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.
Highlights
Studying translocator protein (TSPO) positron emission tomography (PET) has confirmed the role that inflammation plays in lesion evolution, revealing that inflammation is present since the early stages of the disease, even before lesions can be identified on Magnetic resonance imaging (MRI) [51]; activated macrophages and microglia concentrate around Multiple sclerosis (MS) lesions and outside lesions in the normal-appearing white matter (NAWM) and grey matter [50,51,52,53,55]
PET-tracers offer better radiological–pathological correlation when compared to traditional MRI sequences
One of the main drawbacks of PET was its low spatial resolution compared to MRI
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. MRI is a biomarker prototype with a good sensitivity and specificity for MS diagnosis and monitoring inflammatory activity, and OCBs are a proven tool for disease diagnosis. MRI shows a low specificity for pathophysiologic phenomena, such as remyelination or neurodegeneration For these mechanisms of disease progression, a molecular biomarker may be better suited. In vivo molecular imaging approaches with a higher specificity to important pathological substrates see constant development This includes several promising positron emission tomography (PET) tracers for myelin, inflammation, and neurodegeneration, MR spectroscopy (MRS), and advances in sodium channel MRI (NaMRI). These “molecular imaging” modalities can harmoniously depict anatomy and pathophysiology, making for an appealing myelin and neuroaxonal integrity biomarker candidate.
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