Imag(in)ing multiple sclerosis: Time to take better pictures

•Research with advanced MRI has identified that MS is a disease of the whole brain.•This research has sought to establish surrogate markers for diffuse tissue damage.•It is time to renew efforts to use imaging to study MS pathophysiology.

Magnetic resonance imaging (MRI) has led to the identification of widespread brain abnormalities in multiple sclerosis (MS) that extend far beyond the classic white matter lesion. These findings have generated the idea that MS should be understood as a disease of the whole brain, not just the white matter. While it is no doubt the case that many different pathways are ultimately involved in the destruction of brain tissue that occurs in MS, the implications of the accumulated evidence for understanding disease pathophysiology - and hence the overall significance of these imaging findings - are doubtful. Here, I argue that the principled use of imaging can, in fact, address questions about the genesis of these whole-brain abnormalities, rather than simply describe them.