Advanced magnetic resonance imaging metrics: implications for multiple sclerosis clinical trials

Magnetic resonance imaging (MRI) techniques contribute substantially to the management of multiple sclerosis (MS); however, no specific predictive marker of clinical outcome has been identified. Traditional MRI measures are effective diagnostic tools for MS but do not accurately correlate with the progression of neurological impairment and physical disability. Moreover, in studies that apply traditional MRI techniques to evaluate MS disease-modifying therapies (DMTs), the weak correlation between suppression of inflammation and continued progression of disability has initiated an awareness of a "clinico-radiological paradox". Thus, a need exists for alternative MRI measures that more accurately monitor clinical disease activity and measure the efficacy of DMTs. In this regard, advanced MRI measures allow more sensitive quantification of microscopic neuronal damage present in normal-appearing brain tissue and serve as more reliable surrogate markers for neuronal injury and repair. These advanced MRI metrics allow assessment of neuronal metabolite concentrations; assessment of macromolecular density, geometry and structural integrity of neuronal tissue; noninvasive spatial localization of brain function; and high-intensity scanning of microscopic MS lesions. The objective of this review is to provide a brief description of these advanced MRI measures and to discuss preliminary clinical studies that employ these techniques in order to evaluate the efficacy of DMTs.