Hyperpolarized ¹³ C MR metabolic imaging can detect neuroinflammation in vivo in a multiple sclerosis murine model

Significance Cells from the innate immune system, namely microglia and macrophages (mononuclear phagocytes, MPs), play a central role in the progression of neurological disorders such as multiple sclerosis. Such cells can contribute to lesion formations (proinflammatory) or participate in remyelinating processes (neuroprotective). When differentiated to a proinflammatory phenotype, MPs experience metabolic reprogramming leading to increased glycolysis and production of lactate. In this study we showed that a new metabolic imaging method, namely 13 C magnetic resonance spectroscopic imaging (MRSI) of hyperpolarized pyruvate, can detect increased lactate production from proinflammatory MPs, a mechanism mediated by pyruvate dehydrogenase kinase 1 upregulation, in a preclinical model of multiple sclerosis. These findings validate the potential of 13 C MRSI of hyperpolarized pyruvate for in vivo detection of neuroinflammation.