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Abstract #3003

Hyperpolarized 13C MRSI of pyruvate and urea can detect immunomodulatory responses to dimethyl fumarate therapy in a model of multiple sclerosis

Caroline Guglielmetti1,2, Christian Cordano3, Chloe Najac4, Ari Green3, and Myriam M 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

We used hyperpolarized 13C magnetic resonance spectroscopic imaging (HP 13C MRSI) and T1-MRI to assess dimethyl fumarate (DMF) response in a model of multiple sclerosis (MS). Gadolinium-enhanced T1-MRI showed blood-brain-barrier breakdown, regardless of DMF treatment. In contrast, DMF therapy prevented an increase compared to untreated MS animals in HP 13C lactate, HP 13C lactate-to-pyruvate and HP 13C lactate-to-(pyruvate/urea) ratios. HP 13C MRSI findings were further correlated to pyruvate dehydrogenase activity and pro-inflammatory macrophages. Altogether, we demonstrated that HP 13C MRSI has potential to monitor the effect of immunomodulatory therapies within the central nervous system.

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