A myelin-specific contrast agent for magnetic resonance imaging of myelination

Myelination is one of the most fundamental biological processes in the development of vertebrate nervous systems. Abnormal or disrupted myelination occurs in many acquired or inherited neurodegenerative diseases, including multiple sclerosis (MS) and various leukodystrophies. To date, magnetic resonance imaging (MRI) has been the primary tool for diagnosing and monitoring the progression of MS and related diseases; however, any change in signal intensity of conventional MRI reflects a change only in tissue water content, which is a nonspecific measure of the overall changes in macroscopic tissue injury. Thus, the use of MRI as a primary measure of disease activity was shown to be disassociated from the clinical outcome due to the lack of specificity for myelination. In order to increase the MRI specificity for myelin pathologies, we designed and synthesized the first Gd-based T(1) MR contrast agent (MIC) that binds to myelin with high specificity. In this Communication, we demonstrate that MIC localizes in brain regions in proportion to the extent of myelination. In addition, MIC possesses promising MR contrast properties, which allow for direct detection of myelin distribution through T(1) mapping in the mouse brain.