Massimo Filippi and Marco Rovaris.

Neuroimaging Research Unit, Ospedale San Raffaele, Milan, Italy.

Brain inflammation (BI) is associated with a local increase of the blood-brain barrier (BBB) permeability. The leakage of gadolinium (Gd) (a paramagnetic contrast material) through the damaged BBB modifies the T1 relaxation time of the areas where it is concentrated and makes it possible to study BI in vivo using magnetic resonance imaging (MRI). Gd-enhanced MRI has improved our understanding of the inflammatory processes taking place in the brain and provided sensitive and reliable outcome measures to assess the efficacy of several drugs.Nevertheless, imaging BI with Gd-enhanced MRI is not without limitations. First, a large amount of BI goes undetected when using this technique. Second, Gd-enhancement does not allow to quantify the tissue damage which can occur at the site of inflammation and which may influence the clinical outcome.The application of cell-specific imaging and the acquisition of Gd-enhanced MRI in association with other MR techniques, with increased pathological specificity, are likely to go some way towards overcoming such limitations. These new MR techniques have the potential to improve our understanding of the cellular mechanisms of BI and to quantify the amount of the tissue damage associated with it. The major results achieved using MRI to study BI in multiple sclerosis (MS) will be discussed. MS is indeed a model of how MRI of BI might be applied to other diseases, since BI is one of the pathological hallmarks of MS and the application of MRI to MS has dramatically changed our understanding of how this disease evolves.