Abstract #4768

Assessing the optimal preparation strategy to minimize variability of pyruvate dehydrogenase flux measurements with hyperpolarized [1-13C]pyruvate MRS in control and type 2 diabetic rats

Kerstin N Timm¹, Andrew Apps², Vicky Ball¹, Jack J Miller^1,2,3, Michael S Dodd¹, and Damian J Tyler^1,2

¹Department of Physiology Anatomy and Genetics, University of Oxford, Oxford, United Kingdom, ²Oxford Center for Clinical Magnetic Resonance Research, University of Oxford, Oxford, United Kingdom, ³Department of Physics, University of Oxford, Oxford, United Kingdom

Hyperpolarized [1-¹³C] pyruvate MRS measures pyruvate dehydrogenase (PDH) flux in vivo in the heart through ¹³C-label incorporation into bicarbonate. Substrate availability modulates PDH flux; clinical protocols attempt to standardize flux with oral glucose loading prior to scanning, while rodents in preclinical studies are scanned in the fed state. We set out to establish whether feeding or glucose loading leads to more reproducible measurements of PDH flux in control rats, and found a variability of 45.1% in fed and 50.0% in glucose-loaded animals. Furthermore, glucose loading did not alter the low PDH flux seen in type II diabetic rats.

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