Measuring Demyelination and Remyelination in Acute Multiple Sclerosis Lesion Voxels

OBJECTIVE: To validate the use of the magnetization transfer ratio (MTR) as a practical imaging marker of demyelination and remyelination in acute multiple sclerosis lesions. DESIGN: Case study. SETTING: University hospital multiple sclerosis clinic. Patients Six patients with relapsing-remitting multiple sclerosis and acute gadolinium-enhancing lesions were studied serially using a quantitative magnetization transfer examination. MAIN OUTCOME MEASURES: Changes in the water content and macromolecular content, a marker of myelin content that, unlike MTR, is not affected by changes in water content (edema) associated with acute inflammation, and changes in MTR of lesions. RESULTS: Both the macromolecular content and MTR were lower than normal in acute lesions and recovered over several months. The decrease in macromolecular content relative to contralateral normal-appearing white matter was greater than the decrease in MTR (0.46 vs 0.75 at the time of gadolinium enhancement), likely because edema in the acute lesion increased the T1 relaxation time of water and attenuated the decrease in MTR. Nevertheless, there was still a strong correlation between changes in the relative MTR and macromolecular content (R(2) = 0.70; P < .001). CONCLUSION: Our data support the use of MTR as a practical marker of demyelination and remyelination, even in acute lesions where decreases in MTR are attenuated because of the effects of edema.