Magnetic Resonance Imaging Techniques in Phase III Clinical Trials in Multiple Sclerosis

Abstract

When the lesions of multiple sclerosis (MS) were first seen on magnetic resonance images [1], the possibility for being able to measure those lesions was very exciting [2]. Natural history studies of MS patients using frequent scanning [3–6] revealed that new lesions could be seen to form and previously stable lesions could be seen to enlarge. When gadolinium (Gd) enhancement became available, these morphologically active lesions could be seen to enhance [6]. Based upon this natural history experience the concept of using magnetic resonance imaging (MRI), not only in the diagnosis of MS, but also in monitoring therapeutic trials became possible. The direct measurement of pathological events by MRI as they evolved required a systematic approach to repeated imaging and analysis. As the clinical evaluations in therapeutic trials, acute phase monitoring by frequent scanning could identify new pathological activity (the MRI equivalent to relapses) and chronic phase monitoring could measure the extent of the pathology (roughly equivalent for MRI in concept to the Expanded Disability Status Score (EDSS) [7] as a global scale of neurological impairment) [8]. As more experience accumulated, guidelines were adopted for monitoring therapeutic trials [9, 10] including quantitative measures [11].