Introduction

Abstract

Conventional magnetic resonance imaging (MRI) has become established as the most important paraclinical tool for diagnosing MS, visualizing the dynamics of lesion formation and monitoring the efficacy of experimental treatments. This is due to the exquisite sensitivity of MRI for the detection of new lesions, as well as changes over time in lesion size and overall lesion burden. However, conventional MRI techniques have significant limitations. Firstly, the abnormalities seen on T2-weighted images reflect changes in the amount and physical-chemical state of water and can result from edema, inflammation, demyelination, remyelination, axonal loss, or reactive gliosis. These different pathological substrates of T2 change are likely to result in different degrees of neurological impairment. Gadolinium enhancement on postcontrast T1-weighted scans also provides limited pathological information as it reflects the presence of increased blood-brain barrier permeability associated with active inflammation, but gives no information about the extent of associated tissue damage. Secondly, conventional MRI does not detect the full extent of MS pathology. Low-grade inflammation and subtle structural changes (including axonal loss) in the so-called normal-appearing white matter (NAWM) go undetected by standard MRI techniques. Poor pathological specificity and inability to detect the changes in the NAWM are two of the main reasons why the correlation between T2 lesion volumes and irreversible disability is only modest in patients with MS.