Image analysis software allows for quantitative estimation of widths, areas, and/or volumes of central nervous system (CNS) structures directly from digital images. Although atrophy is not pathologically specific, it primarily reflects irreversible tissue loss due to multiple sclerosis (MS), and therefore, it is a valuable marker of disease severity. Brain atrophy can be detected very early in the course of MS, and appears to progress almost from disease onset. Current evidence suggests that atrophy correlates better with neurologic measures of disability than do conventional lesion measurements. Atrophy is an attractive component of a magnetic resonance imaging (MRI)-based outcome assessment in MS clinical trials because it reflects diffuse pathologic processes that are not accounted for by lesion measurements, and yet it can still be measured from images acquired with conventional MRI pulse sequences. Gray matter atrophy may provide a feasible measure of the extent of cortical pathology.

Single photon emission computed tomography (SPECT) and positron emission tomography (PET) are among the earliest developed functional imaging techniques. SPECT images are acquired after administration of a radioactive compound that emits single photons that can be detected by gamma-cameras. Similar to SPECT, PET imaging also uses radioactive biotracers to monitor physiological processes. However, better localization is achieved in PET imaging. Functional magnetic resonance imaging (fMRI) can be used with several different experimental designs to answer distinct questions about brain function. Multiple sclerosis (MS) disease-related brain changes including the presence of focal lesions and atrophy can complicate functional neuroimaging studies. Functional imaging is utilized to study fatigue, depression, motor system, vision, cognition, and for interpretation of cortical reorganization. Functional imaging plays a much larger role in clinical trials for MS involving remyelination, cell grats, neuroprotective treatments, and in illuminating the mechanisms of progressive disease.