Assessing treatment effects on axonal loss - evidence from MRI monitored clinical trials

Magnetic resonance imaging (MRI) is a collection of very sensitive and versatile techniques for detecting multiple sclerosis (MS) related damage in the central nervous system. Each technique is characterised by a particular combination of sensitivity, tissue and pathological specificity, and technical requirements that enable diverse aspects of MS to be explored. MRI techniques also offer the possibility of quantitatively assessing the effects of therapeutic interventions, and to correlate these effects to clinical outcomes. Of special interest are newer MR techniques that correlate more strongly with disability than gadolinium-enhancement and T2 lesion load, and this review focuses on T1 hypointense lesions, MR spectroscopy, and brain atrophy as surrogate markers of axonal loss, and their application in randomised clinical trials. Several disease-modifying therapies appear to have differential effects on inflammation, demyelination and axonal loss as judged by MRI, illustrating the unique capability of MRI to interrogate the pathophysiology of MS. At the same time it illustrates the difficulties in understanding the mechanisms leading to axonal loss and persistent clinical deficit.