MRI measures of neuroprotection and repair in multiple sclerosis

Magnetic resonance imaging (MRI) has had an enormous impact on multiple sclerosis, enabling early diagnosis and providing surrogate markers for monitoring treatment response in clinical trials. Despite these advantages, conventional MRI is limited by lack of pathological specificity and lack of sensitivity to grey matter lesions and to microscopic damage in normal appearing tissue. Quantitative MRI techniques such as measures of parenchymal volume loss, magnetisation transfer imaging, diffusion tensor imaging, and proton magnetic resonance spectroscopy have enhanced our understanding of the nature and mechanism of tissue injury and repair in multiple sclerosis, and provided more specific correlates of neurological deficits and disability accrual. Some of these techniques may be of potential use in clinical trials as surrogate outcome measures for measuring treatment effects on neurodegenerative injury, which is currently difficult to quantify in clinical trials. In this respect, measures of brain volume, T1 hypointensity and magnetisation transfer ratio, and optical coherence tomography appear to be the most promising in the short term. The evidence for a role of neurodegeneration in the pathogenesis of multiple sclerosis, and particularly in the accumulation of irreversible disability, has become increasingly strong over recent years. This has prompted the search for new treatments that can effectively slow down, halt or even reverse such neurodegenerative processes, and in this way restore nervous system function. For this reason, there has been much interest in the development and validation of surrogate markers of neurodegeneration and neuroprotection for use in clinical trials. Advances in magnetic resonance imaging (MRI) technology have allowed the development and implementation of a number of methods that may be promising in this respect. To assess the utility of these methods and to identify needs for further research, sixty experts in neuropathology, clinical measurement, imaging and statistics participated in a meeting held in Amsterdam in 2008 under the aegis of the National Multiple Sclerosis Society. In the proceedings of the meeting, published in 2009 [1], brain volume changes, T1 hypointensity, magnetisation transfer ratio and optical coherence tomography were deemed the most promising measures for screening the neuroprotective capacity of new agents. Other MRI techniques, such as DTI, (1)H-MRS and functional MRI, although potentially useful, require more observational data to help determine the optimal trial design. This article will review some of the issues that were discussed at this meeting, and present some of the imaging techniques that were considered to be the most promising.