Magnetization transfer (MT) is a technique that has the potential for detecting changes in myelin. The rigid macromolecular structure of myelin is the physical basis of MT. By using off-resonance irradiation, macromolecular protons can be saturated. These protons then exchange with free-water protons and produce a decrease in signal intensity of the free-water protons. This can be quantitated by using a magnetization transfer ratio (MTR) of signal intensities (Mo-Ms/Mo. Mo represents the signal intensity without off-resonance irradiation, and Ms represents the signal intensity with off-resonance irradiation). This method has been sensitive to changes in a spectrum of white-matter lesions, including an edema model (EAE), and regions of apparent myelin loss in patients with multiple sclerosis (MS). Furthermore, MTRs may be abnormal in patients with normal-appearing white matter, demonstrated by standard MR imaging. MTRs may enable subcategorization of MS lesions into lesions with low MTRs (presumed to be demyelinating lesions) and lesions with higher values (primarily edematous lesions). Another important use of MT is, in conjunction with gadolinium, to increase the number and extent of enhancing MS lesions. This can improve the detection of blood-brain barrier abnormalities in patients with MS.