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Abstract #0024

Hyperpolarized 13C MRSI detects immunomodulatory responses to dimethyl fumarate and fingolimod therapies in a model of multiple sclerosis

Caroline Guglielmetti1,2, Christian Cordano3, Chloe Najac4, Ari Green3, and Myriam Chaumeil1,2
1Department of Physical Therapy and Rehabilitation Science, University of California San Francisco, San Francisco, CA, United States, 2Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA, United States, 3Department of Neurology, University of California San Francisco, San Francisco, CA, United States, 4Department of Radiology, C.J. Gorter Center for High Field MRI, Leiden University Medical Center, Leiden, Netherlands

Synopsis

Keywords: Multiple Sclerosis, Hyperpolarized MR (Non-Gas)We used hyperpolarized 13C MR spectroscopy imaging (MRSI) in a multiple sclerosis model and showed that we could monitor immune cell activation by measuring hyperpolarized [1-13C]pyruvate conversion to lactate. We further 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. Altogether, we demonstrated that hyperpolarized 13C MRSI has potential to monitor immunomodulatory therapies within the central nervous system.

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