Imaging immunomodulatory treatment responses in multiple sclerosis using hyperpolarized 13C metabolic magnetic resonance imaging

Abstract In recent years, the ability of conventional magnetic resonance imaging (MRI) to monitor high efficacy therapies and predict long-term disability in multiple sclerosis (MS) has been challenged. Here we used hyperpolarized 13C MR spectroscopy (MRS) metabolic imaging in a MS model of inflammatory-mediated demyelinating disease with widespread demyelination of the central nervous system (CNS). We showed that hyperpolarized metabolic imaging could monitor immune cell activation by measuring hyperpolarized [1-13C]pyruvate conversion to lactate and demonstrated that this approach detected response to two existing treatments, fingolimod and dimethyl fumarate. We observed a reduction of pyruvate-to-lactate flux after treatment, that can be explained by increased pyruvate dehydrogenase activity and decrease of immune cells. In addition, we evaluated brain perfusion using hyperpolarized [13C]urea, but saw no therapy effect. In conclusion, hyperpolarized magnetic resonance spectroscopy of [1-13C]pyruvate could provide a new non-invasive way to more directly detect immunological responses to disease-modifying therapies in MS and other diseases of the CNS.