Guidelines for using proton MR spectroscopy in multicenter clinical MS studies

Proton MR spectroscopy (MRS) allows noninvasive characterization of chemical-pathologic changes in the brain. In patients with multiple sclerosis (MS), proton MRS reveals chemical pathology in focal inflammatory lesions as well as in regions of the brain that are not associated with structural abnormalities on conventional MRI. In MS studies, it has been particularly useful as a method for the assessment of neurodegeneration based on decreases in the levels of the neuro-axonal marker compound, N-acetylaspartate. Also, MRS has provided evidence of chemical pathology and repair involving non-neuronal brain cells based on changes in metabolites, including choline, myo-inositol, glutamate, and GABA. Despite its greater pathologic specificity for axonal integrity compared to conventional MRI, MRS has been used only infrequently in clinical trials. This prompted us to review current MRS clinical applications in MS, discuss the potential and limitations of the technique, and suggest recommendations for the application of MRS to clinical trials.