The Role of Molecular Imaging as a Marker of Remyelination and Repair in Multiple Sclerosis

Abstract

The appearance of new disease-modifying therapies in multiple sclerosis (MS) has revolutionized our ability to fight inflammatory relapses and has immensely improved patients’ quality of life. Although remarkable, this achievement has not carried over into reducing long-term disability. In MS, clinical disability progression can continue relentlessly irrespective of acute inflammation. This “silent” disease progression is the main contributor to long-term clinical disability in MS and results from chronic inflammation, neurodegeneration, and repair failure. Investigating silent disease progression and its underlying mechanisms is a challenge. Standard MRI excels in depicting acute inflammation but lacks the pathophysiological lens required for a more targeted exploration of molecular-based processes. Novel modalities that utilize nuclear magnetic resonance’s ability to display in vivo information on imaging look to bridge this gap. Displaying the CNS through a molecular prism is becoming an undeniable reality. This review will focus on “molecular imaging biomarkers” of disease progression, modalities that can harmoniously depict anatomy and pathophysiology, making them attractive candidates to become the first valid biomarkers of neuroprotection and remyelination.

Advanced MRI Techniques: Diagnosis and Follow-Up of Multiple Sclerosis

“…Tracers targeting the translocator protein (TSPO) have been widely used to detect innate immune cell activation [ 150 ], while other tracers target amyloid deposition, myelin, or glucose metabolism. PET imaging has revealed diffuse activation of innate immune cells in both WM lesions and cortical regions and has provided insights into disease evolution and lesion patterns not detectable by traditional MRI techniques [ 151 , 152 , 153 , 154 ].…”

Targeting Fibronectin to Overcome Remyelination Failure in Multiple Sclerosis: The Need for Brain- and Lesion-Targeted Drug Delivery

“…Therefore, in parallel, clinical biomarkers for remyelination should be developed and optimized to assess the effectiveness of (remyelination) therapy. MRI is currently not a reliable measure of remyelination [ 381 ]. Instead, advanced MRI techniques, such as diffusion tensor imaging, which measures the diffusion of water along axons, is particularly useful for the imaging of white matter tracts in the brain [ 381 , 382 ].…”

“…MRI is currently not a reliable measure of remyelination [ 381 ]. Instead, advanced MRI techniques, such as diffusion tensor imaging, which measures the diffusion of water along axons, is particularly useful for the imaging of white matter tracts in the brain [ 381 , 382 ]. Other potential biomarkers or diagnostic tools include the plasma levels of neurofilament light chains [ 383 ], position emission tomography tracers for myelin [ 384 ], and multifocal visually evoked potential [ 385 ].…”