The transition from relapsing-remitting multiple sclerosis to secondarily progressive multiple sclerosis (SPMS) is difficult to identify. Typically, SPMS is diagnosed retrospectively, with a significant delay, on the basis of a clinical history of progressive worsening, independent of relapses. Thus, SPMS is often associated with a considerable period of diagnostic uncertainty. The use of ultra-high field imaging can shed light on the mechanisms of disability progression thanks to its better spatial resolution and advanced imaging techniques. The new morphological imaging techniques make it possible to visualize chronic inflammatory lesions and to evaluate their evolution. It also allows for the precise measurement of brain atrophy, a reference in the evaluation of neurodegeneration. Metabolic imaging via proton spectroscopy allows the analysis of several promising cerebral metabolites that can provide information on cellular energy metabolism, mitochondrial function, or oxidative stress, and can help identify tissues at risk of neurodegeneration. Sodium imaging can provide information on axonal energy metabolism before the occurrence of stable and irreversible axonal damage. This technique is promising as an early marker of neurodegeneration.