MR brain iron mapping in MS

Multiple sclerosis (MS) is a chronic, persistent inflammatory-demyelinating disease, characterized pathologically by the presence of focal demyelinated lesions scattered throughout the CNS. According to the predominant pathologic substrate, MS has been defined as a 2-stage disease, with an early phase in which multifocal inflammation and relapses predominate, and a later phase involving progressive, diffuse neuroaxonal degeneration and increasing disability.1 MRI measures of inflammatory activity, such as number of T1 gadolinium-enhancing lesions and new and enlarged T2-weighted lesions, strongly predict the effect of treatment on relapses, supporting the use of conventional MRI (cMRI) parameters as endpoints in phase II therapy trials.2 However, a role for cMRI measures as surrogate outcome measures in phase III trials has been disclaimed because of the apparently poor correlation with the clinical disease course, in particular progression of disability, which is driven by the neurodegenerative component of the disease.3 Over the last 20 years, the MRI research community has dedicated an enormous effort to overcoming the limited sensitivity of cMRI in assessing the neurodegenerative component of MS by developing new techniques to provide better markers of the pathologic processes underlying the progression of clinical disability (demyelination and axonal loss). The 2 most specific magnetic resonance (MR) methods for detecting this neurodegenerative component are quantitative analysis of global and regional brain volume, particularly the gray matter, and proton MR spectroscopy measurement of N -acetylaspartate, a marker of axonal loss and dysfunction. …