Quantitative MRI has the potential to be tremendously useful in clinical research, but its use has so far been hampered by problems such as low signal-to-noise ratio and low accuracy. In this paper, Mezer et al. show how quantitative MRI can be combined with other imaging techniques to enhance the measurement of the macromolecular tissue volume (MTV) and the quantification of tissue reorganization. They also show that MTV can be used to monitor white matter volume changes in patients with multiple sclerosis — with potential for monitoring neuroanatomical changes in other clinical disorders.