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Abstract #0165

Metabolic imaging of neuroinflammation in the cuprizone mouse model for Multiple Sclerosis using hyperpolarized [1-13C] pyruvate

Caroline Guglielmetti1,2,3, Chloe Najac2, Annemie Van der Linden3, Sabrina Ronen2,4, and Myriam Chaumeil1,2

1Department of Physical Therapy and Rehabilitation Science, University of California San Francisco, San Francisco, CA, United States, 2Surbeck Laboratory of Advanced Imaging, Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA, United States, 3Bio-Imaging Lab, Department Pharmaceutical, Veterinary and Biomedical Sciences, University of Antwerp, Antwerp, Belgium, 4Surbeck Laboratory of Advanced Imaging, Department of Radiology and Biomedical Imaging, San Francisco, CA, United States

Our study demonstrates that metabolic imaging of hyperpolarized [1-13C] pyruvate can detect increased hyperpolarized lactate production in vivo in highly inflammatory white matter lesions in a preclinical model of Multiple Sclerosis. Increased lactate production was associated with the presence of pro-inflammatory macrophages upregulating pyruvate dehydrogenase kinase 1, as well as regional inhibition of pyruvate dehydrogenase, providing a likely mechanism for a decrease subsequent flux of pyruvate towards the Krebs cycle. Our study demonstrates that metabolic imaging of hyperpolarized [1-13C] pyruvate has high potential for in-vivo detection and monitoring of neuroinflammation levels during demyelination and remyelination.

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