Neuroimaging techniques to assess inflammation in multiple sclerosis

Multiple Sclerosis (MS) is a chronic neurological disease that represents a leading cause of disability in young adults and is characterized by inflammation and degeneration of both white matter (WM) and gray matter (GM). Defining the presence or absence of inflammation on individual basis is a key point in choosing the therapy and monitoring the treatment response. Magnetic resonance imaging (MRI) represents the most sensitive non-invasive tool to monitor inflammation in the clinical practice. Indeed, in the early phase of inflammation MRI detects new lesions as extrusion of gadolinium contrast agents across the altered blood-brain-barrier (BBB). The occurrence of MRI lesions is used to confirm diagnosis and has been validated as surrogate marker of relapse to monitor response to treatments. However, focal gadolinium-enhancing lesions represent only an aspect of neuroinflammation. Recent studies have suggested the presence of a widespread inflammation of the central nervous system (CNS), which is mainly related to microglial cells activation occurring both at the edge of chronic focal lesions and throughout the normal-appearing brain tissue. New imaging techniques have been developed to study diffuse inflammation taking place outside the focal plaques. The scope of this review is to examine the various neuroimaging techniques and those biophysical quantities that can be non-invasively detected to enlighten the different aspects of neuroinflammation. Some techniques are commonly used in the clinical practice, while others are used in the research field to better understand the pathophysiological mechanisms of the disease and the role of inflammation.