Disease-modifying drugs (DMD) are effective in reducing relapses and magnetic resonance imaging (MRI) lesions in multiple sclerosis (MS). Nevertheless, individual treatment responses are variable, and accurate and reliable methods to identify DMD responsiveness have not been validated. Although extremely relevant in the study and management of MS, MRI data have not been systematically tested to answer this question yet. Here we present non-conventional MRI data, including magnetisation transfer imaging (MTI), diffusion-weighted imaging (DWI) and proton magnetic resonance spectroscopy ((1)HMRS). As these techniques are more sensitive to microstructural tissue changes and more specific for the heterogeneous pathological substrates of MS lesions, we anticipate their potential role for detecting relevant changes of tissue pathology during treatment of MS patients and, consequently, for a better definition of response status to therapy.