote myelin repair (remyelination) — though many researchers are working to develop them.
“Therapies that rebuild the myelin are still being under investigation, mostly in animal models,” Ruth Schneider, MD, the study’s first author from Ruhr University Bochum, in Germany, said in a press release.
As new remyelination therapies are being developed, researchers have begun to consider how to design a clinical trial to test these therapies. This poses a technical problem: in animal models, myelin content is usually assessed by removing nervous system tissue, staining it, and analyzing it under a microscope. For obvious reasons, this can’t be done in a study with human participants.
“A central problem in human medicine is to determine therapeutic successes such as remyelination in living patients without tissue sections as in animal models,” Schneider said.
What is synthetic MRI?
MRI is a common imaging technique used to assess CNS damage in MS. It uses powerful magnets combined with radio waves to generate images of the body’s internal structures. Synthetic MRI (SyMRI) is a particular MRI sequence that uses a six-minute scan to measure myelin content.
“Myelin quantification often requires lengthy multimodal MRI protocols and sophisticated data processing techniques, which is why they are rarely used in routine clinical practice. In our study, we used SyMRI, a fast, single-sequence multiparametric quantitative MRI method which automatically quantifies” the myelin content, the researchers wrote.
Prior studies have demonstrated that SyMRI can reliably detect myelin damage in people with MS and other neurological diseases. However, no study has yet shown whether the technology can reliably detect myelin repair in people.
To assess this, researchers turned to a genetic metabolic condition called methylenetetrahydrofolate reductase (MTHFR) deficiency. In this rare condition, a genetic mutation leads to abnormally low levels of a molecule called methionine, which ultimately results in myelin damage. Notably, this damage can be alleviated or reversed by giving patients methionine supplements.
This study enrolled three people with MTHFR deficiency — the three patients were cousins, and all were in their 30s. The diagnosis of MTHFR deficiency in one of the patients, who had suddenly started experiencing symptoms in her late 20s, had ultimately led the other two (who had been sick for longer) to be diagnosed in rapid succession.
The patients underwent SyMRI as well as conventional MRI scans, and then they started on methionine supplements. The same MRI scans were repeated again six months later.
In the first patient, initial scans showed reduced myelin content — 6%, compared to 10% in healthy controls. After six months, myelin content modestly improved to 6.6%. A related measure called radial diffusivity decreased (from .00134 to .00119 mm2/second), also indicating a modest increase in myelin content.
SyMRI also showed an increase in myelin content for the other two patients, though it was markedly smaller in these individuals who had been experiencing symptoms for longer before starting treatment. The researchers noted that the two later-diagnosed patients also had less improvement clinically after starting on supplements.
“[Myelin content] increased substantially between baseline and follow-up in the early treated index Patient 1 and, less pronounced, in Patients 2 and 3 with longer disease duration before treatment initiation. … These findings corroborate that automatic global quantification of [myelin content] with SyMRI is suitable for detecting demyelination and remyelination at global levels,” the scientists concluded.
Schneider said: “Using a synthetic MRI sequence, we were able to quantifiably demonstrate the reconstruction of myelin in the brain in humans in vivo after therapy with the missing metabolites. This means we now have an important method to demonstrate the success of new therapies in terms of remyelination.”