Imaging the spinal cord in vivo is challenging for several reasons, which include the small size of the target tissue and the presence of motion artifacts, such as cardiac pulsation and respiration. In detail, the cervical cord cross-sectional area is only about 1 cm in size, and submillimeter spatial resolution is necessary to distinguish with relative accuracy gray matter from white matter. Furthermore, the sensitivity of MTR to detect pathology depends on the available signal-to-noise ratio, and it is necessary to minimize the motion between scans with and without off-resonance saturation pulse. In an attempt to overcome these limitations, we optimized our MTR map creation procedure, which has been described previously,8 by adding 2 coregistrations of magnetization transfer and reference images to improve both gross and fine motion correction. The segmentation of cord gray matter also has a unique advantage in that it is affected only a very tiny amount by cerebrospinal fluid volume averaging because only the inner border of the gray matter is contiguous to the cerebrospinal fluid contained in the central canal. The pixels at the larger outer edge of the cord are contiguous to those of the white matter, which is characterized by higher MTR values than gray matter (thus, if it had any effect, partial volume averaging is likely to have reduced the difference between patients and controls and not the opposite). For the same reasons, we decided a priori to select patients without focal cord lesions (which are known to have MTR values lower than those of normal-appearing tissues) and not to study cord white matter MTR and volumetry. As a consequence, although we cannot exclude contamination of gray matter MTR data from partial volume averaging from the surrounding white matter, we do believe this did not affect our results a great deal; at any rate, it might have worked against the detection of gray matter MTR changes. Furthermore, we acknowledge that these results were obtained from patients with no T2-visible cervical cord lesions and, therefore, might not be representative of the general population of patients with RRMS. Nevertheless, it is conceivable that intrinsic cord lesions might be associated with even more damage to the gray matter due to wallerian and anterograde degeneration.