In Multiple Sclerosis (MS) a dysregulated immune response attacks myelin sheets in the brain and spinal cord, leading to a progressive damage of axons and subsequent loss of neurons (the cells bearing axons). Damaged neurons cannot properly conduct the electrical impulses needed to carry motor, sensitive, balance and other important information within the brain and away from the brain to the rest of the body. This explains why neuronal damage/loss represents the major substrate of clinical-neurological disability in MS.
Myelin is a special membrane enveloping axons which, by acting as a protecting insulator for electrical cables
Within the brain and spinal cord, myelin is formed by specific cells called oligodendrocytes, which repeatedly wrap their lipid-rich cellular membrane around axons to form the myelin sheet. Following the inflammatory-driven myelin damage typically observed in MS plaques, oligodendrocytes and their progenitors cells can sometimes regenerate the previously damaged myelin sheets in a process called “remyelination”.
Restoring myelin in MS can improve axonal conduction speed and metabolic support, thus preventing clinical disability deterioration, or even promote recovery of neurological functions.
Tracking the MS demyelination/remyelination process in vivo (vs. ex vivo observation of myelin status in autopsy tissue) is of pivotal importance for the development of new remyelinating drugs.
Several advanced quantitative and semi-quantitative magnetic resonance imaging (MRI) techniques have shown promise to depict myelin content within MS plaques. However, many of these MRI techniques lack myelin specificity and require long protocols that are not widely available, limiting their use to specialised MS research centres.
Several advanced quantitative and semi-quantitative magnetic resonance imaging (MRI) techniques have shown promise to depict myelin content within MS plaques. However, many of these MRI techniques lack myelin specificity and require long protocols that are not widely available, limiting their use to specialised MS research centres.
Recent evidence from literature suggests that some modified T1 sequences obtained in MRI could be used to track MS demyelination and remyelination, and could be potentially used to measure myelin content and stratify patients in MRI based clinical trials.
T1 mapping together with other T1 relaxometry techniques may be the most adequate tool for inclusion into clinical practice.
T1 sequences are indeed the most suited for examining the normal anatomy of the brain. In addition to MRI, positron emission tomography (PET) imaging offers the unique opportunity to specifically track myelin content using radiotracers that directly bind to myelin. However PET imaging is relatively invasive, is expensive and is not available in the large majority of MS centres worldwide.
In summary, imaging myelin in MS is fairly accurate nowadays, but often requires specialised imaging techniques that are not widely available. In the near future, standardisation of imaging protocols across different MS centres is required in order to ease the development of neuroprotective-remyelinating strategies for MS patients.
Prof. Pietro Maggi, MD,PhD, UCLouvain